The effect of endometrial injury on ongoing pregnancy rate in unselected subfertile women undergoing in vitro fertilization: a randomized controlled trial.

PubMed

Yeung, Tracy Wing Yee; Chai, Joyce; Li, Raymond Hang Wun; Lee, Vivian Chi Yan; Ho, Pak Chung; Ng, Ernest Hung Yu

2014-11-01

Does endometrial injury in the cycle preceding ovarian stimulation for in vitro fertilization (IVF) improve the ongoing pregnancy rate in unselected subfertile women? Endometrial injury induced by endometrial aspiration in the preceding cycle does not improve the ongoing pregnancy rate in unselected subfertile women undergoing IVF. Implantation failure remains one of the major limiting factors for IVF success. Mechanical endometrial injury in the cycle preceding ovarian stimulation of IVF treatment has been shown to improve implantation and pregnancy rates in women with repeated implantation failures. There is limited data on unselected subfertile women, especially those undergoing their first IVF treatment. This randomized controlled trial recruited 300 unselected subfertile women scheduled for IVF/ICSI treatment between March 2011 and August 2013. Subjects were randomized into endometrial aspiration (EA) (n = 150) and non-EA (n = 150) groups according to a computer-generated randomization list. Subjects were recruited and randomized in the assisted reproductive unit at the University of Hong Kong. In the preceding cycle, women in the EA group underwent endometrial aspiration using a Pipelle catheter in mid-luteal phase. All women were treated with a cycle of IVF/ICSI. Pregnancy outcomes were compared. There were no significant differences in baseline or cycle characteristics between the groups. There were 209 subjects (69.7%) who were undergoing their first IVF cycle and 91 (30.3%) subjects who had repeated cycles. There was no significant difference in ongoing pregnancy rates [26.7% (40/150) versus 32.0% (48/150); RR 0.833 (95% CI 0.585-1.187), P = 0.375] in the EA and non-EA groups. The implantation rates [32.8% (67/204) versus 29.7% (68/229); RR 1.080 (95% CI 0.804-1.450), P = 0.120], clinical pregnancy rates [34.0% (51/150) versus 38.0 (57/150); RR 0.895 (95% CI 0.661-1.211), P = 0.548], miscarriage rates [30.3% (17/56) versus 18.6% (11/59), RR 1.628 (95% CI 0.838-3.164), P = 0.150] and multiple pregnancy rates [31.3% (16/51) versus 19.3% (11/57), RR 1.626 (95% CI 0.833-3.172), P = 0.154] were all comparable between the EA and non-EA groups. Subgroup analysis in women having first embryo transfer (n = 209) also demonstrated no significant difference in ongoing pregnancy rates, but for women undergoing repeated cycles (n = 91), the on-going pregnancy rate was significantly lower in the EA group than in the non-EA group. The study aimed at assessing an unselected population of subfertile women by recruiting consecutive women attending our fertility clinic. However, since the majority of the recruited women (69.7%) were having their first IVF treatments, the results may not be generalizable to all women undergoing IVF. Previous RCTs and meta-analyses have suggested improved pregnancy rates after pretreatment endometrial injury in women with repeated implantation failure. A recent RCT also showed increased pregnancy rates in unselected subfertile women after endometrial injury, although that study was terminated early and thus underpowered. Our study showed with adequate power that no significant improvement in pregnancy rates was observed after endometrial injury in unselected women undergoing IVF treatment. The study was supported by the Small Project Funding 201309176012 of the Committee on Research and Conference Grants, University of Hong Kong. The authors have nothing to disclose. HKCTR-1646 and NCT 01977976. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Anxiety and its inducing factors in men undergoing in vitro fertilization and embryo transfer].

PubMed

Shu, Ling; Chen, Dan; Jiang, Ling; Zhang, Qiong; Jiang, Li-Ping

2016-11-01

To explore the prevalence of anxiety and its inducing factors in men undergoing in vitro fertilization and embryo transfer (IVF-ET). We randomly selected 202 men undergoing IVF-ET in the Infertility and Reproduction Center of the Second Xiangya Hospital of Central South University. On the first day of the IVF-ET cycle, we completed an investigation among the men using a self-designed questionnaire, Self-Rating Anxiety Scale (SAS), Social Support Rating Scale (SSRS), and 3 subscales (marital satisfaction, husband-wife communication, and sexual relationship) of Olson Marital Inventory. Mild anxiety was found in 55 (27.2%) of the included men while the other 147 (72.8%) were non-anxiety males. Compared with the non-anxiety group, the anxiety group showed significant decreases in the total SSRS score (38.65±4.87 vs 36.44±4.21), objective support score (9.22±1.82 vs 8.36±1.18), and utility degree of social support score (6.89±1.50 vs 6.24±1.61) on the first day of the treatment cycle (P<0.01) as well as in the total scores of marital satisfaction (103.04±9.97 vs 96.89±9.90), husband-wife communication (32.29±4.24 vs 30.56±5.43), and sexual relationship (38.03±5.27 vs 34.20±4.41) (P<0.05). There were statistically significant differences in the incidence rate of anxiety in the men with different housing conditions, monthly incomes, treatment costs, attitudes towards IVF-ET, pressure from social opinion, status of parenthood (P<0.01). Multivariate logistic regression analysis indicated that the major factors associated with anxiety included the attitude towards IVF-ET, pressure from social opinion, and sexual relationship in the men undergoing IVF-ET (P<0.05). The incidence rate of anxiety is high in males undergoing IVF-ET and it is associated with various factors. Psychological aid is needed to these male patients from the staff of the reproduction center.

Women show a higher level of anxiety during IVF treatment than men and hold different concerns: a cohort study.

PubMed

Schaller, Martin Alexander; Griesinger, Georg; Banz-Jansen, Constanze

2016-05-01

The aim of the present study was to determine levels of anxiety during the course of IVF treatment and gender differences in treatment anxiety. This was a prospective cohort study set in a university affiliated, tertiary care IVF program. 119 women and 82 men entering the clinic to undergo IVF treatment filled out questionnaires containing the Spielberger state-trait-anxiety-inventory (STAI) as well as further items on specific stress triggers. Women and men undergoing IVF have higher levels of anxiety than the average population in Germany. Overall, female patients show significantly higher values (mean ± SD) for state and trait anxiety (47.4 ± 11.0 and 40.1 ± 9.85) than their male partners (41.4 ± 9.66 and 35.3 ± 8.57, p < 0.01). Over the course of several IVF cycles, average STAI scores increased for both genders. When asked about specific stress factors on a 4-point scale from 'not at all' to 'very much so', women report as their main anxiety the failure to achieve a successful pregnancy, scoring significantly higher on questions like 'obtaining a negative pregnancy test' (3.24 ± 0.82, p < 0.01) and 'disclosure of infertility' (3.02 ± 1.10, p < 0.001). Their male partners are more concerned about the health risks the women have to take such as 'side effects of ovarian stimulation' (2.55 ± 0.77, p = 0.002) and 'bleeding or infection after the oocyte aspiration' (2.58 ± 0.84, p = 0.007). Both genders indicated to be very little worried about multiple pregnancies after IVF. Women show a higher level of anxiety during IVF treatment and hold different concerns. Neither of the sexes appears to be familiar with the risks associated with multiple pregnancies, a matter that should better be addressed.

The Effect of Complementary and Alternative Medicine on Subfertile Women with In Vitro Fertilization

PubMed Central

Zhang, Yuehui; Fu, Yiman; Han, Fengjuan; Kuang, Hongying; Hu, Min; Wu, Xiaoke

2014-01-01

About 10–15% of couples have difficulty conceiving at some point in their reproductive lives and thus have to seek specialist fertility care. One of the most commonly used treatment options is in vitro fertilization (IVF) and its related expansions. Despite many recent technological advances, the average IVF live birth rate per single initiated cycle is still only 30%. Consequently, there is a need to find new therapies to promote the efficiency of the procedure. Many patients have turned to complementary and alternative medical (CAM) treatments as an adjuvant therapy to improve their chances of success when they undergo IVF treatment. At present, several CAM methods have been used in infertile couples with IVF, which has achieved obvious effects. However, biologically plausible mechanisms of the action of CAM for IVF have not been systematically reviewed. This review briefly summarizes the current progress of the impact of CAM on the outcomes of IVF and introduces the mechanisms. PMID:24527047

The preconception diet is associated with the chance of ongoing pregnancy in women undergoing IVF/ICSI treatment.

PubMed

Twigt, J M; Bolhuis, M E C; Steegers, E A P; Hammiche, F; van Inzen, W G; Laven, J S E; Steegers-Theunissen, R P M

2012-08-01

Subfertility and poor nutrition are increasing problems in Western countries. Moreover, nutrition affects fertility in both women and men. In this study, we investigate the association between adherence to general dietary recommendations in couples undergoing IVF/ICSI treatment and the chance of ongoing pregnancy. Between October 2007 and October 2010, couples planning pregnancy visiting the outpatient clinic of the Department of Obstetrics and Gynaecology of the Erasmus Medical Centre in Rotterdam, the Netherlands were offered preconception counselling. Self-administered questionnaires on general characteristics and diet were completed and checked during the visit. Six questions, based on dietary recommendations of the Netherlands Nutrition Centre, covered the intake of six main food groups (fruits, vegetables, meat, fish, whole wheat products and fats). Using the questionnaire results, we calculated the Preconception Dietary Risk score (PDR), providing an estimate of nutritional habits. Dietary quality increases with an increasing PDR score. We define ongoing pregnancy as an intrauterine pregnancy with positive heart action confirmed by ultrasound. For this analysis we selected all couples (n=199) who underwent a first IVF/ICSI treatment within 6 months after preconception counselling. We applied adjusted logistic regression analysis on the outcomes of interest using SPSS. After adjustment for age of the woman, smoking of the woman, PDR of the partner, BMI of the couple and treatment indication we show an association between the PDR of the woman and the chance of ongoing pregnancy after IVF/ICSI treatment (odds ratio 1.65, confidence interval: 1.08-2.52; P=0.02]. Thus, a one-point increase in the PDR score associates with a 65% increased chance of ongoing pregnancy. Our results show that increasing adherence to Dutch dietary recommendations in women undergoing IVF/ICSI treatment increases the chance of ongoing pregnancy. These data warrant further confirmation in couples achieving a spontaneous pregnancy and in randomized controlled trials.

Acupuncture to improve live birth rates for women undergoing in vitro fertilization: a protocol for a randomized controlled trial.

PubMed

Smith, Caroline A; de Lacey, Sheryl; Chapman, Michael; Ratcliffe, Julie; Norman, Robert J; Johnson, Neil; Sacks, Gavin; Lyttleton, Jane; Boothroyd, Clare

2012-05-18

IVF is a costly treatment option for women, their partners, and the public. Therefore new therapies that improve reproductive and health outcomes are highly desirable. There is a growing body of research evaluating the effect of acupuncture administered during IVF, and specifically on the day of embryo transfer (ET). Many trials are heterogeneous and results inconsistent. There remains insufficient evidence to determine if acupuncture can enhance live birth rates when used as an adjunct to IVF treatment.The study will determine the clinical effectiveness of acupuncture with improving the proportion of women undergoing IVF having live births. Other objectives include: determination of the cost effectiveness of IVF with acupuncture; and examination of the personal and social context of acupuncture in IVF patients, and examining the reasons why the acupuncture may or may not have worked. We will conduct a randomized controlled trial of acupuncture compared to placebo acupuncture.Inclusion criteria include: women aged less than 43 years; undergoing a fresh IVF or ICSI cycle; and restricted to women with the potential for a lower live birth rate defined as two or more previous unsuccessful ETs; and unsuccessful clinical pregnancies of quality embryos deemed by the embryologist to have been suitable for freezing by standard criteria. Women will be randomized to acupuncture or placebo acupuncture. Treatment is administered on days 6 to 8 of the stimulated cycle and two treatments on the day of ET. A non-randomized cohort of women not using acupuncture will be recruited to the study. The primary study outcome is the proportion of women reporting a live birth. Secondary outcomes include the proportion of women reporting a clinical pregnancy miscarriage prior to 12 weeks, quality of life, and self-efficacy. The sample size of the study is 1,168 women, with the aim of detecting a 7% difference in live births between groups (P = 0.05, 80% power). There remains a need for further research to add significant new knowledge to defining the exact role of certain acupuncture protocols in the management of infertility requiring IVF from a clinical and cost-effectiveness perspective. Australian and New Zealand Clinical Trial Registry ACTRN12611000226909.

Acupuncture to improve live birth rates for women undergoing in vitro fertilization: a protocol for a randomized controlled trial

PubMed Central

2012-01-01

Background IVF is a costly treatment option for women, their partners, and the public. Therefore new therapies that improve reproductive and health outcomes are highly desirable. There is a growing body of research evaluating the effect of acupuncture administered during IVF, and specifically on the day of embryo transfer (ET). Many trials are heterogeneous and results inconsistent. There remains insufficient evidence to determine if acupuncture can enhance live birth rates when used as an adjunct to IVF treatment. The study will determine the clinical effectiveness of acupuncture with improving the proportion of women undergoing IVF having live births. Other objectives include: determination of the cost effectiveness of IVF with acupuncture; and examination of the personal and social context of acupuncture in IVF patients, and examining the reasons why the acupuncture may or may not have worked. Methods We will conduct a randomized controlled trial of acupuncture compared to placebo acupuncture. Inclusion criteria include: women aged less than 43 years; undergoing a fresh IVF or ICSI cycle; and restricted to women with the potential for a lower live birth rate defined as two or more previous unsuccessful ETs; and unsuccessful clinical pregnancies of quality embryos deemed by the embryologist to have been suitable for freezing by standard criteria. Women will be randomized to acupuncture or placebo acupuncture. Treatment is administered on days 6 to 8 of the stimulated cycle and two treatments on the day of ET. A non-randomized cohort of women not using acupuncture will be recruited to the study. The primary study outcome is the proportion of women reporting a live birth. Secondary outcomes include the proportion of women reporting a clinical pregnancy miscarriage prior to 12 weeks, quality of life, and self-efficacy. The sample size of the study is 1,168 women, with the aim of detecting a 7% difference in live births between groups (P = 0.05, 80% power). Discussion There remains a need for further research to add significant new knowledge to defining the exact role of certain acupuncture protocols in the management of infertility requiring IVF from a clinical and cost-effectiveness perspective. Clinical Trial Registration Australian and New Zealand Clinical Trial Registry ACTRN12611000226909 PMID:22607192

Hair mercury concentrations and in vitro fertilization (IVF) outcomes among women from a fertility clinic

PubMed Central

Ehrlich, Shelley; Smith, Kristen; Williams, Paige L.; Chavarro, Jorge E.; Batsis, Maria; Toth, Thomas L.; Hauser, Russ

2015-01-01

Total hair mercury (Hg) was measured among 205 women undergoing in vitro fertilization (IVF) treatment and the association with prospectively collected IVF outcomes (229 IVF cycles) was evaluated. Hair Hg levels (median=0.62 ppm, range: 0.03-5.66 ppm) correlated with fish intake (r=0.59), and exceeded the recommended EPA reference of 1ppm in 33% of women. Generalized linear mixed models with random intercepts accounting for within-woman correlations across treatment cycles were used to evaluate the association of hair Hg with IVF outcomes adjusted for age, body mass index, race, smoking status, infertility diagnosis, and protocol type. Hair Hg levels were not related to ovarian stimulation outcomes (peak estradiol levels, total and mature oocyte yields) or to fertilization rate, embryo quality, clinical pregnancy rate or live birth rate. PMID:25601638

Do Asian women do as well as their Caucasian counterparts in IVF treatment: Cohort study.

PubMed

Kan, Andrew; Leung, Peter; Luo, Kehui; Fay, Louise; Tan, Chunyan Leeann

2015-06-01

To evaluate if there is a difference in pregnancy rate between Asian and Caucasian women when they undergo in vitro fertilization (IVF). This was a retrospective cohort study set in a private reproductive medicine clinic. The study consisted of a total of 2594 patients (Asian, n = 522; Caucasian, n = 2072) undergoing IVF managed by a single doctor over a 10 year period. The main outcome measures were clinical pregnancy rate and live birth rate. Logistic regression was used to control for confounding factors. Asian women achieved a significantly lower clinical pregnancy and live birth rate than their Caucasian counterparts, despite replacement of more embryos. This difference was not significant after controlling for age and duration of infertility. Despite higher doses of gonadotrophin, they achieved fewer oocytes and had resultant fewer embryos for transfer or cryopreservation. In a study designed to reduce the effect of confounding factors by looking at a large number of patients from a single IVF unit under the care of a single doctor, there does not appear to be a difference in IVF pregnancy rate as a result of race. Asian women tend to present for IVF treatment at a later age after having tried for a longer period of time and this contributes significantly to their lower pregnancy rate. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Follicular development and hormonal levels following highly purified or recombinant follicle-stimulating hormone administration in ovulatory women undergoing ovarian stimulation after pituitary suppression for in vitro fertilization: implications for implantation potential.

PubMed

Balasch, J; Fábregues, F; Creus, M; Peñarrubia, J; Vidal, E; Carmona, F; Puerto, B; Vanrell, J A

2000-01-01

The main goal in the present study was to compare follicular development and estradiol levels after ovarian stimulation in pituitary suppressed normally ovulating women undergoing IVF, using highly purified urinary follicle stimulating hormone (FSH) (u-FSH-HP) and recombinant FSH (rec-FSH). A secondary variable in our study was embryo implantation potential, which is closely related to appropriate follicular development and oocyte competence. For the main purpose of this study, 30 IVF patients (group 1) were treated during IVF consecutive cycles, using the same stimulation protocol, with u-FSH-HP in the first treatment study cycle and rec-FSH in the second one. As a control group (group 2) for implantation rates obtained in cycles treated with rec-FSH, 30 additional IVF patients were included who underwent a second IVF attempt again with u-FSH-HP. The total dose of FSH used and ovarian response obtained in terms of estradiol plasma levels and the total number of growing follicles on the day of human chronic gonadotropin (HCG) injection were similar in both treatment cycles in group 1 but better follicular dynamics and oocyte maturity were obtained with rec-FSH. The implantation rate was significantly higher in rec-FSH treated cycles in patients in group 1 than in control women (group 2). rec-FSH is more efficacious than u-FSH-HP when used in the same patient in inducing multiple follicular development in down-regulated cycles as indicated by ovarian performance and oocyte maturity. In addition, rec-FSH yields significantly higher implantation rates than u-FSH-HP when used in patients undergoing their second IVF attempt.

The long path to pregnancy: early experience with dual anonymous gamete donation in a European in vitro fertilisation referral centre

PubMed Central

2010-01-01

Background This investigation describes features of patients undergoing in vitro fertilisation (IVF) and embryo transfer (ET) where both gametes were obtained from anonymous donors. Methods Gamete unsuitability or loss was confirmed in both members of seven otherwise healthy couples presenting for reproductive endocrinology consultation over a 12-month interval in Ireland. IVF was undertaken with fresh oocytes provided by anonymous donors in Ukraine; frozen sperm (anonymous donor) was obtained from a licensed tissue establishment. For recipients, saline-enhanced sonography was used to assess intrauterine contour with endometrial preparation via transdermal estrogen. Results Among commissioning couples, mean±SD female and male age was 41.9 ± 3.7 and 44.6 ± 3.5 yrs, respectively. During this period, female age for non dual anonymous gamete donation IVF patients was 37.9 ± 3 yrs (p < 0.001). Infertility duration was ≥3 yrs for couples enrolling in dual gamete donation, and each had ≥2 prior failed fertility treatments using native oocytes. All seven recipient couples proceeded to embryo transfer, although one patient had two transfers. Clinical pregnancy was achieved for 5/7 (71.4%) patients. Non-transferred cryopreserved embryos were available for all seven couples. Conclusions Mean age of females undergoing dual anonymous donor gamete donation with IVF is significantly higher than the background IVF patient population. Even when neither partner is able to contribute any gametes for IVF, the clinical pregnancy rate per transfer can be satisfactory if both anonymous egg and sperm donation are used concurrently. Our report emphasises the role of pre-treatment counselling in dual anonymous gamete donation, and presents a coordinated screening and treatment approach in IVF where this option may be contemplated. PMID:20701806

The long path to pregnancy: early experience with dual anonymous gamete donation in a European in vitro fertilisation referral centre.

PubMed

Sills, Eric Scott; Mykhaylyshyn, Lyubov O; Dorofeyeva, Ulyana S; Walsh, David J; Salma, Umme; Omar, Ahmed B; Coull, Graham D; David, Ileana A; Brickell, Kathy M; Tsar, Olga M; Walsh, Anthony Ph

2010-08-11

This investigation describes features of patients undergoing in vitro fertilisation (IVF) and embryo transfer (ET) where both gametes were obtained from anonymous donors. Gamete unsuitability or loss was confirmed in both members of seven otherwise healthy couples presenting for reproductive endocrinology consultation over a 12-month interval in Ireland. IVF was undertaken with fresh oocytes provided by anonymous donors in Ukraine; frozen sperm (anonymous donor) was obtained from a licensed tissue establishment. For recipients, saline-enhanced sonography was used to assess intrauterine contour with endometrial preparation via transdermal estrogen. Among commissioning couples, mean+/-SD female and male age was 41.9 +/- 3.7 and 44.6 +/- 3.5 yrs, respectively. During this period, female age for non dual anonymous gamete donation IVF patients was 37.9 +/- 3 yrs (p < 0.001). Infertility duration was >/=3 yrs for couples enrolling in dual gamete donation, and each had >/=2 prior failed fertility treatments using native oocytes. All seven recipient couples proceeded to embryo transfer, although one patient had two transfers. Clinical pregnancy was achieved for 5/7 (71.4%) patients. Non-transferred cryopreserved embryos were available for all seven couples. Mean age of females undergoing dual anonymous donor gamete donation with IVF is significantly higher than the background IVF patient population. Even when neither partner is able to contribute any gametes for IVF, the clinical pregnancy rate per transfer can be satisfactory if both anonymous egg and sperm donation are used concurrently. Our report emphasises the role of pre-treatment counselling in dual anonymous gamete donation, and presents a coordinated screening and treatment approach in IVF where this option may be contemplated.

Comparison of conventional in vitro fertilisation and intracytoplasmic sperm injection outcomes in patients with moderate oligoasthenozoospermia.

PubMed

Shuai, H-L; Ye, Q; Huang, Y-H; Xie, B-G

2015-06-01

The method of choice for assisted reproductive technology treatment in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) is usually based on the evaluation of male infertility factors. Decisions for couples with moderate oligoasthenozoospermia (OA) are often empirical because uniform treatment criteria are lacking. This study aimed to evaluate the effect of patients with moderate OA treated with conventional IVF and ICSI. A total of 199 couples with moderate OA undergoing their first IVF/ICSI cycle were included in the study. The patients were divided into two groups according to the type of insemination: conventional IVF group (n = 97) and ICSI group (n = 102). All patients were randomised to be inseminated either by conventional IVF or ICSI. The fertilisation rate, embryo quality, implantation rate and clinical pregnancy rate were examined. No differences in the fertilisation, implantation and pregnancy rates were observed between conventional IVF and ICSI groups (P > 0.05). However, the number of good-quality embryos was significantly higher in the ICSI group than in the IVF group (P < 0.05). Couples with moderate OA did not influence on the overall clinical outcomes between IVF and ICSI treatments, and a negative influence by ICSI on blastocyst development was not confirmed. © 2014 Blackwell Verlag GmbH.

Hair mercury concentrations and in vitro fertilization (IVF) outcomes among women from a fertility clinic.

PubMed

Wright, Diane L; Afeiche, Myriam C; Ehrlich, Shelley; Smith, Kristen; Williams, Paige L; Chavarro, Jorge E; Batsis, Maria; Toth, Thomas L; Hauser, Russ

2015-01-01

Total hair mercury (Hg) was measured among 205 women undergoing in vitro fertilization (IVF) treatment and the association with prospectively collected IVF outcomes (229 IVF cycles) was evaluated. Hair Hg levels (median=0.62ppm, range: 0.03-5.66ppm) correlated with fish intake (r=0.59), and exceeded the recommended EPA reference of 1ppm in 33% of women. Generalized linear mixed models with random intercepts accounting for within-woman correlations across treatment cycles were used to evaluate the association of hair Hg with IVF outcomes adjusted for age, body mass index, race, smoking status, infertility diagnosis, and protocol type. Hair Hg levels were not related to ovarian stimulation outcomes (peak estradiol levels, total and mature oocyte yields) or to fertilization rate, embryo quality, clinical pregnancy rate or live birth rate. Copyright © 2015 Elsevier Inc. All rights reserved.

Measurement of antral follicle count in patients undergoing in vitro fertilization treatment: results of a worldwide web-based survey.

PubMed

Christianson, Mindy S; Shoham, Gon; Tobler, Kyle J; Zhao, Yulian; Cordeiro, Christina N; Leong, Milton; Shoham, Zeev

2015-10-01

The purpose of the present study was to identify trends in the therapeutic approaches used to measure antral follicle count (AFC) in patients undergoing in vitro fertilization (IVF) treatment worldwide. A retrospective evaluation utilizing the results of a web-based survey, IVF-Worldwide ( www.IVF-Worldwide.com ), was performed. Responses from 796 centers representing 593,200 cycles were evaluated. The majority of respondents (71.2 %) considered antral follicle count as a mandatory part of their practice with most (69.0 %) measuring AFC in the follicular phase. Most respondents (89.7 %) reported that they would modify the IVF stimulation protocol based on the AFC. There was considerable variation regarding a limit for the number of antral follicles required to initiate an IVF cycle with 46.1 % designating three antral follicles as their limit, 39.9 % selecting either four or five follicles as their limit, and 14.0 % reporting a higher cutoff criteria. With respect to antral follicle size, 61.5 % included follicles ranging between 2 and 10 mm in the AFC. When asked to identify the best predictor of ovarian hyper-response during IVF cycles, AFC was selected most frequently (49.4 %), followed by anti-Mullerian hormone level (42.7 %). Age was selected as the best predictor of ongoing pregnancy rate in 81.7 % of respondents. While a large proportion of respondents utilized AFC as part of their daily practice and modified IVF protocol based on the measurement, the majority did not consider AFC as the best predictor of ongoing pregnancy rate.

Embryo yield after in vitro fertilization in women undergoing embryo banking for fertility preservation before chemotherapy.

PubMed

Robertson, Audra D; Missmer, Stacey A; Ginsburg, Elizabeth S

2011-02-01

To evaluate embryo yield after IVF in patients undergoing embryo banking before chemotherapy. A retrospective cohort study. Hospital-based academic medical center. Thirty-eight women diagnosed with cancer or autoimmune disease presenting for IVF cycles, with or without intracytoplasmic sperm injection (ICSI), for embryo cryopreservation before any therapy were compared with 921 presumably fertile women undergoing IVF for male factor infertility from January 2001 through October 2007. Standard IVF or ICSI protocol, embryo freezing, and ET. The number of 2 pronuclear (2PN) embryos created and suitable for cryopreservation or transfer. No statistically significant differences were observed between preservation and male factor groups for number of embryos, number of oocytes, or amount of gonadotropin needed to stimulate follicular development. Peak serum E(2) levels were significantly lower for women with disease-seeking fertility preservation. Women facing chemotherapy as treatment for cancer or systemic autoimmune disease infrequently undergo fertility preservation. If offered this potentially fertility-preserving option, these data suggest equivalent embryo yield compared with women with infertile male partners. Our data report no significant complications in subsequent births in those who sought fertility preservation, which is informative and encouraging for these women and their providers. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Methylprednisolone for prevention of ovarian hyperstimulation syndrome in patients with polycystic ovarian syndrome undergoing in-vitro fertilisation: a randomised controlled trial.

PubMed

Mohammadi Yeganeh, Ladan; Moini, Ashraf; Shiva, Marzieh; Mirghavam, Naimeh; Bagheri Lankarani, Narges

2018-02-01

This study aimed to evaluate the effect of methylprednisolone on prevention of ovarian hyperstimulation syndrome (OHSS) in polycystic ovarian syndrome (PCOS) patients undergoing in-vitro fertilisation (IVF). This randomised controlled trial was carried out between November 2009 and December 2013. A total of 219 eligible patients were randomly allocated for treatment (n = 108) or control groups (n = 111). The treatment group received oral methylprednisolone starting from the first day of stimulation. These patients also received an intravenous dose of methylprednisolone on the days of egg collection and embryo transfer. The control group received no glucocorticoid treatment to prevent OHSS. Nineteen percent of patients (18/93) who received methylprednisolone developed OHSS compared with 16.5% (15/91) in the control group and no significant difference was found (p = .61). There were no significant differences between treatment and control groups in the rates of implantation (10% versus 11%, p = .77) and clinical pregnancy (23.2% versus 17.7%, p = .46). Methylprednisolone did not reduce the incidence and severity of OHSS in PCOS patients undergoing IVF and no improvement in clinical outcomes was observed. Impact statement No significant differences were found in OHSS incidence and clinical outcomes between women who received methylprednisolone and control group. There seems to be no benefit for the routine use of glucocorticoids in IVF/ICSI treatments.

Ultrasound monitoring in patients undergoing in-vitro fertilization after methotrexate treatment for ectopic pregnancy.

PubMed

Provansal, M; Agostini, A; Lacroix, O; Gerbeau, S; Grillo, J-M; Gamerre, M

2009-12-01

To compare sonographic characteristics of the endometrium and follicles during in-vitro fertilization (IVF) before and after methotrexate (MTX) treatment for ectopic pregnancy. This retrospective study, conducted at Conception Hospital from January 2000 to July 2007, included all patients diagnosed with an ectopic pregnancy resulting from IVF treatment that was treated with MTX and who then underwent another IVF cycle. We compared the number and size of follicles and the endometrial thickness and quality on the day of human chorionic gonadotropin injection in the cycles before and after the MTX treatment to determine whether MTX had any effect. Eleven patients were included in the study. The median interval between the IVF cycle resulting in ectopic pregnancy and the first IVF cycle after MTX therapy was 180 (range, 150-900) days. There was no statistically significant difference between the before and after MTX treatment groups with respect to number of follicles (14 (3-20) vs. 9 (4-16), P = 0.12), follicle size (16.5 (14.7-21.7) mm vs. 17.8 (14.9-19.8) mm, P = 0.37), endometrial thickness (10.0 (9.5-12.0) mm vs. 10.0 (7.5-14.0) mm, P = 0.31) or endometrial quality (P = 0.32). Four women became pregnant during the IVF cycle following MTX treatment. Ultrasound monitoring showed no modification of the characteristics of the endometrium or follicles during IVF after MTX treatment for ectopic pregnancy. Copyright 2009 ISUOG. Published by John Wiley & Sons, Ltd.

Serum oxidizability and antioxidant status in patients undergoing in vitro fertilization.

PubMed

Aurrekoetxea, Igor; Ruiz-Sanz, José Ignacio; del Agua, Ainhoa Ruiz; Navarro, Rosaura; Hernández, M Luisa; Matorras, Roberto; Prieto, Begoña; Ruiz-Larrea, M Begoña

2010-09-01

To evaluate the serum oxidizability and antioxidant status in women undergoing an in vitro fertilization (IVF) cycle and to assess the possible relationship of the oxidizability indexes with the pregnancy rate. Prospective, longitudinal study. Public university and public university hospital. Systematically recruited cohort of 125 women undergoing either IVF or intracytoplasmic sperm injection (ICSI). Serum samples were collected before the beginning of the use of gonadotropins (basal) and the day of human chorionic gonadotropin (hCG) administration (final) during an IVF cycle. The Cu2+-induced serum oxidation in terms of the oxidation rate in the lag (Vlag) and propagation (Vmax) phases and the time at which the oxidation rate is maximal (tmax), and measurements of serum total antioxidant activity (TAA), tocopherol, hydrophilic antioxidants, malondialdehyde, and nitric oxide. Albumin, urate, bilirubin, alpha-tocopherol and gamma-tocopherol, TAA, and tmax statistically significantly decreased after the IVF cycle. Conception cycles were associated with a serum more prone to oxidation compared with nonconception cycles. In multivariate logistic regression analysis, the difference (final-basal) of the oxidation index Vlag (OR 1.394) and the body mass index (OR 0.785) were independent predictors of pregnancy. Treatment with IVF induces the production of reactive oxygen species (ROS), which is reflected in a serum less protected against oxidation. The results also suggest a role for ROS in the occurrence of conception in IVF. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Monitoring stimulated cycles during in vitro fertilization treatment with ultrasound only--preliminary results.

PubMed

Wiser, Amir; Gonen, Ofer; Ghetler, Yehudit; Shavit, Tal; Berkovitz, Arie; Shulman, Adrian

2012-06-01

To evaluate if monitoring patients by ultrasound (US) only during in vitro fertilization (IVF) treatment is safe. Randomized prospective study. Patients undergoing their first IVF treatment were randomized into two groups. The ultrasound only group (study group) was monitored by US for follicle size and endometrial thickness without blood tests. In this group, only one blood test was taken before human chorionic gonadotropin (hCG) injection, to ensure a safe level of estradiol (E(2)) regarding ovarian hyperstimulation syndrome (OHSS) risk. The control group was monitored by ultrasound plus serum estradiol and progesterone concentration at each visit. Clinical pregnancy rate. No differences were found between the groups in the parameters of IVF treatment, induction days, number of ampoules, E(2) level of hCG, as well as embryo quality. The clinical pregnancy rate was not statistically different between the groups, 57.5% vs. 40.0%, respectively (p = 0.25). No OHSS cases were found among the study or control groups. Ultrasound as a single monitoring tool for IVF cycles is reliable, safe, patient friendly, and reduces treatment expenses. In an era of cost effectiveness awareness, this regimen should be considered for routine management in IVF programs.

Cumulative Delivery Rate after Providing Full Reimbursement In Vitro Fertilization Programme: A 6-Years Survey

PubMed Central

Vrtacnik, Urban; Vrtacnik Bokal, Eda

2014-01-01

Since 1983, Slovenia has been offering well-established, successful, and fully reimbursed IVF programme to infertile couples. On the grounds of data gathered at the Slovenian IVF units we aimed to determine whether the fully accessible IVF treatment system can provide notable success considering cumulative delivery rate (cDR). Longitudinal analysis of getting cDR was performed in 810 IVF cycles of 395 couples who for the first time attended the IVF programme in year 2006 and were followed until year 2012. We calculated the actual and the optimistic cDR. In women aged <38 years the actual cDR was 54% and optimistic DR was 83%, respectively. In women aged ≥38 years the actual cDR was 24 % and optimistic cDR was 27%. These results enable us to report that prospects of the treatment for the women aged <38 years, if they undergo all 6 available IVF cycles, are very positive and quite comparable to the chances of spontaneous conception. Even in older patients it is beneficial to repeat the IVF procedures. Therefore we consider the existing infertility treatment system in Slovenia as an example of good medical practice with high level of beneficence offered to the patients. PMID:24734248

A prospective investigation of perceived stress, infertility-related stress, and cortisol levels in women undergoing in vitro fertilization: influence on embryo quality and clinical pregnancy rate.

PubMed

Cesta, Carolyn E; Johansson, Anna L V; Hreinsson, Julius; Rodriguez-Wallberg, Kenny A; Olofsson, Jan I; Holte, Jan; Wramsby, Håkan; Wramsby, Margareta; Cnattingius, Sven; Skalkidou, Alkistis; Nyman Iliadou, Anastasia

2018-03-01

Women undergoing fertility treatment experience high levels of stress. However, it remains uncertain if and how stress influences in vitro fertilization (IVF) cycle outcome. This study aimed to investigate whether self-reported perceived and infertility-related stress and cortisol levels were associated with IVF cycle outcomes. A prospective cohort of 485 women receiving fertility treatment was recruited from September 2011 to December 2013 and followed until December 2014. Data were collected by online questionnaire prior to IVF start and from clinical charts. Salivary cortisol levels were measured. Associations between stress and cycle outcomes (clinical pregnancy and indicators of oocyte and embryo quality) were measured by logistic or linear regression, adjusted for age, body mass index, education, smoking, alcohol and caffeine consumption, shiftwork and night work. Ultrasound verified pregnancy rate was 26.6% overall per cycle started and 32.9% per embryo transfer. Stress measures were not associated with clinical pregnancy: when compared with the lowest categories, the adjusted odds ratio (OR) and 95% confidence interval (CI) for the highest categories of the perceived stress score was 1.04 (95% CI 0.58-1.87), infertility-related stress score was OR = 1.18 (95% CI 0.56-2.47), morning and evening cortisol was OR = 1.18 (95% CI 0.60-2.29) and OR = 0.66 (95% CI 0.34-1.30), respectively. Perceived stress, infertility-related stress, and cortisol levels were not associated with IVF cycle outcomes. These findings are potentially reassuring to women undergoing fertility treatment with concerns about the influence of stress on their treatment outcome. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Systemic methotrexate to treat ectopic pregnancy does not affect ovarian reserve.

PubMed

Oriol, Bárbara; Barrio, Ana; Pacheco, Alberto; Serna, José; Zuzuarregui, José Luis; Garcia-Velasco, Juan A

2008-11-01

To evaluate whether methotrexate (MTX) compromises ovarian reserve and future reproductive outcome in women undergoing assisted reproductive technology (ART), when it is used as first-line treatment for ectopic pregnancy (EP). Prospective, observational study. University-affiliated private IVF unit. Twenty-five women undergoing IVF-ICSI who were treated with MTX (1 mg/kg IM) for an EP after ART. Evaluation of reproductive outcome and serum anti-Müllerian hormone (AMH) levels. Serum AMH was evaluated before administering MTX and >or=1 week after the resolution of the EP. Reproductive outcome was evaluated by comparing subsequent IVF-ICSI cycles after EP resolution. Serum AMH levels, cycle length, gonadotropin dose required, peak serum E(2) level, oocytes collected, and embryos obtained. Serum AMH levels before MTX were not statistically significantly different from those after treatment (3.7 +/- 0.3 ng/mL vs. 3.9 +/- 0.3 ng/mL). Patients undergoing a subsequent cycle after systemic treatment for EP had similar cycle durations (10.3 vs. 10.8 d), gonadotropin requirements (2,775 vs. 2,630.3 IU), peak E(2) levels (1,884.3 vs. 1,523.6 pg/mL), number of oocytes retrieved (12.1 vs. 10.5), and total number of embryos obtained (7.1 vs. 6.5). Single-dose MTX is a safe first-treatment choice that does not compromise future reproductive outcomes in women who are diagnosed with EP after ART.

Kisspeptin as a promising oocyte maturation trigger for in vitro fertilisation in humans.

PubMed

Kasum, Miro; Franulić, Daniela; Čehić, Ermin; Orešković, Slavko; Lila, Albert; Ejubović, Emina

2017-08-01

The aim of this review is to analyse the effectiveness of exogenous kisspeptin administration as a novel alternative of triggering oocyte maturation, instead of currently used triggers such as human chorionic gonadotropin (hCG) or gonadotropin releasing hormone (GnRH) agonist, in women undergoing in vitro fertilisation (IVF) treatment. Kisspeptin has been considered a master regulator of two modes of GnRH and hence gonadotropin secretion, pulses and surges. Administration of kisspeptin-10 and kisspeptin-54 induces the luteinising hormone (LH) surge required for egg maturation and ovulation in animal investigations and LH release during the preovulatory phase of the menstrual cycle and hypothalamic amenorrhoea in humans. Exogenous kisspeptin-54 has been successfully administered as a promising method of triggering oocyte maturation, following ovarian stimulation with gonadotropins and GnRH antagonists in women undergoing IVF, due to its efficacy considering achieved pregnancy rates compared to hCG and GnRH agonists. Also, its safety in patients at high risk of developing ovarian hyperstimulation syndrome is noteworthy. Nevertheless, further studies would be desirable to establish the optimal trigger of egg maturation and to improve the reproductive outcome for women undergoing IVF treatment.

Hysteroscopic tubal electrocoagulation versus laparoscopic tubal ligation for patients with hydrosalpinges undergoing in vitro fertilization.

PubMed

El-Mazny, Akmal; Abou-Salem, Nermeen; Hammam, Mohamed; Saber, Walid

2015-09-01

To investigate the use and success rate of hysteroscopic tubal electrocoagulation for the treatment of hydrosalpinx-related infertility among patients undergoing in vitro fertilization (IVF) who have laparoscopic contraindications. A prospective study was conducted among patients who had unilateral or bilateral hydrosalpinges identified on hysterosalpingography and vaginal ultrasonography, and who were undergoing IVF at a center in Cairo, Egypt, between January 1, 2013, and October 30, 2014. All patients who had contraindications for laparoscopy were scheduled for hysteroscopic tubal electrocoagulation (group 1); the other patients underwent laparoscopic tubal ligation (group 2). For all patients, hysterosalpingography was performed 3 months after their procedure to evaluate proximal tubal occlusion. Among 85 enrolled patients, 22 underwent hysteroscopic tubal electrocoagulation and 63 underwent laparoscopic tubal ligation. The procedure was successful in terms of tubal occlusion for 25 (93%) of 27 hydrosalpinges in group 1, and 78 (96%) of 81 hydrosalpinges in group 2 (P=0.597). No intraoperative or postoperative complications were reported. Hysteroscopic tubal electrocoagulation was found to be a successful treatment for hydrosalpinges before IVF when laparoscopy is contraindicated. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Effect of fibroids not distorting the endometrial cavity on the outcome of in vitro fertilization treatment: a retrospective cohort study.

PubMed

Yan, Lei; Ding, Lingling; Li, Chunyan; Wang, Yu; Tang, Rong; Chen, Zi-Jiang

2014-03-01

To investigate the effect of fibroids that do not distort the endometrial cavity on IVF/intracytoplasmic sperm injection (ICSI) outcomes and to identify certain fibroid subgroups that may be deleterious to fertility outcomes. Retrospective cohort study. University-based reproductive medicine center. A total of 10,268 patients undergoing IVF/ICSI between 2009 and 2011 in our unit. Transvaginal ultrasound and hysteroscopy; controlled ovarian hyperstimulation and IVF/ICSI; strict matching criteria. Cycle cancellation, clinical pregnancy, miscarriage, and delivery rates. We included 249 patients with fibroids who underwent IVF/ICSI. Higher day 3 FSH levels were found in women with fibroids compared with in control subjects. No significant differences were found in IVF/ICSI outcomes between the two groups. Patients with intramural fibroids with the largest diameter <2.85 cm or the sum of reported diameters <2.95 cm had a significantly higher delivery rate than patients with larger fibroids. A significant negative effect on delivery rate was noted when intramural fibroids with the largest diameter greater than 2.85 cm were considered, compared with matched controls without fibroids. Our results suggest that although non-cavity-distorting fibroids do not affect IVF/ICSI outcomes, intramural fibroids greater than 2.85 cm in size significantly impair the delivery rate of patients undergoing IVF/ICSI. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The effect of in vitro fertilization on gingival inflammation according to women's periodontal status: clinical data.

PubMed

Pavlatou, Anthodesmi; Tsami, Alexandra; Vlahos, Nicolaos; Mantzavinos, Themis; Vrotsos, Ioannis

2013-04-01

To study whether in vitrofertilization (IVF) treatment has any effect on women's preexisting periodontal status and, if pre-existing women's periodontal status has any impact on IVF outcomes, such as superovulation for multiple follicles maturation, oocyte retrieval and embryo transfer, as well as on pregnancy and its outcomes. Sixty women aged 29 to 41 years were recruited in the study. Gingival inflammation (simplified gingival index, GI-S), plaque levels (plaque control record index, PCR), bleeding on probing (BOP) and probing depth (PD), were recorded for all participants before and after IVF. Blood tests were performed prior to IVF. A statistically significant increase in GI-S after IVF was observed in all women (31.9 +/- 18.7% to 61.7 +/- 23.5%), and was higher in women with gingivitis (37.1 +/- 5.7% to 77.6 +/- 6.7%). Women with periodontitis demonstrated a statistically significant increase in BOP (67.7 +/- 6.6% to 89.5 +/- 7.1%), and in the sum of probing pocket depths (from 243.8 +/- 56.2 mm to 250.5 +/- 58.3 mm). A trend for negative correlation between the number of follicles and transferred embryos and the gingival index, before and after IVF respectively, was recorded in all women. There was a similar trend with bleeding on probing after IVF in women with periodontitis. Periodontal clinical parameters worsened in women undergoing IVF treatment. On the other hand, a poor pre-existing periodontal status seems to be associated with poorer outcomes of IVF treatment.

The impact of atosiban on pregnancy outcomes in women undergoing in vitro fertilization-embryo transfer: A meta-analysis

PubMed Central

Huang, Qian-Yi; Rong, Min-Hua; Lan, Ai-Hua; Lin, Xiao-Miao; Lin, Xing-Gu; He, Rong-Quan; Chen, Gang; Li, Mu-Jun

2017-01-01

Background Atosiban is administered to women undergoing in vitro fertilization-embryo transfer (IVF-ET) to improve pregnancy outcomes. However, the results of this treatment were controversial. We conducted this meta-analysis to investigate whether atosiban improves pregnancy outcomes in the women undergoing in vitro fertilization (IVF). Methods Databases of PubMed, EMBASE, Web of Science, China BioMedicine, and Google Scholar were systematically searched. Meta-analyses were performed to investigate whether atosiban improves pregnancy outcomes in the women undergoing IVF. Results Our results showed that atosiban was associated with higher implantation (OR = 1.63, 95% CI: 1.17–2.27; P = 0.004) and clinical pregnancy (OR = 1.84, 95% CI: 1.31–2.57; P < 0.001) rates. However, atosiban showed no significant association with the miscarriage, live birth, multiple pregnancy or ectopic pregnancy rates. When a further subgroup analysis was performed in the women undergoing repeated implantation failure (RIF), implantation (OR = 1.93, 95% CI: 1.45–2.57; P < 0.001), clinical pregnancy (OR = 2.48, 95% CI: 1.70–3.64; P <0.001) and the live birth (OR = 2.89, 95% CI: 1.78–4.67; P < 0.001) rates were significantly higher in the case group. Nevertheless, no significant difference was detected in the miscarriage and multiple pregnancy rates between the case and control groups. Conclusion Atosiban may be more appropriate for women undergoing RIF and play only a limited role in improving pregnancy outcomes in the general population of women undergoing IVF. These conclusions should be verified in large and well-designed studies. PMID:28422984

ICSI does not increase the cumulative live birth rate in non-male factor infertility.

PubMed

Li, Z; Wang, A Y; Bowman, M; Hammarberg, K; Farquhar, C; Johnson, L; Safi, N; Sullivan, E A

2018-06-12

What is the cumulative live birth rate following ICSI cycles compared with IVF cycles for couples with non-male factor infertility? ICSI resulted in a similar cumulative live birth rate compared with IVF for couples with non-male factor infertility. The ICSI procedure was developed for couples with male factor infertility. There has been an increased use of ICSI regardless of the cause of infertility. Cycle-based statistics show that there is no difference in pregnancy rates between ICSI and IVF in couples with non-male factor infertility. However, evidence indicates that ICSI is associated with an increased risk of adverse perinatal outcomes. A population-based cohort of 14 693 women, who had their first ever stimulated cycle with fertilization performed for at least one oocyte by either IVF or ICSI between July 2009 and June 2014 in Victoria, Australia was evaluated retrospectively. The pregnancy and birth outcomes following IVF or ICSI were recorded for the first oocyte retrieval (fresh stimulated cycle and associated thaw cycles) until 30 June 2016, or until a live birth was achieved, or until all embryos from the first oocyte retrieval had been used. Demographic, treatment characteristics and resulting outcome data were obtained from the Victorian Assisted Reproductive Treatment Authority. Data items in the VARTA dataset were collected from all fertility clinics in Victoria. Women were grouped by whether they had undergone IVF or ICSI. The primary outcome was the cumulative live birth rate, which was defined as live deliveries (at least one live birth) per woman after the first oocyte retrieval. A discrete-time survival model was used to evaluate the cumulative live birth rate following IVF and ICSI. The adjustment was made for year of treatment in which fertilization occurred, the woman's and male partner's age at first stimulated cycle, parity and the number of oocytes retrieved in the first stimulated cycle. A total of 4993 women undergoing IVF and 8470 women undergoing ICSI had 7980 and 13 092 embryo transfers, resulting in 1848 and 3046 live deliveries, respectively. About one-fifth of the women (19.0% of the IVF group versus 17.9% of the ICSI group) had three or more cycles during the study period. For couples who achieved a live delivery, the median time from oocyte retrieval to live delivery was 8.9 months in both IVF (range: 4.2-66.5) and ICSI group (range: 4.5-71.3) (P = 0.474). Fertilization rate per oocyte retrieval was higher in the IVF than in the ICSI group (59.8 versus 56.2%, P < 0.001). The overall cumulative live birth rate was 37.0% for IVF and 36.0% for ICSI. The overall likelihood of a live birth for women undergoing ICSI was not significantly different to that for women undergoing IVF (adjusted hazard ratio (AHR): 0.99, 95% CI: 0.92-1.06). For couples with a known cause of infertility, non-male factor infertility (female factor only or unexplained infertility) was reported for 64.0% in the IVF group and 36.8% in the ICSI group (P < 0.001). Among couples with non-male factor infertility, ICSI resulted in a similar cumulative live birth rate compared with IVF (AHR: 0.96, 95% CI: 0.85-1.10). Data were not available on clinic-specific protocols and processes for IVF and ICSI and the potential impact of these technique aspects on clinical outcomes. The reported causes of infertility were based on the treating clinician's classification which may vary between clinicians. This population-based study found ICSI resulted in a lower fertilization rate per oocyte retrieved and a similar cumulative live birth rate compared to conventional IVF. These data suggest that ICSI offers no advantage over conventional IVF in terms of live birth rate for couples with non-male factor infertility. No specific funding was received to undertake this study. There is no conflict of interest, except that M.B. is a shareholder in Genea Ltd. N/A.

The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis.

PubMed

Harb, H M; Gallos, I D; Chu, J; Harb, M; Coomarasamy, A

2013-10-01

Endometriosis is found in 0.5-5% of fertile women and 25-40% of infertile women. It is known that endometriosis is associated with infertility, but there is uncertainty whether women with endometriosis have adverse pregnancy outcomes in in vitro fertilisation (IVF) treatment. To explore the association between endometriosis and IVF outcome. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science (inception, December 2012) in all languages, together with reference lists of retrieved papers. Studies comparing IVF outcome in women with endometriosis with women without endometriosis. Patients were classified by stage of endometriosis. The outcomes were fertilisation, implantation, clinical pregnancy and live birth rates. Study selection was conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. Data extraction was conducted independently by two reviewers. Relative risks from individual studies were meta-analysed. Twenty-seven observational studies were included, comprising 8984 women. Meta-analysis of these studies showed that fertilisation rates were reduced in stage I/II of endometriosis (relative risk [RR] = 0.93, 95% confidence interval [95% CI] 0.87-0.99, P = 0.03). There was a decrease in the implantation rate (RR = 0.79, 95% CI 0.67-0.93, P = 0.006) and clinical pregnancy rate (RR = 0.79, 95% CI 0.69-0.91, P = 0.0008) in women with stage III/IV endometriosis undergoing IVF treatment. The presence of severe endometriosis (stage III/IV) is associated with poor implantation and clinical pregnancy rates in women undergoing IVF treatment. © 2013 RCOG.

Influence of TP53 Codon 72 Polymorphism Alone or in Combination with HDM2 SNP309 on Human Infertility and IVF Outcome.

PubMed

Chan, Ying; Zhu, Baosheng; Jiang, Hongguo; Zhang, Jinman; Luo, Ying; Tang, Wenru

2016-01-01

To evaluate the association of the TP53 codon 72 (rs 1042522) alone or in combination with HDM2 SNP309 (rs 2279744) polymorphisms with human infertility and IVF outcome, we collected 1450 infertility women undergoing their first controlled ovarian stimulation for IVF treatment and 250 fertile controls in the case-control study. Frequencies, distribution, interaction of genes, and correlation with infertility and IVF outcome of clinical pregnancy were analyzed. We found a statistically significant association between TP53 codon 72 polymorphism and IVF outcome (52.10% vs. 47.40%, OR = 0.83, 95%CI:0.71-0.96, p = 0.01). No significant difference was shown between TP53 codon 72, HDM2 SNP309 polymorphisms, human infertility, and between the combination of two genes polymorphisms and the clinical pregnancy outcome of IVF. The data support C allele as a protective factor for IVF pregnancy outcome. Further researches should be focused on the mechanism of these associations.

Recipient screening in IVF: first data from women undergoing anonymous oocyte donation in Dublin.

PubMed

Walsh, Anthony P H; Omar, Ahmed B; Marron, Kevin D; Walsh, David J; Salma, Umme; Sills, E Scott

2011-04-20

Guidelines for safe gamete donation have emphasised donor screening, although none exist specifically for testing oocyte recipients. Pre-treatment assessment of anonymous donor oocyte IVF treatment in Ireland must comply with the European Union Tissues and Cells Directive (Directive 2004/23/EC). To determine the effectiveness of this Directive when applied to anonymous oocyte recipients in IVF, we reviewed data derived from selected screening tests performed in this clinical setting. Data from tests conducted at baseline for all women enrolling as recipients (n = 225) in the anonymous oocyte donor IVF programme at an urban IVF referral centre during a 24-month period were analysed. Patient age at programme entry and clinical pregnancy rate were also tabulated. All recipients had at least one prior negative test for HIV, Hepatitis B/C, chlamydia, gonorrhoea and syphilis performed by her GP or other primary care provider before reproductive endocrinology consultation. Mean (±SD) age for donor egg IVF recipients was 40.7 ± 4.2 yrs. No baseline positive chlamydia, gonorrhoea or syphilis screening results were identified among recipients for anonymous oocyte donation IVF during the assessment interval. Mean pregnancy rate (per embryo transfer) in this group was 50.5%. When tests for HIV, Hepatitis B/C, chlamydia, gonorrhoea and syphilis already have been confirmed to be negative before starting the anonymous donor oocyte IVF sequence, additional (repeat) testing on the recipient contributes no new clinical information that would influence treatment in this setting. Patient safety does not appear to be enhanced by application of Directive 2004/23/EC to recipients of anonymous donor oocyte IVF treatment. Given the absence of evidence to quantify risk, this practice is difficult to justify when applied to this low-risk population.

Predictors of treatment failure in young patients undergoing in vitro fertilization.

PubMed

Jacobs, Marni B; Klonoff-Cohen, Hillary; Agarwal, Sanjay; Kritz-Silverstein, Donna; Lindsay, Suzanne; Garzo, V Gabriel

2016-08-01

The purpose of the study was to evaluate whether routinely collected clinical factors can predict in vitro fertilization (IVF) failure among young, "good prognosis" patients predominantly with secondary infertility who are less than 35 years of age. Using de-identified clinic records, 414 women <35 years undergoing their first autologous IVF cycle were identified. Logistic regression was used to identify patient-driven clinical factors routinely collected during fertility treatment that could be used to model predicted probability of cycle failure. One hundred ninety-seven patients with both primary and secondary infertility had a failed IVF cycle, and 217 with secondary infertility had a successful live birth. None of the women with primary infertility had a successful live birth. The significant predictors for IVF cycle failure among young patients were fewer previous live births, history of biochemical pregnancies or spontaneous abortions, lower baseline antral follicle count, higher total gonadotropin dose, unknown infertility diagnosis, and lack of at least one fair to good quality embryo. The full model showed good predictive value (c = 0.885) for estimating risk of cycle failure; at ≥80 % predicted probability of failure, sensitivity = 55.4 %, specificity = 97.5 %, positive predictive value = 95.4 %, and negative predictive value = 69.8 %. If this predictive model is validated in future studies, it could be beneficial for predicting IVF failure in good prognosis women under the age of 35 years.

Factors Associated with Failed Treatment: an Analysis of 121,744 Women Embarking on Their First IVF Cycles

PubMed Central

Bhattacharya, Siladitya; Maheshwari, Abha; Mollison, Jill

2013-01-01

Background In-vitro fertilization (IVF) is the treatment of choice for unresolved infertility. It comprises a number of key steps, each of which has to be negotiated before the next is attempted, but the factors which are associated with failure at each stage have not been reported. Methods and Findings We analyzed anonymised national data on women undergoing their first fresh autologous IVF and intracytoplasmic sperm injection (ICSI) cycle in the United Kingdom between 2000 and 2007 to predict factors associated with overall lack of livebirth as well as the chance of non-progress at different stages of an IVF cycle. A total of 121,744 women were included in this analysis. Multivariable models underlined the importance of increased female age and duration of infertility, lack of previous pregnancy, and a diagnosis of tubal or male factor infertility in predicting the risk of not having a live birth in an IVF treatment. At each stage, a woman’s chance of proceeding to the next stage of IVF treatment is affected by increased age and duration of infertility. The intention to use intra-cytoplasmic sperm injection (ICSI) is associated with a decreased risk of treatment failure in women starting an IVF cycle (RR 0.93, 99% CI 0.92, 0.94) but this association is reversed at a later stage once fertilisation has been confirmed (RR=1.01, 99%CI 1.00, 1.03). Conclusions Female age is a key predictor of failure to have a livebirth following IVF as well as the risk of poor performance at each stage of treatment. While increased duration of infertility is also associated with worse outcomes at every stage, its impact appears to be less influential. Women embarking on ICSI treatment for male factor infertility have a lower chance of treatment failure but this does not appear to be due to increased chances of implantation of ICSI embryos. PMID:24349236

Impact of short-term preconceptional exposure to particulate air pollution on treatment outcome in couples undergoing in vitro fertilization and embryo transfer (IVF/ET)

PubMed Central

Maluf, Mariangela; Czeresnia, Carlos Eduardo; Januário, Daniela Aparecida Nicolosi Foltran; Saldiva, Paulo Hilário Nascimento

2010-01-01

Purpose To assess the potential effects of short-term exposure to particulate air pollution during follicular phase on clinical, laboratory, and pregnancy outcomes of women undergoing IVF/ET. Methods Retrospective cohort study of 400 first IVF/ET cycles of women exposed to ambient particulate matter during follicular phase. Particulate matter (PM) was categorized into quartiles (Q1: ≤30.48 µg/m3, Q2: 30.49–42.00 µg/m3, Q3: 42.01–56.72 µg/m3, and Q4: >56.72 µg/m3). Results Clinical, laboratory, or treatment variables were not affected by follicular phase PM exposure periods. Women exposed to Q4 period during the follicular phase of conception cycles had a higher risk of miscarriage (odds ratio, 5.05; 95% confidence interval: 1.04–25.51) when compared to women exposed to Q1–3 periods. Conclusion Our results show an association between brief exposure to high levels of ambient PM during the preconceptional period and early pregnancy loss, although no effect of this exposure on clinical, laboratory, and treatment outcomes was observed. PMID:20405197

Uterine leiomyomas and their effect on in vitro fertilization outcome: a retrospective study.

PubMed

Jun, S H; Ginsburg, E S; Racowsky, C; Wise, L A; Hornstein, M D

2001-03-01

The effect of uterine leiomyomas on the outcome of in vitro fertilization (IVF) treatment has been controversial. This study was undertaken to clarify influence of fibroids on IVF success, in a large population with age and other potential confounding variables controlled for in the analysis. A population of 141 patients with and 406 without leiomyomata undergoing their first IVF cycle was studied. The association between uterine leiomyomas and assisted reproduction treatment outcome was not statistically significant (OR = 0.73, 95% CI: 0.49-1.19, p = 0.21) after controlling for age and other risk factors. Also, fibroids neither affected the risk of spontaneous abortion (OR = 1.06, 95% CI: 0.44-2.60) nor the risk of ectopic pregnancy (OR = 0.78, 95% CI: 0.08-8.02). Location of fibroids (intramural vs. submucosal/subserosal) and their size had no significant effect on pregnancy outcome. Results from our analyses indicated that in vitro fertilization outcome was not affected by the presence of uterine leiomyomas. Therefore, in patients with normal uterine cavities and fibroids less than a certain size (i.e., < 7 cm), undergoing myomectomies as a prerequisite for assisted reproduction treatment is seriously questionable.

A Retrospective Study of Letrozole Treatment Prior to Human Chorionic Gonadotropin in Women with Polycystic Ovary Syndrome Undergoing In Vitro Fertilization at Risk of Ovarian Hyperstimulation Syndrome.

PubMed

Chen, Yilu; Yang, Tanchu; Hao, Cuifang; Zhao, Junzhao

2018-06-20

BACKGROUND Women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) are given letrozole before a trigger injection of human chorionic gonadotropin (hCG) to lower estrogen (E2) levels, but can experience ovarian hyperstimulation syndrome (OHSS). The aim of this study was to evaluate the effect of oral letrozole, prior to administration of hCG, on the outcome of IVF and development of OHSS. MATERIAL AND METHODS Retrospective clinical review included 181 cases of women with PCOS who underwent IVF cycles with intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) (IVF/ICSI-ET). The day before the use of hCG, cases were divided into a letrozole-treated group (N=78) and a non-letrozole group (N=103). An oral dose of 2.5 mg qd of letrozole was given when the peak level of E2 was ≥4000 pg/ml during ovarian stimulation and ceased before the day of egg retrieval. RESULTS The letrozole-treated group had a significant increase in the number of retrieved oocytes, viable embryos, and fresh ET rate (P>0.05); peak levels of E2, and E2 levels on the day of the egg retrieval, were significantly higher, and the fertilization rate was significantly lower (P<0.001). No significant differences were found in the rates of pregnancy, abortion, or ectopic pregnancy between the two groups (P>0.05). The incidence OHSS was lower in the letrozole-treated group, but this difference did not reach statistical significance (P>0.05). CONCLUSIONS Women with PCOS who underwent IVF, oral treatment with letrozole a day prior to treatment with hCG lowered E2 levels, but did not significantly reduce the incidence of OHSS.

Unilateral Salpingectomy and Methotrexate Are Associated With a Similar Recurrence Rate of Ectopic Pregnancy in Patients Undergoing In Vitro Fertilization.

PubMed

Irani, Mohamad; Robles, Alex; Gunnala, Vinay; Spandorfer, Steven D

To determine whether different treatment approaches of ectopic pregnancy (EP), particularly unilateral salpingectomy and methotrexate, affect its recurrence rate in patients undergoing in vitro fertilization (IVF). A retrospective cohort study (Canadian Task Force classification II-2). An academic medical center. Patients with a history of a previous EP who achieved pregnancy after IVF cycles between January 2004 and August 2015 were included. The recurrence rate of EP was compared between patients who underwent different treatment approaches for a previous EP. IVF. A total of 594 patients were included. Seventeen patients had a recurrence of EP (2.9%). Patients with a history of ≥2 EPs were associated with a significantly higher recurrence rate of EP than those with 1 previous EP (8.5% vs. 1.8%; p = .01; odds ratio [OR] = 2.2; 95% confidence interval [CI], 1.2-4.4). Patients who underwent unilateral salpingectomy (n = 245) had a comparable recurrence rate of EP after IVF with those who received methotrexate (n = 283) (3.6% vs. 2.8%; p = .5; OR = 1.3; 95% CI, 0.4-3.4). This OR remained unchanged after adjusting for patient's age, number of previous EPs, number of transferred embryos, and peak estradiol level during stimulation (adjusted OR = 1.4; 95% CI, 0.5-3.8). None of the patients who underwent bilateral salpingectomy (n = 45) or salpingostomy (n = 21) had a recurrence of EP after IVF. The recurrence rate of EP significantly correlates with the number of previous EPs. Treatment of EP with methotrexate has a comparable recurrence rate of EP after IVF with unilateral salpingectomy. Therefore, the risk of recurrence should not be a reason to favor salpingectomy over methotrexate in this population. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

Dermatological Manifestations in Patients Undergoing In Vitro Fertilisation: A Prospective Study.

PubMed

Sood, Aradhana; Sahu, Suvash; Karunakaran, Sandeep; Joshi, Rajneesh K; Raman, Deep Kumar

Changing sociodemographic patterns with an increase in the age of childbirth have affected fertility rates worldwide. With advancing reproductive medicine, assisted reproductive techniques (ARTs) are becoming common. While dermatological manifestations in normal pregnancies have been well documented, there is a paucity of data regarding cutaneous manifestations in patients undergoing ART. The objectives of our study were to estimate the incidence and types of dermatological manifestations in patients undergoing in vitro fertilisation (IVF) and to study their associations with age, type of infertility, and outcome of the procedure. A prospective cohort of 200 patients undergoing IVF in a tertiary care centre was observed for occurrence of any dermatological manifestations from initiation of the IVF protocol to the outcome of the procedure at 3 weeks after embryo transfer. Dermatological manifestations were seen in 27% of the study group, with urticaria being the most common cutaneous finding seen in 13.5%, followed by acneform eruptions (3%). Twenty-six (96.3%) of patients who manifested with urticaria were on progesterone. No statistically significant association was found between the occurrence of dermatological manifestations and the outcome of IVF, type of infertility, history of ART, and ovum donation in our study. Association between the age of the patient and the outcome of IVF cycle was statistically significant. Dermatological manifestations are seen in almost one-quarter of patients undergoing IVF, with progesterone-induced urticaria being the most common. Occurrence of cutaneous manifestations has no significant association with the outcome of IVF.

The effect of chromosomal polymorphisms on the outcomes of fresh IVF/ICSI-ET cycles in a Chinese population.

PubMed

Xu, Xiaojuan; Zhang, Rui; Wang, Wei; Liu, Hongfang; Liu, Lin; Mao, Bin; Zeng, Xiangwu; Zhang, Xuehong

2016-11-01

Chromosomal polymorphisms (CPs) have been reported to be associated with infertility; however, their effects on the outcomes of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) are still controversial. In this retrospective study, we aimed to evaluate the effect of CPs on IVF/ICSI-ET outcomes. To investigate whether CPs affected the outcomes of fresh IVF/ICSI-ET cycles in a Chinese population, we evaluated infertile couples with male carriers of CPs (n = 348), infertile couples with female carriers (n = 99), and unaffected couples (n = 400) who had received their first treatment cycles in our hospital between January 2013 and March 2015. CPs in either male or female carriers seemed to have adverse effects on IVF/ICSI-ET outcomes. CPs in male carriers affected outcomes mainly by decreasing the rates of fertilization, embryo cleavage, good quality embryos, clinical pregnancies, ongoing pregnancies, and deliveries as well as increasing the biochemical pregnancy rate (P < 0.05); CPs in female carriers affected outcomes only by lowering the embryo cleavage rate (P < 0.05). The mean fertilization rate of couples with male CP carriers undergoing IVF was significantly lower than that in those undergoing ICSI (61.1 versus 66.5 %, respectively; P = 0.0004). Our data provide evidence for the involvement of CPs in the poor outcomes of fresh IVF/ICSI-ET cycles in a Chinese population. The use of ICSI might improve outcomes by increasing the fertilization rate for men with CPs.

Outcomes of in vitro fertilization cycles among patients with polycystic ovary syndrome following ovarian puncture for in vitro maturation.

PubMed

Lin, Jia; Wang, Peiyu; Zhao, Junzhao; Xiao, Shiquan; Yu, Rong; Jin, Congcong; Zhu, Ruru

2016-12-01

To investigate the effects of ovarian puncture for in vitro maturation (IVM) on subsequent in vitro fertilization (IVF) embryo transfer cycles in patients with polycystic ovary syndrome (PCOS). A retrospective study included data from patients admitted to the First Affiliated Hospital of Wenzhou Medical University, China, between January 1, 2008 and December 31, 2014. Patients with PCOS undergoing IVF cycles after having been treated with IVM unsuccessfully were included as the study group and an IVF-procedure data-matched control group of patients undergoing their first IVF cycles was included in a 1:4 ratio. Patients with reproductive anomalies were excluded. Endocrine-hormone levels and antral follicle counts were measured and fertilization-related outcomes were evaluated. There were 49 patients included in the study group and 196 included in the control group. Within the study group, basal luteal-hormone, testosterone, and antral follicle count levels were significantly lower following IVM treatment. The total gonadotropin dose was lower (P<0.001) and the duration of stimulation was shorter (P<0.001) in the study group compared with the control group. The clinical-pregnancy rate was higher in the study group (P=0.018) and no difference was observed between the groups in ovarian hyper-stimulation syndrome (P=0.633). Previous IVM resulted in improved endocrine profiles and increased clinical-pregnancy rates among patients with PCOS undergoing IVF cycles. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Impact of presence of antiphospholipid antibodies on in vitro fertilization outcome

PubMed Central

Hong, Yeon Hee; Kim, Se Jeong; Moon, Kyoung Yong; Kim, Seul Ki; Lee, Won Don; Kim, Seok Hyun

2018-01-01

Objective To investigate prevalence of antiphospholipid antibody (APA) in Korean infertile women undergoing the first in vitro fertilization (IVF) treatment and to evaluate the influence of APA on the subsequent IVF outcomes. Method Two hundred nineteen infertile women who destined the first IVF were prospectively enrolled in 2 infertility centers. Male factor or uterine factor infertility and women with past or current endocrine or immunologic disorders were completely excluded. Plasma concentration of lupus anticoagulant was measured by clot-based method, and anticardiolipin antibody (IgG/IgM), and anti-β2-glycoprotein 1 antibody (IgG/IgM) was measured by enzyme-linked immunosorbent assay method before starting ovarian stimulation for IVF. Results APA was positive in 13 women (5.9%). Lupus anticoagulant was positive in 2 women (0.9%), anticardiolipin antibody was positive in 7 women (3.2%), and anti-β2-glycoprotein 1 antibody was positive in 4 women (1.8%). In 193 women entering embryo transfer, clinical characteristics and stimulation outcomes were comparable between APA-positive (n=12) and APA-negative group (n=181). The clinical pregnancy rate (66.7% vs. 45.9%), ongoing pregnancy rate (58.3% vs. 37.0%), and miscarriage rate (12.5% vs. 19.3%) were all similar between APA-positive and APA-negative group. Conclusion The prevalence of APA is low in Korean infertile women undergoing the first IVF cycle, and the presence of APA appears to neither decrease their first IVF success nor increase abortion rate. PMID:29780778

Effect of acupuncture on in vitro fertilization: An updated systematic review and data mining protocol.

PubMed

Wang, Xiaotong; Lin, Haixiong; Chen, Mingzhu; Wang, Jian; Jin, Yuanlin

2018-06-01

Although many patients try to seek acupuncture to improve in vitro fertilization (IVF) outcomes, evidence regarding its efficacy and acupoints characters are lacking. The aim of this protocol is to evaluate the effectiveness and safety, as well as the acupoints characteristics of acupuncture in the treatment of female undergoing IVF, by conducting a systematic review and data mining. The following 6 databases will be searched from their inception to April 30, 2018: PubMed, Chinese National Knowledge Infrastructure, Wanfang, VIP database, Embase, and Cochrane Library. The randomized controlled trials (RCTs) or case-control studies of acupuncture that assess clinical effects and side effects in female undergoing IVF are included. The primary outcome measures will be number of oocytes retrieved, fertilization rate, oocyte cleavage rate, high-quality embryos rate, ovarian hyperstimulation syndrome (OHHS) incidence rate, clinical pregnancy rate (CPR), biochemical pregnancy rate (BPR), implantation rate, and cycle cancellation rate. Two reviewers will independently undertake data extraction and quality assessments. Data will be synthesized by RevMan V.5.3 software. Acupoints characteristics will be excavated using Traditional Chinese Medicine inheritance support system (TCMISS). Reporting bias will be assessed by Funnel plots, Begg test, and Egger test. This review will assess the clinical efficacy and safety, as well as the acupoints characteristics of acupuncture on IVF. These findings will summarize the current evidence of acupuncture on IVF outcomes and may provide guidance for clinicians and infertile women to select acupuncture for IVF.

Direct health services costs of providing assisted reproduction services in older women.

PubMed

Maheshwari, Abha; Scotland, Graham; Bell, Jacqueline; McTavish, Alison; Hamilton, Mark; Bhattacharya, Siladitya

2010-02-01

To assess the total health service costs incurred for each live birth achieved by older women undergoing IVF compared with costs in younger women. Retrospective cross-sectional analysis. In vitro fertilization unit and maternity hospital in a tertiary care setting. Women who underwent their first cycle of IVF between 1997 and 2006. Bottom-up costs were calculated for all interventions in the IVF cycle. Early pregnancy and antenatal care costs were obtained from National Health Service reference costs, Information Services Division Scotland, and local departmental costs. Cost per live birth. The mean cost per live birth (95% confidence interval [CI]) in women undergoing IVF at the age of > or =40 years was pound 40,320 (pound 27,105- pound 65,036), which is >2.5 times higher than those aged 35-39 years (pound 17,096 [pound 15,635- pound 18,937]). The cost per ongoing pregnancy was almost three times in women aged > or =40 (pound 31,642 [pound 21,241- pound 58,979]) compared with women 35-39 years of age (pound 11,300 [pound 10,006- pound 12,938]). The cost of a live birth after IVF rises significantly at the age of 40 years owing to lower success rates. Most of the extra cost is due to the low success of IVF treatment, but some of it is due to higher rates of early pregnancy loss. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of Ding-Kun-Dan for female infertility patients with predicted poor ovarian response undergoing in vitro fertilization/intracytoplasmic sperm injection: study protocol for a randomized controlled trial.

PubMed

Ma, Saihua; Ma, Ruihong; Xia, Tian; Afnan, Masoud; Song, Xueru; Xu, Fengqin; Hao, Guimin; Zhu, Fangfang; Han, Jingpei; Zhao, Zhimei

2018-02-20

Women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) who have a predicted poor ovarian response (POR) present a challenge for reproductive medicine specialists. Traditional Chinese medicine (TCM) is commonly used in China for such patients, in the belief that it will improve the ovarian response and ultimately increase pregnancy rates. However, there is a lack of high-quality evidence about the effect of TCM on improving ovarian response in such patients. The purpose of this study is to evaluate ongoing viable pregnancy rate at 12 weeks' gestation and related indicators of ovarian response in fertile women who have a predicted poor ovarian response having immediate versus delayed IVF/ICSI after 3 months of Ding-Kun-Dan (DKD) pre-treatment. This study is a multicenter, randomized controlled, parallel-group, phase III, superiority clinical trial. Two hundred and seventy-eight eligible female infertility patients with POR will be included in the study and randomly allocated into an immediate treatment group and a DKD group in a 1:1 ratio. Both groups will receive IVF or ICSI as a standard treatment while in the DKD group, a commercially available Chinese medicine, DKD, will be administrated for 3 months before the IVF/ICSI cycle starts. The primary outcome of the study is the ongoing pregnancy rate at 12 weeks' gestation. The secondary outcomes include total gonadotropin dosage, duration of stimulation, estradiol (E 2 ) and progesterone (P) levels on human chorionic gonadotropin (hCG) trigger day, cycle cancellation rate, number of oocytes retrieved, high-quality embryo rate, biochemical pregnancy rate, the change of serum anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and E 2 levels and all side effects, safety outcomes, and any adverse events. The protocol was approved by the Ethics Committee of the First Teaching Hospital of Tianjin university of TCM (approval no. TYLL2017[K] 004). IVF/ICSI is increasingly used to treat couples desiring a baby. Many of these women will have poor ovarian function. In China, DKD is commonly used for these patients prior to undergoing IVF/ICSI. There is no effective treatment for poor ovarian response in Western medicine currently. It is important, therefore, to undertake this randomized control trial to determine whether DKD is effective or not. Chinese Clinical Trial Registry, ID: ChiCTR-IOR-17011697 . Registered on 19 June 2017.

Correlative analysis of social support with anxiety and depression in men undergoing in vitro fertilization embryo transfer for the first time.

PubMed

Dong, Yue-Zhi; Yang, Xiao-Xia; Sun, Ying-Pu

2013-08-01

To explore the correlation between the level of social support and the extent of anxiety and depression in Chinese men undergoing in vitro fertilization embryo transfer (IVF-ET) for the first time, in order to provide a basis for male mental health counselling. Self-administered questionnaires covering general health status, anxiety (self-rating anxiety scale), depression (self-rating depression scale) and social support (social support rating scale) were completed by men undergoing their first round of IVF-ET. A total of 502 completed questionnaires were considered valid and were analysed. The anxiety, depression and social support scores for men undergoing their first round of IVF-ET were significantly higher than those for Chinese normative data. Social support was inversely correlated with anxiety and depression. These findings suggest that health care professionals should provide specific psychological counselling to Chinese men undergoing their first round of IVF-ET, in order to improve their psychological health and to facilitate increased levels of social support.

Hepatitis B virus infection on male partner has negative impact on in-vitro fertilization

NASA Astrophysics Data System (ADS)

Lubis, H. P.; Halim, B.; Adenin, I.; Rusda, M.; Prasetiawan, E.

2018-03-01

It is common to see HBV-infected couple seeking for fertility treatment in reproductive medical centers. The effect of hepatitis B virus (HBV) infection on pregnancy outcome after In Vitro Fertilization (IVF) treatment has been a controversy. The study aims this was to evaluate the outcome of in vitro fertilization in couples with the male partner being HBsAg-seropositive. A retrospective analytic study was in HBV-infected and non-HBV infected male partner groups who have been treated with in vitro fertilization (IVF) from October 2016 until May 2017 in HFC IVF Center. From 101 couples, 17 (16.83%) male partners were HBV seropositive. They had similar semen parameters compared to thenon-HBV infected group. Couples with the male partner being HBsAg-seropositive had significantly lower fertilized oocytes and cleaved embryos compared to thenon-HBV infected group. We also found lower clinical pregnancy rate in infected male partner group compared to control group (23.52% vs 51% respectively). Statistically, there was a significant difference in clinical pregnancy rate between HBV-infected group and control group (p<0.05). An hbv-infected male partner may lower the clinical pregnancy rate in couple undergoing IVF treatment. Therefore, the mechanism of impact of HBV infection on IVF outcome needs further exploration.

Exploratory study of the association of steroid profiles in stimulated ovarian follicular fluid with outcomes of IVF treatment.

PubMed

Kushnir, Mark M; Naessén, Tord; Wanggren, Kjell; Hreinsson, Julius; Rockwood, Alan L; Meikle, A Wayne; Bergquist, Jonas

2016-09-01

Steroid concentrations in stimulated follicular fluid (sFF) samples have been linked to the quality of oocytes used in IVF treatments. Most of the published studies focused on evaluating the association of the IVF outcomes with only a few of the steroids, measured by immunoassays (IA). We performed a treatment outcome, prospective cohort study using stimulated FF sampled from 14 infertile women undergoing IVF treatment; single oocyte was used per IVF cycle. Fourteen endogenous steroids were analyzed in 22 ovarian follicle aspirations, which corresponded to the embryos used in the IVF. Ten oocytes were associated with live birth (LB) and 12 with no pregnancy (NP). Steroids were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Differences in distribution of concentrations in association with the pregnancy outcome (LB or NP), and receiver operating characteristic (ROC) curves analysis were performed for the entire cohort and for within-women data. The predominant androgen and estrogen in stimulated sFF were androstenedione (A4) and estradiol (E2), respectively. Lower concentrations of pregnenolone (Pr), lower ratios of A4/ dehydroepiandrosterone (DHEA), testosterone (Te)/DHEA, and greater ratios of E2/Te, and estrone/A4 were observed in sFF samples associated with LB. Among the oocytes associated with NP, in four out of 12 samples total concentration of androgens was above the distribution of the concentrations in the oocytes corresponding to the LB group. Observations of the study indicated increased consumption of precursors and increased biosynthesis of estrogens in the follicles associated with LB. Our data suggest that potentially steroid profiles in sFF obtained during oocyte retrieval may serve as biomarkers for selection of the best embryo to transfer after IVF. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Conservative management of endometrioma in women undergoing in vitro fertilization].

PubMed

Santulli, P; Somigliana, E; Bourdon, M; Maignien, C; Marcellin, L; Gayet, V; Chapron, C

2017-03-01

Endometriosis is a chronic disease. The pathogenesis is actually still unclear. Endometriosis is responsible for infertility and/or pelvic pain. One of the most important features of the disease is the heterogeneity (clinical and anatomical). Among the different phenotypes of endometriosis, the ovarian endometrioma seems to most important lesion in the management of endometriosis-related infertility. Surgical treatment is associated to a decrease of the ovarian reserve and a potential detrimental effect on in vitro fecondation (IVF) outcomes. Thus, the choice between conservative or surgical management of endometrioma before IVF is actually debated. The advantages and drawback of surgical and conservative management should be discussed before to plan the treatment. In the present review, we aimed at assessing the risks of a conservative management of endometrioma as compared to surgery before IVF. Copyright © 2017. Published by Elsevier Masson SAS.

The cost-effectiveness of IVF in the UK: a comparison of three gonadotrophin treatments.

PubMed

Sykes, D; Out, H J; Palmer, S J; van Loon, J

2001-12-01

The objective of this study was to evaluate the cost-effectiveness of women undergoing IVF treatment with recombinant FSH (rFSH) in comparison with highly purified urinary FSH (uFSH-HP) and human menopausal gonadotrophins (HMG). A decision-analytic model was used to estimate cost-effectiveness ratios for 'the average cost per ongoing pregnancy' and 'incremental cost per additional pregnancy' for women entering into IVF treatment for a maximum of three cycles. The model was constructed based on a previously published large prospective randomized clinical trial comparing rFSH and uFSH-HP. Where necessary, these data were augmented with a combination of expert opinion, evidence from the literature and observational data relating to the management and cost of IVF treatment in the UK. The cost of rFSH, uFSH-HP and HMG were obtained from National Health Service list prices in the UK. The model predicted a cumulative pregnancy rate after three cycles of 57.1% for rFSH and 44.4% for both uFSH-HP and HMG. The cost of IVF treatment was 5135 pounds sterling for rFSH, 4806 pounds sterling for uFSH-HP and 4202 pounds sterling for HMG. When assessed in association with outcomes, the average cost per ongoing pregnancy was more favourable with rFSH (8992 pounds sterling) than with either uFSH-HP (10 834 pounds sterling) or HMG (9472 pounds sterling). The incremental cost per additional pregnancy was 2583 pounds sterling using rFSH instead of uFSH-HP and 7321 pounds sterling using rFSH instead of HMG. These results were robust to changes in the baseline assumptions of the model. rFSH is a cost-effective treatment strategy in ovulation induction prior to IVF.

Best practices for controlled ovarian stimulation in IVF

PubMed Central

Jungheim, Emily S.; Meyer, Melissa; Broughton, Darcy E.

2015-01-01

As applications for IVF have expanded over the years, so too have approaches to controlled ovarian stimulation (COS) for IVF. With this expansion and improved knowledge of basic reproductive biology, there is increasing interest in how COS practice influences IVF outcomes, and whether or not specific treatment scenarios call for personalized approaches to COS. For the majority of women undergoing COS and their treating physicians, the goal is to achieve a healthy live birth through IVF in a fresh cycle. Opinions on how COS strategy best leads to this common goal varies among centers as many clinicians base COS strategy not on evidence obtained through prospective randomized trials, but rather through observational studies and experience. Overall, when it comes to COS most clinicians recognize the approach should not be “one size fits all”, but rather a patient-centered approach that takes the existing evidence into consideration. The pages that follow outline the existing evidence for best practices in COS for IVF highlighting how these practices may be incorporated into a patient-centered approach. PMID:25734345

Heart rate variability among women undergoing in vitro fertilization treatment: Its predictive ability for pregnancy

PubMed Central

Wu, Meng-Hsing; Su, Pei-Fang; Chen, Kuan-Ya; Tie, Tung-Hee; Ke, Hsu-Cheng; Chen, Hau; Su, Yu-Chi; Su, Yu-Chen

2018-01-01

Objective This study aimed to assess predictive ability of heart rate variability (HRV) for pregnancy outcomes with in vitro fertilization (IVF) treatment. Research design and method A total of 180 women with 261 cycles of IVF and 211 embryo transfers (ETs) were analyzed. HRV was measured at four times during IVF treatment: the first date of menstruation, r-HCG (Ovidrel) administration, and before and after ET. Pregnancy indicators included chemical pregnancy, ongoing pregnancy (> 10 weeks), and live birth (pregnancy > 24 weeks). Mixed effect models were applied to identify predictors for IVF pregnancy. The area under the receiver operating characteristic curve (AUC) was used to assess prediction models for pregnancy. Results The HRV values increased during IVF treatment and then decreased after ET. The trend of changes in HRV values during IVF treatment was significant among patients with chemical pregnancy (p < 0.01) and those with live birth (p = 0.02). Women without pregnancy had lower HRV compared to those with IVF pregnancy (p < 0.05). With a one unit increase in HRV difference before and after ET, the odds of chemical pregnancy decreased by 18% (odds ratio; OR: 0.82, 95% CI: 0.70–0.97, p < 0.02). With a one year increase in maternal age, the odds decreased by 16% (OR: 0.84, 95% CI: 0.76–0.93, p < 0.01), 25% (OR: 0.75, 95% CI: 0.58–0.93, p = 0.02), and 28% (OR: 0.72, 95% CI: 0.54–0.91, p = 0.01) for chemical pregnancy, ongoing pregnancy, and live birth, respectively. The AUCs were 0.77 (95% CI: 0.70, 0.84), 0.89 (0.79, 0.98), and 0.91(0.83, 0.99) for the prediction models for chemical pregnancy, ongoing pregnancy, and live birth, respectively. Conclusions Reduced HRV may be an indicator for low chance of IVF pregnancy. The changes in HRV before and after ET and maternal age might be prognostic predictors of IVF pregnancy. PMID:29529100

Previous tubal ectopic pregnancy raises the incidence of repeated ectopic pregnancies in in vitro fertilization-embryo transfer patients.

PubMed

Weigert, Monika; Gruber, Diego; Pernicka, Elisabeth; Bauer, Peter; Feichtinger, Wilfried

2009-01-01

To investigate the incidence of Tubal Ectopic Pregnancies (TEP) in IVF-ET patients with respect to the status of the fallopian tubes after a previous TEP. This retrospective study compares patients undergoing 481 IVF-ET cycles after conservatively or surgically treated TEP(s) with a Control Group (idiopathic or male factor for IVF-ET indication). Medical reports of surgery and/or hysterosalpingograms prior to the IVF cycles classified the status of the fallopian tubes. 12 TEPs (8.95%/Pregnancies (PR)) occurred in the Study Group. In the Control Group one TEP (0.75%/PR; p < 0.001) was found. Smoking increased the probability of TEPs (p = 0.0028) and of pathological pregnancies (abortion, biochemical and ectopic PR; (p = 0.0411)). For statistic evolution logistic regression (PROC GENMOD) and a repeated measure model were applied. Women with a previous TEP should be informed about the significantly increased risk for a further TEP in IVF-ET treatment, especially if they are smoking.

Effect of ethnicity on live birth rates after in vitro fertilisation/intracytoplasmic sperm injection treatment: analysis of UK national database.

PubMed

Maalouf, W; Maalouf, W; Campbell, B; Jayaprakasan, K

2017-05-01

To evaluate the effect of ethnicity of women on the outcome of in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Observational cohort study. UK National Database. Data from 2000 to 2010 involving 38 709 women undergoing their first IVF/ICSI cycle were analysed. Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA), the statutory regulator of IVF and ICSI treatment in the UK. Data analysis was performed by regression analysis with adjustment for age, cause and type of infertility and treatment type (IVF or ICSI) to express results as odds ratio (OR) and 95% confidence intervals (95% CI). Live birth rate per cycle of IVF or ICSI treatment. While white Irish (OR 0.73; 95% CI 0.60-0.90), Indian (0.85; 0.75-0.97), Bangladeshi (0.53: 0.33-0.85), Pakistani (0.68; 0.58-0.80), Black African (0.60; 0.51-0.72), and other non-Caucasian Asian (0.86; 0.73-0.99) had a significantly lower odds of live birth rates per fresh IVF/ICSI cycle than White British women, ethnic groups of White European (1.04; 0.96-1.13), Chinese (1.12; 0.77-1.64), Black Caribbean (0.76; 0.51-1.13), Middle Eastern (0.73; 0.51-1.04), Mediterranean European (1.18; 0.83-1.70) and Mixed race population (0.94; 0.73-1.19) had live birth rates that did not differ significantly. The cumulative live birth rates showed similar patterns across different ethnic groups. Ethnicity is a major determinant of IVF/ICSI treatment outcome as indicated by significantly lower live birth rates in some of the ethnic minority groups compared with white British women. Ethnicity affects IVF outcome with lower live birth rates in some ethnic groups more than in white British. © 2016 Crown copyright. BJOG:An International Journal of Obstetrics and Gynaecology © 2016 Royal College of Obstetricians and Gynaecologists.

The influence of bacterial vaginosis on in-vitro fertilization and embryo implantation during assisted reproduction treatment.

PubMed

Liversedge, N H; Turner, A; Horner, P J; Keay, S D; Jenkins, J M; Hull, M G

1999-09-01

There is growing evidence that the pathogenic effects of bacterial vaginosis may not be confined to the lower genital tract. Possible associations with infertility and effects on fertilization and implantation were studied in patients undergoing in-vitro fertilization (IVF) treatment. High vaginal swabs taken at the time of oocyte collection were assessed by Gram staining. The prevalence of bacterial vaginosis and of intermediate and normal flora in 301 patients was 25.6, 14.0 and 60.4% respectively. Bacterial vaginosis was more prevalent in patients with tubal (31.5%, n = 149) compared with non-tubal (19.7%, n = 152) infertility (odds ratio (OR) 1.87, CI 1.11-3.18, P = 0.02). Bacterial vaginosis did not have an adverse effect on fertilization rate. Further, no significant difference in implantation rates was seen when comparing bacterial vaginosis (15. 8%, OR 1.03, CI 0.66-1.61) and intermediate flora (13.1%, OR 0.82, CI 0.45-1.52) with normal flora (15.5%). Though confidence intervals around the observations were relatively wide, the findings suggest that routine screening for bacterial vaginosis in the hope of improving the success of IVF treatment is not justified. The prevention of complications in pregnancy associated with bacterial vaginosis might be a more relevant indication for screening at the time of IVF treatment, in particular patients with tubal disease, if treatment were shown to be effective for that particular purpose. However, antibiotic treatment before IVF has been shown to be positively disadvantageous for IVF by encouraging other organisms.

Long-term follow-up of women and men after unsuccessful IVF.

PubMed

Filetto, Juliana N; Makuch, Maria Y

2005-10-01

The experience of 92 couples, who had unsuccessfully undergone one or more IVF cycles at a university clinic, was evaluated 3-8 years following their last failed attempt. One member of each couple completed a telephone questionnaire regarding life events during their last IVF cycle performed at the clinic and at the time of the interview. Some couples had continued further treatment and some had not. Multivariate correspondence analysis was used to analyse the data. Regarding the long-term experience of couples who had undergone further treatment, for men the main experiences were psychological problems and having adopted a child. For women, the main experiences were related to problems of self-image, psychological problems, loss of hope, and having adopted a child. These women also presented a strong association with problems in their marital relationship and with adoption. For the group that did not undergo further treatment, the women showed a strong association with considering adoption, and a less intense association with psychological problems and loss of hope. The men presented psychological problems and having adopted a child as associated variables. Comparison between men and women showed that recognizing the impossibility of conceiving a child and giving up treatment were strongly associated. Men and women who had not continued with further treatment were more affected in the long term than those who had undergone further treatment after IVF failure.

Low dosing of gonadotropins in in vitro fertilization cycles for women with poor ovarian reserve: systematic review and meta-analysis.

PubMed

Youssef, Mohamed Abdel-Fattah; van Wely, Madelon; Mochtar, Monique; Fouda, Usama Mohamed; Eldaly, Ashraf; El Abidin, Eman Zein; Elhalwagy, Ahmed; Mageed Abdallah, Ahmed Abdel; Zaki, Sherif Sameh; Abdel Ghafar, Mohamed Sayed; Mohesen, Mohamed Nagi; van der Veen, Fulco

2018-02-01

To evaluate the effectiveness of low doses of gonadotropins and gonadotropins combined with oral compounds compared with high doses of gonadotropins in ovarian stimulation regimens in terms of ongoing pregnancy per fresh IVF attempt in women with poor ovarian reserve undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment. A systematic review and meta-analysis of randomized controlled studies that evaluate the effectiveness of low dosing of gonadotropins alone or combined with oral compounds compared with high doses of gonadotropins in women with poor ovarian reserve undergoing IVF/ICSI treatment. Not applicable. Subfertile women with poor ovarian reserve undergoing IVF/ICSI treatment. We searched the PubMed, EMBASE, Web of Science, the Cochrane Library, and the Clinical Trials Registry using medical subject headings and free text terms up to June 2016, without language or year restrictions. We included randomized controlled studies (RCTs) enrolling subfertile women with poor ovarian reserve undergoing IVF/ICSI treatment and comparing low doses of gonadotropins and gonadotropins combined with oral compounds versus high doses of gonadotropins. We assessed the risk of bias using the criteria recommended by the Cochrane Collaboration. We pooled the results by meta-analysis using the fixed and random effects model. The primary outcome was ongoing pregnancy rate (PR) per woman randomized. We retrieved 787 records. Fourteen RCTs (N = 2,104 women) were included in the analysis. Five studies (N = 717 women) compared low doses of gonadotropins versus high doses of gonadotropins. There was no evidence of a difference in ongoing PR (2 RCTs: risk rate 0.98, 95% confidence interval 0.62-1.57, I 2 = 0). Nine studies (N = 1,387 women) compared ovarian stimulation using gonadotropins combined with the oral compounds letrozole (n = 6) or clomiphene citrate (CC) (n = 3) versus high doses of gonadotropins. There was no evidence of a difference in ongoing PR (3 RCTs: risk rate 0.90, 95% confidence interval 0.63-1.27, I 2 = 0). We found no evidence of a difference in pregnancy outcomes between low doses of gonadotropins and gonadotropins combined with oral compounds compared with high doses of gonadotropins in ovarian stimulation regimens. Whether low doses of gonadotropins or gonadotropins combined with oral compounds is to be preferred is unknown, as they have never been compared head to head. A health economic analysis to test the hypothesis that an ovarian stimulation with low dosing is more cost-effective than high doses of gonadotropins is needed. CRD42016041301. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Reproductive implications of psychological distress for couples undergoing IVF.

PubMed

Quant, Hayley S; Zapantis, Athena; Nihsen, Michael; Bevilacqua, Kris; Jindal, Sangita; Pal, Lubna

2013-11-01

To study implications of psychological distress on in vitro fertilization (IVF) outcome of an infertile couple. Prospective study in an academic infertility practice setting. Couples undergoing embryo transfer (ET) following IVF were offered participation. Female patient (n = 89) and partner (n = 77) completed questionnaires reflecting dysphoria (POMS) and pessimism (LOT) after undergoing ET. Relationship between dysphoria and pessimism and implications of individual and couple's psychological distress on IVF cycle parameters and outcomes were assessed using multivariable analyses. Statistically significant correlations between dysphoria and pessimism were observed within the individual and between partners, (p < 0.01). Higher couple pessimism correlated with longer duration of controlled ovarian hyperstimulation (COH, p = 0.02); higher partner psychological distress related to lower fertilization rate (FR, p = 0.03). On adjusted analyses, partner's depression score was an independent predictor of reduced likelihood of clinical pregnancy (p = 0.03). Our data validate the concept of a "stressed couple". Adverse implications of a couple's psychological distress for gamete biology (longer duration of COH and lower FR with increasing distress) are suggested. Partner's depressive scores negatively correlated with IVF success. These findings suggest the importance of including partner's evaluation in studies that focus on effects of psychological stress on IVF outcome; future studies should examine whether interventions aimed at reducing psychological stress for the infertile couple may improve IVF cycle success.

Urinary paraben concentrations and in vitro fertilization outcomes among women from a fertility clinic.

PubMed

Mínguez-Alarcón, Lidia; Chiu, Yu-Han; Messerlian, Carmen; Williams, Paige L; Sabatini, Mary E; Toth, Thomas L; Ford, Jennifer B; Calafat, Antonia M; Hauser, Russ

2016-03-01

To explore the relationship between urinary paraben concentrations and IVF outcomes among women attending an academic fertility center. Prospective cohort study. Fertility clinic in a hospital setting. A total of 245 women contributing 356 IVF cycles. None. Quantification of urinary concentrations of parabens by isotope-dilution tandem mass spectrometry, and assessment of clinical endpoints of IVF treatments abstracted from electronic medical records at the academic fertility center. Total and mature oocyte counts, proportion of high-quality embryos, fertilization rates, and rates of implantation, clinical pregnancy, and live births. The geometric means of the urinary concentrations of methylparaben, propylparaben, and butylparaben in our study population were 133, 24, and 1.5 μg/L, respectively. In models adjusted for age, body mass index, race/ethnicity, smoking status, and primary infertility diagnosis, urinary methylparaben, propylparaben, and butylparaben concentrations were not associated with IVF outcomes, specifically total and mature oocyte counts, proportion of high embryo quality, and fertilization rates. Moreover, no significant associations were found between urinary paraben concentrations and rates of implantation, clinical pregnancy, and live births. Urinary paraben concentrations were not associated with IVF outcomes among women undergoing infertility treatments. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Male chromosomal polymorphisms reduce cumulative live birth rate for IVF couples.

PubMed

Ni, Tianxiang; Li, Jing; Chen, Hong; Gao, Yuan; Gao, Xuan; Yan, Junhao; Chen, Zi-Jiang

2017-08-01

Chromosomal polymorphisms are associated with infertility, but their effects on assisted reproductive outcomes are still quite conflicting, especially after IVF treatment. This study evaluated the role of chromosomal polymorphisms of different genders in IVF pregnancy outcomes. Four hundred and twenty-five infertile couples undergoing IVF treatment were divided into three groups: 214 couples with normal chromosomes (group A, control group), 86 couples with female polymorphisms (group B), and 125 couples with male polymorphisms (group C). The pregnancy outcomes after the first and cumulative transfer cycles were analyzed, and the main outcome measures were live birth rate (LBR) after the first transfer cycle and cumulative LBR after a complete IVF cycle. Comparison of pregnancy outcomes after the first transfer cycle within group A, group B, and group C demonstrated a similar LBR as well as other rates of implantation, clinical pregnancy, early miscarriage, and ongoing pregnancy (P > 0.05). However, the analysis of cumulative pregnancy outcomes indicated that compared with group A, group C had a significantly lower LBR per cycle (80.4 vs 68.00%), for a rate ratio of 1.182 (95% CI 1.030 to 1.356, P = 0.01) and a significantly higher cumulative early miscarriage rate (EMR) among clinical pregnancies (7.2 vs 14.7%), for a rate ratio of 0.489 (95% CI 0.248 to 0.963, P = 0.035). Couples with chromosomal polymorphisms in only male partners have poor pregnancy outcomes after IVF treatment manifesting as high cumulative EMR and low LBR after a complete cycle.

Effectiveness of acupuncture in women with polycystic ovarian syndrome undergoing in vitro fertilisation or intracytoplasmic sperm injection: a systematic review and meta-analysis.

PubMed

Jo, Junyoung; Lee, Yoon Jae

2017-06-01

The aim of this systematic review was to assess the evidence from randomised controlled trials (RCTs) on the efficacy, effectiveness and safety of acupuncture in women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). We searched a total of 15 databases through October 2015. The participants were women with PCOS (diagnosed using the Rotterdam criteria) undergoing IVF or ICSI. Eligible trials were those with intervention groups receiving manual acupuncture (MA) or electroacupuncture (EA), and control groups receiving sham acupuncture, no treatment or other treatments. Outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), ongoing pregnancy rate (OPR) and incidence of ovarian hyperstimulation syndrome (OHSS) and adverse events (AEs). For statistical pooling, the risk ratio (RR) and its 95% (confidence interval) CI was calculated using a random effects model. Four RCTs including 430 participants were selected. All trials compared acupuncture (MA/EA) against no treatment. Acupuncture significantly increased the CPR (RR 1.33, 95% CI 1.03 to 1.71) and OPR (RR 2.03, 95% CI 1.08 to 3.81) and decreased the risk of OHSS (RR 0.63, 95% CI 0.42 to 0.94); however, there was no significant difference in the LBR (RR 1.61, 95% CI 0.73 to 3.58). None of the RCTs reported on AEs. Acupuncture may increase the CPR and OPR and decrease the risk of OHSS in women with PCOS undergoing IVF or ICSI. Further studies are needed to confirm the efficacy and safety of acupuncture as an adjunct to assisted reproductive technology in this particular population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Outcome of in vitro fertilization in women with subclinical hypothyroidism.

PubMed

Cai, YunYing; Zhong, LanPing; Guan, Jie; Guo, RuiJin; Niu, Ben; Ma, YanPing; Su, Heng

2017-05-25

Previous studies examining associations between subclinical hypothyroidism (SCH) with in vitro fertilization (IVF) outcome indicate some benefits of levothyroxine (LT4) treatment. But IVF outcomes in treated SCH women whose serum Thyroid Stimulating Hormone (TSH) concentration did and did not exceed 2.5 mIU/L before the IVF cycle has not been studied thoroughly. In this study, we performed a prospective cohort study with 270 treated subclinical hypothyroidism patients undergoing their first IVF retrieval cycle at a single cite. SCH in women receiving LT4 replacement with a basal TSH level between 0.2-2.5mIU/L displayed a similar rate of clinical pregnancy (47.4% vs 38.7%, P = .436), miscarriage (7.4% vs 16.7%, P = .379) and live birth (43.9% vs 32.3%, P = .288) compared to women with a basal TSH level between 2.5-4.2 mIU/L. Strictly controlled TSH (less than 2.5 mIU/L) before IVF may have no effect on the pregnancy rate in LT4 treated SCH women.

Expanding reproductive lifespan: a cost-effectiveness study on oocyte freezing.

PubMed

van Loendersloot, L L; Moolenaar, L M; Mol, B W J; Repping, S; van der Veen, F; Goddijn, M

2011-11-01

The average age of women bearing their first child has increased strongly. This is an important reproductive health problem as fertility declines with increasing female age. Unfortunately, IVF using fresh oocytes cannot compensate for this age-related fertility decline. Oocyte freezing could be a solution. We used the Markov model to estimate the cost-effectiveness of three strategies for 35-year-old women who want to postpone pregnancy till the age of 40: Strategy 1: women undergo three cycles of ovarian hyperstimulation at age 35 for oocyte freezing, then at age 40, use these frozen oocytes for IVF; Strategy 2: women at age 40 attempt to conceive without treatment; and the reference strategy: women at age 40 attempt to conceive and, if not pregnant after 1 year, undergo IVF. Sensitivity analyses were carried out to investigate assumptions of the model and to identify which model inputs had most impact on the results. Oocyte freezing (Strategy 1) resulted in a live birth rate of 84.5% at an average cost of €10,419. Natural conception (Strategy 2) resulted in a live birth rate of 52.3% at an average cost of €310 per birth. IVF (the reference strategy) resulted in a cumulative live birth rate of 64.6% at an average cost of €7798. The cost per additional live birth for the oocyte freezing strategy was €13,156 compared to the IVF strategy. If at least 61% of the women return to collect their oocytes, and if there is a willingness to pay €19,560 extra per additional live birth, the oocyte freezing strategy is the most cost-effective strategy. Oocyte freezing is more cost effective compared to IVF, if at least 61% of the women return to collect their oocytes and if one is willing to pay €19,560 extra per additional live birth. Our Markov model shows that, considering all the used assumptions, oocyte freezing provides more value for money than IVF.

The value of HCG serum concentrations after trigger in predicting pregnancy and live birth rates in IVF-ICSI.

PubMed

Zhou, Jianjun; Wang, Shanshan; Wang, Bin; Wang, Junxia; Chen, Hua; Zhang, Ningyuan; Hu, Yali; Sun, Haixiang

2015-06-01

The aim of this study was to determine if an association existed between serum human chorionic gonadotrophin (HCG) level at 12 h after trigger and IVF and intracytoplasmic sperm (ICSI) treatment outcomes. Women undergoing initial IVF-ICSI and embryo transfer treatment using the long luteal phase gonadotrophin-releasing hormone agonist protocol between April 2012 and March 2013 for tubal factor were included (n = 699). In the clinical pregnancy group, HCG after trigger was significantly elevated (276.0 ± 5.1 versus 198.5 ± 6.1 mIU/mL; P < 0.001). The optimal cut-off value proposed by the receiver operating characteristic analysis (area under curve = 0.730) for HCG was 201.2 mIU/ml. Compared with the lower HCG group, the clinical pregnancy rate in the higher HCG group was increased in obese and non-obese patients (77.8% versus 57.3%, P < 0.05; 85.6% versus 53.0%, P < 0.01, respectively). Adjusted for age and body mass index, an increase of HCG was associated with a better IVF-ICSI treatment outcome (OR 4.39, 95% CI 2.99 to 6.45). Clinical pregnancy rate was significantly higher across increasing quartiles of HCG. An elevated level of serum HCG at 12 h after trigger was associated with a better IVF-ICSI outcome. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

A Comparison of Pattern of Pregnancy Loss in Women with Infertility Undergoing IVF and Women with Unexplained Recurrent Miscarriages Who Conceive Spontaneously

PubMed Central

Tamhankar, Vidya A.; Liu, Beiyu; Yan, Junhao; Li, Tin-Chiu

2015-01-01

Objective. Women with infertility and recurrent miscarriages may have an overlapping etiology. The aim of this study was to compare the pregnancy loss in pregnancies after IVF treatment with spontaneous pregnancies in women with recurrent miscarriages and to assess differences related to cause of infertility. Methods. The outcome from 1220 IVF pregnancies (Group I) was compared with 611 spontaneous pregnancies (Group II) in women with recurrent miscarriages. Subgroup analysis was performed in Group I based on cause of infertility: tubal factor (392 pregnancies); male factor (610 pregnancies); and unexplained infertility (218 pregnancies). Results. The clinical pregnancy loss rate in Group I (14.3%) was significantly lower than that of Group II (25.8%, p < 0.001) and this was independent of the cause of infertility. However the timing of pregnancy loss was similar between Groups I and II. The clinical pregnancy loss rate in Group I was similar in different causes of infertility. Conclusions. The clinical pregnancy loss rate following IVF treatment is lower than that of women with unexplained recurrent miscarriages who conceived spontaneously. This difference persists whether the infertility is secondary to tubal factors, male factors, or unexplained cause. PMID:26576157

GnRH antagonist versus long agonist protocols in IVF: a systematic review and meta-analysis accounting for patient type.

PubMed

Lambalk, C B; Banga, F R; Huirne, J A; Toftager, M; Pinborg, A; Homburg, R; van der Veen, F; van Wely, M

2017-09-01

Most reviews of IVF ovarian stimulation protocols have insufficiently accounted for various patient populations, such as ovulatory women, women with polycystic ovary syndrome (PCOS) or women with poor ovarian response, and have included studies in which the agonist or antagonist was not the only variable between the compared study arms. The aim of the current study was to compare GnRH antagonist protocols versus standard long agonist protocols in couples undergoing IVF or ICSI, while accounting for various patient populations and treatment schedules. The Cochrane Menstrual Disorders and Subfertility Review Group specialized register of controlled trials and Pubmed and Embase databases were searched from inception until June 2016. Eligible trials were those that compared GnRH antagonist protocols and standard long GnRH agonist protocols in couples undergoing IVF or ICSI. The primary outcome was ongoing pregnancy rate. Secondary outcomes were: live birth rate, clinical pregnancy rate, number of oocytes retrieved and safety with regard to ovarian hyperstimulation syndrome (OHSS). Separate comparisons were performed for the general IVF population, women with PCOS and women with poor ovarian response. Pre-planned subgroup analyses were performed for various antagonist treatment schedules. We included 50 studies. Of these, 34 studies reported on general IVF patients, 10 studies reported on PCOS patients and 6 studies reported on poor responders. In general IVF patients, ongoing pregnancy rate was significantly lower in the antagonist group compared with the agonist group (RR 0.89, 95% CI 0.82-0.96). In women with PCOS and in women with poor ovarian response, there was no evidence of a difference in ongoing pregnancy between the antagonist and agonist groups (RR 0.97, 95% CI 0.84-1.11 and RR 0.87, 95% CI 0.65-1.17, respectively). Subgroup analyses for various antagonist treatment schedules compared to the long protocol GnRH agonist showed a significantly lower ongoing pregnancy rate when the oral hormonal programming pill (OHP) pretreatment was combined with a flexible protocol (RR 0.74, 95% CI 0.59-0.91) while without OHP, the RR was 0.84, 95% CI 0.71-1.0. Subgroup analysis for the fixed antagonist schedule demonstrated no evidence of a significant difference with or without OHP (RR 0.94, 95% CI 0.79-1.12 and RR 0.94, 95% CI 0.83-1.05, respectively). Antagonists resulted in significantly lower OHSS rates both in the general IVF patients and in women with PCOS (RR 0.63, 95% CI 0.50-0.81 and RR 0.53, 95% CI 0.30-0.95, respectively). No data on OHSS was available from trials in poor responders. In a general IVF population, GnRH antagonists are associated with lower ongoing pregnancy rates when compared to long protocol agonists, but also with lower OHSS rates. Within this population, antagonist treatment prevents one case of OHSS in 40 patients but results in one less ongoing pregnancy out of every 28 women treated. Thus standard use of the long GnRH agonist treatment is perhaps still the approach of choice for prevention of premature luteinization. In couples with PCOS and poor responders, GnRH antagonists do not seem to compromise ongoing pregnancy rates and are associated with less OHSS and therefore could be considered as standard treatment. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

A questionnaire-based audit to assess overall experience and convenience among patients using vaginal progesterone tablets (Lutigest®) for luteal phase support during IVF treatment.

PubMed

Heine, Polly; Sellar, Laura; Whitten, Sue; Bajaj, Priti

2017-01-01

The aim of this audit was to assess the overall experience and patient convenience of vaginal progesterone tablets (Lutigest ® , marketed as Endometrin ® in the USA) used for luteal phase support (LPS) during in vitro fertilization (IVF) treatment. This questionnaire-based audit included responses from 100 patients undergoing IVF treatment at six IVF clinics in the UK from September 2015 to November 2016. Fourteen days after starting progesterone supplementation for LPS during their IVF treatment, patients rated overall experience and perceived convenience of the prescribed progesterone by completing a questionnaire. Of the 100 patients included, 96 received vaginal progesterone tablets for LPS. Overall, 53.1% (51/96) indicated that the progesterone tablets were "very easy" to use; 42.7% (41/96) and 44.8% (43/96) found it "very convenient" or "neither convenient or inconvenient" to administer the tablet, respectively. Overall experience with using progesterone tablets was rated as "very comfortable" by 34.4% (33/96) and "neither comfortable or uncomfortable" by 56.3% (54/96) of patients. The applicator was used by 93.8% (90/96) of patients to administer the tablet, and 86.5% (83/96) indicated that the applicator was easy to clean for repeated use. A total of 33 patients had a previous IVF cycle during which they were prescribed vaginal progesterone pessaries for LPS. Compared with progesterone pessaries, the majority found treatment with progesterone tablets to be more comfortable (60.6%; 20/33) and more convenient (57.6%; 19/33) and indicated that the progesterone tablet was their preferred progesterone formulation for LPS (60.6%; 20/33). These findings offer insights into real-world patient experiences with the progesterone vaginal tablet formulation. The results suggest overall patient convenience, ease, and comfort with using progesterone vaginal tablets for LPS. The majority of patients found progesterone vaginal tablets more convenient and comfortable to use compared with progesterone pessaries.

Effects of a Delphi consensus acupuncture treatment protocol on the levels of stress and vascular tone in women undergoing in-vitro fertilization: a randomized clinical trial protocol.

PubMed

Zhang, Yan; Phy, Jennifer; Scott-Johnson, Chris; Garos, Sheila; Orlando, Jennie; Prien, Samuel; Huang, Jaou-Chen

2017-04-04

The variability of published acupuncture protocols for patients undergoing In-Vitro Fertilization (IVF) complicates the interpretation of data and hinders our understanding of acupuncture's impact. In 2012, an acupuncture treatment protocol developed by a Delphi consensus process was published to describe the parameters of best practice acupuncture for Assisted Reproductive Technology and future research. However, there has been no clinical trial utilizing this protocol to assess the effects of acupuncture. This study aims to assess the implementation of Dephi consensus acupuncture protocol and to examine the impact of acupuncture on stress and uterine and ovarian blood flow among women between ages 21-42 years seeking IVF. This study is a one site prospective, two-arm randomized controlled non-blind clinical trial conducted in a medical school-affiliated fertility center . Participants will be randomized 1:1 into either the acupuncture group or the standard of care (no acupuncture) group using computer generated tables. Both groups will have 3 regular clinical visits as their standard IVF care during an approximately 2 to 3 weeks window. Women who are randomized into the acupuncture group would receive three sessions based on the Delphi consensus acupuncture protocol in addition to the standard care. The first treatment will be administered between days 6 to 8 of the stimulated IVF cycle. The second session will be performed on the day of embryo transfer at least 1 h prior to the transfer. The third session will be performed within 48 h post-embryo transfer. Participants will be followed for their pregnancy test and pregnancy outcome when applicable. The outcomes stress and blood flow will be measured by a validated perceived stress scale and vasoactive molecules, respectively. Although recruitment and scheduling could be challenging at times, the Delphi consensus acupuncture protocol was implemented as planned and well-accepted by the patients. Because of the time-specified sessions around patients' IVF cycle, it is highly recommended to have on-site study acupuncturist(s) to accommodate the schedule. ClinicalTrials NCT02591186 registered on October 7, 2015.

Improvements in IVF in women of advanced age.

PubMed

Gleicher, Norbert; Kushnir, Vitaly A; Albertini, David F; Barad, David H

2016-07-01

Women above age 40 years in the US now represent the most rapidly growing age group having children. Patients undergoing in vitro fertilization (IVF) are rapidly aging in parallel. Especially where egg donations are legal, donation cycles, therefore, multiply more rapidly than autologous IVF cycles. The donor oocytes, however, are hardly ever a preferred patient choice. Since with use of own eggs, live birth rates decline with advancing age but remain stable (and higher) with donor eggs, older patients always face the difficult and very personal choice between poorer chances with own and better chances with donor oocytes. Physician contribution to this decision should in our opinion be restricted to accurate outcome information for both options. Achievable pregnancy and live birth rates in older women are, however, frequently underestimated, thereby mistakenly biasing fertility providers, private insurance companies and even regulatory government agencies. Restriction on access to IVF for older women is then often the consequence. In this review, we summarize the limited published data on best treatments of 'older' ovaries, while also addressing treatment approaches that should be avoided in older women. This focused review, therefore, to a degree is subjective. Research addressing aging ovaries in IVF has been disappointingly sparse, and has in our opinion too heavily concentrated on methods of embryo selection (ES), which, especially in older women, not only fail to improve IVF outcomes, but actually, negatively affect live birth chances. We conclude that, aside from breakthroughs in gamete creation, only pharmacological interventions into early (small growing follicle stages) follicle maturation will offer new potential to positively impact oocyte and embryo quality and, therefore, IVF outcomes. Research, therefore, should be accordingly redirected. © 2016 Society for Endocrinology.

Factors associated with disposition of cryopreserved reproductive tissue.

PubMed

Styer, Aaron K; Cekleniak, Natalie A; Legedza, Anna; Mutter, George L; Hornstein, Mark D

2003-09-01

To study patient characteristics associated with the preferences for the disposition of cryopreserved semen and embryos in the event of death or divorce. Retrospective exploratory study. Tertiary care academic medical center. One hundred twelve men banking sperm, 54 female patients (partners of men banking sperm) undergoing in vitro fertilization (IVF), and 112 women undergoing IVF who were not partners of men banking sperm. Male patients banking sperm and couples undergoing IVF completed a standard consent form detailing their desired dispositions (disposal or release to a surviving party) of cryopreserved sperm and embryos in the event of death or divorce. Effect of marital status, age, reason for sperm banking, infertility diagnosis, partner status (single or significant-other partner) on sperm, and embryo disposition choice. In the event of death, married men were 5.5 times more likely to release banked sperm to a surviving party than were single men. The estimated odds of giving sperm to a survivor were 1.07 times greater with every 1-year increase in age. The choice of sperm disposal was significantly related to the banking reason for the case of banking prior to chemotherapy and/or radiation for malignancy. In the case of male death, the decisions of couples undergoing IVF for embryo disposition agreed with choices of male patients for sperm disposition approximately 33% of the time more often than by chance alone. Decisions surrounding disposition of cryopreserved sperm are significantly associated with marital status, age, and reason for banking sperm. Respective choices of sperm and embryo disposition in couples undergoing IVF were similar in the situation of male death.

Patient-centred quality of care in an IVF programme evaluated by men and women.

PubMed

Holter, Herborg; Sandin-Bojö, Ann-Kristin; Gejervall, Ann-Louise; Wikland, Matts; Wilde-Larsson, Bodil; Bergh, Christina

2014-12-01

Do men and women value the same aspects of quality of care during IVF treatment when measuring rates of importance by the validated instrument, quality from the patient's perspective of in vitro fertilization (QPP-IVF)? Women valued most aspects of care as significantly more important than their partner although men and women evaluated the importance of the different care factors in a similar pattern. A few validated tools measuring patient-centred quality of care during IVF have been developed. Few studies of gender differences concerning experiences of patient-centred quality of care have been reported in the literature to date. A two-centre study was conducted between September 2011 and May 2012. Heterosexual couples (n = 497) undergoing IVF were invited to complete a questionnaire before receiving the result of the pregnancy test. In all, 363 women and 292 men evaluated quality of care by answering the QPP-IVF questionnaire. The measurements consisted of two kinds of evaluations: the rating of the importance of various aspects of treatment (subjective importance) and the rating of perceived quality of care (perceived reality). Comparisons between men and women on importance ratings and perceived reality ratings were performed both on factor (subscale) and single item levels by intra-couple analyses and corrected for age. A stepwise multiple logistic regression analysis was performed in order to select baseline variables independently predicting evaluation at factor level. The response rate was 67.5%, with 363 women (74.2%) and 292 men (60.6%) completing the study. Both the woman and man responded in 251 couples. Women rated the different care aspects as significantly more important than their partner in all factors except the factor, 'Responsibility/continuity'. Both genders gave the factors, 'Medical care' and 'Information after treatment', the highest scores. At item level women rated the majority of items as significantly more important than men. Perceived reality for the majority of factors and items was similarly rated by men and women in the couples. For women, receiving embryo transfer, short duration of infertility, IVF as a method and number of previous cycles were independently correlated to the highest score of importance of certain factors. The lower response rate of men compared with women (60.6 versus 74.2%, respectively) might have influenced the results through selection bias. Only patients who had adequate fluency in the Swedish language participated. This study is an important contribution in comparing the needs of men and women undergoing IVF treatments. The QPP-IVF instrument is a suitable instrument for revealing important care aspects identified by both men and women and a useful tool for stimulating patient-centred quality improvements within and between clinics. The study was supported by the LUA/ALF agreement at Sahlgrenska University Hospital, Gothenburg, Sweden, and by Hjalmar Svensson's Research Foundation. None of the authors declared any conflict of interests. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cost-effectiveness of a mild compared with a standard strategy for IVF: a randomized comparison using cumulative term live birth as the primary endpoint.

PubMed

Polinder, S; Heijnen, E M E W; Macklon, N S; Habbema, J D F; Fauser, B J C M; Eijkemans, M J C

2008-02-01

BACKGROUND Conventional ovarian stimulation and the transfer of two embryos in IVF exhibits an inherent high probability of multiple pregnancies, resulting in high costs. We evaluated the cost-effectiveness of a mild compared with a conventional strategy for IVF. METHODS Four hundred and four patients were randomly assigned to undergo either mild ovarian stimulation/GnRH antagonist co-treatment combined with single embryo transfer, or standard stimulation/GnRH agonist long protocol and the transfer of two embryos. The main outcome measures are total costs of treatment within a 12 months period after randomization, and the relationship between total costs and proportion of cumulative pregnancies resulting in term live birth within 1 year of randomization. RESULTS Despite a significantly increased average number of IVF cycles (2.3 versus 1.7; P < 0.001), lower average total costs over a 12-month period (8333 versus euro10 745; P = 0.006) were observed using the mild strategy. This was mainly due to higher costs of the obstetric and post-natal period for the standard strategy, related to multiple pregnancies. The costs per pregnancy leading to term live birth were euro19 156 in the mild strategy and euro24 038 in the standard. The incremental cost-effectiveness ratio of the standard strategy compared with the mild strategy was euro185 000 per extra pregnancy leading to term live birth. CONCLUSIONS Despite an increased mean number of IVF cycles within 1 year, from an economic perspective, the mild treatment strategy is more advantageous per term live birth. It is unlikely, over a wide range of society's willingness-to-pay, that the standard treatment strategy is cost-effective, compared with the mild strategy.

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

PubMed

Kwan, I; Bhattacharya, S; McNeil, A; van Rumste, M M E

2008-04-16

Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) treatment has included ultrasonography plus serum estradiol concentration to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS). The need for intensive monitoring during ovarian stimulation in IVF is controversial. It has been suggested that close monitoring is time consuming, expensive and inconvenient for the woman and simplification of IVF therapy by using ultrasound only should be considered. This systematic review assessed the effects of ovarian monitoring by ultrasound only versus ultrasound plus serum estradiol measurement on IVF outcomes and the occurrence of OHSS in women undergoing stimulated cycles in IVF and intra-cytoplasmic sperm injection (ICSI) treatment. To quantify the effect of monitoring controlled ovarian stimulation in IVF and ICSI cycles with ultrasound plus serum estradiol concentration versus ultrasound only in terms of live birth rates, pregnancy rates and the incidence of OHSS. We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Central Register of Controlled Trials (CENTRAL) on the latest issue of The Cochrane Library, MEDLINE (1966 to May 2007), EMBASE (1980 to May 2007), CINAHL (1982 to May 2007), the National Research Register, and web-based trial databases such as Current Controlled Trials. There was no language restriction. Additionally all references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with ultrasound plus serum estradiol concentration versus ultrasound only in women undergoing ovarian hyperstimulation for IVF and ICSI treatment were included. Two review authors independently examined the electronic search results for relevant trials, extracted data and assessed trial quality. They resolved disagreements by discussion with two other authors. Outcomes data were pooled when appropriate and summary statistics presented when limited data did not allow meta-analysis. Our search strategy identified 1119 potentially eligible reports, of which two met our inclusion criteria. These involved 411 women who underwent controlled ovarian stimulation monitoring. Our primary outcome of live birth rate was not reported in either study. One trial reported clinical pregnancy rate per woman (33% versus 31%; RR 1.07, 95% CI 0.77 to 1.49), the second trial reported clinical pregnancy rate per oocyte retrieval (22% versus 25%). There was no significant difference between the ultrasound plus estradiol group and the ultrasound alone group in the mean number of oocytes retrieved (WMD -0.55, 95% CI -1.79 to 0.69) and the incidence of ovarian hyperstimulation (RR 0.73, 95% CI 0.30 to 1.78) for the two studies. There is no evidence from randomised trials to support cycle monitoring by ultrasound plus serum estradiol as more efficacious than cycle monitoring by ultrasound only on outcomes of live birth and pregnancy rates. A large well-designed randomised controlled trial is needed that reports on live birth rates and pregnancy, with economic evaluation of the costs involved and the views of the women undergoing cycle monitoring. A randomised trial with sufficiently large sample size to test the effects of different monitoring protocols on OHSS, a rare outcome, will pose a great challenge. Until such a trial is considered feasible, cycle monitoring by transvaginal ultrasound plus serum estradiol may need to be retained as a precautionary good practice point.

Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo transfer cycles following gonadotropin-releasing hormone agonist treatment.

PubMed

Park, Chan Woo; Choi, Min Hye; Yang, Kwang Moon; Song, In Ok

2016-09-01

To determine the preferred regimen for women with adenomyosis undergoing in vitro fertilization (IVF), we compared the IVF outcomes of fresh embryo transfer (ET) cycles with or without gonadotropin-releasing hormone (GnRH) agonist pretreatment and of frozen-thawed embryo transfer (FET) cycles following GnRH agonist treatment. This retrospective study included 241 IVF cycles of women with adenomyosis from January 2006 to January 2012. Fresh ET cycles without (147 cycles, group A) or with (105 cycles, group B) GnRH agonist pretreatment, and FET cycles following GnRH agonist treatment (43 cycles, group C) were compared. Adenomyosis was identified by using transvaginal ultrasound at the initial workup and classified into focal and diffuse types. The IVF outcomes were also subanalyzed according to the adenomyotic region. GnRH agonist pretreatment increased the stimulation duration (11.5±2.1 days vs. 9.9±2.0 days) and total dose of gonadotropin (3,421±1,141 IU vs. 2,588±1,192 IU), which resulted in a significantly higher number of retrieved oocytes (10.0±8.2 vs. 7.9±6.8, p=0.013) in group B than in group A. Controlled ovarian stimulation for freezing resulted in a significantly higher number of retrieved oocytes (14.3±9.2 vs. 10.0±8.2, p=0.022) with a lower dose of gonadotropin (2,974±1,112 IU vs. 3,421±1,141 IU, p=0.037) in group C than in group B. The clinical pregnancy rate in group C (39.5%) tended to be higher than those in groups B (30.5%) and A (25.2%) but without a significant difference. FET following GnRH agonist pretreatment tended to increase the pregnancy rate in patients with adenomyosis. Further large-scale prospective studies are required to confirm this result.

Patients with endometriosis have aneuploidy rates equivalent to their age-matched peers in the in vitro fertilization population.

PubMed

Juneau, Caroline; Kraus, Emily; Werner, Marie; Franasiak, Jason; Morin, Scott; Patounakis, George; Molinaro, Thomas; de Ziegler, Dominique; Scott, Richard T

2017-08-01

To determine whether endometriosis ultimately results in an increased risk of embryonic aneuploidy. Retrospective cohort. Infertility clinic. Patients participating in an in vitro fertilization (IVF) cycle from 2009-2015 using preimplantation genetic screening (PGS) who had endometriosis identified by surgical diagnosis or by ultrasound findings consistent with a persistent space-occupying disease whose sonographic appearance was consistent with endometriosis. None. Rate of aneuploidy in endometriosis patients undergoing IVF compared to controls without endometriosis undergoing IVF. There were 305 patients with endometriosis who produced 1,880 blastocysts that met the criteria for inclusion in the endometriosis group. The mean age of the patients with endometriosis was 36.1 ± 3.9 years. When the aneuploidy rates in patients with endometriosis and aneuploidy rates in patients without endometriosis were stratified by Society for Assisted Reproductive Technology age groups and compared, there were no statistically significant differences in the rate of aneuploidy (odds ratio 0.85; 95% confidence interval, 0.84-0.85). Patients with endometriosis undergoing IVF have aneuploidy rates equivalent to their age-matched peers in IVF population who do not have endometriosis. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Live birth rates are satisfactory following multiple IVF treatment cycles in poor prognosis patients.

PubMed

Mustafa, Kamarul B; Keane, Kevin N; Walz, Nikita L; Mitrovic, Katarina I; Hinchliffe, Peter M; Yovich, John L

2017-03-01

This seven-year retrospective study analysed the live birth rate (LBR) for women undergoing IVF treatment with various antral follicle counts (AFC). The LBR decreased with lower AFC ratings, and in 290 treatment cycles for women in the poorest AFC category, ≤4 follicles (group E), the LBR was the lowest at 10.7%. The pregnancy loss rate (PLR) significantly increased with poorer AFC categories, from 21.8% in AFC group A (≥20 follicles), to 54.4% in AFC group E (p<0.0001). This trend was repeated with advancing age, from 21.6% for younger women (<35years), to 32.9, 48.5 and 100% for ages 35-39, 40-44 and ≥45 years, respectively (p<0.0001). However, LBR within the specific AFC group E cohort was also age-dependent and decreased significantly from 30.0% for <35 years old, to 13.3, 3.9 and 0% for patients aged 35-39, 40-44 and ≥45 years, respectively. Most, importantly, LBR rates within these age groups were not dependent on the number of IVF attempts (1st, 2nd, 3rd or ≥4 cycles), which indicated that cycle number should not be the primary deciding factor for cessation of IVF treatment in responding women <45years old. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Mandatory counseling for gamete donation recipients: ethical dilemmas.

PubMed

Benward, Jean

2015-09-01

Mental health professionals have engaged in mandatory pretreatment counseling and assessment of patients seeking treatment at IVF programs in the United States since the 1980s. At present, most recipient patients undergoing IVF with egg or embryo donation in the United States are required to meet with a mental health professional for one pretreatment session. Mandatory counseling of gamete recipients is fraught with ethical questions for the mental health professional. Attention to issues of autonomy, confidentiality, role clarity, along with self-evaluation and openness with the patient can help lessen the impact of these ethical challenges. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

[Clinical outcomes and economic analysis of two ovulation induction protocols in patients undergoing repeated IVF/ICSI cycles].

PubMed

Chen, Xiao; Geng, Ling; Li, Hong

2014-04-01

To compare the clinical outcomes and cost-effectiveness of luteal phase down-regulation with gonadotrophin-releasing hormone (GnRH) agonist protocol and GnRH antagonist protocol in patients undergoing repeated in vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI) cycles. A retrospective analysis of clinical outcomes and costs was conducted among 198 patients undergoing repeated IVF-ICSI cycles, including 109 receiving luteal phase down-regulation with GnRH agonist protocol (group A) and 89 receiving GnRH antagonist protocol (group B). The numbers of oocytes retrieved and good embryos, clinical pregnancy rate, abortion rate, the live birth rate, mean total cost, and the cost-effective ratio were compared between the two groups. In patients undergoing repeated IVF-ICSI cycles, the two protocols produced no significant differences in the number of good embryos, clinical pregnancy rate, abortion rate, or twin pregnancy rate. Compared with group B, group A had better clinical outcomes though this difference was not statistically significant. The number of retrieved oocytes was significantly greater and live birth rate significantly higher in group A than in group B (9.13=4.98 vs 7.11=4.74, and 20.2% vs 9.0%, respectively). Compared with group B, group A had higher mean total cost per cycle but lower costs for each oocyte retrieved (2729.11 vs 3038.60 RMB yuan), each good embryo (8867.19 vs 9644.85 RMB yuan), each clinical pregnancy (77598.06 vs 96139.85 RMB yuan). For patients undergoing repeated IVF/ICSI cycle, luteal phase down-regulation with GnRH agonist protocol produces good clinical outcomes with also good cost-effectiveness in spite an unsatisfactory ovarian reserve.

Efficacy of the Levonorgestrel-Releasing Intrauterine System on IVF-ET Outcomes in PCOS With Simple Endometrial Hyperplasia.

PubMed

Bian, Jiang; Shao, Hongfang; Liu, Hua; Li, Hui; Fang, Lu; Xing, Changying; Wang, Lihong; Tao, Minfang

2015-06-01

This study investigated the in vitro fertilization (IVF) outcome of levonorgestrel-releasing intrauterine system (LNG-IUS) pretreatment for simple endometrial hyperplasia (EH) in patients with polycystic ovary syndrome (PCOS) undergoing IVF embryo transfer (IVF-ET). One hundred ninety patients with PCOS and simple EH without cytologic atypia were allocated randomly to 2 independent arms, that is, the LNG-IUS group (90 patients) and the non-LNG-IUS group (100 patients). Four hundred fourteen patients with PCOS without endometrial disease comprised the control group. Each patient was reevaluated by transvaginal ultrasonography (TVS) and endometrial biopsy after 6 months. For each patient, IVF outcome measures, such as number of recombinant follicle-stimulating hormone, endometrial thickness on human chorionic gonadotropin (HCG) day, hormone levels (progesterone, luetinizing hormone, and serum estradiol) on HCG day, number of oocytes, fertilization rate, clinical pregnancy rate, and miscarriage rate were compared among the 3 groups. In general, the 3 groups did not differ with respect to the main clinical and biochemical data. After 6 months, patients in LNG-IUS group had an EH resolution rate of 87.77%. In the non-LNG-IUS group, the resolution rate was 15.00%, and 3% of these patients showed progression of EH. The clinical pregnancy rates in the non-LNG-IUS group were significantly lower (28.04%) than that in the LNG-IUS group (46.06%) and the control group (44.65%). The miscarriage rate was highest in the non-LNG-IUS group, but no significant difference in miscarriage rate existed among the 3 groups. The study illustrates that the LNG-IUS can be safely used for 6 months as a treatment for patients with PCOS and simple EH. Additionally, use of the LNG-IUS can increase the clinical pregnancy rates and implantation rates of patients with PCOS and simple EH who undergo gonadotropin-releasing hormone agonist IVF-ET protocols. © The Author(s) 2014.

Hysteroscopic proximal tubal occlusion versus laparoscopic salpingectomy as a treatment for hydrosalpinges prior to IVF or ICSI: an RCT.

PubMed

Dreyer, K; Lier, M C I; Emanuel, M H; Twisk, J W R; Mol, B W J; Schats, R; Hompes, P G A; Mijatovic, V

2016-09-01

Does hysteroscopic proximal tubal occlusion by intratubal devices as a treatment for hydrosalpinges result in comparable ongoing pregnancy rates following IVF/ICSI when compared with laparoscopic salpingectomy? Hysteroscopic proximal tubal occlusion by intratubal devices is inferior to laparoscopic salpingectomy in the treatment of hydrosalpinges in women undergoing IVF/ICSI with respect to ongoing pregnancy rates. It is known that women with hydrosalpinges undergoing IVF have poorer pregnancy outcomes compared with women with other forms of tubal infertility. In these women, both laparoscopic salpingectomy and laparoscopic proximal tubal ligation are known to improve IVF outcomes. At present, it is unclear whether a less-invasive hysteroscopic treatment with intratubal devices leads to similar ongoing pregnancy rates following IVF when compared with laparoscopic salpingectomy. A two-centre, randomized, controlled, non-inferiority trial. Between October 2009 and December 2014 a total of 85 women were included in this study; of whom, 42 were randomized to hysteroscopic proximal occlusion by intratubal device placement and 43 were randomized to laparoscopic salpingectomy. Randomization was based on a computer-generated randomization list. The study was unblinded. The primary outcome was ongoing pregnancy rate, defined as a fetal heartbeat on ultrasound beyond 10-week gestation following one IVF/ICSI treatment (fresh and frozen-thawed embryo transfers). We studied women aged 18-41 years, with uni- or bilateral ultrasound visible hydrosalpinges who were scheduled for an IVF/ICSI treatment. The ongoing pregnancy rates per patient according to the intention-to-treat principle were 11/42 (26.2%) after hysteroscopic proximal occlusion by intratubal devices (intervention group) versus 24/43 (55.8%) after laparoscopic salpingectomy (control group) (P = 0.008) [absolute difference: 26.1%; 95% confidence interval (CI): 0.5-51.7, relative risk (RR): 0.56; 95% CI: 0.31-1.03, P = 0.01]. In the per protocol analysis, the ongoing pregnancy rate per patient following hysteroscopic proximal occlusion by intratubal devices was 9/27 (33.3%) compared with 19/32 (59.4%) following laparoscopic salpingectomy (P = 0.067) (absolute difference: 29.6%; 95% CI: 7.1 to 49.1, RR: 0.47; 95% CI: 0.27-0.83, P = 0.062). Masking participants and investigators would be difficult due to the nature of both interventions. Since we had objective outcome measurements, we withheld sham procedures, leaving the study unblinded. Furthermore, our low sample size resulted in wide CIs. A larger sample size would result in a more accurate treatment effect; however, this was non-feasible for recruitment and inclusion. In the treatment of hydrosalpinges prior to IVF/ICSI, hysteroscopic proximal occlusion by intratubal devices is inferior to laparoscopic salpingectomy. The intratubal devices were received from Conceptus, Inc., San Carlos, CA, USA, which was acquired by Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA in 2013. Conceptus, Inc./Bayer HealthCare Pharmaceuticals, Inc. had no role in the study design, data collection and analyses, decision to publish or preparation of the manuscript. The study as a whole was funded by the SWOG (foundation for scientific investigation in obstetrics and gynaecology of the VU University Medical Centre, Amsterdam, the Netherlands). P.G.A.H. has received non-financial support from Conceptus, Inc. during the conduct of this study. He has received grants from Ferring B.V., Merck Serono and Abbott outside the submitted work. M.H.E. has received personal fees from Smith and Nephew and IQ Medical Ventures outside the submitted work. The Dutch Trial Register: NTR 2073. October 21, 2009. October 26, 2009. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Estrogen supplementation to progesterone as luteal phase support in patients undergoing in vitro fertilization: systematic review and meta-analysis.

PubMed

Zhang, Xiao-Mei; Lv, Fang; Wang, Pin; Huang, Xia-Man; Liu, Kai-Feng; Pan, Yu; Dong, Nai-Jun; Ji, Yu-Rong; She, Hong; Hu, Rong

2015-02-01

Meta-analyses have found conflicting results with respect to the use of progesterone or progesterone plus estrogen as luteal phase support for in vitro fertilization (IVF) protocols involving gonadotropins and/or gonadotropin-releasing hormone analogs. The aim of the present study was to perform an updated meta-analysis on the efficacy of progesterone versus progesterone plus estrogen as luteal phase support. We searched the MEDLINE, Cochrane Library, and Google Scholar databases (up to March 18, 2014). The search terms were (estrogen OR estradiol OR oestradiol) AND (progesterone) AND (IVF OR in vitro fertilization) AND (randomized OR prospective). We did not limit the form of estrogen and included subjects who contributed more than 1 cycle to a study. The primary outcome was clinical pregnancy rate. Secondary outcomes were ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate. A total of 11 articles were included in the present analysis, with variable numbers of studies assessing each outcome measure. Results of statistical analyses indicated that progesterone plus estrogen treatment was more likely to result in clinical pregnancy than progesterone alone (pooled odds ratio 1.617, 95% confidence interval 1.059-2.471; P = 0.026). No significant difference between the 2 treatment regimens was found for the other outcome measures. Progesterone plus estrogen for luteal phase support is associated with a higher clinical pregnancy rate than progesterone alone in women undergoing IVF, but other outcomes such as ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate are the same for both treatments.

Cumulative live birth rates after one or more complete cycles of IVF: a population-based study of linked cycle data from 178,898 women.

PubMed

McLernon, David J; Maheshwari, Abha; Lee, Amanda J; Bhattacharya, Siladitya

2016-03-01

What is the chance of a live birth following one or more linked complete cycles of IVF (including ICSI)? The chance of a live birth after three complete cycles of IVF was 42.3% for treatment commencing from 1999 to 2007. IVF success has generally been reported on the basis of live birth rates after a single episode of treatment resulting in the transfer of a fresh embryo. This fails to capture the real chance of having a baby after a number of complete cycles-each involving the replacement of fresh as well as frozen-thawed embryos. Population-based observational cohort study of 178 898 women between 1992 and 2007. Participants included all women who commenced IVF treatment at a licenced clinic in the UK as recorded in the Human Fertilisation and Embryology Authority (HFEA) national database. Exclusion criteria included women whose treatment involved donor insemination, egg donation, surrogacy and the transfer of more than three embryos. Cumulative rates of live birth, term (>37 weeks) singleton live birth, and multiple pregnancy were estimated for two time-periods, 1992-1998 and 1999-2007. Conservative estimates assumed that women who did not return for IVF would not have the outcome of interest while optimal estimates assumed that these women would have similar outcome rates to those who continued IVF. A total of 71 551 women commenced IVF treatment during 1992-1998 and an additional 107 347 during 1999-2007. After the third complete IVF cycle (defined as three fresh IVF treatments-including replacement of any surplus frozen-thawed embryos), the conservative CLBR in women who commenced IVF during 1992-1998 was 30.8% increasing to 42.3% during 1999-2007. The optimal CLBRs were 44.6 and 57.1%, respectively. After eight complete cycles the optimal CLBR was 82.4% in the latter time period. The conservative rate for multiple pregnancy per pregnant woman fell from 31.9% during the earlier time period to 26.2% during the latter. Linkage of all IVF treatments to individual women was conducted. However, it was not possible to identify with certainty in all cases the episode of ovarian stimulation which generated some of the frozen embryos. Cumulative live birth rates could not be calculated for women who started treatment beyond 2007 as follow-up data were incomplete in some of them. Following a change in legislation in 2008, linked data were only made available for research in women who gave formal consent for this purpose. BMI and ethnicity could not be reported: these demographics are not recorded in the HFEA database. Our results demonstrate, at a national level, the chances of live birth in couples undergoing a number of complete (fresh and frozen) IVF cycles. They reflect improvements in reproductive technology and a more conservative embryo transfer policy. Although most couples in the UK still do not receive three complete IVF cycles; assuming no barriers to continuation of IVF treatment, around 83% of women receiving IVF would achieve a live birth by the eighth complete cycle, similar to the natural live birth rate in a non-contraception practising population. Our results support the call from NICE to develop consistent IVF policies based on three complete cycles. This work was funded by a Chief Scientist Office Postdoctoral Training Fellowship in Health Services Research and Health of the Public Research (Ref PDF/12/06). The views expressed here are those of the authors and not necessarily those of the Chief Scientist Office. S.B. reports grants from Chief Scientist Office Scotland during the conduct of the study. His institution has received support from Pharmaceutical companies (for educational seminars), which is not related to the submitted work. D.J.M., A.M. and A.J.L. have no conflicts of interest to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Chromosomal Aneuploidies and Early Embryonic Developmental Arrest.

PubMed

Maurer, Maria; Ebner, Thomas; Puchner, Manuela; Mayer, Richard Bernhard; Shebl, Omar; Oppelt, Peter; Duba, Hans-Christoph

2015-01-01

Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF) technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH) with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting.

A randomised controlled trial of intra-uterine insemination versus in vitro fertilisation in patients with idiopathic or mild male infertility.

PubMed

Elzeiny, Hossam; Garrett, Claire; Toledo, Manuela; Stern, Kate; McBain, John; Baker, Hugh William Gordon

2014-04-01

The cause of infertility is unexplained or poorly explained in 30-40% of couples undergoing standard investigations, and treatment ranges from expectant management to IUI and IVF. The aim of this study was to compare the clinical pregnancy rates and costs of intra-uterine insemination (IUI) and in vitro fertilisation (IVF) in women where the same ovarian stimulation led to the development of two or three mature follicles. A randomised controlled clinical trial compared the efficacy of IUI and IVF in a tertiary fertility centre (ISRCTN28780587). Primary outcome measures were fetal heart positive pregnancy rate and cost per live birth. The selection criteria were age: females 18-42 years and males 18-60 years, infertility for one year or more, no IVF or IUI for 12 months prior to the trial, and no coital, tubal or ovulatory disorders, oligospermia, untreated endometriosis or contraindication for multiple pregnancy. All women (n = 102) had the same dose FSH stimulation protocol. Those who developed two or three preovulatory follicles were randomised 3:1 to IUI (n = 33) or IVF (n = 10). IUI or IVF was performed 36 h after hCG administration with single or double embryo transfer on day two. Clinical pregnancy rates (40% vs 12%, P = 0.04) and live birth rate (40% vs 6%, P = 0.01) were higher for IVF than IUI. The cost per live birth was AU$8735 for IVF compared with $42,487 for IUI. This study provides evidence that IVF is more successful and cost-effective than IUI using the same doses of FSH. Further confirmatory studies are required. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis.

PubMed

Potdar, Neelam; Gelbaya, Tarek; Nardo, Luciano G

2012-12-01

Mechanical endometrial injury (biopsy/scratch or hysteroscopy) in the cycle preceding ovarian stimulation for IVF has been proposed to improve implantation in women with unexplained recurrent implantation failure (RIF). This is a systematic review and meta-analysis of studies comparing the efficacy of endometrial injury versus no intervention in women with RIF undergoing IVF. All controlled studies of endometrial biopsy/scratch or hysteroscopy performed in the cycle preceding ovarian stimulation were included and the primary outcome measure was clinical pregnancy rate. Pooling of seven controlled studies (four randomized and three non-randomized), with 2062 participants, showed that local endometrial injury induced in the cycle preceding ovarian stimulation is 70% more likely to result in a clinical pregnancy as opposed to no intervention. There was no statistically significant heterogeneity in the methods used, clinical pregnancy rates being twice as high with biopsy/scratch (RR 2.32, 95% CI 1.72-3.13) as opposed to hysteroscopy (RR 1.51, 95% CI 1.30-1.75). The evidence is strongly in favour of inducing local endometrial injury in the preceding cycle of ovarian stimulation to improve pregnancy outcomes in women with unexplained RIF. However, large randomized studies are required before iatrogenic induction of local endometrial injury can be warranted in routine clinical practice. Some women undergoing IVF treatment fail to conceive despite several attempts with good-quality embryos and no identifiable reason. We call this 'recurrent implantation failure' (RIF) where the embryo fails to embed or implant within the lining of the womb. Studies have shown that inducing injury to the lining of the womb in the cycle before starting ovarian stimulation for IVF can help improve the chances of achieving pregnancy. Injury can be induced by either scratching the lining of the womb using a biopsy tube or by telescopic investigation of the womb using a camera. We performed a collective review of the available good-quality studies that used the above two methods in the cycle prior to starting ovarian stimulation for IVF. We pooled results from seven studies, which included 2062 women with RIF and assessed the difference in clinical pregnancy rates for those undergoing injury to the womb lining compared with no injury prior to IVF. The results suggest that inducing injury is 70% more likely to result in a clinical pregnancy as opposed to no treatment. Furthermore, scratching of the lining was 2-times more likely to result in a clinical pregnancy compared with telescopic evaluation of the lining of the womb. This study suggests that in women with RIF, inducing local injury to the womb lining in the cycle prior to starting ovarian stimulation for IVF can improve pregnancy outcomes. However, large studies are required before this can be warranted in routine clinical practice. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Association of high fetuin-B concentrations in serum with fertilization rate in IVF: a cross-sectional pilot study.

PubMed

Floehr, Julia; Dietzel, Eileen; Neulen, Josef; Rösing, Benjamin; Weissenborn, Ute; Jahnen-Dechent, Willi

2016-03-01

Is serum fetuin-B associated with the fertilization rate in in vitro fertilization (IVF)? Serum fetuin-B increased during IVF cycles when oocytes could be fertilized while remained unchanged in fertilization failure. Fetuin-B deficiency in mice causes premature zona pellucida hardening mediated by the zona protease ovastacin. Thus fetuin-B deficiency renders females infertile. We determined the human serum fetuin-B reference range, studying longitudinally, over the course of one month, five male and seven female volunteers without hormone treatment and four female volunteers on varying hormonal contraception. We sampled blood and determined serum fetuin-B, luteinizing hormone (LH), estradiol (E2) and progesterone (P4). In addition, we determined serum fetuin-B and estradiol in eight women undergoing intracytoplasmatic sperm injection (ICSI, nine ICSI cycles) and 19 women undergoing IVF (21 IVF cycles) after ovarian stimulation with recombinant human follicular stimulating hormone (rFSH) and/or a combined medication of FSH and LH. At least three blood samples were analyzed in each cycle. We compared serum fetuin-B and follicular fluid fetuin-B in nine patients by measuring follicular fetuin-B in pooled follicular fluid, and in fluid obtained from individual follicles. Samples were drawn from January 2012 to March 2014. All volunteers and patients gave informed consent. Fetuin-B was measured employing a commercial sandwich enzyme-linked immunosorbent assay. Serum fetuin-B was determined as duplicates in 5 male (34 ± 14.6 years) and 11 female volunteers (29.4 ± 4.1 years) as well as in female volunteers on hormonal contraception (30.0 ± 6.5 years). The duplicate standard deviation was 4.0 ± 2.3%. The contraceptive drugs were mono or combined preparations containing 0-0.03 mg ethinyl estradiol, and 0.15-3.0 mg of various progestins. In addition, serum fetuin-B was determined as triplicates in 27 female patients undergoing conventional IVF (19) or ICSI (8). The triplicate standard deviation was 3.3 ± 1.8%. IVF was declared as 'successful', if at least one oocyte was fertilized, and 'unsuccessful', if no oocyte could be fertilized. Patient age was 34.4 ± 4.4 years in successful IVF, and 35.4 ± 3.3 years in unsuccessful IVF. Serum and follicular fluid of patients undergoing controlled ovarian hyperstimulation were analyzed. Serum was drawn at the day of follicle aspiration. Serum fetuin-B and follicular fluid fetuin-B were not significantly different in six out of nine patients suggesting, in principle, free exchange of fetuin-B between serum and follicular fluid. Thus serum fetuin-B may be used as a proxy of follicular fluid fetuin-B. Serum fetuin-B increased during successful IVF cycles (n = 15, P < 0.0001), but did not change in unsuccessful IVF cycles (n = 6, P = 0.118) despite increased estradiol levels (P = 0.0019 and P = 0.0254, respectively). The female volunteers self-reported their respective hormone medication. Medication was verified by serum estradiol, LH and progesterone measurements. For oocyte harvesting, the vaginal wall was punctured once only to minimize co-morbidity. Low grade cross-contamination of individual follicular fluid aspirates and contamination of the follicular fluid with small amounts of blood were inevitable. Samples were routinely checked for the presence of hemoglobin that would suggest blood contamination. Only samples containing <250 erythrocyte equivalents/µl were used for analysis. Serum fetuin-B may be used as a marker to predict the fertilization success in IVF. Fetuin-B levels attained during IVF stimulation may help to make an informed decision whether oocytes should be fertilized by IVF or by ICSI to overcome the zona pellucida as a barrier. The research was supported by a grant from Deutsche Forschungsgemeinschaft and by the START program of the Medical Faculty of RWTH Aachen University. J.F., E.D., J.N., B.R. and W.J.-D. declare that they are named inventors on the RWTH Aachen University patent application EP 13157317.2, 'Use of fetuin-B for culture of oocytes', applied for by RWTH Aachen University. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Live birth and perinatal outcomes following stimulated and unstimulated IVF: analysis of over two decades of a nationwide data.

PubMed

Sunkara, Sesh Kamal; LaMarca, Antonio; Polyzos, Nikolaos P; Seed, Paul T; Khalaf, Yakoub

2016-10-01

Does ovarian stimulation affect perinatal outcomes of preterm birth (PTB) and low birth weight (LBW) following IVF treatment. Despite no significant differences in the risks of PTB and LBW between stimulated and unstimulated IVF in the present study, the study cannot exclude the effect of ovarian stimulation on the perinatal outcomes following IVF. Pregnancies resulting from assisted reproductive treatments (ART) are associated with a higher risk of pregnancy complications compared to spontaneously conceived pregnancies attributed to the underlying infertility and the in vitro fertilization techniques. It is of interest to determine the effect size of ovarian stimulation use in achieving a live birth and whether ovarian stimulation that is routinely used in IVF, affects perinatal outcomes of birth weight and gestational age at delivery compared to unstimulated IVF. Anonymous data were obtained from the Human Fertilisation and Embryology Authority (HFEA), the statutory regulator of ART in the UK. The HFEA has collected data prospectively on all ART performed in the UK since 1991. Data from 1991 to 2011 comprising a total of 591 003 fresh IVF ± ICSI cycles involving 584 835 stimulated IVF cycles and 6168 unstimulated IVF cycles were analyzed. Data on all women undergoing either stimulated or unstimulated fresh IVF ± ICSI cycles during the period from 1991 to 2011 were analyzed to compare live birth rates, singleton live birth rates, perinatal outcomes of PTB, early PTB (<32 weeks), LBW and very LBW (<1500 grams) among singleton live births. Adjusted logistic regression was performed for each perinatal outcome for confounding factors: female age, period of treatment, cause of infertility, number of previous IVF cycles and previous live birth. Analysis of the large nationwide data demonstrated 3.5 times (95% confidence interval (CI): 3.1-3.9) as many unstimulated IVF cycles being required to achieve one live birth compared to stimulated IVF and 2.9 times (95% CI: 2.6-3.2) as many unstimulated IVF cycles being required to achieve one singleton live birth compared to stimulated IVF. There was no significant difference in the unadjusted odds for PTB (odds ratio (OR) 1.27, 95% CI: 0.80-2.00) and LBW (OR 1.48, 95% CI: 0.90-2.42) between stimulated and unstimulated IVF cycles. There was no significant difference in the risk of the adverse perinatal outcomes after adjusting for potential confounders; PTB (adjusted odds ratio (aOR) 1.43, 95% CI: 0.91-2.26) and LBW (aOR 1.58, 95% CI: 0.96-2.58). Although the analysis was adjusted for a number of important confounders, the dataset had no information on smoking, body mass index (BMI) and the medical history of women during pregnancy to allow adjustment. Anonymized nature of the dataset did not make it permissible to analyse one cycle per woman. Given the smaller number of perinatal events with unstimulated IVF, a larger study is needed to investigate further. Analysis of this large dataset demonstrates that ovarian stimulation has a vital role in maximizing efficacy of IVF. Although there were no significant differences for PTB and LBW following stimulated compared to unstimulated IVF, the CIs were wide enough to include possible clinically important effects. No funding was obtained. There are no competing interests to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Induced endometrial trauma (endometrial scratch) in the mid-luteal menstrual cycle phase preceding first cycle IVF/ICSI versus usual IVF/ICSI therapy: study protocol for a randomised controlled trial.

PubMed

Pye, Clare; Chatters, Robin; Cohen, Judith; Brian, Kate; Cheong, Ying C; Laird, Susan; Mohiyiddeen, Lamiya; Skull, Jonathan; Walters, Stephen; Young, Tracey; Metwally, Mostafa

2018-05-20

Endometrial trauma commonly known as endometrial scratch (ES) has been shown to improve pregnancy rates in women with a history of repeated implantation failure undergoing in vitro fertilisation (IVF), with or without intracytoplasmic sperm injection (ICSI). However, the procedure has not yet been fully explored in women having IVF/ICSI for the first time. This study aims to examine the effect of performing an ES in the mid-luteal phase prior to a first-time IVF/ICSI cycle on the chances of achieving a clinical pregnancy and live birth. If ES can influence this success rate, there would be a significant cost saving to the National Health Service through decreasing the number of IVF/ICSI cycles necessary to achieve a pregnancy, increase the practice of single embryo transfer and consequently have a large impact on risks and costs associated with multiple pregnancies. This 30-month, UK, multicentre, parallel group, randomised controlled trial includes a 9-month internal pilot and health economic analysis recruiting 1044 women from 16 fertility units. It will follow up participants to identify if IVF/ICSI has been successful and live birth has occurred up to 6 weeks post partum. Primary analysis will be on an intention-to-treat basis. A substudy of endometrial samples obtained during the ES will assess the role of immune factors in embryo implantation. Main trial recruitment commenced on January 2017 and is ongoing.Participants randomised to the intervention group will receive the ES procedure in the mid-luteal phase of the preceding cycle prior to first-time IVF/ICSI treatment versus usual IVF/ICSI treatment in the control group, with 1:1 randomisation. The primary outcome is live birth rate after completed 24 weeks gestation. South Central-Berkshire Research Ethics Committee approved the protocol. Findings will be submitted to peer-reviewed journals and abstracts to relevant national and international conferences. ISRCTN23800982; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A questionnaire-based audit to assess overall experience and convenience among patients using vaginal progesterone tablets (Lutigest®) for luteal phase support during IVF treatment

PubMed Central

Heine, Polly; Sellar, Laura; Whitten, Sue; Bajaj, Priti

2017-01-01

Purpose The aim of this audit was to assess the overall experience and patient convenience of vaginal progesterone tablets (Lutigest®, marketed as Endometrin® in the USA) used for luteal phase support (LPS) during in vitro fertilization (IVF) treatment. Patients and methods This questionnaire-based audit included responses from 100 patients undergoing IVF treatment at six IVF clinics in the UK from September 2015 to November 2016. Fourteen days after starting progesterone supplementation for LPS during their IVF treatment, patients rated overall experience and perceived convenience of the prescribed progesterone by completing a questionnaire. Results Of the 100 patients included, 96 received vaginal progesterone tablets for LPS. Overall, 53.1% (51/96) indicated that the progesterone tablets were “very easy” to use; 42.7% (41/96) and 44.8% (43/96) found it “very convenient” or “neither convenient or inconvenient” to administer the tablet, respectively. Overall experience with using progesterone tablets was rated as “very comfortable” by 34.4% (33/96) and “neither comfortable or uncomfortable” by 56.3% (54/96) of patients. The applicator was used by 93.8% (90/96) of patients to administer the tablet, and 86.5% (83/96) indicated that the applicator was easy to clean for repeated use. A total of 33 patients had a previous IVF cycle during which they were prescribed vaginal progesterone pessaries for LPS. Compared with progesterone pessaries, the majority found treatment with progesterone tablets to be more comfortable (60.6%; 20/33) and more convenient (57.6%; 19/33) and indicated that the progesterone tablet was their preferred progesterone formulation for LPS (60.6%; 20/33). Conclusion These findings offer insights into real-world patient experiences with the progesterone vaginal tablet formulation. The results suggest overall patient convenience, ease, and comfort with using progesterone vaginal tablets for LPS. The majority of patients found progesterone vaginal tablets more convenient and comfortable to use compared with progesterone pessaries. PMID:29263708

The place of reconstructive tubal surgery in the era of assisted reproductive techniques.

PubMed

Gomel, Victor

2015-12-01

Assisted reproductive techniques yield high rates of success for women with tubal factor infertility. Because they are potentially effective for all categories of infertility, for two decades, clinical and basic research in infertility has been focused on IVF techniques and outcomes, rather than developing surgical techniques or training infertility subspecialists in tubal microsurgery. Nonetheless, in comparison with IVF, reconstructive tubal surgery is inexpensive and offers multiple opportunities to attempt conception. Performing laparoscopic salpingostomy prior to IVF in women with good prognosis tubal disease may improve the outcome of subsequent IVF, while offering the potential for spontaneous conception. Tubo-tubal anastomosis for reversal of tubal ligation, performed either by a microsurgical technique through a mini-laparotomy or by laparoscopy, is preferable to IVF in younger women with no other fertility factors, because it offers potentially higher cumulative pregnancy rates. Surgery is the only alternative for women with tubal factor infertility who for personal or other reasons are unable to undergo assisted reproductive techniques. Tubal reconstructive surgery and assisted reproductive techniques must be considered complementary forms of treatment for women with tubal factor infertility, and training in tubal reconstructive surgery should be an integral part of subspecialty training in reproductive endocrinology and infertility. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial.

PubMed

van Tilborg, Theodora C; Eijkemans, Marinus J C; Laven, Joop S E; Koks, Carolien A M; de Bruin, Jan Peter; Scheffer, Gabrielle J; van Golde, Ron J T; Fleischer, Kathrin; Hoek, Annemieke; Nap, Annemiek W; Kuchenbecker, Walter K H; Manger, Petra A; Brinkhuis, Egbert A; van Heusden, Arne M; Sluijmer, Alexander V; Verhoeff, Arie; van Hooff, Marcel H A; Friederich, Jaap; Smeenk, Jesper M J; Kwee, Janet; Verhoeve, Harold R; Lambalk, Cornelis B; Helmerhorst, Frans M; van der Veen, Fulco; Mol, Ben Willem J; Torrance, Helen L; Broekmans, Frank J M

2012-09-18

Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. NTR2657.

Psychological consequences of IVF fertilization - Review of research.

PubMed

Malina, Alicja; Pooley, Julie Ann

2017-12-23

Due to the reported efficacy of in vitro fertilization (IVF) this method of dealing with infertility is increasing being used. Experiencing IVF can be a source of psychological and emotional difficulties for couples trying to have a child. A systematic review was performed to discuss IVF as a psychological issue that impacts on the functioning of individuals, couples and families. Ebsco, Science Direct and PsycARTICLES databases were searched using the keywords: IVF fertilization, IVF psychology, infertility, and IVF consequences, using published peer reviewed articles from 2006 onwards. Studies in the English and Polish languages, peer reviewed and investigating general IVF and infertility psychological issues were included. Data was collected by the authors between June 2015-January 2016. Studies indicate that partners going through IVF may not have enough support from their closest social environments. It is argued that these unsupportive social interactions affect the well-being of couples, can hinder conception, and therefore are one of the reasons for attrition from IVF, the most effective assisted reproduction method. There is a need to conduct studies on the effect of supportive social interactions for the functioning of couples undergoing IVF.

A higher prevalence of endometriosis among Asian women does not contribute to poorer IVF outcomes.

PubMed

Yamamoto, Ayae; Johnstone, Erica B; Bloom, Michael S; Huddleston, Heather G; Fujimoto, Victor Y

2017-06-01

The purpose of the study was to determine whether diagnosis of endometriosis or endometriosis with endometrioma influences in vitro fertilization (IVF) outcomes in an ethnically diverse population. Women undergoing a first IVF cycle (n = 717) between January 1, 2008 and December 31, 2009, at a university-affiliated infertility clinic, were retrospectively assessed for an endometriosis diagnosis. Differences in prevalence of endometriosis by ethnicity were determined, as well as differences in IVF success by ethnicity, with a focus on country of origin for Asian women. A multivariate model was generated to assess the relative contributions of country of origin and endometriosis to chance of clinical pregnancy with IVF. Endometriosis was diagnosed in 9.5% of participants; 3.5% also received a diagnosis of endometrioma. Endometriosis prevalence in Asian women was significantly greater than in Caucasians (15.7 vs. 5.8%, p < 0.01). Women of Filipino (p < 0.01), Indian (p < 0.01), Japanese (p < 0.01), and Korean (p < 0.05) origin specifically were more likely to have endometriosis than Caucasian women, although there was no difference in endometrioma presence by race/ethnicity. Oocyte quantity, embryo quality, and fertilization rates did not relate to endometriosis. Clinical pregnancy rates were significantly lower for Asian women, specifically in Indian (p < 0.05), Japanese (p < 0.05), and Korean (p < 0.05) women, compared to Caucasian women, even after controlling for endometriosis status. The prevalence of endometriosis appears to be higher in Filipino, Indian, Japanese, and Korean women presenting for IVF treatment than for Caucasian women; however, the discrepancy in IVF outcomes was conditionally independent of the presence of endometriosis. Future research should focus on improving pregnancy outcomes for Asian populations whether or not they are affected by endometriosis, specifically in the form of longitudinal studies where exposures can be captured prior to endometriosis diagnoses and infertility treatment.

[Effects of Cangfu Congxian Decoction on Oxidative Stress in Polycystic Ovary Syndrome Patients].

PubMed

Liang, Ying; Tian, Qian-hua; Mu, Yu-xia; Du, Hui-lan

2016-06-01

To observe the effect of Cangfu Congxian Decoction (CCD) on oxidative stress in granulosa cells of polycystic ovary syndrome (PCOS) patients. Forty PCOS patients underwent in vitro fertilization-embryo transfer (IVF-ET) were assigned to the treatment group and the control group 1 according to random digit table, 20 in each group. Patients in the treatment group took CCD (200 mL, once in the morning and once in the afternoon) 2 months before IVF-ET, while those in the control group 1 took no Chinese medical decoction. Recruited were another 20 patients undergoing IVF-ET for tubal factors (as the control group 2). The clinical effect of IVF-ET were observed, including oocyte retrieval number, 2 pronuclear (2PN) fertilization rate, good quality embryo rate, clinical pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) induced transplantation cancel rate. The expression of relative oxygen species (ROS) in granulosa cells was detected using cell immunofluorescence combined with confocal microscopy and FCM. Compared with the control group 1, occyte retrieval number, 2PN fertilization rate, and good quality embryo rate increased in the control group 2 and the treatment group (P <0. 05). OHSS induced transplantation cancel rate decreased in the control group 2 (P < 0.05). Fluorescence intensity of ROS decreased in the treatment group and the control group 2, as compared with the control group 1 (P < 0.01). CCD increased good quality embryo rate by down-regulating the expression of ROS protein in ovarian granulosa cells, and correcting in vivo oxidative stress.

Human trophoblast cell during first trimester after IVF-ET differs from natural conceived pregnancy in development and function.

PubMed

Yang, Rui; Liu, Ying-Ying; Zhao, Liang; Wang, Ying; Li, Rong; Liu, Ping; Ma, Cai-Hong; Chen, Xin-Na; Qiao, Jie

2017-03-01

To explore the differences of the trophoblast cell function in first trimester between natural pregnancy and pregnancy after IVF-ET therapy. 102 cases with twin to singleton fetal reduction after IVF-ET treatment from July 2010 to August 2013 in Peking University Third Hospital were involved in analysis, and eight specimens were obtained from this group. 10 natural-pregnancy cases undergoing artificial abortion with unwanted pregnancy were recruited as control. Semi-quantitative immunohistochemical method was used to detect the expression of EGFR, Bcl-2, tubulin-α, metallothionein and AFP in villi in both groups. Of the 102 cases, 14 cases (13.73%) were aborted. Preterm birth occurred in seven cases (7.86%). Low birth weight occurred in three patients (3.37%), and extremely low birth weight occurred in four cases (4.49%). The expression of EGFR, tubulin-α, Bcl-2, and metallothionein in the IVF-ET group was significantly lower than that in the control group (P<0.05). However, AFP expression was significantly higher in IVF-ET group than in control group (P<0.05). In IVF-ET group, the miscarriage case had weaker EGFR, tubulin-α, and metallothionein expression than full-term pregnancy; the early preterm labor case had weaker Bcl-2, tubulin-α, and metallothionein expression; and velamentous cord insertion case had weaker tubulin-α expression. The trophoblast cell function of IVF-ET group in first trimester is different from control group in proliferation, invasion, apoptosis and vascular development, and optimal pregnancy outcome depends on the self-healing balance of trophoblast cells.

Early in vitro fertilization improves development of bovine ova heat stressed during in vitro maturation.

PubMed

Schrock, G E; Saxton, A M; Schrick, F N; Edwards, J L

2007-09-01

The objectives were to examine the development of embryos derived from control (38.5 degrees C) or heat-stressed ova [41.0 degrees C during the first 12 h of in vitro maturation (hIVM)] when in vitro fertilization (IVF) was performed at 16, 18, 20, 24, or 30 hIVM. Effects of heat stress in compromising ovum development depended on when IVF was performed (in vitro maturation temperature x IVF time interaction). When IVF was performed at 24 or 30 hIVM, fewer heat-stressed ova developed to the blastocyst stage compared with the respective controls. In contrast, when IVF was performed at 16, 18, or 20 hIVM, more heat-stressed ova developed to the blastocyst stage compared with the respective controls. Performing IVF earlier than usual was beneficial, because the ability of heat-stressed ova to develop to the blastocyst stage was improved when IVF was performed at 18 or 20 vs. 24 hIVM. Blastocyst stage and quality were equivalent to non-heat-stressed controls regardless of IVF time. Control ova undergoing IVF at 20, 24, 30, or 32 hIVM and heat-stressed ova undergoing IVF at 16, 18, 20, or 24 hIVM were compared for blastocyst development by multisource regression. Although linear and quadratic slopes were similar, heat stress reduced the peak and shifted the developmental response of ova by 7.3 h. In other words, obtaining optimal blastocyst development from heat-stressed ova would depend on performing IVF at 19.5 hIVM compared with 26.7 hIVM for non-heat-stressed controls. Heat-induced reductions in peak blastocyst development significantly reduced the window of time available to perform IVF and obtain > or = 20% blastocyst development. In summary, results support an effect of heat stress to hasten developmentally important events during oocyte maturation. The inability of earlier IVF to fully restore the development of heat-stressed ova to that of non-heat-stressed controls highlights the importance of further study.

Progesterone bioavailability with a progesterone-releasing silicone vaginal ring in IVF candidates.

PubMed

Dragonas, C; Maltaris, T; Binder, H; Kat, M; Mueller, A; Cupisti, S; Hoffmann, I; Beckmann, M W; Dittrich, Ralf

2007-06-27

A vaginal ring made of silicone polymers and barium sulfate, and containing 1 g of pure micronized progesterone, was developed for luteal supplementation in women undergoing cycles of in vitro fertilization (IVF). The ring, modeled on the Estring, was designed as a means of providing continuous intravaginal delivery of progesterone. Bioavailability of progesterone in the blood was demonstrated for 24 hours in IVF candidates who had an endogenous progesterone deficiency after treatment with gonadotropin-releasing hormone (GnRH) analogues. After the first 4 h of increasing release of progesterone from the ring (with mean serum levels of 1.39 +/- 0.8 ng/ml after 4 h), only a slight increase in serum progesterone levels (with a mean peak of 1.5 +/- 0.45 ng/ml after 24 h) was observed during the rest of the test period. Gonadotropin levels were not affected after insertion of the ring. The ring was well tolerated by the patients. The maximum serum progesterone level was lower in comparison with other forms of progesterone application, but it should be sufficiently high, due to the uterine first-pass effect. This study demonstrated that progesterone administration through a silicone ring for luteal support is feasible in IVF treatment. As the vaginal ring is very well tolerated by the patients, these findings may encourage the pharmaceutical industry to design an appropriate progesterone ring for luteal support.

Chromosomal Aneuploidies and Early Embryonic Developmental Arrest

PubMed Central

Maurer, Maria; Ebner, Thomas; Puchner, Manuela; Mayer, Richard Bernhard; Shebl, Omar; Oppelt, Peter; Duba, Hans-Christoph

2015-01-01

Background Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF) technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. Materials and Methods This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH) with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Results Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Conclusion Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting. PMID:26644858

Urinary bisphenol A concentrations and early reproductive health outcomes among women undergoing IVF.

PubMed

Ehrlich, Shelley; Williams, Paige L; Missmer, Stacey A; Flaws, Jodi A; Ye, Xiaoyun; Calafat, Antonia M; Petrozza, John C; Wright, Diane; Hauser, Russ

2012-12-01

In women undergoing IVF, are urinary bisphenol A (BPA) concentrations associated with ovarian response and early reproductive outcomes, including oocyte maturation and fertilization, Day 3 embryo quality and blastocyst formation? Higher urinary BPA concentrations were found to be associated with decreased ovarian response, number of fertilized oocytes and decreased blastocyst formation. Experimental animal and in vitro studies have reported associations between BPA exposure and adverse reproductive outcomes. We previously reported an association between urinary BPA and decreased ovarian response [peak serum estradiol (E(2)) and oocyte count at the time of retrieval] in women undergoing IVF; however, there are limited human data on reproductive health outcomes, such as fertilization and embryo development. Prospective preconception cohort study. One hundred and seventy-four women aged 18-45 years and undergoing 237 IVF cycles were recruited at the Massachusetts General Hospital Fertility Center, Boston, MA, USA, between November 2004 and August 2010. These women were followed until they either had a live birth or discontinued treatment. Cryothaw and donor egg cycles were not included in the analysis. Urinary BPA concentrations were measured by online solid-phase extraction-high-performance liquid chromatography-isotope dilution-tandem mass spectrometry. Mixed effect models, poisson regression and multivariate logistic regression models were used wherever appropriate to evaluate the association between cycle-specific urinary BPA concentrations and measures of ovarian response, oocyte maturation (metaphase II), fertilization, embryo quality and cleavage rate. We accounted for correlation among multiple IVF cycles in the same woman using generalized estimating equations. The geometric mean (SD) for urinary BPA concentrations was 1.50 (2.22) µg/l. After adjustment for age and other potential confounders (Day 3 serum FSH, smoking, BMI), there was a significant linear dose-response association between increased urinary BPA concentrations and decreased number of oocytes (overall and mature), decreased number of normally fertilized oocytes and decreased E(2) levels (mean decreases of 40, 253 and 471 pg/ml for urinary BPA quartiles 2, 3 and 4, when compared with the lowest quartile, respectively; P-value for trend = 0.001). The mean number of oocytes and normally fertilized oocytes decreased by 24 and 27%, respectively, for the highest versus the lowest quartile of urinary BPA (trend test P < 0.001 and 0.002, respectively). Women with urinary BPA above the lowest quartile had decreased blastocyst formation (trend test P-value = 0.08). Potential limitations include exposure misclassification due to the very short half-life of BPA and its high variability over time; uncertainty about the generalizability of the results to the general population of women conceiving naturally and limited sample. The results from this extended study, using IVF as a model to study early reproductive health outcomes in humans, indicate a negative dose-response association between urinary BPA concentrations and serum peak E(2) and oocyte yield, confirming our previous findings. In addition, we found significantly decreased metaphase II oocyte count and number of normally fertilizing oocytes and a suggestive association between BPA urinary concentrations and decreased blastocyst formation, thus indicating that BPA may alter reproductive function in susceptible women undergoing IVF. This work was supported by grants ES009718 and ES000002 from the National Institute of Environmental Health Sciences and grant OH008578 from the National Institute for Occupational Safety and Health. None of the authors has actual or potential competing financial interests. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

Endometrial scratching in women with implantation failure after a first IVF/ICSI cycle; does it lead to a higher live birth rate? The SCRaTCH study: a randomized controlled trial (NTR 5342).

PubMed

van Hoogenhuijze, N E; Torrance, H L; Mol, F; Laven, J S E; Scheenjes, E; Traas, M A F; Janssen, C; Cohlen, B; Teklenburg, G; de Bruin, J P; van Oppenraaij, R; Maas, J W M; Moll, E; Fleischer, K; van Hooff, M H; de Koning, C; Cantineau, A; Lambalk, C B; Verberg, M; Nijs, M; Manger, A P; van Rumste, M; van der Voet, L F; Preys-Bosman, A; Visser, J; Brinkhuis, E; den Hartog, J E; Sluijmer, A; Jansen, F W; Hermes, W; Bandell, M L; Pelinck, M J; van Disseldorp, J; van Wely, M; Smeenk, J; Pieterse, Q D; Boxmeer, J C; Groenewoud, E R; Eijkemans, M J C; Kasius, J C; Broekmans, F J M

2017-07-21

Success rates of assisted reproductive techniques (ART) are approximately 30%, with the most important limiting factor being embryo implantation. Mechanical endometrial injury, also called 'scratching', has been proposed to positively affect the chance of implantation after embryo transfer, but the currently available evidence is not yet conclusive. The primary aim of this study is to determine the effect of endometrial scratching prior to a second fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle on live birth rates in women with a failed first IVF/ICSI cycle. Multicenter randomized controlled trial in Dutch academic and non-academic hospitals. A total of 900 women will be included of whom half will undergo an endometrial scratch in the luteal phase of the cycle prior to controlled ovarian hyperstimulation using an endometrial biopsy catheter. The primary endpoint is the live birth rate after the 2 nd fresh IVF/ICSI cycle. Secondary endpoints are costs, cumulative live birth rate (after the full 2 nd IVF/ICSI cycle and over 12 months of follow-up); clinical and ongoing pregnancy rate; multiple pregnancy rate; miscarriage rate and endometrial tissue parameters associated with implantation failure. Multiple studies have been performed to investigate the effect of endometrial scratching on live birth rates in women undergoing IVF/ICSI cycles. Due to heterogeneity in both the method and population being scratched, it remains unclear which group of women will benefit from the procedure. The SCRaTCH trial proposed here aims to investigate the effect of endometrial scratching prior to controlled ovarian hyperstimulation in a large group of women undergoing a second IVF/ICSI cycle. NTR 5342 , registered July 31 st , 2015. Version 4.10, January 4th, 2017.

Genetic polymorphisms of serotonin transporter and receptor 1A could influence success during embryo implantation and maintenance of pregnancy.

PubMed

Palomares, Arturo R; Lendínez-Ramírez, Ana M; Pérez-Nevot, Beatriz; Cortés-Rodríguez, Miriam; Martínez, Francisco; Garrido, Nicolás; Ruiz-Galdón, Maximiliano; Reyes-Engel, Armando

2013-06-01

To explore whether serotonin-related gene polymorphisms influence clinical outcomes of IVF treatment in recipients using donated oocytes. Nested case-control study. University-affiliated infertility clinic. Two hundred forty-five women undergoing IVF treatment with donated oocytes. None. Genotype and haplotype analysis of the serotonin transporter-linked polymorphic region (5-HTTLPR), rs1800532, rs6295, rs6313, and rs3813929, between recipients grouped according to the results of the oocyte donation for IVF treatment. No differences were found between genotype distribution of the tryptophan hydroxylase 1, serotonin receptor 2A, and serotonin receptor 2C polymorphisms. Recipients carrying the LL genotype for 5-HTTLPR had lower clinical pregnancy rates (PR) and higher biochemical pregnancy loss (BPL) events. Lower implantation rates were found in CC carriers for 5-HT1A.rs6295 who also presented higher BPL rates. A lower incidence of clinical pregnancy was observed for LC haplotypes, corresponding to an increase in BPL rates. A strong association was found between early pregnancy loss and recipients carrying the 5-HTTLPR and rs6295 genetic variants. Identifying biological processes involving serotonin and embryo implantation may help to understand the dynamics of the maternal-embryo dialogue. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Psychological distress and in vitro fertilization outcome

PubMed Central

Pasch, Lauri A.; Gregorich, Steven E.; Katz, Patricia K.; Millstein, Susan G.; Nachtigall, Robert D.; Bleil, Maria E.; Adler, Nancy E.

2016-01-01

Objective To examine whether psychological distress predicts IVF treatment outcome as well as whether IVF treatment outcome predicts subsequent psychological distress. Design Prospective cohort study over an 18-month period. Setting Five community and academic fertility practices. Patients Two hundred and two women who initiated their first IVF cycle. Interventions Women completed interviews and questionnaires at baseline and at 4, 10, and 18 months follow-up. Main Outcome Measures IVF cycle outcome and psychological distress. Results Using a binary logistic model including covariates (woman’s age, ethnicity, income, education, parity, duration of infertility, and time interval), pre-treatment depression and anxiety were not significant predictors of the outcome of the first IVF cycle. Using linear regression models including covariates (woman’s age, income, education, parity, duration of infertility, assessment point, time since last treatment cycle, and pre-IVF depression or anxiety), experiencing failed IVF was associated with higher post-IVF depression and anxiety. Conclusions IVF failure predicts subsequent psychological distress, but pre-IVF psychological distress does not predict IVF failure. Instead of focusing efforts on psychological interventions specifically aimed at improving the chance of pregnancy, these findings suggest that attention be paid to helping patients prepare for and cope with treatment and treatment failure. PMID:22698636

MTHFR polymorphisms C677T and A1298C and associations with IVF outcomes in Brazilian women.

PubMed

D'Elia, Priscila Queiroz; dos Santos, Aline Amaro; Bianco, Bianca; Barbosa, Caio Parente; Christofolini, Denise Maria; Aoki, Tsutomu

2014-06-01

The aim of this study was to investigate the association between MTHFR gene polymorphisms and IVF outcomes in Brazilian women undergoing assisted reproduction treatment. A prospective study was conducted in the Human Reproduction Department at the ABC University School of Medicine and the Ideia Fertility Institute between December 2010 and April 2012. The patient population was 82 women undergoing assisted reproduction cycles. The MTHFR polymorphisms C677T and A1298C were evaluated and compared with laboratory results and pregnancy rates. The C677T variant was associated with proportions of mature (P=0.006) and immature (P=0.003) oocytes whereas the A1298C variant was associated with number of oocytes retrieved (P=0.044). The polymorphisms, whether alone or in combination, were not associated with normal fertilization, good-quality embryo or clinical pregnancy rates. This study suggests that the number and maturity of oocytes retrieved may be related to the MTHFR polymorphisms C677T and A1298C. It is believed that folate has a crucial function in human reproduction and that folate deficiency can compromise the function of the metabolic pathways it is involved in, leading to an accumulation of homocysteine. The gene MTHFR encodes the 5-MTHFR enzyme, which is involved in folate metabolism, and C677T/A1298C polymorphisms of this gene are related to decreased enzyme activity and consequent changes in homocysteine concentration. Folate deficiency and hyperhomocysteinaemia can also compromise fertility and lead to pregnancy complications by affecting the development of oocytes, preparation of endometrial receptivity, implantation of the embryo and pregnancy. In folliculogenesis, hyperhomocysteinaemia can activate apoptosis, leading to follicular atresia and affecting the maturity of oocytes and the quality of embryos cultured in vitro. This study was performed to investigate the association between MTHFR polymorphisms and IVF outcomes in women undergoing assisted reproduction treatment. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Does methotrexate administration for ectopic pregnancy after in vitro fertilization impact ovarian reserve or ovarian responsiveness?

PubMed

Boots, Christina E; Gustofson, Robert L; Feinberg, Eve C

2013-12-01

To evaluate the effects of methotrexate (MTX) on the future fertility of women undergoing IVF by comparing ovarian reserve and ovarian responsiveness in the IVF cycle before and after an ectopic pregnancy (EP) treated with MTX. Retrospective cohort study. Private reproductive endocrinology and infertility practice. Sixty-six women undergoing IVF before and after receiving MTX for an EP. Methotrexate administration and ovarian stimulation. Markers of ovarian reserve (day 3 FSH, antral follicle count), measures of ovarian responsiveness (duration of stimulation, peak E2 level, total dose of gonadotropins, number of oocytes retrieved, fertilization rate), and time from MTX administration to subsequent IVF cycle. There were no differences after MTX administration in body mass index (BMI), FSH, or antral follicle count. A greater dose of gonadotropins was used in the cycle after MTX, but there were no differences in numbers of oocytes retrieved or high quality embryos transferred. As expected, there was a slight increase in age in the subsequent IVF cycle. The pregnancy rates (PR) were comparable to the average PRs within the practice when combining all age groups. Methotrexate remains the first line of therapy for medical management of asymptomatic EP and does not compromise ovarian reserve, ovarian responsiveness, or IVF success in subsequent cycles. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Altered Preconception Fatty Acid Intake Is Associated with Improved Pregnancy Rates in Overweight and Obese Women Undertaking in Vitro Fertilisation.

PubMed

Moran, Lisa J; Tsagareli, Victoria; Noakes, Manny; Norman, Robert

2016-01-04

Maternal preconception diet is proposed to affect fertility. Prior research assessing the effect of altering the fatty acid profile on female fertility is conflicting. The aim of this study was to assess the effect of preconception maternal diet, specifically fatty acid profile, on pregnancies and live births following in vitro fertilisation (IVF). Forty-six overweight and obese women undergoing IVF were randomised to a diet and physical activity intervention (intervention) or standard care (control). Outcome measures included pregnancy, live birth and pre-study dietary intake from food frequency questionnaire. Twenty pregnancies (n = 12/18 vs. n = 8/20, p = 0.12) and 12 live births (n = 7/18 vs. n = 5/20, p = 0.48) occurred following the intervention with no differences between the treatment groups. On analysis adjusted for BMI and smoking status, women who became pregnant had higher levels of polyunsaturated fatty acid (PUFA) intake (p = 0.03), specifically omega-6 PUFA and linoleic acid (LA) (p = 0.045) with a trend for an elevated intake of omega-3 PUFA (p = 0.06). There were no dietary differences for women who did or did not have a live birth. Maternal preconception PUFA, and specifically omega-6 and LA intake, are associated with improved pregnancy rates in overweight and obese women undergoing IVF. This has implications for optimising fertility through preconception nutrition.

Relationships between human sperm protamines, DNA damage and assisted reproduction outcomes.

PubMed

Simon, Luke; Castillo, Judit; Oliva, Rafael; Lewis, Sheena E M

2011-12-01

The exchange of histones with protamines in sperm DNA results in sperm chromatin compaction and protection. Variations in sperm protamine expression are associated with male infertility. The aim of this study was to investigate relationships between DNA fragmentation, sperm protamines and assisted reproduction treatment. Semen and spermatozoa prepared by density-gradient centrifugation (DGC) from 73 men undergoing IVF and 24 men undergoing intracytoplasmic sperm injection (ICSI) were included in the study. Nuclear DNA fragmentation was assessed using the alkaline Comet assay and protamines were separated by acid-urea polyacrylamide gels. Sperm DNA fragmentation and protamine content (P1-DNA, P2-DNA, P1+P2-DNA) decreased in spermatozoa after DGC. Abnormally high and low P1/P2 ratios were associated with increased sperm DNA fragmentation. Couples with idiopathic infertility had abnormally high P1/P2 ratios. Fertilization rates and embryo quality decreased as sperm DNA fragmentation or protamines increased. Sperm DNA fragmentation was lower in couples achieving pregnancies after IVF, but not after ICSI. There was no correlation between protamine content (P1-DNA, P2-DNA, P1+P2-DNA) or P1/P2 ratios and IVF or ICSI pregnancies. Increased sperm DNA fragmentation was associated with abnormal protamination and resulted in lower fertilization rates, poorer embryo quality and reduced pregnancy rates. Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Psychological distress and in vitro fertilization outcome.

PubMed

Pasch, Lauri A; Gregorich, Steven E; Katz, Patricia K; Millstein, Susan G; Nachtigall, Robert D; Bleil, Maria E; Adler, Nancy E

2012-08-01

To examine whether psychological distress predicts IVF treatment outcome as well as whether IVF treatment outcome predicts subsequent psychological distress. Prospective cohort study over an 18-month period. Five community and academic fertility practices. Two hundred two women who initiated their first IVF cycle. Women completed interviews and questionnaires at baseline and at 4, 10, and 18 months' follow-up. IVF cycle outcome and psychological distress. In a binary logistic model including covariates (woman's age, ethnicity, income, education, parity, duration of infertility, and time interval), pretreatment depression and anxiety were not significant predictors of the outcome of the first IVF cycle. In linear regression models including covariates (woman's age, income, education, parity, duration of infertility, assessment point, time since last treatment cycle, and pre-IVF depression or anxiety), experiencing failed IVF was associated with higher post-IVF depression and anxiety. IVF failure predicts subsequent psychological distress, but pre-IVF psychological distress does not predict IVF failure. Instead of focusing efforts on psychological interventions specifically aimed at improving the chance of pregnancy, these findings suggest that attention be paid to helping patients prepare for and cope with treatment and treatment failure. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study.

PubMed

Haggarty, P; McCallum, H; McBain, H; Andrews, K; Duthie, S; McNeill, G; Templeton, A; Haites, N; Campbell, D; Bhattacharya, S

2006-05-06

There is a need to understand what affects the success of in-vitro fertilisation (IVF) and the rate of resulting twin births so that pregnancy rates can be improved and multiple gestations avoided. Our aim was to assess the role of B vitamins and genetics. We did a prospective cohort study of 602 women undergoing fertility treatment. We assessed intake of folate and vitamin B12 with a questionnaire and measured their plasma and red-blood-cell concentrations by radioimmunoassay. We measured five B-vitamin-related gene variants in women who received treatment and in 932 women who conceived naturally. The likelihood of a twin birth after IVF rose with increased concentrations of plasma folate (1.52, 1.01-2.28; p=0.032) and red-cell folate (1.28, 1.00-1.65; p=0.039). There was no association between folate and vitamin B12 levels and likelihood of a successful pregnancy. Women homozygous for the 1298 CC variant of methylenetetrahydro-folate reductase (MTHFR), rather than the AA variant, were less likely to produce a livebirth after IVF (0.24, 0.08-0.71; p=0.003) or to have had a previous pregnancy (0.42, 0.21-0.81; p=0.008). Our findings suggest that MTHFR genotype is linked to a woman's potential to produce healthy embryos (possibly through interaction with genes related to DNA methylation). In women likely to have a successful IVF pregnancy, high folate status increases the likelihood of twin birth after multiple embryo transfer. Proposals to fortify the UK diet with folic acid could lead to an increase in the number of twins born after IVF.

Cumulative live-birth rate in women with polycystic ovary syndrome or isolated polycystic ovaries undergoing in-vitro fertilisation treatment.

PubMed

Li, Hang Wun Raymond; Lee, Vivian Chi Yan; Lau, Estella Yee Lan; Yeung, William Shu Biu; Ho, Pak Chung; Ng, Ernest Hung Yu

2014-02-01

This retrospective cohort study evaluated the cumulative live birth rate in women with polycystic ovary syndrome (PCOS) and isolated polycystic ovaries (PCO) undergoing in-vitro fertilisation (IVF) treatment. We studied 104 women with PCOS, 184 with PCO and 576 age-matched controls undergoing the first IVF treatment cycle between 2002 and 2009. The main outcome measure was cumulative live birth in the fresh plus all the frozen embryo transfers combined after the same stimulation cycle. Women in both the PCOS (n = 104) and isolated PCO groups (n = 184) had higher ovarian response parameters compared to age-matched controls (n = 576), and higher rates of withholding fresh embryo transfer for risk of ovarian hyperstimulation syndrome (OHSS). The actual incidence of moderate to severe OHSS was significantly higher in the PCOS (11.5 %) but not the isolated PCO group (8.2%) compared to controls (4.9%). The live birth rates in the fresh cycle were comparable among the 3 groups, but the PCOS group had a significantly higher miscarriage rate compared to the other 2 groups. Cumulative live birth rate was significantly higher in the isolated PCO group (60.3%), but not the PCOS group (50.0%), compared to controls (47.5%). Women in the isolated PCO group, but not the PCOS group, had a significantly higher cumulative live birth rate compared to controls. This could be explained by the quantitative effect of the higher number of transferable embryos obtained per stimulation cycle, which is uncompromised by the unfavourable embryo competence otherwise observed in PCOS.

Relationship between serum polyunsaturated fatty acids and pregnancy in women undergoing in vitro fertilization.

PubMed

Jungheim, Emily S; Frolova, Antonina I; Jiang, Hui; Riley, Joan K

2013-08-01

Polyunsaturated fatty acids (PUFAs) and their metabolism may be important in normal reproductive function and fertility. Associations between physiologic PUFAs and pregnancy have not been established in women. The purpose of this study was to investigate associations between serum levels of PUFAs and embryo implantation in women undergoing in vitro fertilization (IVF). This was a prospective cohort study conducted between 2010 and 2012. The study was conducted at the Washington University Reproductive Medicine Center. Participants were 200 women undergoing IVF and participating in an ongoing specimen tissue bank. Fasting serum PUFAs were measured with liquid chromatography-mass spectroscopy. PUFAs measured included linoleic acid (LA), α-linolenic acid (ALA), eicosapentaenoic acid, arachidonic acid, and docosahexaenoic acid. Relationships between serum levels of measured PUFAs and embryo implantation in women undergoing IVF were analyzed. In unadjusted analyses, none of the PUFAs alone were associated with a chance of pregnancy; however, women with increased LA:ALA ratios had a higher chance of pregnancy compared with women with lower LA:ALA ratios (relative risk, 1.52; 95% confidence interval, 1.09-2.13). This relationship held after multivariable logistic regression adjusting for age, antral follicle count, body mass index, history of previous pregnancy, and history of endometriosis (odds ratio, 2.7; 95% confidence interval, 1.3-5.7). Embryo implantation rates were also weakly associated with LA:ALA ratios (r = 0.21, P = .003). Our work shows that increased ω-6 to ω-3 PUFA ratios in women undergoing IVF are associated with increased implantation and pregnancy rates. Prospective trials are needed to determine whether manipulation of PUFA ratios through diet or pharmacologic intervention may benefit women planning to conceive.

Melatonin levels in follicular fluid as markers for IVF outcomes and predicting ovarian reserve.

PubMed

Tong, Jing; Sheng, Shile; Sun, Yun; Li, Huihui; Li, Wei-Ping; Zhang, Cong; Chen, Zi-Jiang

2017-04-01

Good-quality oocytes are critical for the success of in vitro fertilization (IVF), but, to date, there is no marker of ovarian reserve available that can accurately predict oocyte quality. Melatonin exerts its antioxidant actions as a strong radical scavenger that might affect oocyte quality directly as it is the most potent antioxidant in follicular fluid. To investigate the precise role of endogenous melatonin in IVF outcomes, we recruited 61 women undergoing treatment cycles of IVF or intracytoplasmic sperm injection (ICSI) procedures and classified them into three groups according to their response to ovarian stimulation. Follicular fluid was collected to assess melatonin levels using a direct RIA method. We found good correlations between melatonin levels in follicular fluid with age, anti-Müllerian hormone (AMH) and baseline follicle-stimulating hormone (bFSH), all of which have been used to predict ovarian reserve. Furthermore, as melatonin levels correlated to IVF outcomes, higher numbers of oocytes were collected from patients with higher melatonin levels and consequently the number of oocytes fertilized, zygotes cleaved, top quality embryos on D3, blastocysts obtained and embryos suitable for transplantation was higher. The blastocyst rate increased in concert with the melatonin levels across the gradient between the poor response group and the high response group. These results demonstrated that the melatonin levels in follicular fluid is associated with both the quantity and quality of oocytes and can predict IVF outcomes as well making them highly relevant biochemical markers of ovarian reserve. © 2017 Society for Reproduction and Fertility.

Extended high dose letrozole regimen versus short low dose letrozole regimen as an adjuvant to gonadotropin releasing hormone antagonist protocol in poor responders undergoing IVF-ET.

PubMed

Fouda, Usama M; Sayed, Ahmed M

2011-12-01

To compare the efficacy and cost-effectiveness of extended high dose letrozole regimen/HPuFSH-gonadotropin releasing hormone antagonist (GnRHant) protocol with short low dose letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET. In this randomized controlled trial, 136 women who responded poorly to GnRH agonist long protocol in their first IVF cycle were randomized into two equal groups using computer generated list and were treated in the second IVF cycle by either extended letrozole regimen (5 mg/day during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days) combined with HPuFSH-GnRHant protocol or short letrozole regimen (2.5 mg/day from cycle day 3-7) combined with HPuFSH-GnRHant protocol. There were no significant differences between both groups with regard to number of oocytes retrieved and clinical pregnancy rate (5.39 ± 2.08 vs. 5.20 ± 1.88 and 22.06% vs. 16.18%, respectively).The total gonadotropins dose and medications cost per cycle were significantly lower in extended letrozole group (44.87 ± 9.16 vs. 59.97 ± 14.91 ampoules and 616.52 ± 94.97 vs. 746.84 ± 149.21 US Dollars ($), respectively).The cost-effectiveness ratio was 2794 $ in extended letrozole group and 4616 $ in short letrozole group. Extended letrozole regimen/HPuFSH-GnRHant protocol was more cost-effective than short letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET.

Patients with cervical Ureaplasma Urealyticum and Chlamydia Trachomatis infection undergoing IVF/ICSI-ET: The need for new paradigm.

PubMed

Xie, Qing-Zhen; Xu, Wang-Ming; Qi, Qian-Rong; Luo, Zeng-Li; Dong, Lan

2016-10-01

Genital tract infections with ureaplasma urealyticum (UU) and chlamydia trachomatis (CT) are the most frequent sexually-transmitted disease worldwide. UU and CT infections are considered to be the leading cause for infertility and adverse pregnancy outcomes. However, little is known about the specific effect of cervical UU and CT infections on the etiology of female infertility, as well as the pregnancy outcomes of the patients undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). In order to find the association between cervical UU and/or CT infection and pregnancy outcomes, we conducted a retrospective case-control study on the patients undergoing IVF/ICSI-ET with cervical UU and/or CT infection. A total of 2208 patients who received IVF/ICSI-ET were enrolled in this study. Data on the general conditions, pregnancy history and clinical pregnant outcomes were analyzed in terms of the cervical UU and CT detection. Our results revealed that cervical UU and CT infections were the risk factors for ectopic pregnancy and tubal factor-induced infertility. Moreover, the pregnancy rate, abortion rate, ectopic pregnancy rate and premature birth rate in patients with UU and/or CT infections showed no significant difference when compared with the control group. We recommend that cervical UU and CT detection should be an optional item for infertility patients and clinical UU detection should differentiate the subtypes of cervical UU. Positive cervical UU and CT infections should not be taken as strict contraindications for IVF/ICSI-ET.

The costs to the NHS of multiple births after IVF treatment in the UK.

PubMed

Ledger, William L; Anumba, Dilly; Marlow, Neil; Thomas, Christine M; Wilson, Edward C F

2006-01-01

To determine the cost to the NHS resulting from multiple pregnancies arising from IVF treatment in the UK, and to compare those costs with the cost to the NHS due to singleton pregnancies resulting from IVF treatment. A modelling study using data from published literature and cost data from national sources in the public domain, calculating direct costs from the diagnosis of a clinical pregnancy until the end of the first year after birth. Academic Unit of Reproductive and Developmental Medicine. Theoretic core modelling study using data from published literature. The analysis was based on the total annual number of births resulting from an IVF treatment in the UK. Main outcome measures total direct costs to the NHS per IVF singleton, twin or triplet family. Cost of singleton, twin and triplet IVF pregnancies in the UK. Total direct costs to the NHS per IVF twin or triplet family (maternal + infant costs) are substantially higher than per IVF singleton family (singleton: pounds 3313; twin: pounds 9122; and triplet: pounds 32,354). Multiple pregnancies after IVF are associated with 56% of the direct cost of IVF pregnancies, although they represent less than 1/3 of the total annual number of maternities in the UK. Multiple pregnancies after IVF are associated with high direct costs to the NHS. Redirection of money saved by implementation of a mandatory 'two embryo transfer' policy into increased provision of IVF treatment could double the number of NHS-funded IVF treatment cycles at no extra cost. Further savings could be made if a selective 'single embryo transfer' policy were to be adopted.

The OPTIMIST study: optimisation of cost effectiveness through individualised FSH stimulation dosages for IVF treatment. A randomised controlled trial

PubMed Central

2012-01-01

Background Costs of in vitro fertilisation (IVF) are high, which is partly due to the use of follicle stimulating hormone (FSH). FSH is usually administered in a standard dose. However, due to differences in ovarian reserve between women, ovarian response also differs with potential negative consequences on pregnancy rates. A Markov decision-analytic model showed that FSH dose individualisation according to ovarian reserve is likely to be cost-effective in women who are eligible for IVF. However, this has never been confirmed in a large randomised controlled trial (RCT). The aim of the present study is to assess whether an individualised FSH dose regime based on an ovarian reserve test (ORT) is more cost-effective than a standard dose regime. Methods/Design Multicentre RCT in subfertile women indicated for a first IVF or intracytoplasmic sperm injection cycle, who are aged < 44 years, have a regular menstrual cycle and no major abnormalities at transvaginal sonography. Women with polycystic ovary syndrome, endocrine or metabolic abnormalities and women undergoing IVF with oocyte donation, will not be included. Ovarian reserve will be assessed by measuring the antral follicle count. Women with a predicted poor response or hyperresponse will be randomised for a standard versus an individualised FSH regime (150 IU/day, 225-450 IU/day and 100 IU/day, respectively). Participants will undergo a maximum of three stimulation cycles during maximally 18 months. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months after randomisation. Secondary outcomes are parameters for ovarian response, multiple pregnancies, number of cycles needed per live birth, total IU of FSH per stimulation cycle, and costs. All data will be analysed according to the intention-to-treat principle. Cost-effectiveness analysis will be performed to assess whether the health and associated economic benefits of individualised treatment of subfertile women outweigh the additional costs of an ORT. Discussion The results of this study will be integrated into a decision model that compares cost-effectiveness of the three dose-adjustment strategies to a standard dose strategy. The study outcomes will provide scientific foundation for national and international guidelines. Trial registration NTR2657 PMID:22989359

Does age of the sperm donor influence live birth outcome in assisted reproduction?

PubMed

Ghuman, N K; Mair, E; Pearce, K; Choudhary, M

2016-03-01

Does age of the sperm donor have an effect on reproductive outcomes (live birth rate and miscarriage occurrence) of donor insemination or in vitro fertilization treatment using donated sperm? Live birth and miscarriage occurrence in assisted reproduction treatment using donor sperms was not found to be affected by the age of sperm donors up to 45 years old. Literature on the effect of sperm donor age on outcome of medically assisted reproduction is scarce. Most researchers agree that semen parameters deteriorate with increasing paternal age. However, there is no substantial evidence to suggest that this deterioration adversely affects the reproductive outcomes in couples undergoing medically assisted reproduction. This retrospective cohort study analysed 46 078 first donor insemination treatments and fresh in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using donated sperm from 1991 to 2012. The first fresh donor insemination and IVF/ICSI treatment cycles (46 078 treatment cycles) using donated sperm from the long-term anonymized data registry from 1991 to 2012 of the HFEA, the UK regulator, were analysed by the binary logistic modelling technique for association between sperm donor age and reproductive outcomes (live birth occurrence and miscarriage occurrence). The statistical package SPSS (version 21) was used for analysis and results were considered to be statistically significant if the P-value was <0.05. Of 46 078 women, 84.6% (N = 38 974) underwent donor insemination treatment and the remainder, 15.4% (N = 7104), had IVF/ICSI treatment with donor sperm. The live birth occurrence decreased with increasing female age in both treatment groups; In the donor insemination treatment group, it was 11.1% in 18-34 year old women, 8.3% in 35-37 year old women and 4.7% in 38-50 year old women. The corresponding figures in the IVF/ICSI treatment group were 28.9, 22.0 and 12.9% respectively. In each of these subgroups, no evidence of declining likelihood of live birth with increasing sperm donor age was found (P > 0.05). The miscarriage occurrence (i.e. number of miscarriages per 100 women commencing treatment) was 1.3% in 18-34 year old women, 1.9% in 35-37 year old women and 1.9% in 38-50 year old women undergoing donor insemination treatment. In the sperm donation IVF/ICSI treatment group, these figures were 5.7, 8.4 and 6.8% respectively. The results were not suggestive of any unfavourable effect of advancing sperm donor age on the odds of miscarriage occurrence (P > 0.05). As sperm donors are a select population based on good semen indices, the generalization of results to the paternal population at large may not be possible. Although the study subgroups were controlled for female age, treatment modality and effect of previous treatment cycles, adjustments for certain potential compounding factors, such as smoking status, BMI of women and stimulation protocol used in IVF/ICSI treatment cycles, were not possible. Live birth and miscarriage occurrence following assisted reproduction weren't adversely affected by increasing sperm donor age up to 45 years. In view of the increasing demand for donor sperm, further studies may be required to ascertain the safe upper age limit for sperm donors. No funding was received from any individual or funding agency. NG was on a Commonwealth Scholarship for the duration of the study. The authors do not have any conflicts of interest to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The effect of ketorolac on pregnancy rates when used immediately after oocyte retrieval.

PubMed

Mesen, Tolga B; Kacemi-Bourhim, Lamya; Marshburn, Paul B; Usadi, Rebecca S; Matthews, Michelle; Norton, H James; Hurst, Bradley S

2013-09-01

To study the effect of ketorolac, a potent anti-inflammatory medication, on in vitro fertilization (IVF) pregnancy outcomes when used at the time of oocyte retrieval. Retrospective review of 454 patients from 2003-2009. Tertiary hospital-affiliated fertility center. Consecutive subfertile women undergoing their first IVF cycle. Ketorolac administration immediately after oocyte retrieval. Pregnancy, implantation, live-birth, and miscarriage rates, and postsurgical visual analog pain score. Of the 454 patients undergoing their first IVF cycle for all indications, 103 received intravenous ketorolac immediately after oocyte retrieval, based on anesthesiologist preference. Patient and procedural characteristics were similar between both groups. The use of ketorolac had no effect on the rates of implantation, miscarriage, pregnancy, live birth, or multiple pregnancy. The patients receiving ketorolac experienced statistically significantly less pain. This study suggests ketorolac has no apparent detrimental effect on IVF pregnancy outcomes when administered immediately after oocyte retrieval. Ketorolac appears to be a safe and effective analgesic to use at the time of oocyte retrieval. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Association between response to ovarian stimulation and miscarriage following IVF: an analysis of 124 351 IVF pregnancies.

PubMed

Sunkara, Sesh Kamal; Khalaf, Yacoub; Maheshwari, Abha; Seed, Paul; Coomarasamy, Arri

2014-06-01

Is there a relationship between ovarian reserve, quantified as ovarian response to stimulation, and miscarriage rate following IVF treatment? There is a strong association between the number of oocytes retrieved and miscarriage rate following IVF treatment, with the miscarriage rate decreasing with an increasing number of oocytes and then levelling off: poor responders have a higher miscarriage rate across all age groups. Poor ovarian response is a manifestation of a decline in the quantity of the primordial follicle pool. Whether poor ovarian response is associated with a decline in oocyte quality contributing to miscarriage is however debated. Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA), the statutory regulator of assisted reproduction treatment (ART) in the UK. The HFEA has collected data on all ART performed in the UK since 1991. Data from 1991 to June 2008 involving 402 185 stimulated fresh IVF cycles and 124 351 pregnancy outcomes were analysed. Data on all women undergoing a stimulated fresh IVF treatment cycle with at least one oocyte retrieved during the period from 1991 to June 2008 were analysed for their early pregnancy outcomes. There was a strong association between the number of oocytes retrieved and the clinical miscarriage rate. The miscarriage rate fell from 20 to 13% with an increasing number of oocytes before levelling off. Stepwise logistic regression identified three cut-off points (4, 10 and 15 oocytes) at or beyond which the probability of clinical miscarriage fell. There was no increase in miscarriage rate with very high oocyte numbers (>20 oocytes). The lowest risk of miscarriage (9.9%) was for women under 38 years of age, with primary infertility without a female cause and producing more than three oocytes. Although the analysis was performed only on stimulated IVF cycles (excluding unstimulated cycles), the data had the limitation that there was no information on the total gonadotrophin consumption. The model was adjusted for age and type of infertility, but the dataset contained no information on other confounders such as body mass index (BMI) of the women to allow adjustment. Analysis of this extensive dataset suggests that poor responders have a higher risk of clinical miscarriage, indicating that poor ovarian response is associated with a parallel decline in both oocyte quantity and quality. The miscarriage rate is also higher with advanced age, secondary infertility and a female cause of infertility compared with a younger age, male factor infertility and unexplained cause.

Is it time for a paradigm shift in understanding embryo selection?

PubMed

Gleicher, Norbert; Kushnir, Vitaly A; Barad, David H

2015-01-11

Embryo selection has been an integral feature of in vitro fertilization (IVF) almost since its inception. Since the advent of extended blastocyst stage embryo culture, and especially with increasing popularity of elective single embryo transfer (eSET), the concept of embryo selection has increasingly become a mainstay of routine IVF. We here, however, argue that embryo selection via blastocyst stage embryo transfer (BSET), as currently practiced, at best improves IVF outcomes only for a small minority of patients undergoing IVF cycles. For a large majority BSET is either ineffective or, indeed, may actually be harmful by decreasing IVF pregnancy chances. Overall, only a small minority of patients, thus, benefit from prolonged embryo culture, while BSET, as a tool to enhance IVF outcomes, is increasingly utilized as routine care in IVF for all patients. Since newer methods of embryo selection, like preimplantation genetic screening (PGS) and closed system embryo incubation with time-lapse photography are practically dependent on BSET, these concepts of embryo selection, currently increasingly adopted in mainstream IVF, require reconsideration. They, automatically, transfer the downsides of BSET, including decreases in IVF pregnancy chances in some patients, to these new procedures, and in addition raise serious questions about cost-effectiveness.

Perception of control, coping and psychological stress of infertile women undergoing IVF.

PubMed

Gourounti, Kleanthi; Anagnostopoulos, Fotios; Potamianos, Grigorios; Lykeridou, Katerina; Schmidt, Lone; Vaslamatzis, Grigorios

2012-06-01

The study aimed to examine: (i) the association between perception of infertility controllability and coping strategies; and (ii) the association between perception of infertility controllability and coping strategies to psychological distress, applying multivariate statistical techniques to control for the effects of demographic variables. This cross-sectional study included 137 women with fertility problems undergoing IVF in a public hospital. All participants completed questionnaires that measured fertility-related stress, state anxiety, depressive symptomatology, perception of control and coping strategies. Pearson's correlation coefficients were calculated between all study variables, followed by hierarchical multiple linear regression. Low perception of personal and treatment controllability was associated with frequent use of avoidance coping and high perception of treatment controllability was positively associated with problem-focused coping. Multivariate analysis showed that, when controlling for demographic factors, low perception of personal control and avoidance coping were positively associated with fertility-related stress and state anxiety, and problem-appraisal coping was negatively and significantly associated with fertility-related stress and depressive symptomatology scores. The findings of this study merit the understanding of the role of control perception and coping in psychological stress of infertile women to identify beforehand those women who might be at risk of experiencing high stress and in need of support. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

A single-cell assay for telomere DNA content shows increasing telomere length heterogeneity, as well as increasing mean telomere length in human spermatozoa with advancing age.

PubMed

Antunes, Danielle M F; Kalmbach, Keri H; Wang, Fang; Dracxler, Roberta C; Seth-Smith, Michelle L; Kramer, Yael; Buldo-Licciardi, Julia; Kohlrausch, Fabiana B; Keefe, David L

2015-11-01

The effect of age on telomere length heterogeneity in men has not been studied previously. Our aims were to determine the relationship between variation in sperm telomere length (STL), men's age, and semen parameters in spermatozoa from men undergoing in vitro fertilization (IVF) treatment. To perform this prospective cross-sectional pilot study, telomere length was estimated in 200 individual spermatozoa from men undergoing IVF treatment at the NYU Fertility Center. A novel single-cell telomere content assay (SCT-pqPCR) measured telomere length in individual spermatozoa. Telomere length among individual spermatozoa within an ejaculate varies markedly and increases with age. Older men not only have longer STL but also have more variable STL compared to younger men. STL from samples with normal semen parameters was significantly longer than that from samples with abnormal parameters, but STL did not differ between spermatozoa with normal versus abnormal morphology. The marked increase in STL heterogeneity as men age is consistent with a role for ALT during spermatogenesis. No data have yet reported the effect of age on STL heterogeneity. Based on these results, future studies should expand this modest sample size to search for molecular evidence of ALT in human testes during spermatogenesis.

Efficacy evaluation of low-dose aspirin in IVF/ICSI patients evidence from 13 RCTs: A systematic review and meta-analysis.

PubMed

Wang, Liping; Huang, Xiaman; Li, Xueli; Lv, Fang; He, Xiao; Pan, Yu; Wang, Li; Zhang, Xiaomei

2017-09-01

We conducted a systematic review and meta-analysis of existing literature to evaluate the different outcomes of low-dose aspirin on patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), including clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate, fertilization rate, number of oocytes retrieved, and so forth. Electronic databases including PubMed, MEDLINE, and Embase were searched between 1997 and March 2016 to identity eligible studies. The following comparisons between treatment groups were included: aspirin versus placebo; aspirin versus control group; aspirin versus aspirin + prednisolone + control. Thirteen randomized controlled trials which included 3104 participants were selected. There were no significant differences in implantation rate (RR = 1.15; 95% CI = 0.78-1.70), live birth rate (RR = 1.06; 95% CI = 0.93-1.21), miscarriage rate (RR = 1.28; 95% CI = 0.93-1.77), fertilization rate (RR = 0.91; 95% CI = 0.75-1.11), and endometrial thickness (WMD = 0.15; 95% CI = -0.38-0.67). But the research showed that aspirin treatment may improve the clinical pregnancy rate (RR = 1.16; 95% CI = 1.04-1.28) compared to placebo or no treatment, and reduce the number of oocytes retrieved (WMD = -0.68; 95% CI = -0.91-0.46). Our findings suggest that low-dose aspirin may improve the pregnancy rate in IVF/ICSI, with the recommended clinical use dose of 100 mg/day. Considering the limitation of included studies, further well-designed large-scaled RCTs are necessary to clarify whether aspirin may improve assisted reproduction outcomes in IVF/ICSI patients.

The direct health services costs of providing assisted reproduction services in overweight or obese women: a retrospective cross-sectional analysis.

PubMed

Maheshwari, Abha; Scotland, Graham; Bell, Jacqueline; McTavish, Alison; Hamilton, Mark; Bhattacharya, Siladitya

2009-03-01

Prevalence of overweight and obesity is rising. Hence, it is likely that a higher proportion of women undergoing assisted reproduction treatment are overweight or obese. In a retrospective cross-sectional analysis using routinely collected data of an IVF Unit and maternity hospital in a tertiary care setting in the UK, direct costs were assessed for all weight classes. Costs for underweight, overweight and obese were compared with those for women with normal body mass index (BMI). Of 1756 women, who underwent their first cycle of IVF between 1997 and 2006, 43 (2.4%) were underweight; 988 (56.3%) had normal BMI; 491 (28.0%) were overweight; 148 (8.4%) were obese (class I) and 86 (4.9%) were obese (class II). The mean (95% CI) cost of each live birth resulting from IVF was pound 18,747 (13 864-27 361) in underweight group; pound 16,497 (15 374-17 817) in women with normal BMI; pound 18,575 (16,648-21,081) in overweight women; pound 18,805 (15 397-23 554) in obese class I; pound 20,282 (15 288-28 424) in obese class II or over. The cost of a live birth resulting from IVF is not different in underweight, overweight and obese class I when compared with women with normal BMI. However, due to increased obstetric complications weight loss should still be recommended prior to commencing IVF even in overweight or obese (class I) women.

Why do couples discontinue unlimited free IVF treatments?

PubMed

Lande, Yechezkel; Seidman, Daniel S; Maman, Ettie; Baum, Micha; Hourvitz, Ariel

2015-03-01

Worldwide, IVF is often discontinued before a live birth is achieved due to high costs. Even when partial financial coverage is provided, often medical providers advise treatment discontinuation. In Israel, unlimited IVF is offered free of charge for a couples' first two children. Our objective was to assess the reasons couples discontinue IVF treatments before achieving two children in a completely unlimited cost-free environment. This cohort study included all primary infertile women, <35 years, referred for their first IVF cycle to Sheba IVF unit between 2001 and 2002. Patients were followed until February 2012. Those who ceased treatments for 12 months were interviewed to assess the main reason they ceased treatments. Of the 134 couples included, only 46 ceased IVF treatments without achieving two children, after performing an average of 6.2 IVF cycles to achieve their first birth. The reasons given were: lost hope of success (13), psychological burden (18), divorce (6), medical staff recommendation (5), bureaucratic difficulties (3) and general medical condition (1). The main reasons for "drop out" in our cost-free environment were as follows: psychological burden and lost hope of success. Due to high availability of treatments, medical staff recommendation was a less significant factor in our study.

Understanding reproducibility of human IVF traits to predict next IVF cycle outcome.

PubMed

Wu, Bin; Shi, Juanzi; Zhao, Wanqiu; Lu, Suzhen; Silva, Marta; Gelety, Timothy J

2014-10-01

Evaluating the failed IVF cycle often provides useful prognostic information. Before undergoing another attempt, patients experiencing an unsuccessful IVF cycle frequently request information about the probability of future success. Here, we introduced the concept of reproducibility and formulae to predict the next IVF cycle outcome. The experimental design was based on the retrospective review of IVF cycle data from 2006 to 2013 in two different IVF centers and statistical analysis. The reproducibility coefficients (r) of IVF traits including number of oocytes retrieved, oocyte maturity, fertilization, embryo quality and pregnancy were estimated using the interclass correlation coefficient between the repeated IVF cycle measurements for the same patient by variance component analysis. The formulae were designed to predict next IVF cycle outcome. The number of oocytes retrieved from patients and their fertilization rate had the highest reproducibility coefficients (r = 0.81 ~ 0.84), which indicated a very close correlation between the first retrieval cycle and subsequent IVF cycles. Oocyte maturity and number of top quality embryos had middle level reproducibility (r = 0.38 ~ 0.76) and pregnancy rate had a relative lower reproducibility (r = 0.23 ~ 0.27). Based on these parameters, the next outcome for these IVF traits might be accurately predicted by the designed formulae. The introduction of the concept of reproducibility to our human IVF program allows us to predict future IVF cycle outcomes. The traits of oocyte numbers retrieved, oocyte maturity, fertilization, and top quality embryos had higher or middle reproducibility, which provides a basis for accurate prediction of future IVF outcomes. Based on this prediction, physicians may counsel their patients or change patient's stimulation plans, and laboratory embryologists may improve their IVF techniques accordingly.

Utilization and success rates of unstimulated in vitro fertilization in the United States: an analysis of the Society for Assisted Reproductive Technology database.

PubMed

Gordon, John David; DiMattina, Michael; Reh, Andrea; Botes, Awie; Celia, Gerard; Payson, Mark

2013-08-01

To examine the utilization and outcomes of natural cycle (unstimulated) IVF as reported to the Society of Assisted Reproductive Technology (SART) in 2006 and 2007. Retrospective analysis. Dataset analysis from the SART Clinical Outcome Reporting System national database. All patients undergoing IVF as reported to SART in 2006 and 2007. None. Utilization of unstimulated IVF; description of patient demographics; and comparison of implantation and pregnancy rates between unstimulated and stimulated IVF cycles. During 2006 and 2007 a total of 795 unstimulated IVF cycles were initiated. Success rates were age dependent, with patients <35 years of age demonstrating clinical pregnancy rates per cycle start, retrieval, and transfer of 19.2%, 26.8%, and 35.9%, respectively. Implantation rates were statistically higher for unstimulated compared with stimulated IVF in patients who were 35 to 42 years old. Unstimulated IVF represents <1% of the total IVF cycles initiated in the United States. The pregnancy and live birth rates per initiated cycle were 19.2% and 15.2%, respectively, in patients <35 years old. The implantation rates in unstimulated IVF cycles compared favorably to stimulated IVF. Natural cycle IVF may be considered in a wide range of patients as an alternative therapy for the infertile couple. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Cost-effectiveness of 'immediate IVF' versus 'delayed IVF': a prospective study.

PubMed

Eijkemans, M J C; Kersten, F A M; Lintsen, A M E; Hunault, C C; Bouwmans, C A M; Roijen, L Hakkaart-van; Habbema, J D F; Braat, D D M

2017-05-01

How does the cost-effectiveness (CE) of immediate IVF compared with postponing IVF for 1 year, depend on prognostic characteristics of the couple? The CE ratio, i.e. the incremental costs of immediate versus delayed IVF per extra live birth, is the highest (range of €15 000 to >€60 000) for couples with unexplained infertility and for them depends strongly on female age and the duration of infertility, whilst being lowest for endometriosis (range 8000-23 000) and, for such patients, only slightly dependent on female age and duration of infertility. A few countries have guidelines for indications of IVF, using the diagnostic category, female age and duration of infertility. The CE of these guidelines is unknown and the evidence base exists only for bilateral tubal occlusion, not for the other diagnostic categories. A modelling approach was applied, based on the literature and data from a prospective cohort study among couples eligible for IVF or ICSI treatment, registered in a national waiting list in The Netherlands between January 2002 and December 2003. A total of 5962 couples was included. Chances of natural ongoing pregnancy were estimated from the waiting list observations and chances of ongoing pregnancy after IVF from follow-up data of couples with primary infertility that began treatment. Prognostic characteristics considered were female age, duration of infertility and diagnostic category. Costs of IVF were assessed from a societal perspective and determined on a representative sample of patients. A cost-effectiveness comparison was made between two scenarios: (I) wait one more year and then undergo IVF for 1 year and (II) immediate IVF during 1 year, and try to conceive naturally in the following year. Comparisons were made for strata determined by the prognostic factors. The final outcome was a live birth. The gain in live birth rate of the immediate IVF scenario versus postponed IVF increased with female age, and was independent from diagnostic category or duration of infertility. By contrast, the corresponding increase in costs primarily depended on diagnostic category and duration of infertility. The lowest CE ratio was just below €10 000 per live birth for endometriosis from age 34 onwards at 1 year duration. The highest CE ratio reached €56 000 per live birth for unexplained infertility at age 30 and 3 years duration, dropping to values below € 30 000 per live birth from age 32 onwards. It reached values below €20 000 per live birth with 3 years duration at age 34 and older. The CE ratio was in between for the three other diagnostic categories (i.e. Male infertility, Hormonal and Immunological/Cervical). We applied estimates of chances with IVF, excluding frozen embryos, for which we had no data. Therefore, we do not know the effect of frozen embryo transfers on the CE. The duration of infertility at which IVF becomes cost-effective depends, firstly, on the level of society's willingness to pay for one extra live birth, and secondly, given a certain level of willingness to pay, on the woman's age and the diagnostic category. In current guidelines, the chances of a natural conception should always be taken into account before deciding whether to start IVF treatment and at which time. Supported by Netherlands Organisation for Health Research and Development (ZonMW, grant 945-12-013). ZonMW had no role in designing the study, data collection, analysis and interpretation of data or writing of the report. Competing interests: none. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

[Correlation between IVF outcomes and Ureaplasma urealyticum infection in male reproductive tract].

PubMed

Fan, Yu-Ping; Pan, Jia-Ping; Hu, Ye; Huang, Wen-Qiang; Wang, Yu; Ruan, Jing-Ling; Li, Yun; Teng, Xiao-Ming

2014-01-01

To investigate the influence of Ureaplasma urealyticum (Uu) infection in the male reproductive tract on the outcomes of IVF and the clinical significance of preoperative Uu test by analyzing the correlation between the results of Uu culture before IVF-ET and the outcomes of IVF-ET. Among 1,059 couples undergoing IVF-ET, we selected 973 after excluding genetic factors and divided them into a Uu negative and a Uu positive group according to the results of culture of Uu in the semen of the males. We compared the rates of IVF fertilization, oocyte cleavage, clinical pregnancy and abortion between the two groups, and analyzed the influence of Uu infection on IVF outcomes. Among the 973 selected subjects, 836 were Uu negative (group A) and 137 Uu positive (group B), and of the latter, 130 were restored to Uu negative after treatment (group B1) and the other 7 remained unchanged (group B2). No significant differences were found between groups A and B in the rates of IVF fertilization (81.6% vs 79.8%, P = 0.13), abnormal fertilization (11.8% vs 12.4%, P = 0.58) and oocyte cleavage (92.0% vs 92.1%, P = 0.94), nor between groups A and B2 (81.6% vs 89.8%, P = 0.10; 11.8% vs 13.2%, P = 0.75; 92.0% vs 92.5%, P = 0.10). Totally, 747 of the patients underwent embryo transfer, including 643 in group A and 104 in group B. There were no significant differences between groups A and B in the rates of clinical pregnancy (38.6% vs 34.7%, P = 0.44) and abortion (16.5% vs 22.2%, P = 0.39), nor between groups A and B2 (38.6% vs 33.3%, P = 0.79; 16.5% vs 0, P = 0.53). Uu infection in the male reproductive tract does not significantly affect the rates of IVF fertilization, oocyte cleavage, clinical pregnancy and abortion. However, more investigations with larger sample sizes of the cases restored from Uu positive to Uu negative are needed to lend further support to our findings.

Associations between paternal urinary phthalate metabolite concentrations and reproductive outcomes among couples seeking fertility treatment

PubMed Central

Dodge, LE; Williams, PL; Williams, MA; Missmer, SA; Souter, I; Calafat, AM; Hauser, R

2015-01-01

INTRODUCTION Limited evidence suggests that male exposure to ubiquitous environmental phthalates may result in poor reproductive outcomes among female partners. METHODS This analysis included male-female couples undergoing in vitro fertilization (IVF) and/or intrauterine insemination (IUI). We evaluated associations between the geometric mean of paternal specific gravity-adjusted urinary phthalate concentrations prior to the female partners’ cycle and fertilization, embryo quality, implantation, and live birth using generalized linear mixed models. RESULTS Two-hundred eighteen couples underwent 211 IVF and 195 IUI cycles. Trends were observed between paternal urinary mono-3-carboxypropyl phthalate (MCPP; P=0.01) and mono(carboxyoctyl) phthalate (MCOP; P=0.01) and decreased odds of implantation. MCPP and MCOP were also associated with decreased odds of live birth following IVF (P=0.01 and P=0.04, respectively), and monobutyl phthalate above the first quartile was significantly associated with decreased odds of live birth following IUI (P=0.04). However, most urinary phthalate metabolites were not associated with these reproductive outcomes. CONCLUSION Selected phthalates were associated with decreased odds of implantation and live birth. PMID:26456810

Influence of mitochondrial membrane potential of spermatozoa on in vitro fertilisation outcome.

PubMed

Marchetti, P; Ballot, C; Jouy, N; Thomas, P; Marchetti, C

2012-04-01

To determine whether the outcome of in vitro fertilisation (IVF) is influenced by the percentage of spermatozoa with functional mitochondria, a total of 91 random couples undergoing IVF were included. Mitochondrial function was determined by flow cytometry and expressed as percentage of spermatozoa. Conventional sperm parameters were studied by light microscopy. Reproductive outcome parameters were fertilisation rate, embryo quality and clinical pregnancy. It was found that the fertilisation rate was correlated with the percentage of spermatozoa (r = 0.24, P = 0.01) as well as with the percentage of highly motile spermatozoa. However, we did not find any relationship between the percentage of spermatozoa and embryo quality. Nevertheless, no patient who exhibited less than 64% of spermatozoa achieved pregnancy. It is concluded that determination of Δψ(m) provides accurate information to guide physicians to identify male patients for whom IVF will be unlikely to result in pregnancy. Therefore, we suggest that the percentage of spermatozoa may contribute to identify the most appropriate treatment for an individual patient. © 2011 Blackwell Verlag GmbH.

Effects of EG-VEGF, VEGF and TGF-β1 on pregnancy outcome in patients undergoing IVF-ET treatment.

PubMed

Gao, Min-zhi; Zhao, Xiao-ming; Lin, Yi; Sun, Zhao-gui; Zhang, Hui-qin

2012-10-01

To investigate the correlation of endocrine gland-derived vascular endothelial growth factor (EG-VEGF), vascular endothelial growth factor (VEGF) and transforming growth factor beta 1 (TGF-β1) with the corresponding reproductive outcome in patients who received in vitro fertilization-embryo transfer (IVF-ET). Sixty-seven women undergoing IVF-ET at a university tertiary hospital were recruited for a prospective study. Concentrations of EG-VEGF, VEGF and TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA) in follicular fluid (FF) collected during oocyte retrieval (OR) and in serum collected 2 days after OR. In FF, concentrations of both EG-VEGF and VEGF were negatively correlated with peak E2 and the number of MII oocytes retrieved, and positively correlated with each other. In serum, concentrations of all the three growth factors were positively correlated with the rate of good quality embryo, and with one another. Patients in the pregnancy group had lower peak E2 concentrations and higher serum EG-VEGF concentrations than those in the non-pregnancy group, but such tendency was not observed in the case of VEGF and TGF-β1. Both concentrations of EG-VEGF and VEGF in FF were negatively correlated with ovarian response and oocyte maturation. Concentrations of all the three growth factors in serum were positively correlated with embryo quality, but only serum concentrations of EG-VEGF were associated with the pregnancy outcome.

Enlightenment about the new Architect-i2000 estradiol (Abbott Laboratories) immunoassay during in vitro fertilization.

PubMed

Taieb, Joëlle; Mendez Lozano, Daniel H; Benattar, Clarisse; Messaoudi, Chérif; Poüs, Christian

2007-12-01

We assessed a new estradiol (E2) immunoassay on the Architect-i2000 (Abbott Laboratories) for monitoring ovulation stimulation for IVF-ET and re-establishing clinical cut-off points. The method has been modified to improve E2 measurements especially at normal and low concentrations. E2 was determined for 552 samples, from 83 women, presenting normal follicular status and undergoing 100 cycles of IVF treatment. We assessed the value of this assay for down-regulation of E2 concentration limit using gonadoliberin-releasing hormone agonist (GnRHa), and monitoring of the ovarian hyperstimulation, expected range of E2 per mature follicle prior to the administration of exogenous hCG and day 3 concentration limit. We compared results with our routine method (E2-6II Advia-Centaur; Siemens-Diagnostics) for which decision-making values were known. Considering E2 concentrations obtained with the new Architect-i2000 assay for patients treated with GnRHa for 2 weeks, the cutoff-point for ovarian down-regulation should be set down at 110 pmol/L to maintain 100% of sensitivity. Considering day 3 concentration limit determination, results were not significantly different from those obtained with our routine method. The mean E2 values per mature follicle fell into the range generally expected. E2 determination with the new E2 Architect-i2000 assay could be used to monitor ovulation, in patients undergoing IVF-ET, in combination with transvaginal ultrasound.

Soy Intake Modifies the Relation Between Urinary Bisphenol A Concentrations and Pregnancy Outcomes Among Women Undergoing Assisted Reproduction.

PubMed

Chavarro, Jorge E; Mínguez-Alarcón, Lidia; Chiu, Yu-Han; Gaskins, Audrey J; Souter, Irene; Williams, Paige L; Calafat, Antonia M; Hauser, Russ

2016-03-01

Experimental data in rodents suggest that the adverse reproductive health effects of bisphenol A (BPA) can be modified by intake of soy phytoestrogens. Whether the same is true in humans is not known. The purpose of this study was to evaluate whether soy consumption modifies the relation between urinary BPA levels and infertility treatment outcomes among women undergoing assisted reproduction. The study was conducted in a fertility center in a teaching hospital. We evaluated 239 women enrolled between 2007 and 2012 in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study, who underwent 347 in vitro fertilization (IVF) cycles. Participants completed a baseline questionnaire and provided up to 2 urine samples in each treatment cycle before oocyte retrieval. IVF outcomes were abstracted from electronic medical records. We used generalized linear mixed models with interaction terms to evaluate whether the association between urinary BPA concentrations and IVF outcomes was modified by soy intake. Live birth rates per initiated treatment cycle were measured. Soy food consumption modified the association of urinary BPA concentration with live birth rates (P for interaction = .01). Among women who did not consume soy foods, the adjusted live birth rates per initiated cycle in increasing quartiles of cycle-specific urinary BPA concentrations were 54%, 35%, 31%, and 17% (P for trend = .03). The corresponding live birth rates among women reporting pretreatment consumption of soy foods were 38%, 42%, 47%, and 49% (P for trend = 0.35). A similar pattern was found for implantation (P for interaction = .02) and clinical pregnancy rates (P for interaction = .03) per initiated cycle, where urinary BPA was inversely related to these outcomes among women not consuming soy foods but unrelated to them among soy consumers. Soy food intake may protect against the adverse reproductive effects of BPA. As these findings represent the first report suggesting a potential interaction between soy and BPA in humans, they should be further evaluated in other populations.

Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial.

PubMed

Aleyasin, Ashraf; Abediasl, Zhila; Nazari, Atefeh; Sheikh, Mahdi

2016-06-01

Recent studies have revealed key roles for granulocyte colony-stimulating factor (GCSF) in embryo implantation process and maintenance of pregnancy, and some studies showed promising results by using local intrauterine infusion of GCSF in patients undergoing in vitro fertilization (IVF). This multicenter, randomized, controlled trial included 112 infertile women with repeated IVF failure to evaluate the efficacy of systemic single-dose subcutaneous GCSF administration on IVF success in these women. In this study, the Long Protocol of ovarian stimulation was used for all participants. Sealed, numbered envelopes assigned 56 patients to receive subcutaneous 300 µg GCSF before implantation and 56 in the control group. The implantation (number of gestational sacs on the total number of transferred embryos), chemical pregnancy (positive serum β-HCG), and clinical pregnancy (gestational sac and fetal heart) rates were compared between the two groups. This trial is registered at www.irct.ir (IRCT201503119568N11). The successful implantation (18% vs 7.2%, P=0.007), chemical pregnancy (44.6% vs 19.6%, P=0.005), and clinical pregnancy (37.5% vs 14.3%, P=0.005) rates were significantly higher in the intervention group than in the control group. After adjustment for participants' age, endometrial thickness, good-quality oocyte counts, number of transferred embryos, and anti-Mullerian hormone levels, GCSF treatment remained significantly associated with successful implantation (OR=2.63, 95% CI=1.09-6.96), having chemical pregnancy (OR= 2.74, 95% CI=1.11-7.38) and clinical pregnancy (OR=2.94, 95% CI=1.23-8.33). In conclusion, administration of single-dose systemic subcutaneous GCSF before implantation significantly increases the IVF success, implantation, and pregnancy rates in infertile women with repeated IVF failure. © 2016 Society for Reproduction and Fertility.

Protective role of melatonin in progesterone production by human luteal cells.

PubMed

Taketani, Toshiaki; Tamura, Hiroshi; Takasaki, Akihisa; Lee, Lifa; Kizuka, Fumie; Tamura, Isao; Taniguchi, Ken; Maekawa, Ryo; Asada, Hiromi; Shimamura, Katsunori; Reiter, Russel J; Sugino, Norihiro

2011-09-01

This study investigated whether melatonin protects luteinized granulosa cells from reactive oxygen species (ROS) as an antioxidant to enhance progesterone production in the follicle during ovulation. Follicular fluid was sampled at the time of oocyte retrieval in women undergoing in vitro fertilization and embryo transfer (IVF-ET). Melatonin concentrations in the follicular fluid were positively correlated with progesterone concentrations (r = 0.342, P < 0.05) and negatively correlated with the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker (r = -0.342, P < 0.05). The progesterone and 8-OHdG concentrations were negatively correlated (r = -0.246, P < 0.05). Luteinized granulosa cells were obtained at the time of oocyte retrieval in women undergoing IVF-ET. Cells were incubated with H(2)O(2) (30, 50, 100 μm) in the presence or absence of melatonin (1, 10, 100 μg/mL). Progesterone production by luteinized granulosa cells was significantly inhibited by H(2)O(2). Melatonin treatment overcame the inhibitory effect of H(2) O(2) . Twenty-five patients who had luteal phase defect (serum progesterone concentrations <10 ng/mL during the mid-luteal phase) were divided into two groups during the next treatment cycle: 14 women were given melatonin (3 mg/day at 22:00 hr) throughout the luteal phase and 11 women were given no medication as a control. Melatonin treatment improved serum progesterone concentrations (>10 ng/mL during the mid-luteal phase) in nine of 14 women (64.3%), whereas only two of 11 women (18.1%) showed normal serum progesterone levels in the control group. In conclusion, melatonin protects granulosa cells undergoing luteinization from ROS in the follicle and contributes to luteinization for progesterone production during ovulation. © 2011 John Wiley & Sons A/S.

Sperm chromatin structure assay results after swim-up are related only to embryo quality but not to fertilization and pregnancy rates following IVF.

PubMed

Niu, Zhi-Hong; Shi, Hui-Juan; Zhang, Hui-Qin; Zhang, Ai-Jun; Sun, Yi-Juan; Feng, Yun

2011-11-01

The aim of this study was to investigate whether the sperm chromatin structure assay (SCSA) results after swim-up are related to fertilization rates, embryo quality and pregnancy rates following in vitro fertilization (IVF). A total of 223 couples undergoing IVF in our hospital from October 2008 to September 2009 were included in this study. Data on the IVF process and sperm chromatin structure assay results were collected. Fertilization rate, embryo quality and IVF success rates of different DNA fragmentation index (DFI) subgroups and high DNA stainability (HDS) subgroups were compared. There were no significant differences in fertilization rate, clinical pregnancy or delivery rates between the DFI and HDS subgroups. However, the group with abnormal DFI had a lower good embryo rate. So, we concluded that the SCSA variables, either DFI or HDS after swim-up preparation, were not valuable in predicting fertilization failure or pregnancy rate, but an abnormal DFI meant a lower good embryo rate following IVF.

Association of blood groups with ovarian reserve and outcome of in vitro fertilization treatment.

PubMed

Awartani, Khalid; Al Ghabshi, Rahma; Al Shankiti, Hanan; Al Dossari, Mohamed; Coskun, Serdar

2016-01-01

The association between ABO blood groups and ovarian reserve in infertile patients has been a point of controversy. The aim of this study was to assess the correlation of certain blood groups with ovarian reserve and response to treatment in patients undergoing infertility treatment. Retrospective medical record review. Infertility clinic in the assisted reproductive technology (ART) unit at King Faisal Specialist Hospital and Research Center, Riyadh Saudi Arabia. All patients under 40 years of age who attended the infertility clinic at a tertiary care centre in 2010 and underwent in vitro fertilization (IVF) treatment in 2010 and 2011 were divided into groups according to blood type, and clinical parameters were compared. The association between blood groups and ovarian reserve using day 3 luteinzing hormone (LH) and follicular stimulating hormone (FSH) levels, and antral follical count (AFC). In 424 patients who underwent 566 IVF cycles, age, LH, FSH and AFC were similar among the different blood groups (P=.9, .1, .5, respectively). with controlled ovarian stimulation, no difference was observed among the four groups in menopausal gonadotrophin (hMG) dose or the duration of stimulation. The number of oocytes retrieved, fertilization rate, cleavage rate, and number of embryos transferred were similar. There was no difference in the cancellation rate or pregnancy rate among the groups. There was no significant association between blood type and ovarian reserve or response during IVF treatment in our population. Anti-Mullerian hormone levels are best correlated with ovarian reserve testing. Unavailability of AMH levels. Retrospective design.

[Embryo selection in IVF/ICSI cycles using time-lapse microscopy and the clinical outcomes].

PubMed

Chen, Minghao; Huang, Jun; Zhong, Ying; Quan, Song

2015-12-01

To compare the clinical outcomes of embryos selected using time-lapse microscopy and traditional morphological method in IVF/ICSI cycles and evaluate the clinical value of time-lapse microscopy in early embryo monitoring and selection. e retrospectively analyzed the clinical data of 139 IVF/ICSI cycles with embryo selection based on time-lapse monitoring (TLM group, n=68) and traditional morphological method (control group, n=71). The βHCG-positive rate, clinical pregnancy rate and embryo implantation rate were compared between the 2 groups. Subgroup analysis was performed in view of female patients age and the fertilization type. The βHCG-positive rate, clinical pregnancy rate and implantation rate were 66.2%, 61.8% and 47.1% in TLM group, significantly higher than those in the control group (47.9%, 43.7% and 30.3%, respectively; P<0.05). Compared with patients below 30 years of age, patients aged between 31 and 35 years benefited more from time-lapse monitoring with improved clinical outcomes. time-lapse monitoring significantly increased the βHCG-positive rate, clinical pregnancy rate and implantation rate for patients undergoing IVF cycles, but not for those undergoing ICSI or TESA cycles. Compared with those selected using traditional morphological method, the embryos selected with time-lapse microscopy have better clinical outcomes, especially in older patients (31-35 years of age) and in IVF cycles.

The effects of insurance mandates on choices and outcomes in infertility treatment markets.

PubMed

Hamilton, Barton H; McManus, Brian

2012-08-01

For the 10% to 15% of American married couples who experience reproductive problems, in vitro fertilization (IVF) is the leading technologically advanced treatment procedure. However, IVF's expense may prevent many couples from receiving treatment, and those who are treated may take an overly aggressive approach to reduce the probability of failure. Aggressive treatment, which occurs through an increase in the number of embryos transferred during IVF, can lead to medically dangerous multiple births. We evaluated the principle policy proposal-insurance mandates-for improving IVF access and outcomes. We used data from US markets during 1995-2003 to show that broad insurance mandates for IVF result in not only large increases in treatment access but also significantly less aggressive treatment. More limited insurance mandates, which may apply to a subset of insurers or provide weaker guidelines for insurer behavior, generally have little effect on IVF markets. Copyright © 2011 John Wiley & Sons, Ltd.

Preimplantation genetic screening for all 24 chromosomes by microarray comparative genomic hybridization significantly increases implantation rates and clinical pregnancy rates in patients undergoing in vitro fertilization with poor prognosis

PubMed Central

Majumdar, Gaurav; Majumdar, Abha; Lall, Meena; Verma, Ishwar C.; Upadhyaya, Kailash C.

2016-01-01

CONTEXT: A majority of human embryos produced in vitro are aneuploid, especially in couples undergoing in vitro fertilization (IVF) with poor prognosis. Preimplantation genetic screening (PGS) for all 24 chromosomes has the potential to select the most euploid embryos for transfer in such cases. AIM: To study the efficacy of PGS for all 24 chromosomes by microarray comparative genomic hybridization (array CGH) in Indian couples undergoing IVF cycles with poor prognosis. SETTINGS AND DESIGN: A retrospective, case–control study was undertaken in an institution-based tertiary care IVF center to compare the clinical outcomes of twenty patients, who underwent 21 PGS cycles with poor prognosis, with 128 non-PGS patients in the control group, with the same inclusion criterion as for the PGS group. MATERIALS AND METHODS: Single cells were obtained by laser-assisted embryo biopsy from day 3 embryos and subsequently analyzed by array CGH for all 24 chromosomes. Once the array CGH results were available on the morning of day 5, only chromosomally normal embryos that had progressed to blastocyst stage were transferred. RESULTS: The implantation rate and clinical pregnancy rate (PR) per transfer were found to be significantly higher in the PGS group than in the control group (63.2% vs. 26.2%, P = 0.001 and 73.3% vs. 36.7%, P = 0.006, respectively), while the multiple PRs sharply declined from 31.9% to 9.1% in the PGS group. CONCLUSIONS: In this pilot study, we have shown that PGS by array CGH can improve the clinical outcome in patients undergoing IVF with poor prognosis. PMID:27382234

Cost-effectiveness of primary offer of IVF vs. primary offer of IUI followed by IVF (for IUI failures) in couples with unexplained or mild male factor subfertility.

PubMed

Pashayan, Nora; Lyratzopoulos, Georgios; Mathur, Raj

2006-06-23

In unexplained and mild male factor subfertility, both intrauterine insemination (IUI) and in-vitro fertilisation (IVF) are indicated as first line treatments. Because the success rate of IUI is low, many couples failing IUI subsequently require IVF treatment. In practice, it is therefore important to examine the comparative outcomes (live birth-producing pregnancy), costs, and cost-effectiveness of primary offer of IVF, compared with primary offer of IUI followed by IVF for couples failing IUI. Mathematical modelling was used to estimate comparative clinical and cost effectiveness of either primary offer of one full IVF cycle (including frozen cycles when applicable) or "IUI + IVF" (defined as primary IUI followed by IVF for IUI failures) to a hypothetical cohort of subfertile couples who are eligible for both treatment strategies. Data used in calculations were derived from the published peer-reviewed literature as well as activity data of local infertility units. Cost-effectiveness ratios for IVF, "unstimulated-IUI (U-IUI) + IVF", and "stimulated IUI (S-IUI) + IVF" were 12,600 pounds sterling, 13,100 pound sterling and 15,100 pound sterling per live birth-producing pregnancy respectively. For a hypothetical cohort of 100 couples with unexplained or mild male factor subfertility, compared with primary offer of IVF, 6 cycles of "U-IUI + IVF" or of "S-IUI + IVF" would cost an additional 174,200 pounds sterling and 438,000 pounds sterling, representing an opportunity cost of 54 and 136 additional IVF cycles and 14 to 35 live birth-producing pregnancies respectively. For couples with unexplained and mild male factor subfertility, primary offer of a full IVF cycle is less costly and more cost-effective than providing IUI (of any modality) followed by IVF.

Cost-effectiveness of primary offer of IVF vs. primary offer of IUI followed by IVF (for IUI failures) in couples with unexplained or mild male factor subfertility

PubMed Central

Pashayan, Nora; Lyratzopoulos, Georgios; Mathur, Raj

2006-01-01

Background In unexplained and mild male factor subfertility, both intrauterine insemination (IUI) and in-vitro fertilisation (IVF) are indicated as first line treatments. Because the success rate of IUI is low, many couples failing IUI subsequently require IVF treatment. In practice, it is therefore important to examine the comparative outcomes (live birth-producing pregnancy), costs, and cost-effectiveness of primary offer of IVF, compared with primary offer of IUI followed by IVF for couples failing IUI. Methods Mathematical modelling was used to estimate comparative clinical and cost effectiveness of either primary offer of one full IVF cycle (including frozen cycles when applicable) or "IUI + IVF" (defined as primary IUI followed by IVF for IUI failures) to a hypothetical cohort of subfertile couples who are eligible for both treatment strategies. Data used in calculations were derived from the published peer-reviewed literature as well as activity data of local infertility units. Results Cost-effectiveness ratios for IVF, "unstimulated-IUI (U-IUI) + IVF", and "stimulated IUI (S-IUI) + IVF" were £12,600, £13,100 and £15,100 per live birth-producing pregnancy respectively. For a hypothetical cohort of 100 couples with unexplained or mild male factor subfertility, compared with primary offer of IVF, 6 cycles of "U-IUI + IVF" or of "S-IUI + IVF" would cost an additional £174,200 and £438,000, representing an opportunity cost of 54 and 136 additional IVF cycles and 14 to 35 live birth-producing pregnancies respectively. Conclusion For couples with unexplained and mild male factor subfertility, primary offer of a full IVF cycle is less costly and more cost-effective than providing IUI (of any modality) followed by IVF. PMID:16796733

Female Couples Undergoing IVF with Partner Eggs (Co-IVF): Pathways to Parenthood.

PubMed

Yeshua, Arielle; Lee, Joseph A; Witkin, Georgia; Copperman, Alan B

2015-06-01

Egg sharing in female couples can be used to allow dual participation of female couples in the pregnancy process. The oocyte donor-partner provides the eggs and the recipient partner provides the uterine environment for gestation. We present descriptive data of our experience in female couples to establish a better understanding of utilization of co-in vitro fertilization (Co-IVF) for social and medical reasons. Female couples enrolled in a third party reproduction program that engaged in at least one Co-IVF cycle were included. Previous assisted reproductive technology (ART) cycle data, Co-IVF cycle information and pregnancy outcomes were evaluated. Female couples (n=21) who participated in Co-IVF cycles were analyzed. Over time, 16/21 (76%) of couples achieved at least one pregnancy, 9 (42%) couples delivered, and there are another 5 (23%) ongoing pregnancies. Our analysis presents descriptive data and sheds realistic expectations for Co-IVF couples. Co-IVF cycles can result in a shared experience with regard to the process of creating a family, while preserving a female couple's desire for dual partner participation in the gestational process. We encourage centers treating female couples to consider departing from traditional nomenclature of "donors" and "recipients" and adopting the nomenclature "Co-IVF" to describe the modern understanding of the shared experience. Even if female couples have experienced prior unsuccessful cycles, couples ultimately retain an excellent prognosis for reproductive success using Co-IVF.

Immunocytogenetic effects of gonadotropin releasing hormone analogue: Triptorelin Pamoate (Decapeptyl) during in vitro fertilization treatment.

PubMed

Al-Qashi, S; Al-Qaoud, K M; Ja'fer, M; Khali, A M

2006-10-01

In this study, the immunocytogenetic effects of Decapeptyl (Triptorelin Pamoate) were assessed in the peripheral blood lymphocytes of females undergoing in vitro fertilization (IVF) treatment. Blood samples were taken from 34 females (23 treated and 11 controls), cultured and examined for sister chromatid exchanges (SCE) and cell replication index (CRI). The SCE frequency increased around ovulation time in the controls, and around the time of human chorionic gonadotropin administration in the IVF group. However, the SCE rate was significantly higher in the latter group. Furthermore, the white blood cells (WBC) count was significantly higher on the day of ovum pick up compared to the day preceding luteinizing hormone (LH) and follicle stimulating hormone (FSH) treatment. Similar observations were recorded with respect to phagocytic activity tested by nitroblue tetrazolium (NBT) assay. The nitric oxide production abilities of macrophages were not significantly changed in the LH, FSH-treated group relative to its control. Finally, the 50% complement hemolytic activity (CH50) assay results indicated that Decapeptyl lacks a significant potential to affect the complement system.

HIV seroconversion in a woman preparing for assisted reproduction: an inherent risk in caring for HIV-serodiscordant couples.

PubMed

Sauer, Mark V; Choi, Janet

2006-03-01

A woman preparing to undergo IVF and intracytoplasmic sperm injection to avoid horizontal viral transmission of HIV from her seropositive husband was discovered to be HIV seropositive, presumably secondary to a condom break or unprotected intercourse. Had this event occurred after treatment, the sperm-washing technique used to avoid infection would have undoubtedly been called into question. Nearly all HIV-serodiscordant couples are sexually active and therefore at risk for transmitting infection, either due to improper condom use or unprotected intercourse. Physicians willing to treat HIV-serodiscordant couples must accept the inevitability of viral transmission in occasional individuals. Furthermore, it should not be presumed that all patients who experience seroconversions after either intrauterine insemination or IVF procedures do so as a result of inadequacies in the sperm preparation technique.

Association of common thrombophilias and antiphospholipid antibodies with success rate of in vitro fertilisation.

PubMed

Steinvil, Arie; Raz, Raanan; Berliner, Shlomo; Steinberg, David M; Zeltser, David; Levran, David; Shimron, Orit; Sella, Tal; Chodick, Gabriel; Shalev, Varda; Salomon, Ophira

2012-12-01

Assisted reproductive technology (ART) is extensively used as a tool for pregnancy achievement in subfertile couples. Congenital and acquired thrombophilias have been suggested by some investigators to play a role in abnormal embryo implantation and placentation. The objective of this study was to assess the role of common thrombophilias in women with unexplained infertility undergoing in vitro fertilisation (IVF). We retrospectively analysed 594 women from a large healthcare maintenance organisation going through IVF and who had a thrombophilia workup, and compared them for prevalence of thrombophilia to two reference groups consisting of 637 fertile women from previous work and 17,337 women members of the same healthcare organisation with no history of venous thromboembolism. The mean age of the women at the first cycle of IVF was 30.9 years (SD: 4.1).The mean number of IVF cycles was 7.3 (SD: 5.0), and the mean fertility success rate per woman was 14.6% (SD: 19.0%). None of the common thrombophilias tested was found to be significantly associated with the number of IVF cycles or with lower fertility success rate. Rather, women who had APCR and /or factor V Leiden and lupus anticoagulant had significantly higher live birth rates (12.3% and 12.6%, respectively) in comparison to women who were tested negative (9.0% and 9.7%, respectively). Thus, hypercoagulability is not associated with failure to achieve pregnancy. These data suggest that neither screening for thrombophilia nor anticoagulant treatment is indicated in cases with unexplained reproductive failure.

"Anti-Mullerian Hormone: Marker for Ovarian Response in Controlled Ovarian Stimulation for IVF Patients": A First Pilot Study in the Indian Population.

PubMed

Singh, Neeta; Malik, Ekta; Banerjee, Ayan; Chosdol, Kunzang; Sreenivas, V; Mittal, Suneeta

2013-08-01

To measure the levels of early follicular phase Anti-Mullerian hormone (AMH) in Indian patients of IVF and to evaluate the AMH as a predictive marker of ovarian response in assisted reproductive technology outcome. Sixty women (age 25-40 years) selected for in vitro fertilization treatment were included in this study. Analysis of day-2 serum samples was done for the AMH, FSH, Inhibin B, and LH by ELISA kit methods. USG was done for the antral follicle count (AFC) and oocytes' retrieval. Hormone parameters were compared and correlated with the oocytes' retrieval count and the AFC. The discriminant analysis was done to compare relevance of different parameters for predicting ovarian response. The Anti-Mullerian hormone showed a significant correlation with the oocytes' retrieval after ovulation induction for IVF (r = 0.648, p < 0.0001) and no correlation was seen with serum FSH, LH, and Inhibin. Serum AMH levels show 80 % sensitivity and 80 % specificity in predicting poor ovarian response. There is a significant correlation between day-2 serum AMH levels and the oocytes' retrieval count in women undergoing ovulation induction for IVF, and the AMH is a good marker as the negative predictive values for the success of ART. There is no correlation found between other hormonal ovarian reserve markers and the oocytes' retrieval count.

A comparison of the cost-effectiveness of in vitro fertilization strategies and stimulated intrauterine insemination in a Canadian health economic model.

PubMed

Bhatt, Taimur; Baibergenova, Akerke

2008-05-01

In vitro fertilization (IVF) with single embryo transfer (SET) has been proposed as a means of reducing multiple pregnancies associated with infertility treatment. All existing cost-effectiveness studies of IVF-SET have compared it with IVF with multiple embryo transfer but not with intrauterine insemination with gonadotropin stimulation (sIUI). We conducted a systematic review of studies of cost-effectiveness of IVF-SET versus IVF with double embryo transfer (DET). Further, we developed a health economy model that compared three strategies: (1) IVF-SET, (2) IVF-DET, and (3) sIUI. The decision analysis considered three cycles for each treatment option. IVF treatment was assumed to be a combination of cycles with transfer of fresh and frozen-thawed embryos. Probabilities used to populate the model were taken from published randomized clinical trials and observational studies. Cost estimates were based on average costs of associated procedures in Canada. The results of published studies on the cost-effectiveness of IVF-SET versus IVF-DET were not consistent. In our analysis, IVF-DET proved to be the most cost-effective strategy at $35,144/live birth, followed by sIUI at $66,960/live birth, and IVF-SET at $109,358/live birth. The results were sensitive both to the cost of IVF cycles and to the probability of live birth. This economic analysis showed that IVF-DET was the most cost-effective strategy of the options, and IVF-SET was the least cost-effective. The results in this model were insensitive to various probability inputs and to the costs associated with sIUI and IVF procedures.

Emergency IVF for embryo freezing to preserve female fertility: a French multicentre cohort study.

PubMed

Courbiere, B; Decanter, C; Bringer-Deutsch, S; Rives, N; Mirallié, S; Pech, J C; De Ziegler, D; Carré-Pigeon, F; May-Panloup, P; Sifer, C; Amice, V; Schweitzer, T; Porcu-Buisson, G; Poirot, C

2013-09-01

What are the outcomes of French emergency IVF procedures involving embryo freezing for fertility preservation before gonadotoxic treatment? Pregnancy rates after emergency IVF, cryopreservation of embryos, storage, thawing and embryo transfer (embryo transfer), in the specific context of the preservation of female fertility, seem to be similar to those reported for infertile couples undergoing ART. A French retrospective multicentre cohort study initiated by the GRECOT network-the French Study Group for Ovarian and Testicular Cryopreservation. We sent an e-mail survey to the 97 French centres performing the assisted reproduction technique in 2011, asking whether the centre performed emergency IVF and requesting information about the patients' characteristics, indications, IVF cycles and laboratory and follow-up data. The response rate was 53.6% (52/97). Fourteen French centres reported that they performed emergency IVF (56 cycles in total) before gonadotoxic treatment, between 1999 and July 2011, in 52 patients. The patients had a mean age of 28.9 ± 4.3 years, and a median length of relationship of 3 years (1 month-15 years). Emergency IVF was indicated for haematological cancer (42%), brain tumour (23%), sarcoma (3.8%), mesothelioma (n = 1) and bowel cancer (n = 1). Gynaecological problems accounted for 17% of indications. In 7.7% of cases, emergency IVF was performed for autoimmune diseases. Among the 52 patients concerned, 28% (n = 14) had undergone previous courses of chemotherapy before beginning controlled ovarian stimulation (COS). The initiation of gonadotoxic treatment had to be delayed in 34% of the patients (n = 19). In total, 56 cycles were initiated. The mean duration of stimulation was 11.2 ± 2.5 days, with a mean peak estradiol concentration on the day on which ovulation was triggered of 1640 ± 1028 pg/ml. Three cycles were cancelled due to ovarian hyperstimulation syndrome (n = 1), poor response (n = 1) and treatment error (n = 1). A mean of 8.2 ± 4.8 oocytes were retrieved, with 6.1 ± 4.2 mature oocytes and 4.4 ± 3.3 pronuclear-stage embryos per cycle. The mean number of embryos frozen per cycle was 4.2 ± 3.1. During follow-up, three patients died from the consequences of their disease. For the 49 surviving patients, 22.5% of the couples concerned (n = 11) requested embryo replacement. A total of 33 embryos were thawed with a post-thawing survival rate of 76%. Embryo replacement was finally performed for 10 couples with a total of 25 embryos transferred, leading to one biochemical pregnancy, one miscarriage and three live births. Clinical pregnancy rate and live birth per couple who wanted a pregnancy after cancer were, respectively, 36% (95% CI = 10.9-69.2%) and 27% (95% CI = 6.0-61%). The overall response rate for clinics was 53.6%. Therefore, it is not only that patients may not have been included, but also that those that were included were biased towards the University sector with a response rate of 83% (25/30) for a small number of patients. According to literature, malignant disease is a risk factor for a poor response to COS. However, patients having emergency IVF before gonadotoxic treatment have a reasonable chance of pregnancy after embryo replacement. Embryo freezing is a valuable approach that should be included among the strategies used to preserve fertility. No external funding was sought for this study. None of the authors has any conflict of interest to declare.

The effect of elevated progesterone levels before oocyte retrieval in women undergoing ovarian stimulation for IVF treatment on the genomic profile of peri-implantation endometrium.

PubMed

Liu, Liu; Huang, Jin; Li, Tin Chiu; Hong, Xu Tao; Laird, Susan; Dai, Yong Dong; Tong, Xiao Mei; Zhu, Hai Yan; Zhang, Songying

2017-06-01

To evaluate the effects of high progesterone prior to oocyte retrieval on the genomic profile of peri-implantation endometrium, we conducted this single-center, prospective cohort study. Depending on whether or not the progesterone level on the day of hCG administration and the day after hCG administration were elevated, a total of 20 women undergoing IVF treatment who did not have fresh embryo transfer were included: Group 1 refers to subjects with normal progesterone level on both days; Group 2 refers to subjects with normal progesterone level on the day of hCG administration and high progesterone level on the day after hCG administration; Group 3 refers to subjects with high progesterone level on the day of hCG administration and normal progesterone level on the day after hCG administration; Group 4 refers to subjects with high progesterone level on both days. Five subjects were included in each group. Endometrial samples were obtained 7days after hCG administration. We found that high progesterone level prior to oocyte retrieval predominantly affected components of the NK cell mediated cytotoxicity pathway in the endometrium and that significant differences were only seen when progesterone measurements on both the day of and day after hCG administration were considered together. Copyright © 2017 Elsevier B.V. All rights reserved.

A Randomized Clinical Trial to Determine Optimal Infertility Treatment in Older Couples: The Forty and Over Treatment Trial (FORT-T)

PubMed Central

Goldman, Marlene B.; Thornton, Kim L.; Ryley, David; Alper, Michael M.; Fung, June L.; Hornstein, Mark D.; Reindollar, Richard H.

2014-01-01

Objective To determine optimal infertility therapy in women at the end of their reproductive potential. Design Randomized clinical trial. Setting Academic medical centers and private infertility center in a state with mandated insurance coverage. Patients Couples with ≥ 6 months of unexplained infertility; female partner aged 38–42. Interventions Randomized to treatment with 2 cycles of clomiphene citrate (CC) and intrauterine insemination (IUI), follicle stimulating hormone (FSH)/IUI, or immediate IVF, followed by IVF if not pregnant. Main Outcome Measures Proportion with a clinically recognized pregnancy, number of treatment cycles, and time to conception after 2 treatment cycles and at the end of treatment. Results 154 couples were randomized to receive CC/IUI (N=51), FSH/IUI (N=52), or immediate IVF (N=51); 140 (90.9%) couples initiated treatment. Cumulative clinical pregnancy rates per couple after the first 2 cycles of CC/IUI, FSH/IUI, or immediate IVF were 21.6%, 17.3%, and 49.0%, respectively. After all treatment, 71.4% (110/154) of couples conceived a clinically recognized pregnancy and 46.1% delivered at least one live-born baby. 84.2% of all live born infants resulting from treatment were achieved from IVF. There were 36% fewer treatment cycles in the IVF arm compared to either COH/IUI arm and couples conceived a pregnancy leading to a live birth after fewer treatment cycles. Conclusions An RCT to compare treatment initiated with 2 cycles of COH/IUI to immediate IVF in older women with unexplained infertility demonstrated superior pregnancy rates with fewer treatment cycles in the immediate IVF group. PMID:24796764

Resource allocation of in vitro fertilization: a nationwide register-based cohort study.

PubMed

Klemetti, Reija; Gissler, Mika; Sevón, Tiina; Hemminki, Elina

2007-12-21

Infertility is common and in vitro fertilization (IVF) is a widely used treatment. In IVF the need increases and the effectiveness and appropriateness decrease by age. The purpose of this study was to describe allocation of resources for IVF by women's age, socioeconomic position, area of residence and treatment sector (public vs. private) and to discuss how fairly the IVF resources are allocated in Finland. Women who received IVF between 1996 and 1998 (N = 9175) were identified from the reimbursement records of the Social Insurance Institution (SII). Information on IVF women's background characteristics came from the Central Population Register and the SII, on treatment costs from IVF clinics and the SII, and on births from the Medical Birth Register. The main outcome measures were success of IVF by number of cycles and treated women, expenditures per IVF cycles, per women, per live-birth, and per treatment sector, and private and public expenditures. Expenditures were estimated from health care visits and costs. During a mean period of 1.5 years, older women (women aged 40 or older) received 1.4 times more IVF treatment cycles than younger women (women aged below 30). The success rate decreased by age: from 22 live births per 100 cycles among younger women to 6 per 100 among older women. The mean cost of a live birth increased by age: compared to younger women, costs per born live birth of older women were 3-fold. Calculated by population, public expenditure was allocated most to young women and women from the highest socioeconomic position. Regional differences were not remarkable. Children of older infertile women involve more expense due to the lower success rates of IVF. Socioeconomic differences suggest unfair resource allocation in Finland.

Resource allocation of in vitro fertilization: a nationwide register-based cohort study

PubMed Central

Klemetti, Reija; Gissler, Mika; Sevón, Tiina; Hemminki, Elina

2007-01-01

Background Infertility is common and in vitro fertilization (IVF) is a widely used treatment. In IVF the need increases and the effectiveness and appropriateness decrease by age. The purpose of this study was to describe allocation of resources for IVF by women's age, socioeconomic position, area of residence and treatment sector (public vs. private) and to discuss how fairly the IVF resources are allocated in Finland. Methods Women who received IVF between 1996 and 1998 (N = 9175) were identified from the reimbursement records of the Social Insurance Institution (SII). Information on IVF women's background characteristics came from the Central Population Register and the SII, on treatment costs from IVF clinics and the SII, and on births from the Medical Birth Register. The main outcome measures were success of IVF by number of cycles and treated women, expenditures per IVF cycles, per women, per live-birth, and per treatment sector, and private and public expenditures. Expenditures were estimated from health care visits and costs. Results During a mean period of 1.5 years, older women (women aged 40 or older) received 1.4 times more IVF treatment cycles than younger women (women aged below 30). The success rate decreased by age: from 22 live births per 100 cycles among younger women to 6 per 100 among older women. The mean cost of a live birth increased by age: compared to younger women, costs per born live birth of older women were 3-fold. Calculated by population, public expenditure was allocated most to young women and women from the highest socioeconomic position. Regional differences were not remarkable. Conclusion Children of older infertile women involve more expense due to the lower success rates of IVF. Socioeconomic differences suggest unfair resource allocation in Finland. PMID:18154645

Prediction value of anti-Mullerian hormone (AMH) serum levels and antral follicle count (AFC) in hormonal contraceptive (HC) users and non-HC users undergoing IVF-PGD treatment.

PubMed

Bas-Lando, Maayan; Rabinowitz, Ron; Farkash, Rivka; Algur, Nurit; Rubinstein, Esther; Schonberger, Oshrat; Eldar-Geva, Talia

2017-10-01

Use of hormone contraceptives (HC) is very popular in the reproductive age and, therefore, evaluation of ovarian reserve would be a useful tool to accurately evaluate the reproductive potential in HC users. We conducted a retrospective cohort study of 41 HC users compared to 57 non-HC users undergoing IVF-preimplantation genetic diagnosis (PGD) aiming to evaluate the effect of HC on the levels of anti-Mullerian hormone (AMH), small (2-5 mm), large (6-10 mm) and total antral follicle count (AFC) and the ability of these markers to predict IVF outcome. Significant differences in large AFC (p = 0.04) and ovarian volume (p < 0.0001) were seen, however, there were no significant differences in small and total AFC or in serum AMH and FSH levels. Oocyte number significantly correlated with AMH and total AFC in HC users (p < 0.001) while in non-HC users these correlations were weaker. In HC users, the significant predictors of achieving <6 and >18 oocytes were AFC (ROC-AUC; 0.958, p = 0.001 and 0.883, p = 0.001) and AMH (ROC-AUC-0.858, p = 0.01 and 0.878, p = 0.001), respectively. The predictive values were less significant in non-HC users. These findings are important in women treated for PGD, in ovum donors and for assessing the fertility prognosis in women using HC and wishing to postpone pregnancy.

Lipidomic Components Alterations of Human Follicular Fluid Reveal the Relevance of Improving Clinical Outcomes in Women Using Progestin-Primed Ovarian Stimulation Compared to Short-Term Protocol.

PubMed

Wen, Xiaowei; Kuang, Yanping; Zhou, Lixia; Yu, Baofeng; Chen, Qiuju; Fu, Yonglun; Yan, Zheng; Guo, Haiyan; Lyu, Qifeng; Xie, Jun; Chai, Weiran

2018-05-21

BACKGROUND Increasing the success rate of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is a duty of clinicians that has made many seek a variety of protocols. This study was undertaken to use a liquid chromatography-mass spectrometry (LC-MS) to define the alterations of follicular fluid (FF) lipid metabolites in patients undergoing progestin-primed ovarian stimulation (PPOS) compared with short-term protocol, revealing potential correlations between the differentially expressed lipids and ameliorative clinical outcomes. MATERIAL AND METHODS Ninety-three infertile women undergoing IVF/ICSI treatment with PPOS (n=62) or a short-term protocol (n=31) were prospectively enrolled in a randomized controlled trial. FF samples were obtained from dominant follicles at the time of oocyte retrieval. Lipid metabolism profiles were analyzed using LC-MS. RESULTS Twelve lipids were found to be higher in patients treated with the PPOS protocol than in those receiving the short-term protocol, including triacylglycerols (TAG-34: 1+NH4, TAG-58: 0+NH4, TAG-64: 3+NH4, and TAG-64: 8+NH4), diacylglycerol DAG-38: 6+NH4, phosphatidylglycerols (PG-26: 0, PG-30: 2, and PG-40: 5), phosphatidylethanolamine PE-32: 2, lysophosphatidylethanolamine LPE-14: 1, lysophosphatidylinositol LPI-12: 0, and lysophosphatidylcholine LPC-16: 0. CONCLUSIONS Our data demonstrate that the PPOS protocol increases the levels of 12 lipids in FF, which reveals a strong association between the differentially elevated lipids and better IVF/ICSI outcomes.

Hypertensive disorders of in-vitro fertilization pregnancies: A study from Kosovo

PubMed Central

Vuniqi-Krasniqi, Merita; Paçarada, Myrvete; Daka, Qëndresë; Dervishi, Zeqir; Bimbashi, Astrit; Dakaj, Kushtrim

2018-01-01

Background: Relationships between in-vitro fertilization (IVF), gestational hypertension, and pregnancy outcomes are demonstrated in a number of studies. However, it is still debated if IVF treatment or specific characteristics of infertile patients are responsible for worse obstetrical and neonatal outcomes. Objective: The aim of this study was to investigate maternal characteristics associated with hypertensive disorders (HD) in IVF conceived pregnancies and to assess the obstetrical and neonatal outcomes. Materials and Methods: In this observational, cross-sectional study, 207 pregnant women who underwent IVF treatment were consecutively divided into two groups: a group that had no HD during pregnancy (IVF group) and a group that had HD during pregnancy (IVF+HD group). Maternal, obstetrical and neonatal data of the two groups were compared. Results: Some maternal characteristics were significantly higher in IVF+HD compared to IVF group such as: older age (p=0.0001), primiparity (p=0.038), obesity (p=0.0001), and cigarette smoking (p=0.0001). There were no significant differences between the groups in regard to obstetrical outcomes besides premature rupture of membranes time that was significantly higher in IVF+HD group compared to IVF group (p=0.036). In regard to neonatal outcomes, the only statistically significant difference was in the 5th min Apgar score, which was higher in IVF+HD group compared to IVF group without HD (p=0.002). Conclusion: With regard to significantly higher differences in maternal characteristics of IVF conceived pregnancies complicated with HD, compared to uncomplicated ones, development of a specific national prevention measure for HD of IVF conceived pregnancies in Kosovo is strongly suggested. In addition, setting up of a national registry is recommended in order to evaluate the outcomes of IVF treatments properly. PMID:29675491

Modified natural cycle IVF and mild IVF: a 10 year Swedish experience.

PubMed

Aanesen, Arthur; Nygren, Karl-Gösta; Nylund, Lars

2010-01-01

Modified natural cycle IVF (mnc-IVF) or mild IVF (m-IVF) was offered to selected patients between 1996 and 2007; 43 patients during 129 cycles were treated with mnc-IVF and 145 couples during 250 cycles were treated with m-IVF. Comparison with outcome from conventional IVF cycles during the same time period and in the same clinic was performed. Although 53.5 and 39.6% of started cycles respectively never reached embryo transfer, the ongoing pregnancy rates per embryo transfer were 26.7% for mnc-IVF and 27.2% for m-IVF. During the same time period, cancellation rate for conventional IVF was 13.7% and the ongoing pregnancy rate per embryo transfer was 34.3%. For patients > or =38years of age, the ongoing pregnancy rate per embryo transfer was 17.5% in the m-IVF group. None of the patients aged > or =38years in the mnc-IVF group achieved an ongoing pregnancy. For patients treated with conventional IVF, the > or =38years of age pregnancy rate per embryo transfer was 27.0%. Costs of medication for m-IVF and mnc-IVF were 96.3 and 97.5% less than for the least expensive conventional IVF cycle respectively. Pregnancy rates per embryo transfer are acceptable for these treatment modalities, the cost for medication is low, risks for complications are dramatically reduced, and the treatments may be more psychologically acceptable to the patients. Copyright (c) 2009 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Fresh versus frozen embryo transfers in assisted reproduction.

PubMed

Wong, Kai Mee; van Wely, Madelon; Mol, Femke; Repping, Sjoerd; Mastenbroek, Sebastiaan

2017-03-28

In general, in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) implies a single fresh and one or more frozen-thawed embryo transfers. Alternatively, the 'freeze-all' strategy implies transfer of frozen-thawed embryos only, with no fresh embryo transfers. In practice, both strategies can vary technically including differences in freezing techniques and timing of transfer of cryopreservation, that is vitrification versus slow freezing, freezing of two pro-nucleate (2pn) versus cleavage-stage embryos versus blastocysts, and transfer of cleavage-stage embryos versus blastocysts.In the freeze-all strategy, embryo transfers are disengaged from ovarian stimulation in the initial treatment cycle. This could avoid a negative effect of ovarian hyperstimulation on the endometrium and thereby improve embryo implantation. It could also reduce the risk of ovarian hyperstimulation syndrome (OHSS) in the ovarian stimulation cycle by avoiding a pregnancy.We compared the benefits and risks of the two treatment strategies. To evaluate the effectiveness and safety of the freeze-all strategy compared to the conventional IVF/ICSI strategy in women undergoing assisted reproductive technology. We searched the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Studies (CRSO), MEDLINE, Embase, PsycINFO, CINAHL, and two registers of ongoing trials in November 2016 together with reference checking and contact with study authors and experts in the field to identify additional studies. We included randomised clinical trials comparing a freeze-all strategy with a conventional IVF/ICSI strategy which includes fresh transfer of embryos in women undergoing IVF or ICSI treatment. We used standard methodological procedures recommended by Cochrane. The primary review outcomes were cumulative live birth and OHSS. Secondary outcomes included other adverse effects (miscarriage rate). We included four randomised clinical trials analysing a total of 1892 women comparing a freeze-all strategy with a conventional IVF/ICSI strategy. The evidence was of moderate to low quality due to serious risk of bias and (for some outcomes) serious imprecision. Risk of bias was associated with unclear blinding of investigators for preliminary outcomes of the study, unit of analysis error, and absence of adequate study termination rules.There was no clear evidence of a difference in cumulative live birth rate between the freeze-all strategy and the conventional IVF/ICSI strategy (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.91 to 1.31; 4 trials; 1892 women; I 2 = 0%; moderate-quality evidence). This suggests that if the cumulative live birth rate is 58% following a conventional IVF/ICSI strategy, the rate following a freeze-all strategy would be between 56% and 65%.The prevalence of OHSS was lower after the freeze-all strategy compared to the conventional IVF/ICSI strategy (OR 0.24, 95% CI 0.15 to 0.38; 2 trials; 1633 women; I 2 = 0%; low-quality evidence). This suggests that if the OHSS rate is 7% following a conventional IVF/ICSI strategy, the rate following a freeze-all strategy would be between 1% and 3%.The freeze-all strategy was associated with fewer miscarriages (OR 0.67, 95% CI 0.52 to 0.86; 4 trials; 1892 women; I 2 = 0%; low-quality evidence) and a higher rate of pregnancy complications (OR 1.44, 95% CI 1.08 to 1.92; 2 trials; 1633 women; low-quality evidence). There was no difference in multiple pregnancies per woman after the first transfer (OR 1.11, 95% CI 0.85 to 1.44; 2 trials; 1630 women; low-quality evidence), and no data were reported for time to pregnancy. We found moderate-quality evidence showing that one strategy is not superior to the other in terms of cumulative live birth rates. Time to pregnancy was not reported, but it can be assumed to be shorter using a conventional IVF/ICSI strategy in the case of similar cumulative live birth rates, as embryo transfer is delayed in a freeze-all strategy. Low-quality evidence suggests that not performing a fresh transfer lowers the OHSS risk for women at risk of OHSS.

In-vitro maturation versus IVF with GnRH antagonist for women with polycystic ovary syndrome: treatment outcome and rates of ovarian hyperstimulation syndrome.

PubMed

Das, Mausumi; Son, Weon-Young; Buckett, William; Tulandi, Togas; Holzer, Hananel

2014-11-01

In-vitro maturation (IVM) treatment has gained popularity for decreasing the incidence of ovarian hyperstimulation syndrome (OHSS) by eliminating or minimizing the use of gonadotrophins in women with polycystic ovary syndrome (PCOS). Studies have shown that IVF with GnRH-antagonist protocol is associated with a lower incidence of OHSS. Data comparing the relative success of these two treatments is, however, lacking. Treatment outcome and rates of OHSS were compared in patients with PCOS who underwent assisted conception with either IVM or IVF with GnRH-antagonist protocol between 2006 and 2011. The number of oocytes retrieved was higher in the IVM group, whereas the number of mature oocytes, fertilization rate and number of embryos cleaved were comparable. The implantation rate was higher in the IVF group. The clinical pregnancy rates per embryo transfer were not statistically different (IVF: 45.8% versus IVM: 32.4%). The live-birth rate was higher in the IVF group (IVF: 40.7% versus IVM: 23.5%; P = 0.04). Five women developed moderate or severe OHSS in the IVF group, whereas none did in the IVM group. Both IVM and IVF with GnRH-antagonist protocol seem to be effective treatment regimens in women with PCOS, although IVM is associated with a lower risk of OHSS. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Effects of Liuwei Dihuang Granule ([symbols; see text]) on the outcomes of in vitro fertilization pre-embryo transfer in infertility women with Kidney-yin deficiency syndrome and the proteome expressions in the follicular fluid.

PubMed

Lian, Fang; Wu, Hai-cui; Sun, Zhen-gao; Guo, Ying; Shi, Lei; Xue, Ming-yue

2014-07-01

To observe the effects of Liuwei Dihuang Granule ([symbols; see text], LDG) for tonifying Kidney (Shen) on the outcomes of in vitro fertilization pre-embryo transfer (IVF-ET) of infertility women with Kidney-yin deficiency syndrome and to explore its mechanism by detecting the proteome expression in the follicular fluid. Sixty-six infertility patients of Kidney-yin deficiency syndrome who would undergo IVF-ET, were randomly assigned to a treatment group and a control group according to a random number table, 33 cases in each group. Another 33 cases of non-Kidney-yin deficiency syndrome was taken as a syndrome-control group. Besides Western routine therapy, LDG was given 3 menstrual cycles before IVF to the treatment group, and a placebo granule to the control and syndrome-control groups. The scores of Kidney-yin deficiency symptoms (sore waist and knees, dry vagina, dysphoria with feverish sensation in the chest, palms and soles, etc.) were assessed, the number of retrieved oocytes, rates of high quality oocytes and embryos, fertility rate and clinical pregnancy rate were recorded, and the follicular fluid was collected on the day when the ovum was picked up, the differential protein expression was detected using two-dimensional gel electrophoresis, and then, matrix assisted laser desorption ionization time-of flight mass spectrometry (MALDI-TOF-MS) was applied to identify the proteins. The syndrome score in the treatment group decreased significantly from 16.09±2.58 to 8.67±2.13, while it changed insignificantly in the control group, with a significant difference in the lowering score between the two groups (P<0.05); the high quality rates of oocytes and embryos and clinical pregnancy rate were all superior in the treatment group to the control group (82.29% vs 78.08%, 76.76% vs 68.79%, 63.64% vs 36.36%, all P<0.05). The protein expression map from the follicular fluid showed that compared with the control group, 33 differential protein expressions were found in the syndrome-control group, among which 18 were down-regulated, and 15 up-regulated; in the treatment group 28 differential protein expressions were found, among which 15 were down-regulated, and 13 up-regulated. Through MALDI-TOF-MS, 14 proteins were identified (P<0.05). For the infertility patients undergoing IVF, LDG could alleviate clinical symptoms, improve rates of high quality oocytes and embryos, so as to raise clinical pregnancy rate. The mechanism may be through regulating proteome expression in the follicular fluid to improve the developmental microenvironment for oocytes which would lead to a successful embryo implantation.

The effect of intrauterine HCG injection on IVF outcome: a systematic review and meta-analysis.

PubMed

Osman, A; Pundir, J; Elsherbini, M; Dave, S; El-Toukhy, T; Khalaf, Y

2016-09-01

In this systematic review and meta-analysis, the effect of intrauterine HCG infusion before embryo transfer on IVF outcomes (live birth rate, clinical pregnancy rate and spontaneous aboretion rate) was investigated. Searches were conducted on MEDLINE, EMBASE and The Cochrane Library. Randomized studies in women undergoing IVF and intracytoplasmic sperm injection comparing intrauterine HCG administration at embryo transfer compared with no intrauterine HCG were eligible for inclusion. Eight randomized controlled trials were eligible for inclusion in the meta-analysis. A total of 3087 women undergoing IVF and intracytoplasmic sperm injection cycles were enrolled (intrauterine HCG group: n = 1614; control group: n = 1473). No significant difference was found in the live birth rate (RR 1.13; 95% CI 0.84 to 1.53) and spontaneous abortion rate (RR 1.00, 95% CI 0.74 to 1.34) between women who received intrauterine HCG and those who did not receive HCG. Although this review was extensive and included randomized controlled trials, no significant heterogeneity was found, and the overall included numbers are relatively small. In conclusion the current evidence does not support the use of intrauterine HCG administration before embryo transfer. Well-designed multicentre trials are needed to provide robust evidence. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Decreased live births among women of Middle Eastern/North African ethnicity compared to Caucasian women.

PubMed

Salem, W H; Abdullah, A; Abuzeid, O; Bendikson, K; Sharara, F I; Abuzeid, M

2017-05-01

The objective of this study is to determine if IVF outcome disparities exist among MENA women in the USA in comparison to a control group of Caucasian women. A retrospective cohort study comparing MENA (N = 190) and Caucasian (N = 200) women undergoing their first IVF cycle between 5/2006 and 5/2014 was carried out at an academically affiliated fertility practice. All MENA cycles during that time period undergoing IVF/ICSI using autologous embryos and blastocyst transfers were compared to a control group of Caucasian women. MENA women were significantly younger (32.9 vs 34.5, P < 0.005) and had a lower BMI (25.2 vs 27.1, P < 0.001). Male factor infertility was higher among partners of MENA women (62 vs 50%, P < 0.05). MENA women experienced decreased live birth rates per blastocyst transfer compared to Caucasian women after controlling for age and BMI (OR 0.55, 95% CI 0.35-0.85 P = 0.007). The odds of a miscarriage were also significantly higher among MENA women (OR 2.55, 95% CI 1.04-6.27 P = 0.036). Middle Eastern/North African women have worse IVF outcomes with decreased live birth rates per blastocyst transfer and increased miscarriage rates compared to Caucasian women.

Is IVF-served two different ways-more cost-effective than IUI with controlled ovarian hyperstimulation?

PubMed

Tjon-Kon-Fat, R I; Bensdorp, A J; Bossuyt, P M M; Koks, C; Oosterhuis, G J E; Hoek, A; Hompes, P; Broekmans, F J; Verhoeve, H R; de Bruin, J P; van Golde, R; Repping, S; Cohlen, B J; Lambers, M D A; van Bommel, P F; Slappendel, E; Perquin, D; Smeenk, J; Pelinck, M J; Gianotten, J; Hoozemans, D A; Maas, J W M; Groen, H; Eijkemans, M J C; van der Veen, F; Mol, B W J; van Wely, M

2015-10-01

What is the cost-effectiveness of in vitro fertilization (IVF) with conventional ovarian stimulation, single embryo transfer (SET) and subsequent cryocycles or IVF in a modified natural cycle (MNC) compared with intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) as a first-line treatment in couples with unexplained subfertility and an unfavourable prognosis on natural conception?. Both IVF strategies are significantly more expensive when compared with IUI-COH, without being significantly more effective. In the comparison between IVF-MNC and IUI-COH, the latter is the dominant strategy. Whether IVF-SET is cost-effective depends on society's willingness to pay for an additional healthy child. IUI-COH and IVF, either after conventional ovarian stimulation or in a MNC, are used as first-line treatments for couples with unexplained or mild male subfertility. As IUI-COH is less invasive, this treatment is usually offered before proceeding to IVF. Yet, as conventional IVF with SET may lead to higher pregnancy rates in fewer cycles for a lower multiple pregnancy rate, some have argued to start with IVF instead of IUI-COH. In addition, IVF in the MNC is considered to be a more patient friendly and less costly form of IVF. We performed a cost-effectiveness analysis alongside a randomized noninferiority trial. Between January 2009 and February 2012, 602 couples with unexplained infertility and a poor prognosis on natural conception were allocated to three cycles of IVF-SET including frozen embryo transfers, six cycles of IVF-MNC or six cycles of IUI-COH. These couples were followed until 12 months after randomization. We collected data on resource use related to treatment, medication and pregnancy from the case report forms. We calculated unit costs from various sources. For each of the three strategies, we calculated the mean costs and effectiveness. Incremental cost-effectiveness ratios (ICER) were calculated for IVF-SET compared with IUI-COH and for IVF-MNC compared with IUI-COH. Nonparametric bootstrap resampling was used to investigate the effect of uncertainty in our estimates. There were 104 healthy children (52%) born in the IVF-SET group, 83 (43%) the IVF-MNC group and 97 (47%) in the IUI-COH group. The mean costs per couple were €7187 for IVF-SET, €8206 for IVF-MNC and €5070 for IUI-COH. Compared with IUI-COH, the costs for IVF-SET and IVF-MNC were significantly higher (mean differences €2117; 95% CI: €1544-€2657 and €3136, 95% CI: €2519-€3754, respectively).The ICER for IVF-SET compared with IUI-COH was €43 375 for the birth of an additional healthy child. In the comparison of IVF-MNC to IUI-COH, the latter was the dominant strategy, i.e. more effective at lower costs. We only report on direct health care costs. The present analysis is limited to 12 months. Since we found no evidence in support of offering IVF as a first-line strategy in couples with unexplained and mild subfertility, IUI-COH should remain the treatment of first choice. The study was supported by a grant from ZonMw, the Netherlands Organization for Health Research and Development, (120620027) and a grant from Zorgverzekeraars Nederland, the Netherlands' association of health care insurers (09-003). Current Controlled Trials ISRCTN52843371; Nederlands Trial Register NTR939. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

IVF with planned single-embryo transfer versus IUI with ovarian stimulation in couples with unexplained subfertility: an economic analysis.

PubMed

van Rumste, Minouche M E; Custers, Inge M; van Wely, Madelon; Koks, Carolien A; van Weering, Hans G I; Beckers, Nicole G M; Scheffer, Gabrielle J; Broekmans, Frank J M; Hompes, Peter G A; Mochtar, Monique H; van der Veen, Fulco; Mol, Ben W J

2014-03-01

Couples with unexplained subfertility are often treated with intrauterine insemination (IUI) with ovarian stimulation, which carries the risk of multiple pregnancies. An explorative randomized controlled trial was performed comparing one cycle of IVF with elective single-embryo transfer (eSET) versus three cycles of IUI-ovarian stimulation in couples with unexplained subfertility and a poor prognosis for natural conception, to assess the economic burden of the treatment modalities. The main outcome measures were ongoing pregnancy rates and costs. This study randomly assigned 58 couples to IVF-eSET and 58 couples to IUI-ovarian stimulation. The ongoing pregnancy rates were 24% in with IVF-eSET versus 21% with IUI-ovarian stimulation, with two and three multiple pregnancies, respectively. The mean cost per included couple was significantly different: €2781 with IVF-eSET and €1876 with IUI-ovarian stimulation (P<0.01). The additional costs per ongoing pregnancy were €2456 for IVF-eSET. In couples with unexplained subfertility, one cycle of IVF-eSET cost an additional €900 per couple compared with three cycles of IUI-ovarian stimulation, for no increase in ongoing pregnancy rates or decrease in multiple pregnancies. When IVF-eSET results in higher ongoing pregnancy rates, IVF would be the preferred treatment. Couples that have been trying to conceive unsuccessfully are often treated with intrauterine insemination (IUI) and medication to improve egg production (ovarian stimulation). This treatment carries the risk of multiple pregnancies like twins. We performed an explorative study among those couples that had a poor prognosis for natural conception. One cycle of IVF with transfer of one selected embryo (elective single-embryo transfer, eSET) was compared with three cycles of IUI-ovarian stimulation. The aim of this study was to assess the economic burden of both treatments. The Main outcome measures were number of good pregnancies above 12weeks and costs. We randomly assigned 58 couples to IVF-eSET and 58 couples to IUI-ovarian stimulation. The ongoing pregnancy rates were comparable: 24% with IVF-eSET versus 21% with IUI-ovarian stimulation. There were two multiple pregnancies with IVF-eSET and three multiple pregnancies with IUI-ovarian stimulation. The mean cost per included couple was significantly different, €2781 with IVF-eSET and €1876 with IUI-ovarian stimulation. The additional costs per ongoing pregnancy were €2456 for IVF-eSET. In couples with unexplained subfertility, one cycle of IVF-eSET costed an additional €900 per couple compared to three cycles of IUI-ovarian stimulation, for no increase in ongoing pregnancy rates or decrease in multiple pregnancies. We conclude that IUI-ovarian stimulation is the preferred treatment to start with. When IVF-eSET results in a higher ongoing pregnancy rate (>38%), IVF would be the preferred treatment. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

IVF or IUI as first-line treatment in unexplained subfertility: the conundrum of treatment selection markers.

PubMed

Tjon-Kon-Fat, R I; Tajik, P; Zafarmand, M H; Bensdorp, A J; Bossuyt, P M M; Oosterhuis, G J E; van Golde, R; Repping, S; Lambers, M D A; Slappendel, E; Perquin, D; Pelinck, M J; Gianotten, J; Maas, J W M; Eijkemans, M J C; van der Veen, F; Mol, B W; van Wely, M

2017-05-01

Are there treatment selection markers that could aid in identifying couples, with unexplained or mild male subfertility, who would have better chances of a healthy child with IVF with single embryo transfer (IVF-SET) than with IUI with ovarian stimulation (IUI-OS)? We did not find any treatment selection markers that were associated with better chances of a healthy child with IVF-SET instead of IUI-OS in couples with unexplained or mild male subfertility. A recent trial, comparing IVF-SET to IUI-OS, found no evidence of a difference between live birth rates and multiple pregnancy rates. It was suggested that IUI-OS should remain the first-line treatment instead of IVF-SET in couples with unexplained or mild male subfertility and female age between 18 and 38 years. The question remains whether there are some couples that may have higher pregnancy chances if treated with IVF-SET instead of IUI. We performed our analyses on data from the INeS trial, where couples with unexplained or mild male subfertility and an unfavourable prognosis for natural conception were randomly allocated to IVF-SET, IVF in a modified natural cycle or IUI-OS. In view of the aim of this study, we only used data of the comparison between IVF-SET (201 couples) and IUI-OS (207 couples). We pre-defined the following baseline characteristics as potential treatment selection markers: female age, ethnicity, smoking status, type of subfertility (primary/secondary), duration of subfertility, BMI, pre-wash total motile count and Hunault prediction score. For each potential treatment selection marker, we explored the association with the chances of a healthy child after IVF-SET and IUI-OS and tested if there was an interaction with treatment. Given the exploratory nature of our analysis, we used a P-value of 0.1. None of the markers were associated with higher chances of a healthy child from IVF-SET compared to IUI-OS (P-value for interaction >0.10). Since this is the first large study that looked at potential treatment selection markers for IVF-SET compared to IUI-OS, we had no data on which to base a power calculation. The sample size was limited, making it difficult to detect any smaller associations. We could not identify couples with unexplained or mild male subfertility who would have had higher chances of a healthy child from immediate IVF-SET than from IUI-OS. As in the original trial IUI-OS had similar effectiveness and was less costly compared to IVF-SET, IUI-OS should remain the preferred first-line treatment in these couples. The study was supported by a grant from the Netherlands Organization for Health Research and Development, and a grant from the Netherlands' association of health care insurers. There are no conflicts of interest. The trial was registered at the Dutch trial registry (NTR939). © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Pre-term birth and low birth weight following preimplantation genetic diagnosis: analysis of 88 010 singleton live births following PGD and IVF cycles.

PubMed

Sunkara, Sesh Kamal; Antonisamy, Belavendra; Selliah, Hepsy Y; Kamath, Mohan S

2017-02-01

Is PGD associated with the risk of adverse perinatal outcomes such as pre-term birth (PTB) and low birth weight (LBW)? There was no increase in the risk of adverse perinatal outcomes of PTB, and LBW following PGD compared with autologous IVF. Pregnancies resulting from ART are associated with a higher risk of pregnancy complications compared with spontaneously conceived pregnancies. The possible reason of adverse obstetric outcomes following ART has been attributed to the underlying infertility itself and embryo specific epigenetic modifications due to the IVF techniques. It is of interest whether interventions such as embryo biopsy as performed in PGD affect perinatal outcomes. Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA), the statutory regulator of ART in the UK. The HFEA has collected data prospectively on all ART performed in the UK since 1991. Data from 1996 to 2011 involving a total of 88 010 singleton live births were analysed including 87 571 following autologous stimulated IVF ± ICSI and 439 following PGD cycles. Data on all women undergoing either a stimulated fresh IVF ± ICSI treatment cycle or a PGD cycle during the period from 1996 to 2011 were analysed to compare perinatal outcomes of PTB and LBW among singleton live births. Logistic regression analysis was performed adjusting for female age category, year of treatment, previous IVF cycles, infertility diagnosis, number of oocytes retrieved, whether IVF or ICSI was used and day of embryo transfer. There was no increase in the risk of PTB and LBW following PGD versus autologous stimulated IVF ± ICSI treatment, unadjusted odds of PTB (odds ratio (OR) 0.68, 95% CI: 0.46-0.99) and LBW (OR 0.56, 95% CI: 0.37-0.85). After adjusting for the potential confounders, there was again no increase in the risk of the adverse perinatal outcomes following PGD: PTB (adjusted odds ratio (aOR) 0.66, 95% CI: 0.45-0.98) and LBW (aOR 0.58, 95% CI: 0.38-0.88). Although the analysis was adjusted for a number of important confounders, the data set had no information on confounders such as smoking, body mass index and the medical history of women during pregnancy to allow adjustment. There was no information on the stage of embryo at biopsy, whether blastomere or trophectoderm biopsy. The demonstration that PGD is not associated with higher risk of PTB and LBW provides reassurance towards its current expanding application. No funding was obtained. There are no competing interests to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

IV crystalloid fluid for acute alcoholic intoxication prolongs ED length of stay.

PubMed

Homma, Yosuke; Shiga, Takashi; Hoshina, Yuiko; Numata, Kenji; Mizobe, Michiko; Nakashima, Yoshiyuki; Takahashi, Jin; Inoue, Tetsuya; Takahashi, Osamu; Funakoshi, Hiraku

2018-04-01

Acute alcohol intoxication is often treated in emergency departments by intravenous crystalloid fluid (IVF), but it is not clear that this shortens the time to achieving sobriety. The study aim was to investigate the association of IVF infusion and length of stay in the ED. This single-center retrospective cohort study was conducted in Japan and included patients aged ≥20years of age and treated for acute alcohol intoxication without or with IVF. The primary outcome was the length of the ED stay and the treatments were compared by time-to-event analysis. A total of 106 patients, 42 treated without IVF and 64 with IVF. The baseline characteristics of the two groups were similar. Kaplan-Meier analysis and the generalized Wilcoxon test found no significant difference between the two treatments in the time to ED discharge. The median time was 189 (IQR 160-230) minutes without IVF and 254.5 (203-267 minutes with IVF; p=0.052). A Cox proportional hazards regression model adjusted for potential confounding variables found that patients treated with IVF were less likely to be discharged earlier than those treated without IVF (HR 0.54, 95% CI: 0.35-0.84, p=0.006). IVF for treatment of acute alcoholic intoxication prolonged ED length of stay even after adjustment for potential confounders. Patients given IVF for acute alcohol intoxication should be selected with care. Copyright © 2017 Elsevier Inc. All rights reserved.

Clomiphene citrate is associated with favorable cycle characteristics but impaired outcomes of obese women with polycystic ovarian syndrome undergoing ovarian stimulation for in vitro fertilization

PubMed Central

Jiang, Shutian; Kuang, Yanping

2017-01-01

Abstract The aim of this study was to explore the effect of clomiphene citrate (CC) on the cycle characteristics and outcomes of obese women with polycystic ovarian syndrome (PCOS) undergoing ovarian stimulation for in vitro fertilization (IVF). This is a retrospective cohort study, and it was conducted at the tertiary-care academic medical center. This study included 174 obese PCOS patients undergoing IVF. In the study group (n = 90), CC and human menopausal gonadotropin (HMG) were administered simultaneously beginning on cycle day 3, while in control group (n = 84) HMG was used only. Both of the 2 groups used medroxyprogesterone acetate (MPA) for preventing premature luteinizing hormone (LH) surges. Ovulation was cotriggered by a GnRH agonist and hCG when dominant follicles matured. The primary outcome measure was the number of oocytes retrieved. Secondary outcomes included the number of top-quality embryos, maturation rate, fertilization rate, cleavage rate, incidence of premature LH surge, and OHSS. The study group received obviously lower total HMG dose [1650 (975–4800) vs 2025 (1350–3300) IU, P = 2.038E–4] but similar HMG duration. While the antral follicle count (AFC) is higher in study group, the number of oocytes retrieved and top-quality embryos are remarkably less [5 (0–30) vs 13 (0–42), P = 6.333E–5; 2 (0–14) vs 3.5 (0–15), P = .003; respectively]. The mature oocyte rate is higher in study group (P = .036). No significant differences were detected in fertilization rate and cleavage rate between 2 groups. CC has a positive influence on cycle characteristics, but might be correlated with the impaired IVF outcomes (less oocytes retrieved and top quality embryos, lower oocyte retrieval rate) in obese PCOS patients undergoing IVF, when HMG and MPA are used simultaneously. PMID:28796038

The efficacy and adverse effects of in vitro fertilization and embryo transfer.

PubMed

Corabian, P; Hailey, D

1999-01-01

This paper examines the current status of in vitro fertilization and embryo transfer (IVF-ET) as a treatment for various types of infertility. We reviewed studies on the efficacy and safety of IVF-ET and intracytoplasmic sperm injection (ICSI) plus IVF-ET, compared with conventional treatment or no treatment for various infertility diagnoses. Material retrieved included English language publications between 1992 and January 1997 that reported the results of prospective controlled clinical trials, cohort studies, and retrospective comparative studies with large series, and reviews presenting risks, complications, and longer-term health consequences associated with IVF-ET and ICSI. No adequate prospective comparative studies of sufficient power on the use of IVF-ET for specific infertility diagnoses have been reported to date. Most of the published reports concerning results with IVF-ET as a treatment of infertility have been based upon small, uncontrolled studies, with various methodological weaknesses. Reported results are not directly comparable. There are few follow-up data on outcomes after pregnancy is established or on long-term health consequences of the use of IVF-ET on mothers and their babies. IVF-ET has diffused widely without comprehensive assessment of its efficacy and safety. The available evidence supports its use only for severe bilateral tubal occlusion. For other diagnoses of infertility the evidence is limited and does not establish whether IVF-ET is effective. Long-term, well-designed, prospective clinical trials are required to determine when and for what indications IVF-ET is effective and what its health effects are on both mothers and their babies.

Soy Intake Modifies the Relation Between Urinary Bisphenol A Concentrations and Pregnancy Outcomes Among Women Undergoing Assisted Reproduction

PubMed Central

Mínguez-Alarcón, Lidia; Chiu, Yu-Han; Gaskins, Audrey J.; Souter, Irene; Williams, Paige L.; Calafat, Antonia M.; Hauser, Russ

2016-01-01

Context: Experimental data in rodents suggest that the adverse reproductive health effects of bisphenol A (BPA) can be modified by intake of soy phytoestrogens. Whether the same is true in humans is not known. Objective: The purpose of this study was to evaluate whether soy consumption modifies the relation between urinary BPA levels and infertility treatment outcomes among women undergoing assisted reproduction. Setting: The study was conducted in a fertility center in a teaching hospital. Design: We evaluated 239 women enrolled between 2007 and 2012 in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study, who underwent 347 in vitro fertilization (IVF) cycles. Participants completed a baseline questionnaire and provided up to 2 urine samples in each treatment cycle before oocyte retrieval. IVF outcomes were abstracted from electronic medical records. We used generalized linear mixed models with interaction terms to evaluate whether the association between urinary BPA concentrations and IVF outcomes was modified by soy intake. Main Outcome Measure: Live birth rates per initiated treatment cycle were measured. Results: Soy food consumption modified the association of urinary BPA concentration with live birth rates (P for interaction = .01). Among women who did not consume soy foods, the adjusted live birth rates per initiated cycle in increasing quartiles of cycle-specific urinary BPA concentrations were 54%, 35%, 31%, and 17% (P for trend = .03). The corresponding live birth rates among women reporting pretreatment consumption of soy foods were 38%, 42%, 47%, and 49% (P for trend = 0.35). A similar pattern was found for implantation (P for interaction = .02) and clinical pregnancy rates (P for interaction = .03) per initiated cycle, where urinary BPA was inversely related to these outcomes among women not consuming soy foods but unrelated to them among soy consumers. Conclusion: Soy food intake may protect against the adverse reproductive effects of BPA. As these findings represent the first report suggesting a potential interaction between soy and BPA in humans, they should be further evaluated in other populations. PMID:26815879

Effects of multiple inherited and acquired thrombophilia on outcomes of in-vitro fertilization.

PubMed

Di Nisio, Marcello; Ponzano, Adalisa; Tiboni, Gianmario; Guglielmi, Maria Domenica; Rutjes, Anne Wilhelmina Saskia; Porreca, Ettore

2018-05-09

The effects of multiple inherited and acquired thrombophilic defects on the outcome of in-vitro fertilization (IVF) remain unexplored. The aim of this study was to evaluate the association between multiple thrombophilia and clinical outcomes in a large prospective cohort of women undergoing IVF. Consecutive women scheduled for IVF were eligible. The primary study outcome was live birth. Secondary outcomes included spontaneous abortion, clinical pregnancy, and symptomatic venous thromboembolism. 687 women with a mean age of 34.6 (±3.2) years were included. Overall, 22 women (3.2%) had two or more thrombophilic defects. The probability of live birth was not statistically significantly different between women with ≥2 thrombophilia (odds ratio [OR] 0.62; 95% confidence interval [CI], 0.18 to 2.11) or ≥1 thrombophilia (OR 0.67;95% CI, 0.41 to 1.09) and women without any thrombophilia. None of the individual inherited thrombophilia nor positivity to antiphospholipid antibodies or lupus anticoagulant were associated with live birth. Single positivity for lupus anticoagulant carried a more than threefold higher risk of abortion (OR 3.74; 95% CI, 1.30 to 10.75). There were no statistically significant associations between individual or multiple thrombophilic defects and clinical pregnancy or pregnancy test results. No woman had a history of venous thromboembolism and none developed a thrombotic event during the study. In women undergoing IVF, the presence of two or more thrombophilic defects was rare and showed no statistically significant associations with IVF outcomes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Tax credits, insurance, and in vitro fertilization in the U.S. military health care system.

PubMed

Wu, Mae; Henne, Melinda; Propst, Anthony

2012-06-01

The FAMILY Act, an income tax credit for infertility treatments, was introduced into the U.S. Senate on May 12, 2011. We estimated the costs and utilization of in vitro fertilization (IVF) in the military if infertility treatment became a tax credit or TRICARE benefit. We surveyed 7 military treatment facilities (MTFs) that offer IVF, with a 100% response rate. We first modeled the impact of the FAMILY Act on the MTFs. We then assessed the impact and costs of a TRICARE benefit for IVF. In 2009, MTFs performed 810 IVF cycles with average patient charges of $4961 and estimated pharmacy costs of $2K per cycle. With implementation of the FAMILY Act, we estimate an increase in IVF demand at the MTFs to 1165 annual cycles. With a TRICARE benefit, estimated demand would increase to 6,924 annual IVF cycles. MTF pharmacy costs would increase to $7.3 annually. TRICARE medical and pharmacy costs would exceed $24.4 million and $6.5 million, respectively. In conclusion, if the FAMILY Act becomes law, demand for IVF at MTFs will increase 29%, with a 50% decrease in patient medical expenses after tax credits. MTF pharmacy costs will rise, and additional staffing will be required to meet the demand. If IVF becomes a TRICARE benefit, demand for IVF will increase at least 2-fold. Current MTFs would be unable to absorb the increased demand, leading to increased TRICARE treatment costs at civilian centers.

IVF twins: buy one get one free?

PubMed

Ismail, Laura; Mittal, Monica; Kalu, Emmanuel

2012-10-01

There has been an overall increase in the incidence of multiple pregnancies and assisted reproduction technology is largely responsible for this rise. Although twins may appeal to couples undergoing in vitro fertilisation (IVF), they have been associated with serious health consequences to the babies, their mothers and the family unit, as well as having massive financial implications for the National Health Service. Transfer of more than one embryo during IVF is mainly responsible for IVF twins, and elective transfer of a single embryo at a time with cryopreservation of surplus embryos for later transfer has been shown to be an effective strategy to minimise the risk of twins without compromising IVF success rates. Factors that will impact on the success of the policy of elective single embryo transfer (eSET) include improvement in embryo selection for transfer, better cryopreservation techniques and adequate state funding for IVF. However, in implementing the policy of eSET it is important that each case is assessed on an individual basis since in some situations (e.g. in older women) the transfer of two embryos may be more cost effective. Adequate and continuous education of all stakeholders is essential if the policy of eSET is to be successful in the UK.

A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.

PubMed

Youssef, M A; van Wely, M; Al-Inany, H; Madani, T; Jahangiri, N; Khodabakhshi, S; Alhalabi, M; Akhondi, M; Ansaripour, S; Tokhmechy, R; Zarandi, L; Rizk, A; El-Mohamedy, M; Shaeer, E; Khattab, M; Mochtar, M H; van der Veen, F

2017-01-01

In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. Ongoing pregnancy rate was 12.8% (25/195) for mild ovarian stimulation versus 13.6% (27/199) for conventional ovarian stimulation leading to a risk ratio of 0.95 (95% CI: 0.57-1.57), representing an absolute difference of -0.7% (95% CI: -7.4 to 5.9). This 95% CI does not extend below the predefined threshold of 10% for inferiority. The duration of ovarian stimulation was significantly lower in the mild ovarian stimulation strategy than in the conventional ovarian stimulation strategy (mean difference -1.2 days, 95% CI: -1.88 to -0.62). Also, a significantly lower amount of gonadotropins was used in the mild simulation strategy, with a mean difference of 3135 IU (95% CI: -3331 to -2940). A limitation of our study was the lack of data concerning the cryopreservation of surplus embryos, so we are not informed on cumulative pregnancy rates. Another limitation is that we were not able to follow up on the ongoing pregnancies in all centers, so we are not informed on live birth rates. The results are directly applicable in daily clinical practice and may lead to considerable cost savings as high dosages of gonadotropins are not necessary in women with poor ovarian reserve undergoing IVF. A health economic analysis of our data planned to test the hypothesis that mild ovarian stimulation strategy is more cost-effective than the conventional ovarian stimulation strategy is underway. This study was supported by NUFFIC scholarship (the Netherlands) and STDF short-term fellowship (Egypt). NTR2788 (Trialregister.nl). 01 March 2011. May 2011. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Live-Birth Rate Associated With Repeat In Vitro Fertilization Treatment Cycles.

PubMed

Smith, Andrew D A C; Tilling, Kate; Nelson, Scott M; Lawlor, Debbie A

The likelihood of achieving a live birth with repeat in vitro fertilization (IVF) is unclear, yet treatment is commonly limited to 3 or 4 embryo transfers. To determine the live-birth rate per initiated ovarian stimulation IVF cycle and with repeated cycles. Prospective study of 156,947 UK women who received 257,398 IVF ovarian stimulation cycles between 2003 and 2010 and were followed up until June 2012. In vitro fertilization, with a cycle defined as an episode of ovarian stimulation and all subsequent separate fresh and frozen embryo transfers. Live-birth rate per IVF cycle and the cumulative live-birth rates across all cycles in all women and by age and treatment type. Optimal, prognosis-adjusted, and conservative cumulative live-birth rates were estimated, reflecting 0%, 30%, and 100%, respectively, of women who discontinued due to poor prognosis and having a live-birth rate of 0 had they continued. Among the 156,947 women, the median age at start of treatment was 35 years (interquartile range, 32-38; range, 18-55), and the median duration of infertility for all 257,398 cycles was 4 years (interquartile range, 2-6; range, <1-29). In all women, the live-birth rate for the first cycle was 29.5% (95% CI, 29.3%-29.7%). This remained above 20% up to and including the fourth cycle. The cumulative prognosis-adjusted live-birth rate across all cycles continued to increase up to the ninth cycle, with 65.3% (95% CI, 64.8%-65.8%) of women achieving a live birth by the sixth cycle. In women younger than 40 years using their own oocytes, the live-birth rate for the first cycle was 32.3% (95% CI, 32.0%-32.5%) and remained above 20% up to and including the fourth cycle. Six cycles achieved a cumulative prognosis-adjusted live-birth rate of 68.4% (95% CI, 67.8%-68.9%). For women aged 40 to 42 years, the live-birth rate for the first cycle was 12.3% (95% CI, 11.8%-12.8%), with 6 cycles achieving a cumulative prognosis-adjusted live-birth rate of 31.5% (95% CI, 29.7%-33.3%). For women older than 42 years, all rates within each cycle were less than 4%. No age differential was observed among women using donor oocytes. Rates were lower for women with untreated male partner-related infertility compared with those with any other cause, but treatment with either intracytoplasmic sperm injection or sperm donation removed this difference. Among women in the United Kingdom undergoing IVF, the cumulative prognosis-adjusted live-birth rate after 6 cycles was 65.3%, with variations by age and treatment type. These findings support the efficacy of extending the number of IVF cycles beyond 3 or 4.

Highly purified human-derived follicle-stimulating hormone (Bravelle®) has equivalent efficacy to follitropin-beta (Follistim ®) in infertile women undergoing in vitro fertilization

PubMed Central

Dickey, Richard P; Nichols, John E; Steinkampf, Michael P; Gocial, Benjamin; Thornton, Melvin; Webster, Bobby W; Bello, Sandra M; Crain, Jack; Marshall, Dennis C

2003-01-01

Background These data compare the efficacy and safety of highly purified human-derived follicle-stimulating hormone (Bravelle(R)) and recombinant follitropin-β (Follistim(R)) in women undergoing in vitro fertilization. Methods This report describes the pooled data from two, nearly identical, randomized, controlled, parallel-group, multicenter studies conducted in a total of 19 academic and private IVF-ET centers in the United States. Infertile premenopausal women underwent pituitary down-regulation using leuprolide acetate followed by a maximum of 12 days of subcutaneous Bravelle(R) (n = 120) or Follistim(R) (n = 118), followed by administration of human chorionic gonadotropin, oocyte retrieval and embryo transfer. The primary efficacy measure was the mean number of oocytes retrieved; secondary efficacy measures included the total dose and duration of gonadotropin treatment; peak serum estradion levels; embryo transfer and implantation rates; chemical, clinical and continuing pregnancies; and live birth rates. All adverse events were recorded and injection site pain was recorded daily using a patient, self-assessment diary. Results Similar efficacy responses were observed for all outcome parameters in the two treatment groups. Although patients receiving Bravelle(R) consistently reported a greater number of chemical, clinical and continuing pregnancies, as well as an increased rate of live birth, the data did not attain statistical significance (P > 0.05). The overall incidence of adverse events was similar in both groups, but compared to Follistim(R), injections of Bravelle(R) were reported by patients to be significantly less painful (P < 0.001). Conclusions Bravelle(R) and Follistim(R) had comparable efficacy in controlled ovarian hyperstimulation in women undergoing IVF-ET. There were no differences in the nature or number of adverse events between the treatment groups although Bravelle(R) injections were reported to be significantly less painful. PMID:14609434

Toward optimal set of single nucleotide polymorphism investigation before IVF.

PubMed

Ivanov, A V; Dedul, A G; Fedotov, Y N; Komlichenko, E V

2016-10-01

At present, the patient preparation for IVF needs to undergo a series of planned tests, including the genotyping of single nucleotide polymorphism (SNP) alleles of some genes. In former USSR countries, such investigation was not included in overwhelming majority of health insurance programs and paid by patient. In common, there are prerequisites to the study of more than 50 polymorphisms. An important faced task is to determine the optimal panel for SNP genotyping in terms of price/number of SNP. During 2009-2015 in the University Hospital of St. Petersburg State University, blood samples were analyzed from 550 women with different reproductive system disorders preparing for IVF and 46 healthy women in control group. In total, 28 SNP were analyzed in the genes of thrombophilia factors, folic acid cycle, detoxification system, and the renin-angiotensin system. The method used was real-time PCR. A significant increase in the frequency of pathological alleles of some polymorphisms in patients with habitual failure of IVF was shown, compared with the control group. As a result, two options defined panels for optimal typing SNP before IVF were composed. Standard panel includes 8 SNP, 5 in thromborhilic factors, and 3 in folic acid cycle genes. They are 20210 G > A of FII gene, R506Q G > A of FV gene (mutation Leiden), -675 5G > 4G of PAI-I gene, L33P T > C of ITGB3 gene, -455 G > A of FGB gene, 667 C > T of MTHFR gene, 2756 A > G of MTR gene, and 66 A > G of MTRR gene. Extended panel of 15 SNP also includes 807 C > T of ITGA2 gene, T154M C > T of GP1BA gene, second polymorphism 1298 A > C in MTHFR gene, polymorphisms of the renin-angiotensin gene AGT M235T T > C and -1166 A > C of AGTR1 gene, polymorphisms I105V A > G and A114V C > T of detoxification system gene GSTP. The results of SNP genotyping can be adjusted for treatment tactics and IVF, and also medical support getting pregnant. The success rate of IVF is increased as the result, especially in the group with the usual failure of IVF.

Suppression of LH during ovarian stimulation: analysing threshold values and effects on ovarian response and the outcome of assisted reproduction in down-regulated women stimulated with recombinant FSH.

PubMed

Balasch, J; Vidal, E; Peñarrubia, J; Casamitjana, R; Carmona, F; Creus, M; Fábregues, F; Vanrell, J A

2001-08-01

It has been recently suggested that gonadotrophin-releasing hormone agonist down-regulation in some normogonadotrophic women may result in profound suppression of LH concentrations, impairing adequate oestradiol synthesis and IVF and pregnancy outcome. The aims of this study, where receiver-operating characteristic (ROC) analysis was used, were: (i) to assess the usefulness of serum LH measurement on stimulation day 7 (S7) as a predictor of ovarian response, IVF outcome, implantation, and the outcome of pregnancy in patients treated with recombinant FSH under pituitary suppression; and (ii) to define the best threshold value, if any, to discriminate between women with 'low' or 'normal' LH concentrations. A total of 144 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included. Seventy-two consecutive patients having a positive pregnancy test (including 58 ongoing pregnancies and 14 early pregnancy losses) were initially selected. As a control non-pregnant group, the next non-conception IVF/ICSI cycle after each conceptual cycle in our assisted reproduction programme was used. The median and range of LH values in non-conception cycles, conception cycles, ongoing pregnancies, and early pregnancy losses, clearly overlapped. ROC analysis showed that serum LH concentration on S7 was unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.52; 95% CI: 0.44 to 0.61) or ongoing pregnancy versus early pregnancy loss groups (AUC(ROC) = 0.59; 95% CI: 0.46 to 0.70). To assess further the potential impact of suppressed concentrations of circulating LH during ovarian stimulation on the outcome of IVF/ICSI treatment, the three threshold values of mid-follicular serum LH proposed in the literature (<1, < or =0.7, <0.5 IU/l) to discriminate between women with 'low' or 'normal' LH were applied to our study population. No significant differences were found with respect to ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy between 'low' and 'normal' S7 LH women as defined by those threshold values. Our results do not support the need for additional exogenous LH supplementation in down-regulated women receiving a recombinant FSH-only preparation.

Medium-based noninvasive preimplantation genetic diagnosis for human α-thalassemias-SEA.

PubMed

Wu, Haitao; Ding, Chenhui; Shen, Xiaoting; Wang, Jing; Li, Rong; Cai, Bing; Xu, Yanwen; Zhong, Yiping; Zhou, Canquan

2015-03-01

To develop a noninvasive medium-based preimplantation genetic diagnosis (PGD) test for α-thalassemias-SEA. The embryos of α-thalassemia-SEA carriers undergoing in vitro fertilization (IVF) were cultured. Single cells were biopsied from blastomeres and subjected to fluorescent gap polymerase chain reaction (PCR) analysis; the spent culture media that contained embryo genomic DNA and corresponding blastocysts as verification were subjected to quantitative-PCR (Q-PCR) detection of α-thalassemia-SEA. The diagnosis efficiency and allele dropout (ADO) ratio were calculated, and the cell-free DNA concentration was quantitatively assessed in the culture medium. The diagnosis efficiency of medium-based α-thalassemias-SEA detection significantly increased compared with that of biopsy-based fluorescent gap PCR analysis (88.6% vs 82.1%, P < 0.05). There is no significant difference regarding ADO ratio between them. The optimal time for medium-based α-thalassemias-SEA detection is Day 5 (D5) following IVF. Medium-based α-thalassemias-SEA detection could represent a novel, quick, and noninvasive approach for carriers to undergo IVF and PGD.

Survey of reasons for discontinuation from in vitro fertilization treatment among couples attending infertility clinic

PubMed Central

Kulkarni, Grishma; Mohanty, Nimain C.; Mohanty, Ipseeta Ray; Jadhav, Pradeep; Boricha, B. G.

2014-01-01

BACKGROUND: With the increase in infertility burden, more and more couples are opting for in vitro fertilization (IVF). Despite the availability of various treatment options, the major concern that needs to be addressed is the reasons why such couples, initially motivated so strongly, drop out in fairly high numbers from IVF cycles. With this point of view the study was designed. AIM: The objective of this study was to explore the reasons why couples discontinue fertility treatment. SETTINGS AND DESIGN: This retrospective study was carried out among couples in the age group of 20-40 years who opted for IVF at Tertiary care hospital and a private infertility center. MATERIALS AND METHODS: Medical records for 3 years (2009-2012) were taken out and included in the study for analysis. Socio-demographic details along with indication for IVF and reasons for drop-separate IVF therapy were recorded on case record form and were analyzed. RESULTS: Twenty-one percent of the patients had tubal pathology, thus making it the commonest female related factor for indication of IVF. Oligoasthenospermia (13%) was the commonest cause of male related infertility factor. Financial burden was the primary cause for terminating treatment in majority of the IVF cases. CONCLUSIONS: Financial burden (62.5%) was the commonest reason for drop out among couples from IVF cycle. PMID:25624660

In vitro fertilization (IVF) versus gonadotropins followed by IVF as treatment for primary infertility: a cost-based decision analysis.

PubMed

Kansal-Kalra, Suleena; Milad, Magdy P; Grobman, William A

2005-09-01

To compare the economic consequences of proceeding directly to IVF to those of proceeding with gonadotropins followed by IVF in patients <35 years of age with unexplained infertility. A decision-tree model. The model incorporated the cost and success of each infertility regimen as well as the pregnancy-associated costs of singleton or multiple gestations and the risk and cost of cerebral palsy. Cost per live birth. Both treatment arms resulted in a >80% chance of birth. The gonadotropin arm was over four times more likely to result in a high-order multiple pregnancy (HOMP). Despite this, when the base case estimates were utilized, immediate IVF emerged as more costly per live birth. In sensitivity analysis, immediate IVF became less costly per live birth when IVF was more likely to achieve birth (55.1%) or cheaper (11,432 dollars) than our base case assumptions. After considering the risk and cost of HOMP, immediate IVF is more costly per live birth than a trial of gonadotropins prior to IVF.

Comparison of clinical outcomes between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in IVF-ICSI split insemination cycles.

PubMed

Lee, Sun Hee; Lee, Jae Hyun; Park, Yong-Seog; Yang, Kwang Moon; Lim, Chun Kyu

2017-06-01

This study aimed to compare the clinical outcomes between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in sibling oocytes. Additionally, we evaluated whether the implementation of split insemination contributed to an increase in the number of ICSI procedures. A total of 571 cycles in 555 couples undergoing split insemination cycles were included in this study. Among them, 512 cycles (89.7%) were a couple's first IVF cycle. The patients were under 40 years of age and at least 10 oocytes were retrieved in all cycles. Sibling oocytes were randomly allocated to IVF or ICSI. Total fertilization failure was significantly more common in IVF cycles than in ICSI cycles (4.0% vs. 1.4%, p <0.05), but the low fertilization rate among retrieved oocytes (as defined by fertilization rates greater than 0% but <30%) was significantly higher in ICSI cycles than in IVF cycles (17.2% vs. 11.4%, p <0.05). The fertilization rate of ICSI among injected oocytes was significantly higher than for IVF (72.3%±24.3% vs. 59.2%±25.9%, p <0.001), but the fertilization rate among retrieved oocytes was significantly higher in IVF than in ICSI (59.2%±25.9% vs. 52.1%±22.5%, p <0.001). Embryo quality before embryo transfer was not different between IVF and ICSI. Although the sperm parameters were not different between the first cycle and the second cycle, split insemination or ICSI was performed in 18 of the 95 cycles in which a second IVF cycle was performed. The clinical outcomes did not differ between IVF and ICSI in split insemination cycles. Split insemination can decrease the risk of total fertilization failure. However, unnecessary ICSI is carried out in most split insemination cycles and the use of split insemination might make ICSI more common.

Comparison of clinical outcomes between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in IVF-ICSI split insemination cycles

PubMed Central

Lee, Sun Hee; Lee, Jae Hyun; Park, Yong-Seog; Yang, Kwang Moon

2017-01-01

Objective This study aimed to compare the clinical outcomes between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in sibling oocytes. Additionally, we evaluated whether the implementation of split insemination contributed to an increase in the number of ICSI procedures. Methods A total of 571 cycles in 555 couples undergoing split insemination cycles were included in this study. Among them, 512 cycles (89.7%) were a couple's first IVF cycle. The patients were under 40 years of age and at least 10 oocytes were retrieved in all cycles. Sibling oocytes were randomly allocated to IVF or ICSI. Results Total fertilization failure was significantly more common in IVF cycles than in ICSI cycles (4.0% vs. 1.4%, p<0.05), but the low fertilization rate among retrieved oocytes (as defined by fertilization rates greater than 0% but <30%) was significantly higher in ICSI cycles than in IVF cycles (17.2% vs. 11.4%, p<0.05). The fertilization rate of ICSI among injected oocytes was significantly higher than for IVF (72.3%±24.3% vs. 59.2%±25.9%, p<0.001), but the fertilization rate among retrieved oocytes was significantly higher in IVF than in ICSI (59.2%±25.9% vs. 52.1%±22.5%, p<0.001). Embryo quality before embryo transfer was not different between IVF and ICSI. Although the sperm parameters were not different between the first cycle and the second cycle, split insemination or ICSI was performed in 18 of the 95 cycles in which a second IVF cycle was performed. Conclusion The clinical outcomes did not differ between IVF and ICSI in split insemination cycles. Split insemination can decrease the risk of total fertilization failure. However, unnecessary ICSI is carried out in most split insemination cycles and the use of split insemination might make ICSI more common. PMID:28795049

Variability in in vitro fertilization outcomes of prepubertal goat oocytes explained by basic semen analyses.

PubMed

Palomo, M J; Quintanilla, R; Izquierdo, M D; Mogas, T; Paramio, M T

2016-12-01

This work analyses the changes that caprine spermatozoa undergo during in vitro fertilization (IVF) of in vitro matured prepubertal goat oocytes and their relationship with IVF outcome, in order to obtain an effective model that allows prediction of in vitro fertility on the basis of semen assessment. The evolution of several sperm parameters (motility, viability and acrosomal integrity) during IVF and their relationship with three IVF outcome criteria (total penetration, normal penetration and cleavage rates) were studied in a total of 56 IVF replicates. Moderate correlation coefficients between some sperm parameters and IVF outcome were observed. In addition, stepwise multiple regression analyses were conducted that considered three grouping of sperm parameters as potential explanatory variables of the three IVF outcome criteria. The proportion of IVF outcome variation that can be explained by the fitted models ranged from 0.62 to 0.86, depending upon the trait analysed and the variables considered. Seven out of 32 sperm parameters were selected as partial covariates in at least one of the nine multiple regression models. Among these, progressive sperm motility assessed immediately after swim-up, the percentage of dead sperm with intact acrosome and the incidence of acrosome reaction both determined just before the gamete co-culture, and finally the proportion of viable spermatozoa at 17 h post-insemination were the most frequently selected sperm parameters. Nevertheless, the predictive ability of these models must be confirmed in a larger sample size experiment.

A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome

PubMed Central

Simon, Luke; Zini, Armand; Dyachenko, Alina; Ciampi, Antonio; Carrell, Douglas T

2017-01-01

Sperm DNA damage is prevalent among infertile men and is known to influence natural reproduction. However, the impact of sperm DNA damage on assisted reproduction outcomes remains controversial. Here, we conducted a meta-analysis of studies on sperm DNA damage (assessed by SCSA, TUNEL, SCD, or Comet assay) and clinical pregnancy after IVF and/or ICSI treatment from MEDLINE, EMBASE, and PUBMED database searches for this analysis. We identified 41 articles (with a total of 56 studies) including 16 IVF studies, 24 ICSI studies, and 16 mixed (IVF + ICSI) studies. These studies measured DNA damage (by one of four assays: 23 SCSA, 18 TUNEL, 8 SCD, and 7 Comet) and included a total of 8068 treatment cycles (3734 IVF, 2282 ICSI, and 2052 mixed IVF + ICSI). The combined OR of 1.68 (95% CI: 1.49–1.89; P < 0.0001) indicates that sperm DNA damage affects clinical pregnancy following IVF and/or ICSI treatment. In addition, the combined OR estimates of IVF (16 estimates, OR = 1.65; 95% CI: 1.34–2.04; P < 0.0001), ICSI (24 estimates, OR = 1.31; 95% CI: 1.08–1.59; P = 0.0068), and mixed IVF + ICSI studies (16 estimates, OR = 2.37; 95% CI: 1.89–2.97; P < 0.0001) were also statistically significant. There is sufficient evidence in the existing literature suggesting that sperm DNA damage has a negative effect on clinical pregnancy following IVF and/or ICSI treatment. PMID:27345006

[Comparision of in vitro maturation applied in PCOS and non-PCOS patients undergo stimulated and unstimulated protocols].

PubMed

Wang, Peiyu; Zhao, Junzhao; Jin, Congcong; Yu, Rong; Lin, Jia; Zhu, Ruru; Wu, Yonggen

2014-12-01

To compare the laboratory and clinical results between unstimulated in vitro maturation (IVM) and IVM converted from in vitro fertilization (IVF) in polycystic ovarian syndrome (PCOS) and non-PCOS patients. We divided 591 IVM cycles in the First Affiliated Hospital of Wenzhou Medical Univesity from Jan. 2008 to Dec. 2013 into 4 groups: group A1B1, PCOS patients underwent unstimulated IVM protocol, 240 cycles; group A1B2, PCOS patients underwent IVM converted from conventional stimulated IVF protocol, 153 cycles; group A2B1, non-PCOS patients underwent unstimutlated IVM protocol, 103 cycles; group A2B2, non-PCOS patient underwent IVM converted from conventional stimulated IVF protocol, 95 cycles. Multiple linear regression method and binary logistic regression method were used to assess the influence of PCOS and protocols for IVM on laboratory and clinical outcomes. The mean number of oocytes retrieved was positively related with PCOS [partial regression coefficient (B) = 3.37, P < 0.01]. The maturation rate of oocytes was positively related with hCG-prime prior to oocyte aspiration (B = 0.05, P = 0.010). High-quality embryo rate was positively related with PCOS and IVM converted from IVF (B = 0.08, P = 0.010; B = 0.09, P = 0.001), as well as implantation rate related with them (B = 0.07, P = 0.010; B = 0.10, P < 0.01). PCOS and IVM converted from IVF improved hCG positive (hCG>10 U/L) rate (OR = 1.636, 95%CI: 1.113-2.204, P < 0.05; OR = 1.861, 95%CI: 1.307-2.649, P < 0.05) and the clinical pregnancy rate (OR = 1.507, 95%CI: 1.041-2.240, P < 0.05; OR = 1.881, 95%CI: 1.312-2.696, P < 0.05). IVM converted from IVF protocol decreased the spontaneous abortion rate (OR = 0.490, 95%CI: 0.245-0.978, P < 0.05). Multiple gestation rate and ectopic pregnancy rate were not affected by PCOS condition and protocol used (P > 0.05). PCOS and IVM converted from IVF protocol improved the high-quality embryo rate, implantation rate, hCG positive rate and clinical pregnancy rate. IVM converted from IVF protocol reduced the spontaneous abortion rate. PCOS patients may be more suitable for the IVM treatment. No matter PCOS or non-PCOS patients, IVM converted from IVF protocol had better pregnancy outcome than that of unstimulated cycle.

Cost-saving treatment strategies in in vitro fertilization: a combined economic evaluation of two large randomized clinical trials comparing highly purified human menopausal gonadotropin and recombinant follicle-stimulating hormone alpha.

PubMed

Wechowski, Jaroslaw; Connolly, Mark; Schneider, Dirk; McEwan, Philip; Kennedy, Richard

2009-04-01

To assess the cost-effectiveness of two gonadotropin treatments that are available in the United Kingdom in light of limited public funding and the fundamental role of costs in IVF treatment decisions. An economic evaluation based on two large randomized clinical trials in IVF patients using a simulation model. Fifty-three fertility clinics in 13 European countries and Israel. Women indicated for treatment with IVF (N = 986), aged 18-38, participating in double-blind, randomized controlled trials. Highly purified menotropin (HP-hMG, Menopur) or recombinant follitropin alpha (rFSH, Gonal-F). Cost per IVF cycle and cost per live birth for HP-hMG and rFSH alpha. HP-hMG was more effective and less costly versus rFSH for both IVF cost per live birth and for IVF cost per baby (incremental cost-effectiveness ratio was negative). The mean costs per IVF treatment for HP-hMG and rFSH were 2408 pounds (95% confidence interval [CI], 2392 pounds, 2421 pounds) and 2660 pounds (95% CI 2644 pounds, 2678 pounds), respectively. The mean cost saving of 253 pounds per cycle using HP-hMG allows one additional cycle to be delivered for every 9.5 cycles. Treatment with HP-hMG was dominant compared with rFSH in the United Kingdom. Gonadotropin costs should be considered alongside live-birth rates to optimize outcomes using scarce health-care resources.

Multiple thrombophilic single nucleotide polymorphisms lack a significant effect on outcomes in fresh IVF cycles: an analysis of 1717 patients.

PubMed

Patounakis, George; Bergh, Eric; Forman, Eric J; Tao, Xin; Lonczak, Agnieszka; Franasiak, Jason M; Treff, Nathan; Scott, Richard T

2016-01-01

The aim of the study is to determine if thrombophilic single nucleotide polymorphisms (SNPs) affect outcomes in fresh in vitro fertilization (IVF) cycles in a large general infertility population. A prospective cohort analysis was performed at a university-affiliated private IVF center of female patients undergoing fresh non-donor IVF cycles. The effect of the following thrombophilic SNPs on IVF outcomes were explored: factor V (Leiden and H1299R), prothrombin (G20210A), factor XIII (V34L), β-fibrinogen (-455G → A), plasminogen activator inhibitor-1 (4G/5G), human platelet antigen-1 (a/b9L33P), and methylenetetrahydrofolate reductase (C677T and A1298C). The main outcome measures included positive pregnancy test, clinical pregnancy, embryo implantation, live birth, and pregnancy loss. Patients (1717) were enrolled in the study, and a total of 4169 embryos were transferred. There were no statistically significant differences in positive pregnancy test, clinical pregnancy, embryo implantation, live birth, or pregnancy loss in the analysis of 1717 patients attempting their first cycle of IVF. Receiver operator characteristics and logistic regression analyses showed that outcomes cannot be predicted by the cumulative number of thrombophilic mutations present in the patient. Individual and cumulative thrombophilic SNPs do not affect IVF outcomes. Therefore, initial screening for these SNPs is not indicated.

Increased circulating cell-derived microparticle count is associated with recurrent implantation failure after IVF and embryo transfer.

PubMed

Martínez-Zamora, M Angeles; Tàssies, Dolors; Reverter, Juan Carlos; Creus, Montserrat; Casals, Gemma; Cívico, Salvadora; Carmona, Francisco; Balasch, Juan

2016-08-01

Cell-derived microparticles (cMPs) are small membrane vesicles that are released from many different cell types in response to cellular activation or apoptosis. Elevated cMP counts have been found in almost all thrombotic diseases and pregnancy wastage, such as recurrent spontaneous abortion and in a number of conditions associated with inflammation, cellular activation and angiogenesis. cMP count was investigated in patients experiencing unexplained recurrent implantation failure (RIF). The study group was composed of 30 women diagnosed with RIF (RIF group). The first control group (IVF group) (n = 30) comprised patients undergoing a first successful IVF cycle. The second control group (FER group) included 30 healthy women who had at least one child born at term and no history of infertility or obstetric complications. cMP count was significantly higher in the RIF group compared with the IVF and FER groups (P < 0.05 and P < 0.01, respectively) (RIF group: 15.8 ± 6.2 nM phosphatidylserine equivalent [PS eq]; IVF group: 10.9 ± 5.3 nM PS eq; FER group: 9.6 ± 4.0 nM PS eq). No statistical difference was found in cMP count between the IVF and FER groups. Increased cMP count is, therefore, associated with RIF after IVF and embryo transfer. Copyright © 2016. Published by Elsevier Ltd.

Variation of DNA Fragmentation Levels During Density Gradient Sperm Selection for Assisted Reproduction Techniques

PubMed Central

Muratori, Monica; Tarozzi, Nicoletta; Cambi, Marta; Boni, Luca; Iorio, Anna Lisa; Passaro, Claudia; Luppino, Benedetta; Nadalini, Marco; Marchiani, Sara; Tamburrino, Lara; Forti, Gianni; Maggi, Mario; Baldi, Elisabetta; Borini, Andrea

2016-01-01

Abstract Predicting the outcome of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) is one main goal of the present research on assisted reproduction. To understand whether density gradient centrifugation (DGC), used to select sperm, can affect sperm DNA integrity and impact pregnancy rate (PR), we prospectively evaluated sperm DNA fragmentation (sDF) by TUNEL/PI, before and after DGC. sDF was studied in a cohort of 90 infertile couples the same day of IVF/ICSI treatment. After DGC, sDF increased in 41 samples (Group A, median sDF value: 29.25% [interquartile range, IQR: 16.01–41.63] in pre- and 60.40% [IQR: 32.92–93.53] in post-DGC) and decreased in 49 (Group B, median sDF value: 18.84% [IQR: 13.70–35.47] in pre- and 8.98% [IQR: 6.24–15.58] in post-DGC). PR was 17.1% and 34.4% in Group A and B, respectively (odds ratio [OR]: 2.58, 95% confidence interval [CI]: 0.95–7.04, P = 0.056). After adjustment for female factor, female and male age and female BMI, the estimated OR increased to 3.12 (95% CI: 1.05–9.27, P = 0.041). According to the subgroup analysis for presence/absence of female factor, heterogeneity in the association between the Group A and B and PR emerged (OR: 4.22, 95% CI: 1.16–15.30 and OR: 1.53, 95% CI: 0.23–10.40, respectively, for couples without, n = 59, and with, n = 31, female factor). This study provides the first evidence that the DGC procedure produces an increase in sDF in about half of the subjects undergoing IVF/ICSI, who then show a much lower probability of pregnancy, raising concerns about the safety of this selection procedure. Evaluation of sDF before and after DGC configures as a possible new prognostic parameter of pregnancy outcome in IVF/ICSI. Alternative sperm selection strategies are recommended for those subjects who undergo the damage after DGC. PMID:27196465

Variation of DNA Fragmentation Levels During Density Gradient Sperm Selection for Assisted Reproduction Techniques: A Possible New Male Predictive Parameter of Pregnancy?

PubMed

Muratori, Monica; Tarozzi, Nicoletta; Cambi, Marta; Boni, Luca; Iorio, Anna Lisa; Passaro, Claudia; Luppino, Benedetta; Nadalini, Marco; Marchiani, Sara; Tamburrino, Lara; Forti, Gianni; Maggi, Mario; Baldi, Elisabetta; Borini, Andrea

2016-05-01

Predicting the outcome of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) is one main goal of the present research on assisted reproduction. To understand whether density gradient centrifugation (DGC), used to select sperm, can affect sperm DNA integrity and impact pregnancy rate (PR), we prospectively evaluated sperm DNA fragmentation (sDF) by TUNEL/PI, before and after DGC. sDF was studied in a cohort of 90 infertile couples the same day of IVF/ICSI treatment. After DGC, sDF increased in 41 samples (Group A, median sDF value: 29.25% [interquartile range, IQR: 16.01-41.63] in pre- and 60.40% [IQR: 32.92-93.53] in post-DGC) and decreased in 49 (Group B, median sDF value: 18.84% [IQR: 13.70-35.47] in pre- and 8.98% [IQR: 6.24-15.58] in post-DGC). PR was 17.1% and 34.4% in Group A and B, respectively (odds ratio [OR]: 2.58, 95% confidence interval [CI]: 0.95-7.04, P = 0.056). After adjustment for female factor, female and male age and female BMI, the estimated OR increased to 3.12 (95% CI: 1.05-9.27, P = 0.041). According to the subgroup analysis for presence/absence of female factor, heterogeneity in the association between the Group A and B and PR emerged (OR: 4.22, 95% CI: 1.16-15.30 and OR: 1.53, 95% CI: 0.23-10.40, respectively, for couples without, n = 59, and with, n = 31, female factor).This study provides the first evidence that the DGC procedure produces an increase in sDF in about half of the subjects undergoing IVF/ICSI, who then show a much lower probability of pregnancy, raising concerns about the safety of this selection procedure. Evaluation of sDF before and after DGC configures as a possible new prognostic parameter of pregnancy outcome in IVF/ICSI. Alternative sperm selection strategies are recommended for those subjects who undergo the damage after DGC.

Increased risk of multiple sclerosis relapse after in vitro fertilisation.

PubMed

Michel, Laure; Foucher, Yohann; Vukusic, Sandra; Confavreux, Christian; de Sèze, Jérome; Brassat, David; Clanet, Michel; Clavelou, Pierre; Ouallet, Jean-Christophe; Brochet, Bruno; Pelletier, Jean; Labauge, Pierre; Lebrun, Christine; Lepage, Emmanuelle; Le Frere, Fabienne; Jacq-Foucher, Marylène; Barriere, Paul; Wiertlewski, Sandrine; Laplaud, David-Axel

2012-08-01

Exogenous sexual steroids together with pregnancy have been shown to influence the risk of relapses in multiple sclerosis (MS). Treatments used during assisted reproductive techniques may consequently influence the short term evolution of MS by modifying the hormonal status of the patient. The objective of this study was to determine if there was an increased risk of developing exacerbations in women with MS after in vitro fertilisation (IVF). MS and IVF data were either automatically extracted from 13 French university hospital databases or obtained from referring neurologists. After matching databases, patient clinical files were systematically reviewed to collect information about MS and the treatments used for IVF. The association between IVF and the occurrence of MS relapses was analysed in detail using univariate and multivariate statistical tests. During the 11 year study period, 32 women with MS had undergone 70 IVF treatments, 48 using gonadotrophin releasing hormone (GnRH) agonists and 19 using GnRH antagonists. A significant increase in the annualised relapse rate (ARR) was observed during the 3 month period following IVF (mean ARR 1.60, median ARR 0) compared with the same period just before IVF (mean ARR 0.80, median ARR 0) and to a control period 1 year before IVF (mean ARR 0.68, median ARR 0). The significant increase in relapses was associated with the use of GnRH agonists (Wilcoxon paired test, p=0.025) as well as IVF failure (Wilcoxon paired test, p=0.019). An increased relapse rate was observed in this study after IVF in patients with MS and may be partly related both to IVF failure and the use of GnRH agonists.

In Vitro Fertilization and Multiple Pregnancies

PubMed Central

2006-01-01

Executive Summary Objective The objective of this health technology policy assessment was to determine the clinical effectiveness and cost-effectiveness of IVF for infertility treatment, as well as the role of IVF in reducing the rate of multiple pregnancies. Clinical Need: Target Population and Condition Typically defined as a failure to conceive after a year of regular unprotected intercourse, infertility affects 8% to 16% of reproductive age couples. The condition can be caused by disruptions at various steps of the reproductive process. Major causes of infertility include abnormalities of sperm, tubal obstruction, endometriosis, ovulatory disorder, and idiopathic infertility. Depending on the cause and patient characteristics, management options range from pharmacologic treatment to more advanced techniques referred to as assisted reproductive technologies (ART). ART include IVF and IVF-related procedures such as intra-cytoplasmic sperm injection (ICSI) and, according to some definitions, intra-uterine insemination (IUI), also known as artificial insemination. Almost invariably, an initial step in ART is controlled ovarian stimulation (COS), which leads to a significantly higher rate of multiple pregnancies after ART compared with that following natural conception. Multiple pregnancies are associated with a broad range of negative consequences for both mother and fetuses. Maternal complications include increased risk of pregnancy-induced hypertension, pre-eclampsia, polyhydramnios, gestational diabetes, fetal malpresentation requiring Caesarean section, postpartum haemorrhage, and postpartum depression. Babies from multiple pregnancies are at a significantly higher risk of early death, prematurity, and low birth weight, as well as mental and physical disabilities related to prematurity. Increased maternal and fetal morbidity leads to higher perinatal and neonatal costs of multiple pregnancies, as well as subsequent lifelong costs due to disabilities and an increased need for medical and social support. The Technology Being Reviewed IVF was first developed as a method to overcome bilateral Fallopian tube obstruction. The procedure includes several steps: (1) the woman’s egg is retrieved from the ovaries; (2) exposed to sperm outside the body and fertilized; (3) the embryo(s) is cultured for 3 to 5 days; and (4) is transferred back to the uterus. IFV is considered to be one of the most effective treatments for infertility today. According to data from the Canadian Assisted Reproductive Technology Registry, the average live birth rate after IVF in Canada is around 30%, but there is considerable variation in the age of the mother and primary cause of infertility. An important advantage of IVF is that it allows for the control of the number of embryos transferred. An elective single embryo transfer in IVF cycles adopted in many European countries was shown to significantly reduce the risk of multiple pregnancies while maintaining acceptable birth rates. However, when number of embryos transferred is not limited, the rate of IVF-associated multiple pregnancies is similar to that of other treatments involving ovarian stimulation. The practice of multiple embryo transfer in IVF is often the result of pressures to increase success rates due to the high costs of the procedure. The average rate of multiple pregnancies resulting from IVF in Canada is currently around 30%. An alternative to IVF is IUI. In spite of reported lower success rates of IUI (pregnancy rates per cycle range from 8.7% to 17.1%) it is generally attempted before IVF due to its lower invasiveness and cost. Two major drawbacks of IUI are that it cannot be used in cases of bilateral tubal obstruction and it does not allow much control over the risk of multiple pregnancies compared with IVF. The rate of multiple pregnancies after IUI with COS is estimated to be about 21% to 29%. Ontario Health Insurance Plan Coverage Currently, the Ontario Health Insurance Plan covers the cost of IVF for women with bilaterally blocked Fallopian tubes only, in which case it is funded for 3 cycles, excluding the cost of drugs. The cost of IUI is covered except for preparation of the sperm and drugs used for COS. Diffusion of Technology According to Canadian Assisted Reproductive Technology Registry data, in 2004 there were 25 infertility clinics across Canada offering IVF and 7,619 IVF cycles performed. In Ontario, there are 13 infertility clinics with about 4,300 IVF cycles performed annually. Literature Review Royal Commission Report on Reproductive Technologies The 1993 release of the Royal Commission report on reproductive technologies, Proceed With Care, resulted in the withdrawal of most IVF funding in Ontario, where prior to 1994 IVF was fully funded. Recommendations of the Commission to withdraw IVF funding were largely based on findings of the systematic review of randomized controlled trials (RCTs) published before 1990. The review showed IVF effectiveness only in cases of bilateral tubal obstruction. As for nontubal causes of infertility, there was not enough evidence to establish whether IVF was effective or not. Since the field of reproductive technology is constantly evolving, there have been several changes since the publication of the Royal Commission report. These changes include: increased success rates of IVF; introduction of ICSI in the early 1990’s as a treatment for male factor infertility; and improved embryo implantation rates allowing for the transfer of a single embryo to avoid multiple pregnancies after IVF. Studies After the Royal Commission Report: Review Strategy Three separate literature reviews were conducted in the following areas: clinical effectiveness of IVF, cost-effectiveness of IVF, and outcomes of single embryo transfer (SET) in IVF cycles. Clinical effectiveness of IVF: RCTs or meta-analyses of RCTs that compared live birth rates after IVF versus alternative treatments, where the cause of infertility was clearly stated or it was possible to stratify the outcome by the cause of infertility. Cost effectiveness of IVF: All relevant economic studies comparing IVF to alternative methods of treatment were reviewed Outcomes of IVF with SET: RCTs or meta-analyses of RCTs that compared live birth rates and multiple birth rates associated with transfer of single versus double embryos. OVID MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Library, the International Agency for Health Technology Assessment database, and websites of other health technology assessment agencies were searched using specific subject headings and keywords to identify relevant studies. Summary of Findings Comparative Clinical Effectiveness of IVF Overall, there is a lack of well composed RCTs in this area and considerable diversity in both definition and measurement of outcomes exists between trials. Many studies used fertility or pregnancy rates instead of live birth rates. Moreover, the denominator for rate calculation varied from study to study (e.g. rates were calculated per cycle started, per cycle completed, per couple, etc...). Nevertheless, few studies of sufficient quality were identified and categorized by the cause of infertility and existing alternatives to IVF. The following are the key findings: A 2005 meta-analysis demonstrated that, in patients with idiopathic infertility, IVF was clearly superior to expectant management, but there were no statistically significant differences in live birth rates between IVF and IUI, nor between IVF and gamete-intra-Fallopian transfer. A subset of data from a 2000 study showed no significant differences in pregnancy rates between IVF and IUI for moderate male factor infertility. In patients with moderate male factor infertility, standard IVF was also compared with ICSI in a 2002 meta-analysis. All studies included in the meta-analysis showed superior fertilization rates with ICSI, and the pooled risk ratio for oocyte fertilization was 1.9 (95% Confidence Interval 1.4-2.5) in favour of ICSI. Two other RCTs in this area published after the 2002 meta-analysis had similar results and further confirmed these findings. There were no RCTs comparing IVF with ICSI in patients with severe male factor infertility, mainly because based on the expert opinion, ICSI might only be an effective treatment for severe male factor infertility. Cost-Effectiveness of IVF Five economic evaluations of IVF were found, including one comprehensive systematic review of 57 health economic studies. The studies compared cost-effectiveness of IVF with a number of alternatives such as observation, ovarian stimulation, IUI, tubal surgery, varicocelectomy, etc... The cost-effectiveness of IVF was analyzed separately for different types of infertility. Most of the reviewed studies concluded that due to the high cost, IVF has a less favourable cost-effectiveness profile compared with alternative treatment options. Therefore, IVF was not recommended as the first line of treatment in the majority of cases. The only two exceptions were bilateral tubal obstruction and severe male factor infertility, where an immediate offer of IVF/ICSI might the most cost-effective option. Clinical Outcomes After Single Versus Double Embryo Transfer Strategies of IVF Since the SET strategy has been more widely adopted in Europe, all RCT outcomes of SET were conducted in European countries. The major study in this area was a large 2005 meta-analysis, followed by two other published RCTs. All of these studies reached similar conclusions: Although a single SET cycle results in lower birth rates than a single double embryo transfer (DET) cycle, the cumulative birth rate after 2 cycles of SET (fresh + frozen-thawed embryos) was comparable to the birth rate after a single DET cycle (~40%). SET was associated with a significant reduction in multiple births compared with DET (0.8% vs. 33.1% respectively in the largest RCT). Most trials on SET included women younger than 36 years old with a sufficient number of embryos available for transfer that allowed for selection of the top quality embryo(s). A 2006 RCT, however, compared SET and DET strategies in an unselected group of patients without restrictions on the woman’s age or embryo quality. This study demonstrated that SET could be applied to older women. Estimate of the Target Population Based on results of the literature review and consultations with experts, four categories of infertile patients who may benefit from increased access to IVF/ICSI were identified: Patients with severe male factor infertility, where IVF should be offered in conjunction with ICSI; Infertile women with serious medical contraindications to multiple pregnancy, who should be offered IVF-SET; Infertile patients who want to avoid the risk of multiple pregnancy and thus opt for IVF-SET; and Patients who failed treatment with IUI and wish to try IVF. Since, however, the latter indication does not reflect any new advances in IVF technology that would alter existing policy, it was not considered in this analysis. Economic Analysis Economic Review: Cost–Effectiveness of SET Versus DET Conclusions of published studies on cost-effectiveness of SET versus DET were not consistent. While some studies found that SET strategy is more cost-effective due to avoidance of multiple pregnancies, other studies either did not find any significant differences in cost per birth between SET and DET, or favoured DET as a more cost-effective option. Ontario-Based Economic Analysis An Ontario-based economic analysis compared cost per birth using three treatment strategies: IUI, IVF-SET, and IVF-DET. A decision-tree model assumed three cycles for each treatment option. Two separate models were considered; the first included only fresh cycles of IVF, while the second had a combination of fresh and frozen cycles. Even after accounting for cost-savings due to avoidance of multiple pregnancies (only short-term complications), IVF-SET was still associated with a highest cost per birth. The approximate budget impact to cover the first three indications for IVF listed above (severe male factor infertility, women with medical contraindications to multiple pregnancy, and couples who wish to avoid the risk of multiple pregnancy) is estimated at $9.8 to $12.8 million (Cdn). Coverage of only first two indications, namely, ICSI in patients with severe male factor infertility and infertile women with serious medical contraindications to multiple pregnancy, is estimated at $3.8 to $5.5 million Cdn. Other Considerations International data shows that both IVF utilization and the average number of embryos transferred in IVF cycles are influenced by IVF funding policy. The success of the SET strategy in European countries is largely due to the fact that IVF treatment is subsidized by governments. Surveys of patients with infertility demonstrated that a significant proportion (~40%) of patients not only do not mind having multiple babies, but consider twins being an ideal outcome of infertility treatment. A women’s age may impose some restrictions on the implementation of a SET strategy. Conclusions and Recommendations A review of published studies has demonstrated that IVF-SET is an effective treatment for infertility that avoids multiple pregnancies. However, results of an Ontario-based economic analysis shows that cost savings associated with a reduction in multiple pregnancies after IVF-SET does not justify the cost of universal IVF-SET coverage by the province. Moreover, the province currently funds IUI, which has been shown to be as effective as IVF for certain types of infertility and is significantly less expensive. In patients with severe male factor infertility, IVF in conjunction with ICSI may be the only effective treatment. Thus, 2 indications where additional IVF access should be considered include: IVF/ICSI for patients with severe male factor infertility IVF-SET in infertile women with serious medical contraindications to multiple pregnancy PMID:23074488

Antral follicle counts are strongly associated with live-birth rates after assisted reproduction, with superior treatment outcome in women with polycystic ovaries.

PubMed

Holte, Jan; Brodin, Thomas; Berglund, Lars; Hadziosmanovic, Nermin; Olovsson, Matts; Bergh, Torbjörn

2011-09-01

To evaluate the association of antral follicle count (AFC) with in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) outcome in a large unselected cohort of patients covering the entire range of AFC. Prospective observational study. University-affiliated private infertility center. 2,092 women undergoing 4,308 IVF-ICSI cycles. AFC analyzed for associations with treatment outcome and statistically adjusted for repeated treatments and age. Pregnancy rate, live-birth rate, and stimulation outcome parameters. The AFC was log-normally distributed. Pregnancy rates and live-birth rates were positively associated with AFC in a log-linear way, leveling out above AFC ∼30. Treatment outcome was superior among women with polycystic ovaries, independent from ovulatory status. The findings were significant also after adjustment for age and number of oocytes retrieved. Pregnancy and live-birth rates are log-linearly related to AFC. Polycystic ovaries, most often excluded from studies on ovarian reserve, fit as one extreme in the spectrum of AFC; a low count constitutes the other extreme, with the lowest ovarian reserve and poor treatment outcome. The findings remained statistically significant also after adjustment for the number of oocytes retrieved, suggesting this measure of ovarian reserve comprises information on oocyte quality and not only quantity. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The diversity of regulation and public financing of IVF in Europe and its impact on utilization.

PubMed

Berg Brigham, K; Cadier, B; Chevreul, K

2013-03-01

How do the different forms of regulation and public financing of IVF affect utilization in otherwise similar European welfare state systems? Countries with more liberal social eligibility regulations had higher levels of IVF utilization, which diminished as the countries' policies became more restrictive. Europe is a world leader in the development and utilization of IVF, yet surveillance reveals significant differences in uptake among countries which have adopted different approaches to the regulation and and public financing of IVF. A descriptive and comparative analysis of legal restrictions on access to IVF in 13 of the EU15 countries that affirmatively regulate and publicly finance IVF. Using 2009 data from the European Society of Human Reproduction and Embryology study of regulatory frameworks in Europe and additional legislative research, we examined and described restrictions on access to IVF in terms of general eligibility, public financing and the scope of available services. Multiple correspondence analysis was used to identify patterns of regulation and groups of countries with similar regulatory patterns and to explore the effects on utilization of IVF, using data from the most recent European and international IVF monitoring reports. Regulations based on social characteristics of treatment seekers who are not applicable to other medical treatments, including relationship status and sexual orientation, appear to have the greatest impact on utilization. Countries with the most generous public financing schemes tend to restrict access to covered IVF to a greater degree. However, no link could be established between IVF utilization and the manner in which coverage was regulated or the level of public financing. Owing to the lack of data regarding the actual level of public versus private financing of IVF it is impossible to draw conclusions regarding equity of access. Moreover, the regulatory and utilization data were not completely temporally matched in what can be a quickly changing regulatory landscape. Whether motivated by cost, eligility restrictions or the availability of particular services, cross-border treatment seeking is driven by regulatory policies, underscoring the extra-territorial implications of in-country political decisions regarding access to IVF. There was no funding source for this study. The authors have no conflicts of interest to declare.

Can Women Have Children and a Career? IV Evidence from IVF Treatments.

PubMed

Lundborg, Petter; Plug, Erik; Rasmussen, Astrid Wurtz

2017-06-01

This paper introduces a new IV strategy based on IVF (in vitro fertilization) induced fertility variation among childless women to estimate the causal effect of having children on their career. For this purpose, we use administrative data on IVF treated women in Denmark. Because observed chances of IVF success do not depend on labor market histories, IVF treatment success provides a plausible instrument for childbearing. Our IV estimates indicate that fertility effects on earnings are: (i) negative, large, and long-lasting; (ii) driven by fertility effects on hourly earnings and not so much on labor supply; and (iii) much stronger at the extensive margin than at the intensive margin.

Effect of myo-inositol and alpha-lipoic acid on oocyte quality in polycystic ovary syndrome non-obese women undergoing in vitro fertilization: a pilot study.

PubMed

Rago, R; Marcucci, I; Leto, G; Caponecchia, L; Salacone, P; Bonanni, P; Fiori, C; Sorrenti, G; Sebastianelli, A

2015-01-01

The aim of the present study was to evaluate the effectiveness of the combined administration of myo-inositol and α-lipoic acid in polycystic ovary syndrome (PCOS) patients with normal body mass index (BMI), who had previously undergone intracytoplasmic sperm injection (ICSI) and received myo-inositol alone. Thirty-six of 65 normal-weight patients affected by PCOS who did not achieve pregnancy and one patient who had a spontaneous abortion were re-enrolled and given a cycle of treatment with myo-inositol and α-lipoic acid. For all female partners of the treated couples, the endocrine-metabolic and ultrasound parameters, ovarian volume, oocyte and embryo quality, and pregnancy rates were assessed before and after three months of treatment and compared with those of previous in vitro fertilization (IVF) cycle(s). After supplementation of myo-inositol with α-lipoic acid, insulin levels, BMI and ovarian volume were significantly reduced compared with myo-inositol alone. No differences were found in the fertilization and cleavage rate or in the mean number of transferred embryos between the two different treatments, whereas the number of grade 1 embryos was significantly increased, with a significant reduction in the number of grade 2 embryos treated with myo-inositol plus α-lipoic acid. Clinical pregnancy was not significantly different with a trend for a higher percentage for of myo-inositol and α-lipoic acid compared to the myo-inositol alone group. Our preliminary data suggest that the supplementation of myo-inositol and α-lipoic acid in PCOS patients undergoing an IVF cycle can help to improve their reproductive outcome and also their metabolic profiles, opening potential for their use in long-term prevention of PCOS.

Prediction of individual probabilities of livebirth and multiple birth events following in vitro fertilization (IVF): a new outcomes counselling tool for IVF providers and patients using HFEA metrics

PubMed Central

Jones, Christopher A.; Christensen, Anna L.; Salihu, Hamisu; Carpenter, William; Petrozzino, Jeffrey; Abrams, Elizabeth; Sills, Eric Scott; Keith, Louis G.

2011-01-01

In vitro fertilization (IVF) has become a standard treatment for subfertility after it was demonstrated to be of value to humans in 1978. However, the introduction of IVF into mainstream clinical practice has been accompanied by concerns regarding the number of multiple gestations that it can produce, as multiple births present significant medical consequences to mothers and offspring. When considering IVF as a treatment modality, a balance must be set between the chance of having a live birth and the risk of having a multiple birth. As IVF is often a costly decision for patients—financially, medically, and emotionally—there is benefit from estimating a patient’s specific chance that IVF could result in a birth as fertility treatment options are contemplated. Historically, a patient’s “chance of success” with IVF has been approximated from institution-based statistics, rather than on the basis of any particular clinical parameter (except age). Furthermore, the likelihood of IVF resulting in a twin or triplet outcome must be acknowledged for each patient, given the known increased complications of multiple gestation and consequent increased risk of poor birth outcomes. In this research, we describe a multivariate risk assessment model that incorporates metrics adapted from a national 7.5-year sampling of the Human Fertilisation & Embryology Authority (HFEA) dataset (1991–1998) to predict reproductive outcome (including estimation of multiple birth) after IVF. To our knowledge, http://www.formyodds.com is the first Software-as-a-Service (SaaS) application to predict IVF outcome. The approach also includes a confirmation functionality, where clinicians can agree or disagree with the computer-generated outcome predictions. It is anticipated that the emergence of predictive tools will augment the reproductive endocrinology consultation, improve the medical informed consent process by tailoring the outcome assessment to each patient, and reduce the potential for adverse outcomes with IVF. PMID:21991292

Prediction of individual probabilities of livebirth and multiple birth events following in vitro fertilization (IVF): a new outcomes counselling tool for IVF providers and patients using HFEA metrics.

PubMed

Jones, Christopher A; Christensen, Anna L; Salihu, Hamisu; Carpenter, William; Petrozzino, Jeffrey; Abrams, Elizabeth; Sills, Eric Scott; Keith, Louis G

2011-01-01

In vitro fertilization (IVF) has become a standard treatment for subfertility after it was demonstrated to be of value to humans in 1978. However, the introduction of IVF into mainstream clinical practice has been accompanied by concerns regarding the number of multiple gestations that it can produce, as multiple births present significant medical consequences to mothers and offspring. When considering IVF as a treatment modality, a balance must be set between the chance of having a live birth and the risk of having a multiple birth. As IVF is often a costly decision for patients-financially, medically, and emotionally-there is benefit from estimating a patient's specific chance that IVF could result in a birth as fertility treatment options are contemplated. Historically, a patient's "chance of success" with IVF has been approximated from institution-based statistics, rather than on the basis of any particular clinical parameter (except age). Furthermore, the likelihood of IVF resulting in a twin or triplet outcome must be acknowledged for each patient, given the known increased complications of multiple gestation and consequent increased risk of poor birth outcomes. In this research, we describe a multivariate risk assessment model that incorporates metrics adapted from a national 7.5-year sampling of the Human Fertilisation & Embryology Authority (HFEA) dataset (1991-1998) to predict reproductive outcome (including estimation of multiple birth) after IVF. To our knowledge, http://www.formyodds.com is the first Software-as-a-Service (SaaS) application to predict IVF outcome. The approach also includes a confirmation functionality, where clinicians can agree or disagree with the computer-generated outcome predictions. It is anticipated that the emergence of predictive tools will augment the reproductive endocrinology consultation, improve the medical informed consent process by tailoring the outcome assessment to each patient, and reduce the potential for adverse outcomes with IVF.

First line fertility treatment strategies regarding IUI and IVF require clinical evidence.

PubMed

Bahadur, G; Homburg, R; Muneer, A; Racich, P; Alangaden, T; Al-Habib, A; Okolo, S

2016-06-01

The advent of intracytoplasmic sperm injection (ICSI) has contributed to a significant growth in the delivery of assisted conception technique, such that IVF/ICSI procedures are now recommended over other interventions. Even the UK National Institute for Health Care Excellence (NICE) guidelines controversially recommends against intrauterine insemination (IUI) procedures in favour of IVF. We reflect on some of the clinical, economic, financial and ethical realities that have been used to selectively promote IVF over IUI, which is less intrusive and more patient friendly, obviates the need for embryo storage and has a global application. The evidence strongly favours IUI over IVF in selected couples and national funding strategies should include IUI treatment options. IUI, practised optimally as a first line treatment in up to six cycles, would also ease the pressures on public funds to allow the provision of up to three IVF cycles for couple who need it. Fertility clinics should also strive towards ISO15189 accreditation standards for basic semen diagnosis for male infertility used to triage ICSI treatment, to reduce the over-diagnosis of severe male factor infertility. Importantly, there is a need to develop global guidelines on inclusion policies for IVF/ICSI procedures. These suggestions are an ethically sound basis for constructing the provision of publicly funded fertility treatments. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The problem of IVF cost in developing countries: has natural cycle IVF a place?

PubMed

Shahin, Ahmed Y

2007-07-01

Infertility represents a national health problem in some African countries. Limited financial health resources in developing countries are a major obstacle facing infertility management. IVF is the definitive line of treatment for many couples. Stimulation cycles are associated with risks of ovarian hyperstimulation syndrome and multiple pregnancy. This study evaluates the client acceptability of stimulated versus natural cycle IVF among couples attending one infertility clinic, with respect to cost and pregnancy outcome. Of the patients who were indicated for IVF, 15% (16/107) cancelled, due mostly (12/16, 75%) to financial reasons. The majority of patients who completed their IVF treatment (82/91, 90.1%) felt the price of the medical service offered was high, and 68.1% (62/91) accepted the idea of having cheaper drugs with fewer side effects but with possibly lower chances of pregnancy. Natural cycle IVF has emerged as a potential option that might be suitable for patients worldwide, especially in developing countries.

Universal coverage of IVF pays off.

PubMed

Vélez, M P; Connolly, M P; Kadoch, I-J; Phillips, S; Bissonnette, F

2014-06-01

What was the clinical and economic impact of universal coverage of IVF in Quebec, Canada, during the first calendar year of implementation of the public IVF programme? Universal coverage of IVF increased access to IVF treatment, decreased the multiple pregnancy rate and decreased the cost per live birth, despite increased costs per cycle. Public funding of IVF assures equality of access to IVF and decreases multiple pregnancies resulting from this treatment. Public IVF programmes usually mandate a predominant SET policy, the most effective approach for reducing the incidence of multiple pregnancies. This prospective comparative cohort study involved 7364 IVF cycles performed in Quebec during 2009 and 2011 and included an economic analysis. IVF cycles performed in the five centres offering IVF treatment in Quebec during 2009, before implementation of the public IVF programme, were compared with cycles performed at the same centres during 2011, the first full calendar year following implementation of the programme. Data were obtained from the Canadian Assisted Reproductive Technologies Register (CARTR). Comparisons were made between the two periods in terms of utilization, pregnancy rates, multiple pregnancy rates and costs. The number of IVF cycles performed in Quebec increased by 192% after the new policy was implemented. Elective single-embryo transfer was performed in 1.6% of the cycles during Period I (2009), and increased to 31.6% during Period II (2011) (P < 0.001). Although the clinical pregnancy rate per embryo transfer was lower in 2011 than in 2009 (24.9 versus 39.9%, P < 0.001), the multiple pregnancy rate was greatly reduced (6.4 versus 29.4%, P < 0.001). The public IVF programme increased government costs per IVF treatment cycle from CAD$3730 to CAD$4759. Despite increased costs per cycle, the efficiency defined by the cost per live birth, which factored in downstream health costs up to 1 year post delivery, decreased from CAD$49 517 to CAD$43 362 per baby conceived by either fresh and frozen cycles. The costs described in the economic model are likely an underestimate as they do not factor in many of the long-term costs that can occur after 1 year of age. The information collected in the Canadian ART register precludes the calculation of cumulative pregnancy rates. Our study confirms that the implementation of a public IVF programme favouring eSET not only sharply decreases the incidence of multiple pregnancy, but also reduces the cost per live birth. M.P.V. holds a fellowship award from the Canadian Institutes of Health Research (CIHR). The economic analysis performed by M.P.C. was supported by an unrestricted grant from Ferring Pharmaceutical.

The influence of IVF/ICSI treatment on human embryonic growth trajectories.

PubMed

Eindhoven, S C; van Uitert, E M; Laven, J S E; Willemsen, S P; Koning, A H J; Eilers, P H C; Exalto, N; Steegers, E A P; Steegers-Theunissen, R P M

2014-12-01

Is in vitro fertilization treatment with or without intracytoplasmatic sperm injection (IVF/ICSI) associated with changes in first and second trimester embryonic and fetal growth trajectories and birthweight in singleton pregnancies? Embryonic and fetal growth trajectories and birthweight are not significantly different between pregnancies conceived with IVF/ICSI treatment and spontaneously conceived pregnancies with reliable pregnancy dating. IVF/ICSI treatment has been associated with increased risks of preterm birth, fetal growth restriction and low birthweight. Decreased first-trimester crown-rump length (CRL) in the general population has been inversely associated with the same adverse pregnancy outcomes. In a prospective periconception birth cohort study conducted in a tertiary centre, 146 singleton pregnancies with reliable pregnancy dating and nonmalformed live borns were investigated, comprised of 88 spontaneous and 58 IVF/ICSI pregnancies. Serial 3D ultrasound scans were performed from 6 to 12 weeks of gestation. As estimates of embryonic growth, CRL and embryonic volume (EV) were measured using the I-Space virtual reality system. General characteristics were obtained from self-administered questionnaires at enrolment. Fetal growth parameters at 20 weeks and birthweight were obtained from medical records. To assess associations between IVF/ICSI and embryonic growth trajectories, estimated fetal weight and birthweight, stepwise linear mixed model analyses and linear regression analyses were performed using square root transformed CRL and fourth root transformed EV. In 146 pregnancies, 934 ultrasound scans were performed of which 849 (90.9%) CRLs and 549 (58.8%) EVs could be measured. Embryonic growth trajectories were comparable between IVF/ICSI pregnancies and spontaneously conceived pregnancies (CRL: βIVF/ICSI = 0.10√mm; P = 0.10; EV: βIVF/ICSI = 0.03(4)√cm³; P = 0.13). Estimated fetal weight and birthweight were also comparable between both groups (βIVF/ICSI = 6 g; P = 0.36 and βIVF/ICSI = 80 g; P = 0.24, respectively). Variations in embryonic growth trajectories of spontaneously conceived pregnancies with reliable pregnancy dating may partially be a result of less precise pregnancy dating and differences in endometrium receptivity compared with IVF/ICSI pregnancies. The absence of a significant difference in embryonic and fetal growth trajectories suggests safety of IVF/ICSI treatment with regard to early embryonic growth. However, further research is warranted to ascertain the influence of IVF/ICSI treatments in a larger study population, and to estimate the impact of the underlying causes of the subfertility and other periconceptional exposures on human embryonic and fetal growth trajectories. This study was supported by the Department of Obstetrics and Gynaecology of the Erasmus MC, University Medical Centre. No competing interests are declared. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prevalence of chronic endometritis in repeated unexplained implantation failure and the IVF success rate after antibiotic therapy.

PubMed

Cicinelli, Ettore; Matteo, Maria; Tinelli, Raffaele; Lepera, Achiropita; Alfonso, Raffaello; Indraccolo, Ugo; Marrocchella, Sonia; Greco, Pantaleo; Resta, Leonardo

2015-02-01

What is the prevalence of chronic endometritis (CE) in women with repeated unexplained implantation failure (RIF) at IVF, and how does antibiotic treatment affect the reproductive outcome? Chronic endometritis, associated with infection with common bacteria or mycoplasma, is common in women complaining of RIF and antibiotic treatment significantly improves the reproductive outcome at a subsequent IVF cycle. We have reported that CE is a frequent finding in women with repeated pregnancy loss and a significantly higher rate of successful pregnancies was achieved after adequate antibiotic treatment. Moreover, CE was identified in 30.3% of patients with repeated implantation failure at IVF and women diagnosed with CE had lower implantation rates (11.5%) after IVF cycles. In contrast, other authors reported that the clinical implication of CE should be considered minimal and that the reproductive outcome at IVF/ICSI cycles was not negatively affected by CE. A retrospective study was performed from January 2009 through June 2012 on 106 women with unexplained infertility and a history of RIF. All patients underwent hysteroscopy and endometrial sampling for histology and microbiological investigations. Women diagnosed with CE underwent antibiotic treatment and the effect of treatment was confirmed by hysteroscopy with biopsy. Within 6 months after treatment all women had a further IVF attempt. The IVF outcomes were compared in women without signs of CE (Group 1) and persistent CE (Group 2) after antibiotic treatment. Clinical pregnancy rate (PR), and live birth rate (LBR) were compared at post-treatment IVF attempt. Seventy (66.0%) women were diagnosed with CE at hysteroscopy. In 61 (57.5%) CE was confirmed by histology and 48 (45.0%) by cultures. Common bacteria and mycoplasma were the most prevalent agents. In 46 (75.4%) out of 61 women, with diagnosis of CE at hysteroscopy and histology, examinations were normal after appropriate antibiotic treatment control (Group 1) while in 15 (24.6%) cases signs of CE were still present (Group 2). At IVF attempt after treatment, a significantly higher PR and LBR was reported in women from Group 1 compared with women from Group 2 (65.2 versus 33.0% P = 0.039; 60.8 versus 13.3%, P = 0.02, respectively). Possible biases related to retrospective studies and to preferential referral of patients with CE, and limited number of cases. A prospective randomized clinical trial is needed to confirm our findings but in women with RIF a hysteroscopic evaluation of the uterine cavity to exclude CE should be considered and appropriate antibiotic treatment should be given before submitting the patient to a further IVF attempt. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Do intrauterine or genetic influences explain the foetal origins of chronic disease? A novel experimental method for disentangling effects

PubMed Central

Thapar, Anita; Harold, Gordon; Rice, Frances; Ge, XiaoJia; Boivin, Jacky; Hay, Dale; van den Bree, Marianne; Lewis, Allyson

2007-01-01

Background There is much evidence to suggest that risk for common clinical disorders begins in foetal life. Exposure to environmental risk factors however is often not random. Many commonly used indices of prenatal adversity (e.g. maternal gestational stress, gestational diabetes, smoking in pregnancy) are influenced by maternal genes and genetically influenced maternal behaviour. As mother provides the baby with both genes and prenatal environment, associations between prenatal risk factors and offspring disease maybe attributable to true prenatal risk effects or to the "confounding" effects of genetic liability that are shared by mother and offspring. Cross-fostering designs, including those that involve embryo transfer have proved useful in animal studies. However disentangling these effects in humans poses significant problems for traditional genetic epidemiological research designs. Methods We present a novel research strategy aimed at disentangling maternally provided pre-natal environmental and inherited genetic effects. Families of children aged 5 to 9 years born by assisted reproductive technologies, specifically homologous IVF, sperm donation, egg donation, embryo donation and gestational surrogacy were contacted through fertility clinics and mailed a package of questionnaires on health and mental health related risk factors and outcomes. Further data were obtained from antenatal records. Results To date 741 families from 18 fertility clinics have participated. The degree of association between maternally provided prenatal risk factor and child outcome in the group of families where the woman undergoing pregnancy and offspring are genetically related (homologous IVF, sperm donation) is compared to association in the group where offspring are genetically unrelated to the woman who undergoes the pregnancy (egg donation, embryo donation, surrogacy). These comparisons can be then examined to infer the extent to which prenatal effects are genetically and environmentally mediated. Conclusion A study based on children born by IVF treatment and who differ in genetic relatedness to the woman undergoing the pregnancy is feasible. The present report outlines a novel experimental method that permits disaggregation of maternally provided inherited genetic and post-implantation prenatal effects. PMID:17587444

"One for Sorrow, Two for Joy?": American embryo transfer guideline recommendations, practices, and outcomes for gestational surrogate patients.

PubMed

White, Pamela M

2017-04-01

In January 2016, Melissa Cook, a California gestational surrogate experiencing a multiple-birth pregnancy following the in vitro fertilization (IVF) transfer of three embryos comprised of donor eggs and sperm provided by the intended father, went to the media when the intended father requested that she undergo a fetal reduction because twins were less expensive to raise than triplets. Much of the legal interest in this case to date has centered on the enforceability of surrogacy contracts. However, the Cook case also raises troubling issues about fertility treatment practices involving gestational surrogates, twin preference, and third-party reproduction medical decision-making. This paper focuses on multiple-embryo transfers in the context of US surrogacy arrangements. Offering an original analysis of data obtained from the US national-assisted reproduction registry, it examines single- and multiple-embryo transfer trends over a 12-year period (2003 to 2014). Findings reveal that recommended guidelines were followed in fewer than 42% of the cases in 2014. The paper argues that ensuring equitable medical treatment for all recipients of IVF requires the adoption of treatment guidelines tailored to, and offering protections for, specific patient groups, and that, once in place, guidelines must be robustly implemented.

Natural cycle in vitro fertilisation (IVF) for subfertile couples.

PubMed

Allersma, Thomas; Farquhar, Cindy; Cantineau, Astrid E P

2013-08-30

Subfertility affects 15% to 20% of couples trying to conceive. In vitro fertilisation (IVF) is one of the assisted reproduction techniques developed to improve chances of achieving pregnancy. In the standard IVF method with controlled ovarian hyperstimulation (COH), growth and development of multiple follicles are stimulated by using gonadotrophins, often combined with a gonadotrophin-releasing hormone (GnRH) agonist or antagonist. Although it is an established method of conception for subfertile couples, the treatment is expensive and has a high risk of adverse effects. Studies have shown that IVF in a natural cycle (NC) or a modified natural cycle (MNC) might be a promising low risk and low cost alternative to the standard stimulated IVF treatment since the available dominant follicle of each cycle is used. In this review, we included available randomised controlled studies comparing natural cycle IVF (NC and MNC) with standard IVF. To compare the efficacy and safety of natural cycle IVF (including both NC-IVF and MNC-IVF) with controlled ovarian hyperstimulation IVF (COH-IVF) in subfertile couples. An extended search including of the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ClinicalTrials.gov, conference abstracts in the Web of Knowledge, the World Health Organization International Trials Registry Platform search portal, LILACS database, PubMed and the OpenSIGLE database was conducted according to Cochrane guidelines. The last search was on 31st July 2013. All randomised controlled trials (RCTs) comparing either natural cycle IVF or modified natural cycle IVF versus standard IVF in subfertile couples were included. Data selection and extraction and risk of bias assessment were carried out independently by two authors (TA and AC). The primary outcome measures were live birth rate and ovarian hyperstimulation syndrome (OHSS) rate per randomised woman. We calculated Mantel-Haenszel odds ratios for each dichotomous outcome and either the mean difference or the standardised mean difference (SMD) for continuous outcomes, with 95% confidence intervals (CIs). A fixed effect model was used unless there was substantial heterogeneity, in which case a random effects model was used. Six randomised controlled trials with a total of 788 women were included. The largest of these trials included 396 women eligible for this review.No evidence of a statistically significant difference was found between natural cycle and standard IVF in live birth rates (OR 0.68, 95% CI 0.46 to 1.01, two studies, 425 women, I(2)= 0%, moderate quality evidence). The evidence suggests that for a woman with a 53% chance of live birth using standard IVF, the chance using natural cycle IVF would range from 34% to 53%. There was no evidence of a statistically significant difference between natural cycle and standard IVF in rates of OHSS (OR 0.19, 95% CI 0.01 to 4.06, one study, 60 women, very low quality evidence), clinical pregnancy (OR 0.52 95% CI 0.17 to 1.61, 4 studies, 351 women, I(2)=63%, low quality evidence), ongoing pregnancy (OR 0.72, 95% CI 0.50 to 1.05, three studies, 485 women, I(2)=0%, moderate quality evidence), multiple pregnancy (OR 0.76, 95% CI 0.25 to 2.31, 2 studies, 527 women, I(2)=0%, very low quality evidence), gestational abnormalities (OR 0.44 95% CI 0.03 to 5.93, 1 study, 18 women, very low quality evidence) or cycle cancellations (OR 8.98, 95% CI 0.20 to 393.66, 2 studies, 159 women, I(2)=83%, very low quality evidence). One trial reported that the oocyte retrieval rate was significantly lower in the natural cycle group (MD -4.40, 95% CI -7.87 to -0.93, 60 women, very low quality evidence). There were insufficient data to draw any conclusions about rates of treatment cancellation. Findings on treatment costs were inconsistent and more data are awaited. The evidence was limited by imprecision. Findings for pregnancy rate and for cycle cancellation were sensitive to the choice of statistical model: for these outcomes, use of a fixed effect model suggested a benefit for the standard IVF group. Moreover the largest trial has not yet completed follow up, though data have been reported for over 95% of women. Further evidence from well conducted large trials is awaited on natural cycle IVF treatment. Future trials should compare natural cycle IVF with standard IVF. Outcomes should include cumulative live birth and pregnancy rates, the number of treatment cycles necessary to reach live birth, treatment costs and adverse effects.

Can we identify subfertile couples that benefit from immediate in vitro fertilisation over intrauterine insemination?

PubMed

Tjon-Kon-Fat, Raïssa I; Tajik, Parvin; Custers, Inge M; Bossuyt, Patrick M M; van der Veen, Fulco; van Wely, Madelon; Mol, Ben W; Zafarmand, Mohammad H

2016-07-01

Available treatment options in couples with unexplained or mild male subfertility are intrauterine insemination with controlled ovarian hyperstimulation (IUI-COH) and in vitro fertilisation (IVF). IUI-COH is a less invasive treatment that is often used before proceeding with IVF. Yet as the IVF success rates might be higher and time to pregnancy shorter, expedited access to IVF might be the preferred option. To identify couples that could benefit from immediate IVF over IUI-COH, we assessed whether female age, duration of subfertility or prewash total motile count (TMC) can help to identify couples that would benefit from IVF over IUI-COH. We performed a secondary data-analysis of a multicentre open-label randomised controlled trial in three university and six teaching hospitals in the Netherlands. 116 couples with unexplained or mild male subfertility were randomised to one cycle of IVF with elective single embryo transfer with subsequent frozen-thawed embryo transfers or 3 cycles of IUI-COH. The primary outcome was an ongoing pregnancy within 4 months after randomisation. Our aim was to explore a possible differential effect of specific markers on the effectiveness of treatment. We chose to therefore assess female age, duration of subfertility and TMC as these have previously been identified as predictors. For each prognostic factor we developed a logistic regression model to predict ongoing pregnancy with that prognostic factor, treatment and a factor-by-treatment interaction term. Female age and duration of subfertility were not associated with better ongoing pregnancy chances after IVF compared to IUI-COH (p-value for interaction=0.65 and 0.26, respectively). Only when TMC was lower than 110 (×10(6)spermatozoa/mL), the probability of ongoing pregnancy was higher in women allocated to IVF (p-value for interaction=0.06). In couples with unexplained or mild male subfertility, a low TMC might lead to higher pregnancy rates after IVF than after IUI-COH. This finding needs to be validated in a larger trial before it can be applied in clinical practice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pregnancy and childhood health and developmental outcomes with the use of posthumous human sperm.

PubMed

Robson, Stephen J; Campbell, Simone; McDonald, Janelle; Tremellen, Kelton; Carlin, Emily; Maybury, Genevieve

2015-10-01

Although there is now considerable experience in obtaining sperm from a cadaver, there is little or no published data regarding pregnancy, birth and long-term childhood health and development outcomes when posthumous sperm is used in in vitro fertilisation (IVF). We report the results from treatment of four women undergoing IVF treatment using posthumously acquired human sperm from their deceased partners. In all cases, testicular tissue was obtained in a mortuary setting, and the duration from death to posthumous sperm retrieval ranged from 12 to 48 h. The age of women treated ranged from 31 to 41 years. Fertilization rates ranged from 40 to 100%. Singleton pregnancies were obtained for each of the four women. One pregnancy was complicated by preterm birth at 31 weeks; the other three delivered at term. One baby was growth restricted but morphologically normal; the other children had term birthweights in the normal range. All four children were have shown normal health and developmental outcomes, with the follow-up ranging from 1 to 7 years. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Combined assessment of polymorphisms in the LHCGR and FSHR genes predict chance of pregnancy after in vitro fertilization.

PubMed

Lindgren, I; Bååth, M; Uvebrant, K; Dejmek, A; Kjaer, L; Henic, E; Bungum, M; Bungum, L; Cilio, C; Leijonhufvud, I; Skouby, S; Andersen, C Yding; Giwercman, Y Lundberg

2016-03-01

Can gonadotrophin receptor variants separately or in combination, be used for the prediction of pregnancy chances in in vitro fertilization (IVF) trials? The luteinizing hormone/human chorionic gonadotrophin receptor (LHCGR) variant N312S and the follicle-stimulating hormone receptor (FSHR) variant N680S can be utilized for the prediction of pregnancy chances in women undergoing IVF. The FSHR N680S polymorphism has been shown to affect the ovarian response in response to gonadotrophin treatment, while no information is currently available regarding variants of the LHCGR in this context. Cross-sectional study, duration from September 2010 to February 2015. Women undergoing IVF were consecutively enrolled and genetic variants compared between those who became pregnant and those who did not. The study was subsequently replicated in an independent sample. Granulosa cells from a subset of women were investigated regarding functionality of the genetic variants. Women undergoing IVF (n = 384) were enrolled in the study and genotyped. Clinical variables were retrieved from medical records. For replication, an additional group of n = 233 women was utilized. Granulosa cells from n = 135 women were isolated by flow cytometry, stimulated with Follitropin alpha or Menotropin, and the downstream targets 3',5'-cyclic adenosine monophosphate (cAMP) and inositol 1,4,5-trisphosphate (IP3) measured with enzyme-linked immunosorbent assay. Women homozygous for serine (S) in both polymorphisms displayed higher pregnancy rates than women homozygous asparagine (N) (OR = 14.4, 95% CI: [1.65, 126], P = 0.016). Higher pregnancy rates were also evident for women carrying LHCGR S312, regardless of FSHR variant (OR = 1.61, 95% CI: [1.13, 2.29], P = 0.008). These women required higher doses of FSH for follicle recruitment than women homozygous N (161 versus 148 IU, P = 0.030). When combining the study cohort with the replication cohort (n = 606), even stronger associations with pregnancy rates were noted for the combined genotypes (OR = 11.5, 95% CI: [1.86, 71.0], P = 0.009) and for women carrying LHCGR S312 (OR = 1.49, 95% CI: [1.14, 1.96], P = 0.004). A linear significant trend with pregnancy rate and increasing number of G alleles was also evident in the merged study population (OR = 1.34, 95% CI: [1.10, 1.64], P = 0.004). A lower cAMP response in granulosa cells was noted following Follitropin alpha stimulation for women homozygous N in both polymorphisms, compared with women with other genotypes (0.901 pmol cAMP/mg total protein versus 2.19 pmol cAMP/mg total protein, P = 0.035). Due to racial differences in LHCGR genotype distribution, these results may not be applicable for all populations. Despite that >250 000 cycles of gonadotrophin stimulations are performed annually worldwide prior to IVF, it has not been possible to predict neither the pregnancy outcome, nor the response to the hormone with accuracy. If LHCGR and FSHR variants are recognized as biomarkers for chance of pregnancy, more individualized and thereby more efficient treatment modalities can be developed. This work was supported by Interreg IV A, EU (grant 167158) and ALF governments grant (F2014/354). Merck-Serono (Darmstadt, Germany) supported the enrollment of the subjects. The authors declare no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The inSIGHT study: costs and effects of routine hysteroscopy prior to a first IVF treatment cycle. A randomised controlled trial.

PubMed

Smit, Janine G; Kasius, Jenneke C; Eijkemans, Marinus J C; Koks, Carolien A M; Van Golde, Ron; Oosterhuis, Jurjen G E; Nap, Annemiek W; Scheffer, Gabrielle J; Manger, Petra A P; Hoek, Annemiek; Kaplan, Mesrure; Schoot, Dick B C; van Heusden, Arne M; Kuchenbecker, Walter K H; Perquin, Denise A M; Fleischer, Kathrin; Kaaijk, Eugenie M; Sluijmer, Alexander; Friederich, Jaap; Laven, Joop S E; van Hooff, Marcel; Louwe, Leonie A; Kwee, Janet; Boomgaard, Jantien J; de Koning, Corry H; Janssen, Ineke C A H; Mol, Femke; Mol, Ben W J; Torrance, Helen L; Broekmans, Frank J M

2012-08-08

In in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI) treatment a large drop is present between embryo transfer and occurrence of pregnancy. The implantation rate per embryo transferred is only 30%. Studies have shown that minor intrauterine abnormalities can be found in 11-45% of infertile women with a normal transvaginal sonography or hysterosalpingography. Two randomised controlled trials have indicated that detection and treatment of these abnormalities by office hysteroscopy after two failed IVF cycles leads to a 9-13% increase in pregnancy rate. Therefore, screening of all infertile women for intracavitary pathology prior to the start of IVF/ICSI is increasingly advocated. In absence of a scientific basis for such a policy, this study will assess the effects and costs of screening for and treatment of unsuspected intrauterine abnormalities by routine office hysteroscopy, with or without saline infusion sonography (SIS), prior to a first IVF/ICSI cycle. Multicenter randomised controlled trial in asymptomatic subfertile women, indicated for a first IVF/ICSI treatment cycle, with normal findings at transvaginal sonography. Women with recurrent miscarriages, prior hysteroscopy treatment and intermenstrual blood loss will not be included. Participants will be randomised for a routine fertility work-up with additional (SIS and) hysteroscopy with on-the-spot-treatment of predefined intrauterine abnormalities versus the regular fertility work-up without additional diagnostic tests. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months of IVF/ICSI treatment after randomisation. Secondary study outcome parameters are the cumulative implantation rate; cumulative miscarriage rate; patient preference and patient tolerance of a SIS and hysteroscopy procedure. All data will be analysed according to the intention-to-treat principle, using univariate and multivariate logistic regression and cox regression. Cost-effectiveness analysis will be performed to evaluate the costs of the additional tests as routine procedure. In total 700 patients will be included in this study. The results of this study will help to clarify the significance of hysteroscopy prior to IVF treatment. NCT01242852.

The inSIGHT study: costs and effects of routine hysteroscopy prior to a first IVF treatment cycle. A randomised controlled trial

PubMed Central

2012-01-01

Background In in vitro fertilization (IVF) and intracytoplasmatic sperm injection (ICSI) treatment a large drop is present between embryo transfer and occurrence of pregnancy. The implantation rate per embryo transferred is only 30%. Studies have shown that minor intrauterine abnormalities can be found in 11–45% of infertile women with a normal transvaginal sonography or hysterosalpingography. Two randomised controlled trials have indicated that detection and treatment of these abnormalities by office hysteroscopy after two failed IVF cycles leads to a 9–13% increase in pregnancy rate. Therefore, screening of all infertile women for intracavitary pathology prior to the start of IVF/ICSI is increasingly advocated. In absence of a scientific basis for such a policy, this study will assess the effects and costs of screening for and treatment of unsuspected intrauterine abnormalities by routine office hysteroscopy, with or without saline infusion sonography (SIS), prior to a first IVF/ICSI cycle. Methods/design Multicenter randomised controlled trial in asymptomatic subfertile women, indicated for a first IVF/ICSI treatment cycle, with normal findings at transvaginal sonography. Women with recurrent miscarriages, prior hysteroscopy treatment and intermenstrual blood loss will not be included. Participants will be randomised for a routine fertility work-up with additional (SIS and) hysteroscopy with on-the-spot-treatment of predefined intrauterine abnormalities versus the regular fertility work-up without additional diagnostic tests. The primary study outcome is the cumulative ongoing pregnancy rate resulting in live birth achieved within 18 months of IVF/ICSI treatment after randomisation. Secondary study outcome parameters are the cumulative implantation rate; cumulative miscarriage rate; patient preference and patient tolerance of a SIS and hysteroscopy procedure. All data will be analysed according to the intention-to-treat principle, using univariate and multivariate logistic regression and cox regression. Cost-effectiveness analysis will be performed to evaluate the costs of the additional tests as routine procedure. In total 700 patients will be included in this study. Discussion The results of this study will help to clarify the significance of hysteroscopy prior to IVF treatment. Trial registration NCT01242852 PMID:22873367

Recombinant luteinizing hormone priming in early follicular phase for women undergoing in vitro fertilization: systematic review and meta-analysis.

PubMed

Hu, Linli; Bu, Zhiqin; Wang, Keyan; Sun, Yingpu

2014-04-01

To investigate the effect of recombinant human luteinizing hormone supplementation (rLH priming) during the early follicular phase on in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) outcomes. In order to evaluate available evidence regarding the efficacy of rLH priming in IVF/ICSI procedures, a systematic review and meta-analysis was preformed. Searches were conducted on MEDLINE®, EMBASE and the Cochrane Database of Clinical Trials without language limitation, but were restricted to randomized controlled trials (RCTs). Three RCTs including 346 patients were included in this meta-analysis, which demonstrated that rLH priming did not increase ongoing pregnancy rate. Although less recombinant follicle-stimulating hormone (rFSH) was required and the oestradiol level was higher on the day of human chorionic gonadotropin administration in the rLH priming group, the numbers of oocytes retrieved and embryos produced were comparable between patients treated with rLH priming and those treated with rFSH alone. This systematic review and meta-analysis has demonstrated that at present there is insufficient evidence that patients undergoing IVF/ICSI may benefit from rLH priming during the early follicular phase.

Effects of women's body mass index on in vitro fertilization success: a retrospective cohort study.

PubMed

Haghighi, Zahra; Rezaei, Zahra; Es-Haghi Ashtiani, Somayyeh

2012-07-01

The purpose of this study is to evaluate the influence of body mass index (BMI) on the reproductive outcomes and clinical pregnancy rate after in vitro fertilization (IVF). This retrospective study was performed on 230 women undergoing first cycle of standard IVF between October 2008 and February 2010. The patients were classified into three groups according to their BMI (BMI < 20 kg/m², 20 kg/m² < BMI < 27.9 kg/m² and BMI > 28 kg/m²). Information regarding clinical pregnancy was compared within these three groups. There was no significant relation between BMI and age, the number of aspirated follicles, transferred embryos, mature oocytes, days of taking human menopausal gonadotropin (HMG) ampules and the total number of HMG ampules among three BMI studied groups. Statistically significant difference was detected between BMI and endometrial thickness. BMI has no effect on IVF outcomes and clinical pregnancy after IVF. However, losing weight in obese women seems reasonable to prevent possible obstetrics complications.

FERTILITY TREATMENT RESPONSE: IS IT BETTER TO BE MORE OPTIMISTIC OR LESS PESSIMISTIC?

PubMed Central

Bleil, Maria E.; Pasch, Lauri A.; Gregorich, Steven E.; Millstein, Susan G.; Katz, Patricia P.; Adler, Nancy E.

2011-01-01

Objective To evaluate the prospective relation between dispositional traits of optimism and pessimism and IVF treatment failure among women seeking medical intervention for infertility. Methods Among 198 women (ages 24-45, M=35.1[4.1]; 77% white), the outcome of each participant’s first IVF treatment cycle was examined. Treatment outcome was classified as being successful (vs. failed) if the woman either delivered a baby or was pregnant as a result of the cycle by the end of the 18-month study period. At baseline, optimism and pessimism were measured as a single bipolar dimension and as separate unipolar dimensions according to the Life Orientation Test (LOT) total score and the optimism and pessimism subscale scores, respectively. Results Optimism/pessimism, measured as a single bipolar dimension, predicted IVF treatment failure initially (B = -.09; p = .02; OR = 0.917; 95% CI = 0.851 – 0.988), but this association attenuated following statistical control for trait negative affect (B = -.06; p = .13; OR = 0.938; 95% CI = 0.863 – 1.020). When examined as separate unipolar dimensions, pessimism (B = .14; p = .04; OR = 1.146; 95% CI = 1.008 – 1.303), but not optimism (B = -.09; p = .12; OR = 0.912; 95% CI = 0.813 – 1.023), predicted IVF treatment failure independently of risk factors for poor IVF treatment response as well as trait negative affect. Conclusions Being pessimistic may be a risk factor for IVF treatment failure. Future research should attempt to delineate the biological and behavioral mechanisms by which pessimism may negatively affect treatment outcomes. PMID:22286845

The INeS study: prevention of multiple pregnancies: a randomised controlled trial comparing IUI COH versus IVF e SET versus MNC IVF in couples with unexplained or mild male subfertility.

PubMed

Bensdorp, Alexandra J; Slappendel, Els; Koks, Carolien; Oosterhuis, Jur; Hoek, Annemieke; Hompes, Peter; Broekmans, Frank; Verhoeve, Harold; de Bruin, Jan Peter; van Weert, Janne Meije; Traas, Maaike; Maas, Jacques; Beckers, Nicole; Repping, Sjoerd; Mol, Ben W; van der Veen, Fulco; van Wely, Madelon

2009-12-18

Multiple pregnancies are high risk pregnancies with higher chances of maternal and neonatal mortality and morbidity. In the past decades the number of multiple pregnancies has increased. This trend is partly due to the fact that women start family planning at an increased age, but also due to the increased use of ART.Couples with unexplained or mild male subfertility generally receive intrauterine insemination IUI with controlled hormonal stimulation (IUI COH). The cumulative pregnancy rate is 40%, with a 10% multiple pregnancy rate.This study aims to reveal whether alternative treatments such as IVF elective Single Embryo Transfer (IVF e SET) or Modified Natural Cycle IVF (MNC IVF) can reduce the number of multiple pregnancy rates, but uphold similar pregnancy rates as IUI COH in couples with mild male or unexplained subfertility. Secondly, the aim is to perform a cost effective analyses and assess treatment preference of these couples. We plan a multicentre randomised controlled clinical trial in the Netherlands comparing six cycles of intra-uterine insemination with controlled ovarian hyperstimulation or six cycles of Modified Natural Cycle (MNC) IVF or three cycles with IVF-elective Single Embryo Transfer (eSET) plus cryo-cycles within a time frame of 12 months.Couples with unexplained subfertility or mild male subfertility and a poor prognosis for treatment independent pregnancy will be included. Women with anovulatory cycles, severe endometriosis, double sided tubal pathology or serious endocrine illness will be excluded.Our primary outcome is the birth of a healthy singleton. Secondary outcomes are multiple pregnancy, treatment costs, and patient experiences in each treatment arm. The analysis will be performed according tot the intention to treat principle. We will test for non-inferiority of the three arms with respect to live birth. As we accept a 12.5% loss in pregnancy rate in one of the two IVF arms to prevent multiple pregnancies, we need 200 couples per arm (600 couples in total). Determining the safest and most cost-effective treatment will ensure optimal chances of pregnancy for subfertile couples with substantially diminished perinatal and maternal complications. Should patients find the most cost-effective treatment acceptable or even preferable, this could imply the need for a world wide shift in the primary treatment. Current Controlled Trials ISRCTN 52843371.

Anti-müllerian hormone levels are associated with live birth rates in ART, but the predictive ability of anti-müllerian hormone is modest.

PubMed

Alson, Sara S E; Bungum, Leif J; Giwercman, Aleksander; Henic, Emir

2018-06-01

The aim was to evaluate the association between serum Anti-Müllerian Hormone (AMH) level and cumulative live birth rates (LBR) in patients undergoing their first in vitro fertilization (IVF) treatment cycle, and to compare serum AMH levels with Antral Follicle Count (AFC) and Ovarian Sensitivity Index (OSI) as predictors of live birth. A prospective cohort study of 454 patients under the age of 40 and with a regular menstrual cycle of 21-35 days, undergoing their first IVF treatment cycles between September 2010 and June 2015. Participants were divided into three groups based on their AMH level, (AMH ≤10, AMH 10-<30 and AMH ≥30 pmol/l). Any difference in AMH-distribution between patients with or without live birth was analyzed using a Mann-Whitney-test, and live birth rates were compared between groups by a chi-squared test for linear trend. The ability of AMH, OSI and AFC as predictors of live birth was assessed by a receiver operating characteristics-analysis and the area under the curve (AUC) was calculated. Patients with live birth had a higher AMH, median (range) 26 [0-137] pmol/l, compared with patients without live birth, AMH 22 [0-154] pmol/l, p = 0.035. Mean live birth rate (SD) was 0.36 (0.48) in the total cohort, 0.26 (0.44) in AMH-group <10, 0.34 (0.48) in AMH-group 10-<30, and 0.41(0.49) in AMH-group ≥30. Thus live birth rates increased with 8% per AMH-group (95% CI: 0.02 -0.14, p = 0.015). The AUC for AFC was 0.56, for AMH 0.57 and for OSI 0.63, respectively. AMH concentration in serum is associated with live birth rates after IVF. Our results suggest that both AMH, AFC and OSI have an equal but modest predictive ability in relation to live birth rate. Copyright © 2018 Elsevier B.V. All rights reserved.

Relationship between antithyroid antibody and pregnancy outcome following in vitro fertilization and embryo transfer.

PubMed

Zhong, Yi-ping; Ying, Ying; Wu, Hai-tao; Zhou, Can-quan; Xu, Yan-wen; Wang, Qiong; Li, Jie; Shen, Xiao-ting; Li, Jin

2012-01-01

To investigate the impact of antithyroid antibody on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET). A total of 90 patients (156 cycles) positive for antithyroid antibody (ATA+ group) and 676 infertile women (1062 cycles) negative for antithyroid antibody (ATA- group) undergoing IVF/ICSI from August 2009 to August 2010 were retrospectively analyzed. There was no significant difference in the days of ovarian stimulation, total gonadotropin dose, serum E2 level of HCG day and number of oocytes retrieved between the two groups. The fertilization rate, implantation rate and pregnancy rate following IVF-ET were significantly lower in women with antithyroid antibody than in control group (64.3% vs 74.6%, 17.8% vs 27.1% and 33.3% vs 46.7%, respectively), but the abortion rate was significantly higher in patients with antithyroid antibody (26.9% vs 11.8%). Patients with antithyroid antibody showed significantly lower fertilization rate, implantation rate and pregnancy rate and higher risk for abortion following IVF-ET when compared with those without antithyroid antibody. Thus, the presence of antithyroid antibody is detrimental for the pregnancy outcome following IVF-ET.

Relationship between Antithyroid Antibody and Pregnancy Outcome following in Vitro Fertilization and Embryo Transfer

PubMed Central

Zhong, Yi-ping; Ying, Ying; Wu, Hai-tao; Zhou, Can-quan; Xu, Yan-wen; Wang, Qiong; Li, Jie; Shen, Xiao-ting; Li, Jin

2012-01-01

Objective: To investigate the impact of antithyroid antibody on pregnancy outcome following the in vitro fertilization and embryo transfer (IVF-ET). Methods: A total of 90 patients (156 cycles) positive for antithyroid antibody (ATA+ group) and 676 infertile women (1062 cycles) negative for antithyroid antibody (ATA- group) undergoing IVF/ICSI from August 2009 to August 2010 were retrospectively analyzed. Results: There was no significant difference in the days of ovarian stimulation, total gonadotropin dose, serum E2 level of HCG day and number of oocytes retrieved between the two groups. The fertilization rate, implantation rate and pregnancy rate following IVF-ET were significantly lower in women with antithyroid antibody than in control group (64.3% vs 74.6%, 17.8% vs 27.1% and 33.3% vs 46.7%, respectively), but the abortion rate was significantly higher in patients with antithyroid antibody (26.9% vs 11.8%). Conclusion: Patients with antithyroid antibody showed significantly lower fertilization rate, implantation rate and pregnancy rate and higher risk for abortion following IVF-ET when compared with those without antithyroid antibody. Thus, the presence of antithyroid antibody is detrimental for the pregnancy outcome following IVF-ET. PMID:22253557

Successive and cyclic oral contraceptive pill pretreatment improves IVF/ICSI outcomes of PCOS patients and ameliorates hyperandrogenism and antral follicle excess.

PubMed

Pan, Jie-Xue; Liu, Ye; Ke, Zhang-Hong; Zhou, Cheng-Liang; Meng, Qing; Ding, Guo-Lian; Xu, Gu-Feng; Sheng, Jian-Zhong; Huang, He-Feng

2015-04-01

To evaluate different oral contraceptive pill (OCP) pretreatment associated differential in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes of polycystic ovary syndrome (PCOS) patients and explore enhanced hormonal balance induced by the pretreatment. This retrospective study included 500 PCOS women and 565 normal ovulating counterparts undergoing IVF/ICSI. The PCOS patients were divided into three groups based on the OCP pretreatment regimens: non-OCP (without OCP pretreatment), unsuccessive OCP (the period of successive pretreatment ≤2 months) and successive OCP (the period of successive pretreatment ≥3 months) groups. Comprehensive hormonal and ultra-sonographic assessments were performed before/after IVF pretreatment. Confounding factors affecting pregnancy outcomes were analyzed with logistic regression. PCOS patients with significant endocrine disorders had reduced implantation and pregnancy rates and increased miscarriage rate. Successive, not unsuccessive OCP pretreatment, significantly improved the implantation and pregnancy rates, and reduced the incidence of monotocous small-for-gestational age infants, which was accompanied by remarkably decreased hyperandrogenism and antral follicles. PCOS is an independent risk factor for poor IVF outcome. Successive, not unsuccessive, OCP cyclical pretreatment could improve pregnancy outcome of PCOS patients, associated with reduction of hyperandrogenism and antral follicle excess.

Optimization of IVF pregnancy outcomes with donor spermatozoa.

PubMed

Wang, Jeff G; Douglas, Nataki C; Prosser, Robert; Kort, Daniel; Choi, Janet M; Sauer, Mark V

2009-03-01

To identify risk factors for suboptimal IVF outcomes using insemination with donor spermatozoa and to define a lower threshold that may signal a conversion to fertilization by ICSI rather than insemination. Retrospective, age-matched, case-control study of women undergoing non-donor oocyte IVF cycles using either freshly ejaculated (N=138) or cryopreserved donor spermatozoa (N=69). Associations between method of fertilization, semen sample parameters, and pregnancy rates were analyzed. In vitro fertilization of oocytes with donor spermatozoa by insemination results in equivalent fertilization and pregnancy rates compared to those of freshly ejaculated spermatozoa from men with normal semen analyses when the post-processing motility is greater than or equal to 88%. IVF by insemination with donor spermatozoa when the post-processing motility is less than 88% is associated with a 5-fold reduction in pregnancy rates when compared to those of donor spermatozoa above this motility threshold. When the post-processing donor spermatozoa motility is low, fertilization by ICSI is associated with significantly higher pregnancy rates compared to those of insemination. While ICSI does not need to be categorically instituted when using donor spermatozoa in IVF, patients should be counseled that conversion from insemination to ICSI may be recommended based on low post-processing motility.

Does gravidity influence the success of in vitro fertilization-embryo transfer cycles?

PubMed

Rabinson, Jacob; Bar-Hava, Itai; Meltcer, Simion; Zohav, Efraim; Anteby, Eyal; Orvieto, Raoul

2006-04-01

To evaluate the influence of gravidity on the results of in vitro fertilization (IVF)-embryo transfer (ET) cycles. All consecutive women aged <35 years admitted to our IVF unit from January 2002 to December 2004 were enrolled in the study. Only patients undergoing one of their first three IVF cycle attempts were included. Gravidity, ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and clinical pregnancy rate were assessed. Three hundred and forty-two consecutive IVF cycles were evaluated. One hundred and sixty-one cycles were from nulligravidas and 181 from women with a history of at least one previous clinical pregnancy. Forty-eight (29.8%) clinical pregnancies were observed in the nulligravida group and 56 (30.9%) in the gravida group. There were no differences between nulligravidas and gravidas in causes of infertility, length of ovarian stimulation, peak estradiol and progesterone levels, number of oocytes retrieved, fertilization rate and number of embryos transferred. Gravidas were significantly older (30.4 vs. 27.6 years, p < 0.001) and used more gonadotropin ampoules (36.1 vs. 31.8, p < 0.004) compared with the nulligravidas. Patient gravidity has no influence on the likelihood of achieving pregnancy in IVF-ET cycles.

Use of various gonadotropin and biosimilar formulations for in vitro fertilization cycles: results of a worldwide Web-based survey.

PubMed

Christianson, Mindy S; Shoham, Gon; Tobler, Kyle J; Zhao, Yulian; Monseur, Brent; Leong, Milton; Shoham, Zeev

2017-08-01

The purpose of this study was to identify trends in gonadotropin therapy in patients undergoing in vitro fertilization (IVF) treatment worldwide. Retrospective evaluation utilizing the results of a Web-based survey, IVF-Worldwide ( www.IVF-worldwide.com ) was performed. Three hundred fourteen centers performing a total of 218,300 annual IVF cycles were evaluated. Respondents representing 62.2% of cycles (n = 135,800) did not believe there was a difference between urinary and recombinant gonadotropins in terms of efficacy and live birth rate. Of the respondents, 67.3% (n = 146,800) reported no difference between recombinant and urinary formulations in terms of short-term safety and risk of ovarian hyperstimulation syndrome. In terms of long-term safety using human urinary gonadotropins, 50.6% (n = 110,400) of respondents believe there are potential long-term risks including prion disease. For 95.3% of units (n = 208,000), the clinician was the decision maker determining which specific gonadotropins are used for IVF. Of the units, 62.6% (n = 136,700) identified efficacy as the most important factor in deciding which gonadotropin to prescribe. While most (67.3%, n = 146,800) were aware of new biosimilar recombinant FSH products entering the market, 92% (n = 201,000) reported they would like more information. A fraction of respondents (25.6%, n = 55,900) reported having experience with these new products, and of these, 80.3% (n = 46,200) reported that they were similar in efficacy as previously used gonadotropins in a similar patient group. Respondents representing the majority of centers do not believe a difference exists between urinary and recombinant gonadotropins with respect to efficacy and live birth rates. While many are aware of new biosimilar recombinant FSH products entering the market, over 90% desire more information on these products.

In vitro fertilization and multiple pregnancies: an evidence-based analysis.

PubMed

2006-01-01

The objective of this health technology policy assessment was to determine the clinical effectiveness and cost-effectiveness of IVF for infertility treatment, as well as the role of IVF in reducing the rate of multiple pregnancies. TARGET POPULATION AND CONDITION Typically defined as a failure to conceive after a year of regular unprotected intercourse, infertility affects 8% to 16% of reproductive age couples. The condition can be caused by disruptions at various steps of the reproductive process. Major causes of infertility include abnormalities of sperm, tubal obstruction, endometriosis, ovulatory disorder, and idiopathic infertility. Depending on the cause and patient characteristics, management options range from pharmacologic treatment to more advanced techniques referred to as assisted reproductive technologies (ART). ART include IVF and IVF-related procedures such as intra-cytoplasmic sperm injection (ICSI) and, according to some definitions, intra-uterine insemination (IUI), also known as artificial insemination. Almost invariably, an initial step in ART is controlled ovarian stimulation (COS), which leads to a significantly higher rate of multiple pregnancies after ART compared with that following natural conception. Multiple pregnancies are associated with a broad range of negative consequences for both mother and fetuses. Maternal complications include increased risk of pregnancy-induced hypertension, pre-eclampsia, polyhydramnios, gestational diabetes, fetal malpresentation requiring Caesarean section, postpartum haemorrhage, and postpartum depression. Babies from multiple pregnancies are at a significantly higher risk of early death, prematurity, and low birth weight, as well as mental and physical disabilities related to prematurity. Increased maternal and fetal morbidity leads to higher perinatal and neonatal costs of multiple pregnancies, as well as subsequent lifelong costs due to disabilities and an increased need for medical and social support. IVF was first developed as a method to overcome bilateral Fallopian tube obstruction. The procedure includes several steps: (1) the woman's egg is retrieved from the ovaries; (2) exposed to sperm outside the body and fertilized; (3) the embryo(s) is cultured for 3 to 5 days; and (4) is transferred back to the uterus. IFV is considered to be one of the most effective treatments for infertility today. According to data from the Canadian Assisted Reproductive Technology Registry, the average live birth rate after IVF in Canada is around 30%, but there is considerable variation in the age of the mother and primary cause of infertility. An important advantage of IVF is that it allows for the control of the number of embryos transferred. An elective single embryo transfer in IVF cycles adopted in many European countries was shown to significantly reduce the risk of multiple pregnancies while maintaining acceptable birth rates. However, when number of embryos transferred is not limited, the rate of IVF-associated multiple pregnancies is similar to that of other treatments involving ovarian stimulation. The practice of multiple embryo transfer in IVF is often the result of pressures to increase success rates due to the high costs of the procedure. The average rate of multiple pregnancies resulting from IVF in Canada is currently around 30%. An alternative to IVF is IUI. In spite of reported lower success rates of IUI (pregnancy rates per cycle range from 8.7% to 17.1%) it is generally attempted before IVF due to its lower invasiveness and cost. Two major drawbacks of IUI are that it cannot be used in cases of bilateral tubal obstruction and it does not allow much control over the risk of multiple pregnancies compared with IVF. The rate of multiple pregnancies after IUI with COS is estimated to be about 21% to 29%. Ontario Health Insurance Plan Coverage Currently, the Ontario Health Insurance Plan covers the cost of IVF for women with bilaterally blocked Fallopian tubes only, in which case it is funded for 3 cycles, excluding the cost of drugs. The cost of IUI is covered except for preparation of the sperm and drugs used for COS. DIFFUSION OF TECHNOLOGY: According to Canadian Assisted Reproductive Technology Registry data, in 2004 there were 25 infertility clinics across Canada offering IVF and 7,619 IVF cycles performed. In Ontario, there are 13 infertility clinics with about 4,300 IVF cycles performed annually. ROYAL COMMISSION REPORT ON REPRODUCTIVE TECHNOLOGIES: The 1993 release of the Royal Commission report on reproductive technologies, Proceed With Care, resulted in the withdrawal of most IVF funding in Ontario, where prior to 1994 IVF was fully funded. Recommendations of the Commission to withdraw IVF funding were largely based on findings of the systematic review of randomized controlled trials (RCTs) published before 1990. The review showed IVF effectiveness only in cases of bilateral tubal obstruction. As for nontubal causes of infertility, there was not enough evidence to establish whether IVF was effective or not. Since the field of reproductive technology is constantly evolving, there have been several changes since the publication of the Royal Commission report. These changes include: increased success rates of IVF; introduction of ICSI in the early 1990's as a treatment for male factor infertility; and improved embryo implantation rates allowing for the transfer of a single embryo to avoid multiple pregnancies after IVF. STUDIES AFTER THE ROYAL COMMISSION REPORT: REVIEW STRATEGY THREE SEPARATE LITERATURE REVIEWS WERE CONDUCTED IN THE FOLLOWING AREAS: clinical effectiveness of IVF, cost-effectiveness of IVF, and outcomes of single embryo transfer (SET) in IVF cycles. CLINICAL EFFECTIVENESS OF IVF: RCTs or meta-analyses of RCTs that compared live birth rates after IVF versus alternative treatments, where the cause of infertility was clearly stated or it was possible to stratify the outcome by the cause of infertility.COST EFFECTIVENESS OF IVF: All relevant economic studies comparing IVF to alternative methods of treatment were reviewedOUTCOMES OF IVF WITH SET: RCTs or meta-analyses of RCTs that compared live birth rates and multiple birth rates associated with transfer of single versus double embryos.OVID MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Library, the International Agency for Health Technology Assessment database, and websites of other health technology assessment agencies were searched using specific subject headings and keywords to identify relevant studies. COMPARATIVE CLINICAL EFFECTIVENESS OF IVF: Overall, there is a lack of well composed RCTs in this area and considerable diversity in both definition and measurement of outcomes exists between trials. Many studies used fertility or pregnancy rates instead of live birth rates. Moreover, the denominator for rate calculation varied from study to study (e.g. rates were calculated per cycle started, per cycle completed, per couple, etc...). Nevertheless, few studies of sufficient quality were identified and categorized by the cause of infertility and existing alternatives to IVF. The following are the key findings: A 2005 meta-analysis demonstrated that, in patients with idiopathic infertility, IVF was clearly superior to expectant management, but there were no statistically significant differences in live birth rates between IVF and IUI, nor between IVF and gamete-intra-Fallopian transfer.A subset of data from a 2000 study showed no significant differences in pregnancy rates between IVF and IUI for moderate male factor infertility.In patients with moderate male factor infertility, standard IVF was also compared with ICSI in a 2002 meta-analysis. All studies included in the meta-analysis showed superior fertilization rates with ICSI, and the pooled risk ratio for oocyte fertilization was 1.9 (95% Confidence Interval 1.4-2.5) in favour of ICSI. Two other RCTs in this area published after the 2002 meta-analysis had similar results and further confirmed these findings. There were no RCTs comparing IVF with ICSI in patients with severe male factor infertility, mainly because based on the expert opinion, ICSI might only be an effective treatment for severe male factor infertility. COST-EFFECTIVENESS OF IVF: Five economic evaluations of IVF were found, including one comprehensive systematic review of 57 health economic studies. The studies compared cost-effectiveness of IVF with a number of alternatives such as observation, ovarian stimulation, IUI, tubal surgery, varicocelectomy, etc... The cost-effectiveness of IVF was analyzed separately for different types of infertility. Most of the reviewed studies concluded that due to the high cost, IVF has a less favourable cost-effectiveness profile compared with alternative treatment options. Therefore, IVF was not recommended as the first line of treatment in the majority of cases. The only two exceptions were bilateral tubal obstruction and severe male factor infertility, where an immediate offer of IVF/ICSI might the most cost-effective option. CLINICAL OUTCOMES AFTER SINGLE VERSUS DOUBLE EMBRYO TRANSFER STRATEGIES OF IVF: Since the SET strategy has been more widely adopted in Europe, all RCT outcomes of SET were conducted in European countries. The major study in this area was a large 2005 meta-analysis, followed by two other published RCTs. All of these studies reached similar conclusions: Although a single SET cycle results in lower birth rates than a single double embryo transfer (DET) cycle, the cumulative birth rate after 2 cycles of SET (fresh + frozen-thawed embryos) was comparable to the birth rate after a single DET cycle (~40%).SET was associated with a significant reduction in multiple births compared with DET (0.8% vs. 33.1% respectively in the largest RCT). (ABSTRACT TRUNCATED)

Vitamin D deficiency and pregnancy rates in women undergoing single embryo, blastocyst stage, transfer (SET) for IVF/ICSI.

PubMed

Polyzos, Nikolaos P; Anckaert, Ellen; Guzman, Luis; Schiettecatte, Johan; Van Landuyt, Lisbet; Camus, Michel; Smitz, Johan; Tournaye, Herman

2014-09-01

What is the influence of vitamin D deficiency on pregnancy rates among women undergoing IVF/ICSI and Day 5 (blastocyst stage) single embryo transfer (SET)? Vitamin D deficiency results in significantly lower pregnancy rates in women undergoing single blastocyst transfer. Preliminary experiments have identified the presence of vitamin D receptors in the female reproductive system. However, results regarding the effect of vitamin D deficiency on clinical outcomes are conflicting. None of the previous studies adopted a SET strategy. Serum vitamin D concentration was measured retrospectively in patients who underwent SET on Day 5. Overall 368 consecutive infertile women treated within a period of 15 months were included in the study. All patients underwent ovarian stimulation for IVF/ICSI and Day 5 SET. Serum samples were obtained 7 days prior to embryo transfer and stored frozen at -20°C. Samples were collectively analyzed for their 25-OH vitamin D content. Vitamin D deficiency was defined as serum 25-OH vitamin D levels <20 ng/ml in accordance with the Institute of Medicine and the Endocrine Society clinical practice guidelines. Clinical pregnancy rates were significantly lower in women with vitamin D deficiency compared with those with higher vitamin D values (41 versus 54%, P = 0.015).Logistic regression analysis was performed to identify whether vitamin D deficiency is independently associated with clinical pregnancy rates after controlling for 16 potential confounding factors. According to our results vitamin D deficiency was independently associated with lower clinical pregnancy rates, odds ratios [ORs (95% confidence interval (CI) 0.61 (0.39-0.95)] for vitamin D deficiency (deficient versus non-deficient women), P = 0.030. Finally, even when restricting our analysis to women undergoing elective SET (274 patients), vitamin D deficiency was again independently associated with pregnancy rates [OR (95% CI) 0.56 (0.33-0.93), P = 0.024]. Our results refer only to patients undergoing Day 5 SET. Although vitamin D deficiency appears to compromise pregnancy rates in this population, no guidance can be provided regarding a potential relationship between vitamin D deficiency and ovarian reserve or response to ovarian stimulation. Vitamin D deficiency impairs pregnancy rates in women undergoing single blastocyst transfer. Future prospective confirmatory studies are needed to validate our results and examine the exact underlying mechanism by which vitamin D levels may impair pregnancy rates in infertile women undergoing IVF/ICSI. None declared. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Health outcomes of children born after IVF/ICSI: a review of current expert opinion and literature.

PubMed

Fauser, B C J M; Devroey, P; Diedrich, K; Balaban, B; Bonduelle, M; Delemarre-van de Waal, H A; Estella, C; Ezcurra, D; Geraedts, J P M; Howles, C M; Lerner-Geva, L; Serna, J; Wells, D

2014-02-01

The Sixth Evian Annual Reproduction (EVAR) Workshop Group Meeting was held to evaluate the impact of IVF/intracytoplasmic sperm injection on the health of assisted-conception children. Epidemiologists, reproductive endocrinologists, embryologists and geneticists presented data from published literature and ongoing research on the incidence of genetic and epigenetic abnormalities and congenital malformations in assisted-conception versus naturally conceived children to reach a consensus on the reasons for potential differences in outcomes between these two groups. IVF-conceived children have lower birthweights and higher peripheral fat, blood pressure and fasting glucose concentrations than controls. Growth, development and cognitive function in assisted-conception children are similar to controls. The absolute risk of imprinting disorders after assisted reproduction is less than 1%. A direct link between assisted reproduction and health-related outcomes in assisted-conception children could not be established. Women undergoing assisted reproduction are often older, increasing the chances of obtaining abnormal gametes that may cause deviations in outcomes between assisted-conception and naturally conceived children. However, after taking into account these factors, it is not clear to what extent poorer outcomes are due to the assisted reproduction procedures themselves. Large-scale, multicentre, prospective epidemiological studies are needed to investigate this further and to confirm long-term health consequences in assisted-conception children. Assisted reproduction treatment is a general term used to describe methods of achieving pregnancy by artificial means and includes IVF and sperm implantation. The effect of assisted reproduction treatment on the health of children born using these artificial methods is not fully understood. In April 2011, fertility research experts met to give presentations based on research in this area and to look carefully at the evidence for the effects of assisted reproduction treatment on children's health. The purpose of this review was to reach an agreement on whether there are differences in the health of assisted-conception children with naturally conceived children. The researchers discovered no increased risk in birth defects in assisted-conception children compared with naturally conceived children. They found that IVF-conceived children have lower birth weights and higher fat under the skin, higher blood pressure and higher fasting glucose concentrations than naturally conceived children; however, growth, development and cognitive function are similar between groups. A very low risk of disorders of genetic control was observed in assisted-conception children. Overall, there did not appear to be a direct link between assisted reproduction treatment and children's health. The researchers concluded that the cause of some differences in the health of children conceived using assisted reproduction treatment may be due to the age of the woman receiving treatment. Large-scale, research studies are needed to study the long-term health of children conceived using assisted reproduction treatment. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

An economic evaluation of highly purified HMG and recombinant FSH based on a large randomized trial.

PubMed

Wechowski, Jaroslaw; Connolly, Mark; McEwan, Philip; Kennedy, Richard

2007-11-01

Public funding for IVF is increasingly being challenged by health authorities in an attempt to minimize health service costs. In light of treatment rationing, the need to consider costs in relation to outcomes is paramount. To assess the cost implications of gonadotrophin treatment options, an economic evaluation comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) has been conducted. The analysis is based on individual patient data from a large randomized controlled trial (n = 731) in a long agonist IVF protocol. The economic evaluation uses a discrete event simulation model to assess treatment costs in relation to live births for both treatments based on published UK costs. After one cycle the mean costs per IVF treatment for HP-HMG and rFSH were pound2396 (95% CI pound2383-2414) and pound2633 ( pound2615-2652), respectively. The average cost-saving of pound237 per IVF cycle using HP-HMG allows one additional cycle to be delivered for every 10 cycles. With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound8893 compared with pound11,741 for rFSH (P < 0.001). The cost-saving potential of HP-HMG in IVF was still apparent after varying critical cost parameters in the probabilistic sensitivity analysis.

IVF endocrinology: the Edwards era.

PubMed

Hillier, Stephen G

2013-12-01

Through pioneering human IVF as a global infertility treatment, Robert Edwards and his clinical partner Patrick Steptoe launched the field of IVF endocrinology. Following repeated failures with oocytes collected in human menopausal gonadotrophin (HMG) primed cycles timed to injection of human chorionic gonadotrophin (HCG), the first successful IVF pregnancy came from a spontaneous menstrual cycle. Intensive endocrine monitoring was used to track pre-ovulatory follicular development and collect a single ripe egg timed to the natural LH surge. Despite this groundbreaking achievement, ovulation induction was clearly required to make IVF treatment clinically robust and reliable. Ovarian stimulation with clomiphene citrate was used to achieve the first maternity from a superovulated human IVF cycle in 1980. HMG/HCG regimens were then successfully introduced-including substitution of 'pure' follicle-stimulating hormone as the principal ovarian stimulant. The application and success of IVF treatment were dramatically enhanced by the introduction of gonadotrophin-releasing hormone analogues that enabled elective control of endogenous gonadotrophin release during ovarian stimulation. Programmed gonadotrophin regimes yielding double-digit oocyte numbers became normal: 'more is better' was the ethos. Bob Edwards expressed increasing concern over the cost, complexity and potential long-term health risks of such high-order ovarian stimulation. In later life he repeatedly called for a return to minimalist approaches based on the natural menstrual cycle to improve oocyte quality over quantity. This article reviews the application of ovulation induction to human IVF and celebrates Edwards' abiding impact on the field, which firmly grounds him in the reproductive endocrinology pantheon.

Men's body mass index in relation to embryo quality and clinical outcomes in couples undergoing in vitro fertilization.

PubMed

Colaci, Daniela S; Afeiche, Myriam; Gaskins, Audrey J; Wright, Diane L; Toth, Thomas L; Tanrikut, Cigdem; Hauser, Russ; Chavarro, Jorge E

2012-11-01

To evaluate the association between men's body mass index (BMI), early embryo quality, and clinical outcomes in couples undergoing in vitro fertilization (IVF). Prospective cohort study. Fertility clinic in an academic medical center. 114 couples who underwent 172 assisted reproduction cycles. None. Fertilization rate, embryo quality, implantation rate, clinical pregnancy rate, and live birth rate. The fertilization rate was higher among obese men than among normal weight men in conventional IVF cycles. No statistically significant associations were found between men's BMI and the proportion of poor-quality embryos on day 3, slow embryo cleavage rate, or accelerated embryo cleavage rate. Men's BMI was unrelated to positive β-human chorionic gonadotropin rate, clinical pregnancy rate, or live-birth rate per embryo transfer. Among couples undergoing intracytoplasmic sperm injection, the odds of live birth in couples with obese male partners was 84% lower than the odds in couples with men with normal BMI. Our data suggest a possible deleterious effect of male obesity on the odds of having a live birth among couples undergoing intracytoplasmic sperm injection. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Growth Hormone Supplementation in the Luteal Phase Before Microdose GnRH Agonist Flare Protocol for In Vitro Fertilization.

PubMed

Dunne, Caitlin; Seethram, Ken; Roberts, Jeffrey

2015-09-01

Growth hormone (GH) acts in both early and late follicular development to stimulate the proliferation and differentiation of granulosa cells and to increase the production of estradiol in animal and human ovaries. Investigators have therefore explored GH supplementation to improve outcomes in women undergoing in vitro fertilization, with the greatest interest in women with diminished ovarian reserve. Recent meta-analyses indicate that GH supplementation can be beneficial for poor responders undergoing IVF. In most studies, GH has been given concomitantly with gonadotropins during the follicular phase; this may not be optimal, since follicular recruitment begins during the preceding luteal phase. We therefore wished to examine the effect of GH supplementation in the luteal phase before controlled ovarian stimulation (COH) with a microdose GnRH agonist flare (MDF) protocol in women undergoing in vitro fertilization. We performed a retrospective matched case-control study of patients undergoing treatment at a private IVF facility between June 2012 and July 2013. Patients identified as poor responders to COH were offered adjuvant GH treatment as part of their ovarian stimulation regimen. The patients in the experimental group chose to take GH, 3.33 mg daily by subcutaneous injection for 14 days, before starting COH. All patients had an MDF stimulation protocol using 450 IU of follicle stimulating hormone (FSH) daily. A total of 42 women were included in the study. There were 14 women in the experimental group (GH) and 28 controls (C) matched for age, BMI, and day 3 FSH level. There was no difference between the groups in clinical pregnancy rate (GH = 29%, C = 32%, P = 0.99), number of mature oocytes retrieved (GH = 2.5, C = 5.0, P = 0.13), cycle cancellation rate (GH = 21%, C = 14%, P = 0.88), duration of COH (GH = 10.1, C = 10.1, P = 0.93), or mean peak estradiol level (GH = 4174 pmol/L, C = 5105 pmol/L, P = 0.44). The administration of growth hormone during the luteal phase before a microdose GnRH agonist flare protocol for in vitro fertilization did not improve outcomes in "poor responder" patients.

Report of results obtained in 2,934 women using donor sperm: donor insemination versus in vitro fertilization according to indication.

PubMed

Viloria, Thamara; Garrido, Nicolas; Minaya, Francisco; Remohí, José; Muñoz, Manuel; Meseguer, Marcos

2011-11-01

To demonstrate that the use of donor sperm leads to varying outcome rates and that its use has evolved. Retrospective observational cohort study. University-affiliated private IVF setting. Women (2,934) undergoing donor insemination (DI) or IVF with donor sperm (IVF-D). None. We evaluated the distribution of the clinical indications for the use of donated sperm, studying the reproductive outcome. A total of 1,663 DI (57%) and 1,271 IVF-D (43%) were performed. There were significant differences in the indications for the use of donated sperm (DI vs. IVF-D). Regarding pregnancy rates (PR), cases of nonobstructive azoospermia presented the highest rate (29.1%), whereas cases of intracytoplasmic sperm injection (ICSI) failures and single women showed rates of 27.6% and 22.6%, respectively. Meanwhile, patients with ICSI failures achieved the highest PRs in IVF cycles (48.7%), whereas nonobstructive azoospermia and single women showed rates of 42.0% and 38.2%, respectively. There have been significant increases in the use of donated sperm in single women. Single women, which also represented the oldest group, show a lower probability of achieving pregnancy, and thus represent a subfertile population. Associated factors could include advanced maternal age. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

A case-control pilot study of low-intensity IVF in good-prognosis patients.

PubMed

Gleicher, Norbert; Weghofer, Andrea; Barad, David H

2012-04-01

Low-intensity IVF (LI-IVF) is rapidly gaining in popularity. Yet studies comparing LI-IVF to standard IVF are lacking. This is a case-control pilot study, reporting on 14 first LI-IVF and 14 standard IVF cycles in women with normal age-specific ovarian reserve under age 38, matched for age, laboratory environment, staff and time of cycle. LI-IVF cycles underwent mild ovarian stimulation, utilizing clomiphene citrate, augmented by low-dose gonadotrophin stimulation. Control patients underwent routine ovarian stimulation. LI-IVF and regular IVF patients were similar in age, body mass index, FSH and anti-Müllerian hormone. Standard IVF utilized more gonadotrophins (P<0.001), yielded more oocytes (P<0.001) and cryopreserved more embryos (P<0.001). With similar embryo numbers transferred, after ethnicity adjustments, standard IVF demonstrated better odds for pregnancy (OR 7.07; P=0.046) and higher cumulative pregnancy rates (63.3% versus 21.4%; OR 6.6; P=0.02). Adjustments for age, ethnicity and diagnosis maintained significance but oocyte adjustment did not. Cost assessments failed to reveal differences between LI-IVF and standard IVF. In this small study, LI-IVF reduced pregnancy chances without demonstrating cost advantages, raising questions about its utility. In the absence of established clinical and/or economic foundations, LI-IVF should be considered an experimental procedure. Low-intensity IVF (LI-IVF) is increasingly propagated as an alternative to standard IVF. LI-IVF has, however, never been properly assessed in comparison to standard IVF. Such a comparison is presented in the format of a small pilot study, matching LI-IVF cycles with regular IVF cycles and comparing outcomes as well as costs. The study suggests that LI-IVF, at least in this setting, is clinically inferior and economically at best similar to standard IVF. LI-IVF should, therefore, as of this point not be offered as routine IVF treatment but only as an experimental procedure. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Infertility Evaluation and Treatment among Women in the United States

PubMed Central

Kessler, Lawrence M.; Craig, Benjamin M.; Plosker, Shayne M.; Reed, Damon R.; Quinn, Gwendolyn P.

2013-01-01

Objective To examine the characteristics of women seeking infertility evaluation and treatment. Design Cross-sectional survey based on in-person interviews, followed by two-step hurdle analysis. Participants 4,558 married or cohabitating women ages 25–44 Setting U.S. household population of women based on the 2006–2010 National Survey of Family Growth Intervention None Main Outcome Measure(s) Likelihood of seeking preliminary infertility evaluation. Likelihood of seeking infertility treatment once evaluated. Treatment type provided. Results 623 women (13.7%) reported seeking infertility evaluation, of which 328 reported undergoing subsequent infertility treatment. Age at marriage, marital status, education, health insurance status, race/ethnicity, and religion were associated with the likelihood of seeking infertility evaluation. For example, the predicted probability that a non-White woman who married at 25 will seek evaluation was 12%. This probability increased to 34% for White women with a graduate degree who married at age 30. Among women who are evaluated, income, employment status, and ethnicity correlated strongly with the likelihood of seeking infertility treatment. Infertility drug therapy was the most frequent treatment used. Reproductive surgery and in vitro fertilization (IVF) were used the least. Conclusions The use of infertility services is not random and understanding the socio-demographic factors correlated with use may assist new couples with family planning. Roughly 50% of the women evaluated for infertility progressed to treatment, and only a small proportion were treated with more advanced assisted reproductive technologies (ARTs) such as IVF therapy. Future research aimed at improving access to effective healthcare treatments within the boundaries of affordability is warranted. PMID:23849845

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

PubMed

Kwan, Irene; Bhattacharya, Siladitya; Kang, Angela; Woolner, Andrea

2014-08-24

Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) treatment has included transvaginal ultrasonography (TVUS) plus serum estradiol levels to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS) whilst achieving the good ovarian response needed for assisted reproduction treatment. The need for combined monitoring (using TVUS and serum estradiol) during ovarian stimulation in assisted reproduction is controversial. It has been suggested that combined monitoring is time consuming, expensive and inconvenient for women and that simplification of IVF and ICSI therapy by using TVUS only should be considered. To assess the effect of monitoring controlled ovarian hyperstimulation (COH) in IVF and ICSI cycles in subfertile couples with TVUS only versus TVUS plus serum estradiol concentration, with respect to rates of live birth, pregnancy and OHSS. We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, the National Research Register, and web-based trial registers such as Current Controlled Trials. The last search was conducted in May 2014. There was no language restriction applied. All references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with TVUS only versus TVUS plus serum estradiol concentrations in women undergoing COH for IVF and ICSI treatment were included. Three review authors independently selected the studies, extracted data and assessed risk of bias. They resolved disagreements by discussion with the rest of the authors. Outcomes data were pooled and summary statistics were presented when appropriate. The quality of the evidence was rated using the GRADE methods. With this update, four new studies were identified resulting in a total of six trials including 781 women undergoing monitoring of COH with either TVUS alone or a combination of TVUS and serum estradiol concentration during IVF or ICSI treatment.None of the six studies reported our primary outcome of live birth rate. Pooled data showed no evidence of a difference in clinical pregnancy rate per woman between monitoring with TVUS only and combined monitoring (odds ratio (OR) 1.10; 95% confidence interval (CI) 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). This suggests that compared with women with a 34% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate in women using TVUS only was between 29% and 44%.There was no evidence of a difference between the groups in the reported cases of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that compared with women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate in women monitored by TVUSS only was between 2% and 8%.There was no evidence of a difference between the groups in the mean number of oocytes retrieved pre woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; low quality evidence).The evidence was low quality for all comparisons. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in treatment protocols. Quality assessment was hampered by the lack of methodological descriptions in several studies. This review update found no evidence from randomised trials to suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS. The number of oocytes retrieved appeared similar for both monitoring protocols. The data suggest that both these monitoring methods are safe and reliable. However, these results should be interpreted with caution because the overall quality of the evidence was low. Results were compromised by imprecision and poor reporting of study methodology. A combined monitoring protocol including both TVUS and serum estradiol may need to be retained as precautionary good clinical practice and as a confirmatory test in a subset of women to identify those at high risk of OHSS. An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.

IVF, same-sex couples and the value of biological ties.

PubMed

Di Nucci, Ezio

2016-12-01

Ought parents, in general, to value being biologically tied to their children? Is it important, in particular, that both parents be biologically tied to their children? I will address these fundamental questions by looking at a fairly new practice within IVF treatments, so-called IVF-with-ROPA (Reception of Oocytes from Partner), which allows lesbian couples to 'share motherhood', with one partner providing the eggs while the other becomes pregnant. I believe that IVF-with-ROPA is, just like other IVF treatments, morally permissible, but here I argue that the increased biological ties which IVF-with-ROPA allows for do not have any particular value beside the satisfaction of a legitimate wish, because there is no intrinsic value in a biological tie between parents and children; further, I argue that equality within parental projects cannot be achieved by redistributing biological ties. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Cost-effectiveness of treatment strategies in women with PCOS who do not conceive after six cycles of clomiphene citrate.

PubMed

Moolenaar, Lobke M; Nahuis, Marleen J; Hompes, Peter G; van der Veen, Fulco; Mol, Ben Willem J

2014-05-01

This study evaluated the cost-effectiveness of treatments for women with polycystic ovary syndrome (PCOS) who ovulate on clomiphene citrate but do not conceive after six cycles. A decision-analytic framework was developed for six scenarios: (1) three cycles of IVF; (2) continuation of clomiphene citrate for six cycles, followed by three cycles of IVF in case of no birth; (3) six cycles of gonadotrophins and three cycles of IVF; (4) 12 cycles of gonadotrophins and three cycles of IVF; (5) continuation of clomiphene citrate for six cycles, six cycles of gonadotrophins and three cycles of IVF; (6) continuation of clomiphene citrate for six cycles, 12 cycles of gonadotrophins and three cycles of IVF. Two-year cumulative birth rates were 58%, 74%, 89%, 97%, 93% and 98% and costs per couple were € 9518, € 7530, € 9711, € 9764, € 7651 and € 7684 for scenarios 1-6, respectively. Scenario 2 was the lowest cost option. The extra cost for at least one live birth in scenario 5 was € 629 and in scenario 6 € 630. In these subjects, continuation of treatment for six cycles of clomiphene citrate, 6 or 12 cycles of gonadotrophins and IVF is potentially cost-effective. These results should be confirmed in a randomized clinical trial. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Parental contributions to early embryo development: influences of urinary phthalate and phthalate alternatives among couples undergoing IVF treatment.

PubMed

Wu, Haotian; Ashcraft, Lisa; Whitcomb, Brian W; Rahil, Tayyab; Tougias, Ellen; Sites, Cynthia K; Pilsner, J Richard

2017-01-01

Are preconception urinary concentrations of phthalates and phthalate alternatives associated with diminished early stage embryo quality in couples undergoing IVF? Male, but not female, urinary concentrations of select metabolites of phthalates and phthalate alternatives are associated with diminished blastocyst quality. Although phthalates are endocrine disrupting compounds associated with adverse reproductive health, they are in widespread use across the world. Male and female preconception exposures to select phthalates have been previously associated with adverse reproductive outcomes in both the general population and in those undergoing IVF. This prospective cohort included 50 subfertile couples undergoing IVF in western Massachusetts. This study includes the first 50 couples recruited from the Baystate Medical Center's Fertility Center in Springfield, MA, as part of the Sperm Environmental Epigenetics and Development Study (SEEDS). Relevant data from both partners, including embryo quality at the cleavage (Day 3) and blastocyst (Day 5) stages, were collected by clinic personnel during the normal course of an IVF cycle. A spot urine sample was collected from both male and female partners on the same day as semen sample procurement and oocyte retrieval. Concentrations of 17 urinary metabolite were quantified by liquid chromatography mass spectrometry and normalized via specific gravity. Generalized estimating equations were used to estimate odds ratios (OR) and 95% CI, with urinary phthalates and phthalate alternatives fitted as continuous variables and embryo quality as a binary variable. The 50 couples contributed 761 oocytes, of which 423 progressed to the cleavage stage, 261 were high-quality cleavage stage embryos, 137 were transferrable quality blastocysts and 47 were high-quality blastocysts. At the cleavage stage, male urinary monoethyl phthalate concentrations were positively associated with high-quality cleavage stage embryos (OR = 1.20, 95% CI 1.01-1.43, P = 0.04); no other significant associations were observed at this stage. At the blastocyst stage, male urinary concentrations of monobenzyl phthalate (OR = 0.55, 95% CI 0.36-0.84, P = 0.01), mono-3-hydroxybutyl phthalate (OR = 0.37, 95% CI 0.18-0.76, P = 0.01), mono-n-butyl phthalate (OR = 0.55, 95% CI 0.42-0.73, P < 0.01) and monomethyl phthalate (OR = 0.39, 95% CI 0.26-0.60, P < 0.01) were inversely associated with high-quality blastocysts. A borderline statistically significant relationship was observed for male concentrations of mono(2-ethylhexyl) phthalate (OR = 0.52, 95% CI 0.27-1.00, P = 0.05) and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (OR = 0.21, 95% CI 0.04-1.03, P = 0.05) at the blastocyst stage. Similar inverse associations were observed between male urinary phthalate metabolite concentrations and likelihood of transferrable quality blastocysts. For female partners, select metabolites were positively associated with odds of high or transferrable blastocyst quality, but the observed associations were not consistent across blastocyst quality measures or between sex-specific and couples-level models. All models were adjusted for age of both partners, urinary metabolite concentrations of female partners and male infertility status, while models of blastocysts were additionally adjusted for embryo quality at cleavage stage. Our modest sample included only 50 couples contributing one cycle each. In addition, non-differential misclassification of exposure remains a concern given the single-spot urine collection and the short half-life of phthalates. Our results suggest an inverse association between male preconception concentrations of select phthalate metabolites and blastocyst quality, likely occurring after genomic activation. If corroborated with other studies, such findings will have public health and clinical significance for both the general population and those undergoing IVF. This work was generously supported by grant K22-ES023085 from the National Institute of Environmental Health Sciences. The authors declare no competing interests. N/A. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Comparison of luteal estradiol patch and gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation versus microdose gonadotropin-releasing hormone agonist protocol for patients with a history of poor in vitro fertilization outcomes.

PubMed

Weitzman, Vanessa N; Engmann, Lawrence; DiLuigi, Andrea; Maier, Donald; Nulsen, John; Benadiva, Claudio

2009-07-01

To compare IVF outcomes in poor-responder patients undergoing stimulation after luteal phase E(2) patch/GnRH antagonist (LPG) protocol versus microdose GnRH agonist protocol. Retrospective analysis. University-based IVF center. Forty-five women undergoing ovarian stimulation for IVF using the LPG protocol were compared with 76 women stimulated with the microdose GnRH agonist protocol from May 2005 to April 2006. Cancellation rate, number of oocytes retrieved, and clinical pregnancy rates. The mean number of oocytes (9.1 +/- 4.1 vs. 8.9 +/- 4.3) and mature oocytes (6.7 +/- 3.5 vs. 6.8 +/- 3.1) retrieved were similar, as were the fertilization rates (70.0% +/- 24.2% vs. 69.9% +/- 21.5%) and the number of embryos transferred (2.5 +/- 1.1 vs. 2.7 +/- 1.3). The cancellation rate was not significantly different between the groups (13/45, 28.9% vs. 23/76, 30.3%). Likewise, there were no significant differences among the implantation rate (15.0% vs. 12.5%), clinical pregnancy rate (43.3% vs. 45.1%), and ongoing pregnancy rate per transfer (33.3% vs. 26.0%) between both groups. This study demonstrates that the use of an E(2) patch and a GnRH antagonist during the preceding luteal phase in patients with a history of failed cycles can provide similar IVF outcomes when compared with the microdose GnRH agonist protocol.

Certain Less Invasive Infertility Treatments Associated with Different Levels of Pregnancy-Related Anxiety in Pregnancies Conceived via In Vitro Fertilization.

PubMed

Stevenson, Eleanor Lowndes; Sloane, Richard

2017-01-01

Research supports that in vitro fertilization causes anxiety and that anxiety can continue into the resulting pregnancy. Most women who have IVF will have a less invasive treatment for infertility prior to IVF; however, it is unclear if specific less invasive treatment cycles impact anxiety that is experienced in the pregnancy resulting from IVF. A prospective study was conducted for women who became pregnant via IVF, and data was collected about reported previous non-IVF treatment cycles as well as Pregnancy Related Anxiety Measure. Latent Class Analysis was conducted A p-value of ≤0.05 was considered significant. 144 subjects participated and were highly educated, affluent, married, and primarily white. The LCA process yielded two groups that on average had similar levels on most items except for use of intra uterine insemination and/or ovarian stimulation. This information was used to generate four exhaustive and mutually exclusive groups: Stimulation Only (stim-only), Stimulation and Intra uterine Insemination (stim-IUI), Intra uterine Insemination only (IUI only), or No Treatment (No Tx). ANOVA found that those in the Stim Only group had statistically significantly higher PRAM scores than the Stim IUI (p=0.0036), the IUI only group (p=0.05), and the No Tx group (p=0.0013). Women who become pregnant via IVF and had a history of non- in vitro fertilization cycles that only involved ovarian stimulation experienced more pregnancy-specific anxiety in the pregnancy that results from in vitro fertilization.

Which factors are most predictive for live birth after in vitro fertilization and intracytoplasmic sperm injection (IVF/ICSI) treatments? Analysis of 100 prospectively recorded variables in 8,400 IVF/ICSI single-embryo transfers.

PubMed

Vaegter, Katarina Kebbon; Lakic, Tatevik Ghukasyan; Olovsson, Matts; Berglund, Lars; Brodin, Thomas; Holte, Jan

2017-03-01

To construct a prediction model for live birth after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and single-embryo transfer (SET) after 2 days of embryo culture. Prospective observational cohort study. University-affiliated private infertility center. SET in 8,451 IVF/ICSI treatments in 5,699 unselected consecutive couples during 1999-2014. A total of 100 basal patient characteristics and treatment data were analyzed for associations with live birth after IVF/ICSI (adjusted for repeated treatments) and subsequently combined for prediction model construction. Live birth rate (LBR) and performance of live birth prediction model. Embryo score, treatment history, ovarian sensitivity index (OSI; number of oocytes/total dose of FSH administered), female age, infertility cause, endometrial thickness, and female height were all independent predictors of live birth. A prediction model (training data set; n = 5,722) based on these variables showed moderate discrimination, but predicted LBR with high accuracy in subgroups of patients, with LBR estimates ranging from <10% to >40%. Outcomes were similar in an internal validation data set (n = 2,460). Based on 100 variables prospectively recorded during a 15-year period, a model for live birth prediction after strict SET was constructed and showed excellent calibration in internal validation. For the first time, female height qualified as a predictor of live birth after IVF/ICSI. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Corifollitropin alfa compared to daily rFSH or HP-HMG in GnRH antagonist controlled ovarian stimulation protocol for patients undergoing assisted reproduction.

PubMed

Souza, Priscila Morais Galvão; Carvalho, Bruno Ramalho de; Nakagawa, Hitomi Miura; Rassi, Thalita Reis Esselin; Barbosa, Antônio César Paes; Silva, Adelino Amaral

2017-06-01

This study aimed to compare the outcomes of controlled ovarian stimulation (COS) with corifollitropin alfa versus daily recombinant follicle-stimulating hormone (rRFSH) or highly purified human menopausal gonadotropin (HP-HMG) in patients undergoing in vitro fertilization (IVF) cycles based on gonadotropin-releasing hormone (GnRH) antagonist protocols. The primary endpoints were total number of oocytes and mature oocytes. This retrospective study looked into 132 controlled ovarian stimulation cycles from IVF or oocyte cryopreservation performed in a private human reproduction center between January 1 and December 31, 2014. Enrollment criteria: women aged < 40 years submitted to COS with corifollitropin alfa 100µg or 150µg (n = 26) and rFSH or HP-HMG in the first seven days of treatment with daily doses of 150-225 IU (n = 106); all subjects were on GnRH antagonist protocols. The groups had similar mean ages and duration of stimulation. The mean number ± standard deviation of total aspirated oocytes and MII oocytes was 11.9±10 and 10.3±7.9 in the corifollitropin alfa group, and 10.9±7.2 and 8.6±5.7 in the group on rFSH or HMG (p>0.05). There were no significant differences in fertilization (76.9% vs. 76.8%, p=1.0), biochemical pregnancy (66.7% vs. 47.2%, p=0.1561) or embryo implantation rates (68.7% vs. 50%, p=0.2588) between the groups using corifollitropin alfa and rFSH or HMG, respectively. Corifollitropin alfa seems to be as effective as rFSH or HP-HMG when used in the first seven days of ovulation induction for patients undergoing assisted reproduction in GnRH antagonist protocols.

Minimal stimulation protocol using letrozole versus microdose flare up GnRH agonist protocol in women with poor ovarian response undergoing ICSI.

PubMed

Mohsen, Iman Abdel; El Din, Rasha Ezz

2013-02-01

To compare the IVF outcomes of letrozole/antagonist and microdose GnRH agonist flare up protocols in poor ovarian responders undergoing intracytoplasmic sperm injection. A randomized controlled trial was performed in patients with one or more previous failed IVF cycles in which four or less oocytes were retrieved when the gonadotrophin starting dose was at least 300 IU/day. Sixty patients were randomized by computer-generated list to receive either letrozole/antagonist (mild stimulation) n = 30 or GnRH-a protocol (microdose flare) n = 30. Both groups were similar with respect to background and hormonal characteristics (age, duration of infertility, BMI, FSH, LH and E2). The clinical pregnancy rate per cycle was similar in both groups (13.3 vs. 16.6%; OR = 0.769; 95% CI = 0.185, 3.198). The doses of used gonadotropins and the number of stimulation days were significantly lower in the letrozole/antagonist protocol. The peak E2 level on the day of hCG, the endometrial thickness, the retrieved oocytes, the number of fertilized oocytes, the number of transferred embryos and the cancellation rate were statistically similar in both groups. The letrozole/antagonist protocol is a cost-effective and patient-friendly protocol that may be used in poor ovarian responders for IVF/ICSI.

GnRH agonist versus GnRH antagonist in ovarian stimulation: is the emperor naked?

PubMed

Orvieto, R; Rabinson, J; Meltzer, S; Homburg, R; Anteby, E; Zohav, E

2006-01-01

The aim of the study was to evaluate the influence of type of GnRH-analog used during controlled ovarian hyperstimulation (COH) on the outcome of in vitro fertilization (IVF) cycles. All consecutive women aged < or = 35 years admitted to our IVF unit from January 2001 to December 2004 were enrolled in the study. Only patients undergoing up to their third IVF cycle attempt were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryos transferred, and clinical pregnancy rate were compared between women given GnRH-agonist or GnRH-antagonist during COH. Four hundred and eighty-seven consecutive IVF cycles were evaluated, 226 in the agonist group and 261 in the antagonist group. A clinical pregnancy was achieved in 93 patients in the agonist group (pregnancy rate 41.2% per cycle) and 66 patients in the antagonist grup (pregnancy rate 25.3%); this difference was statistically significant (p < 0.01). The agonist group also used significantly more gonadotropin ampoules, required longer stimulation, and had higher estradiol levels on the day of human chorionic gonadotropin administration. The midluteal long GhRH-agonist suppressive protocol should be the protocol of choice in young patients in their first three IVF cycle attempts.

Embryo quality and implantation rate in two different culture media: ISM1 versus Universal IVF Medium.

PubMed

Xella, Susanna; Marsella, Tiziana; Tagliasacchi, Daniela; Giulini, Simone; La Marca, Antonio; Tirelli, Alessandra; Volpe, Annibale

2010-04-01

To compare the outcome of two different culture media marketed by the MediCult AS Company (Jyllinge, Denmark)-Universal IVF Medium and ISM1 Medium culture-which, in addition to glucose, pyruvate, and energy-providing components, also contain amino acids, nucleotides, vitamins, and cholesterol. Laboratory and retrospective clinical study. University teaching hospital. A total of 726 patients, undergoing IVF-intracytoplasmic sperm injection procedure, comparable in mean age range, oocyte retrieval, and infertility indication, were included in the study. Laboratory quality and standard procedures were maintained unaffected. Oocyte retrieval, different embryo culture media. Embryo quality, ongoing pregnancy, and implantation rate. The frequency of good-quality embryos (79% vs. 74%) and the percentages of ongoing pregnancy (27.5% vs. 18%) and implantation rate (15% vs. 10%) were significantly higher in the group treated with ISM1 Medium rather than Universal IVF Medium. ISM1 Medium culture seems to improve the performance of embryonic growth and development, as well as increasing the percentage of pregnancy. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Serum anti-Mullerian hormone assessment of ovarian reserve and polycystic ovary syndrome status over the reproductive lifespan.

PubMed

Tremellen, Kelton; Zander-Fox, Deidre

2015-08-01

To determine normal ranges for serum anti-Mullerian hormone (AMH) using the new automated Elecsys AMH assay platform, with a view to establishing values that signify premature loss of ovarian reserve, increased risk for an excessive response during IVF stimulation and a likely diagnosis of polycystic ovary syndrome (PCOS). Serum AMH was measured by the Elecsys automated electrochemiluminescence assay in 654 women undergoing gynaecological assessment. Serum AMH levels peaked before 25 years of age, with mean AMH levels halving by 36 and falling to a quarter of their peak by 40 years of age. Overall, AMH results of 95% of patients with PCOS exceeded the 50th percentile for their age, with 72.1% having an AMH result in the top quartile for age. ROC analysis suggested that a serum AMH ≥36 pmol L(-1) is the best determinant of PCOS status (sensitivity 83.7% and specificity 82.3%). Serum AMH exhibited an excellent correlation with ultrasound-assessed antral follicle count (AFC) (r = 0.836, P < 0.0001), with a result of 20 pmol L(-1) corresponding to an AFC of 16 and, therefore, increased risk of ovarian hyperstimulation syndrome (OHSS) during IVF treatment. Serum AMH is a sensitive marker of age-related decline in ovarian reserve status. A serum AMH result >36 pmol L(-1) , or above the 75th percentile for age, is highly suggestive of a diagnosis of PCOS. A serum AMH result below the 10th percentile for age suggests accelerated loss of ovarian reserve, while an AMH result exceeding 20 pmol L(-1) suggests an increased risk of OHSS during IVF treatment. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Pregnancy outcome using general anesthesia versus spinal anesthesia for in vitro fertilization.

PubMed

Azmude, Azra; Agha'amou, Shahrzad; Yousefshahi, Fardin; Berjis, Katayoun; Mirmohammad'khani, Majid; Sadaat'ahmadi, Farahnaz; Ghods, Kamran; Dabbagh, Ali

2013-09-01

There is a considerable rate of fertility failure and this causes a great burden of untoward effects for patients. Usually a considerable number of these patients undergo anesthesia for their treatment. This study was designed to compare the effects of general and spinal anesthesia on these patients. In a randomized clinical trial, after taking informed written consent from the patients, 200 patients entered the study; 100 in each. During a 2 year period, women aged 20 to 40 years entered the study (one group receiving spinal anesthesia and the other, receiving general anesthesia). Ovum retrieval protocols were the same. Nonparametric and parametric analyses were used for data analysis. P value less than 0.05 was considered significant. There was no difference between the two groups regarding demographic variables. 15 of 100 patients (15%) in the general anesthesia group and 27 of 100 patients (27%) in the spinal anesthesia group had successful pregnancy after IVF; so, spinal anesthesia increased significantly the chance of IVF success (P value < 0.001; Chi Square). The results of this study demonstrated that spinal anesthesia increased the chance of fertilization success.

Microorganisms within Human Follicular Fluid: Effects on IVF

PubMed Central

Pelzer, Elise S.; Allan, John A.; Waterhouse, Mary A.; Ross, Tara; Beagley, Kenneth W.; Knox, Christine L.

2013-01-01

Our previous study reported microorganisms in human follicular fluid. The objective of this study was to test human follicular fluid for the presence of microorganisms and to correlate these findings with the in vitro fertilization (IVF) outcomes. In this study, 263 paired follicular fluids and vaginal swabs were collected from women undergoing IVF cycles, with various causes for infertility, and were cultured to detect microorganisms. The cause of infertility and the IVF outcomes for each woman were correlated with the microorganisms detected within follicular fluid collected at the time of trans-vaginal oocyte retrieval. Microorganisms isolated from follicular fluids were classified as: (1) ‘colonizers’ if microorganisms were detected within the follicular fluid, but not within the vaginal swab (at the time of oocyte retrieval); or (2) ‘contaminants’ if microorganisms detected in the vagina at the time of oocyte retrieval were also detected within the follicular fluid. The presence of Lactobacillus spp. in ovarian follicular fluids was associated with embryo maturation and transfer. This study revealed microorganisms in follicular fluid itself and that the presence of particular microorganisms has an adverse affect on IVF outcomes as seen by an overall decrease in embryo transfer rates and pregnancy rates in both fertile and infertile women, and live birth rates in women with idiopathic infertility. Follicular fluid microorganisms are a potential cause of adverse pregnancy outcomes in IVF in both infertile women and in fertile women with infertile male partners. PMID:23554970

3P: Personalized Pregnancy Prediction in IVF Treatment Process

NASA Astrophysics Data System (ADS)

Uyar, Asli; Ciray, H. Nadir; Bener, Ayse; Bahceci, Mustafa

We present an intelligent learning system for improving pregnancy success rate of IVF treatment. Our proposed model uses an SVM based classification system for training a model from past data and making predictions on implantation outcome of new embryos. This study employs an embryo-centered approach. Each embryo is represented with a data feature vector including 17 features related to patient characteristics, clinical diagnosis, treatment method and embryo morphological parameters. Our experimental results demonstrate a prediction accuracy of 82.7%. We have obtained the IVF dataset from Bahceci Women Health, Care Centre, in Istanbul, Turkey.

The impact of endometriosis on the outcome of Assisted Reproductive Technology.

PubMed

González-Comadran, Mireia; Schwarze, Juan Enrique; Zegers-Hochschild, Fernando; Souza, Maria do Carmo B; Carreras, Ramon; Checa, Miguel Ángel

2017-01-24

Endometriosis has been described to impair fertility through various mechanisms. However, studies evaluating the reproductive outcomes of women undergoing assisted reproductive technologies show controversial results. The aim of this study is to assess whether the reproductive outcome is impaired among women with endometriosis-associated infertility undergoing IVF. A retrospective cohort study was performed, including women undergoing IVF reported by the Red Latinoamericana de Reproduccion Asistida (Redlara) registry, between January 2010 and December 2012. The study group included women with endometriosis-associated infertility, and the control group women with tubal factor, endocrine disorders or unexplained infertility. Women above 40 years, severe male factor and premature ovarian failure were excluded. The reproductive outcomes of between both groups were compared. The primary outcome was live birth. Secondary outcomes included clinical pregnancy, miscarriage, number of oocytes retrieved and number of fertilized oocytes. Outcomes were assessed after the first fresh IVF cycle, and were adjusted for age and number of embryos transferred. A total of 22.416 women were included (3.583 with endometriosis and 18.833 in the control group). Mean age of patients in the endometriosis group and control group was 34.86 (3.47) and 34.61 (3.91) respectively, p = 0.000. The mean number of oocytes retrieved were 8.89 (6.23) and 9.86 (7.02) respectively, p = 0.000. No significant differences were observed between groups in terms of live birth (odds ratio (OR) 1.032, p = 0.556), clinical pregnancy (OR 1.044, p = 0.428) and miscarriage rates (OR 1.049, p = 0.623). Women with endometriosis had significantly lower number of oocytes retrieved (incidence risk ratio (IRR) 0.917, 95% CI 0.895-0.940), however, the number of fertilized oocytes did not differ among the two groups when adjusting for the number of oocytes retrieved (IRR 1.003, p = 0.794). An age-stratified analysis was performed, and no differences were observed in the reproductive outcomes between groups for women aged under 35 and 35 to 40. Reproductive outcomes among women undergoing IVF and diagnosed with endometriosis-associated infertility do not differ significantly from women without the disease. Although women with endometriosis generate fewer oocytes, fertilization rate is not impaired and the likelihood of achieving a live birth is also not affected.

[Regret of female sterilization].

PubMed

Öhman, Malin Charlotta; Andersen, Lars Franch

2015-11-16

Regret of sterilization is inversely correlated to age at the time of sterilization. The minimum age for legal sterilization in Denmark has recently been lowered to 18 years. In Denmark surgical refertilization has almost completely been replaced by in vitro fertilization (IVF). In recent literature pregnancy results after surgical refertilization are easily comparable to IVF. Refertilization may in some cases be advantageous to IVF treatment. Women requesting reversal of sterilization should be offered individualized evaluation and differentiated treatment. It is recommended that surgical refertilization is performed at very few centres.

[Current program of in-vitro fertilization at the Erasmus Hospital: initial results and original ethical aspects].

PubMed

Englert, Y; Van den Bergh, M; Rodesch, C; Van der Vorst, P; Berberoglugil, P; Laruelle, C; Biramane, J; Gervy, C; Schwers, J

1991-10-01

The clinical results including all in vitro fertilization (IVF) cycles with oocyte pick-up in 1990 are presented. Different types of treatment including classical IVF and embryo transfer, laparoscopic replacement of zygotes in the fallopian tube (ZIFT), IVF with donor sperm (IVF-D), cross fertilization test, embryo freezing, oocyte donation and IVF with epididymal sperm were performed. The total pregnancy rate obtained reaches 38% per oocyte pick-up, 30% of clinical pregnancies (including 4 pregnancies obtained with frozen and thawed embryos). The anticipated "Take Home Baby Rate" will be around 25% per oocyte pick-up, 26 of these 40 pregnancies being today over 20 weeks of gestation. Particular ethical aspects of the program are presented: a study on couple's attitudes regarding embryo freezing as well as the final destination of possibly remaining supernumerary embryos will stress the importance of a precise clear decision on that matter before entering IVF treatment. Indeed the couple's idea on embryo destiny were very precise but also very different. The oocyte donation program has the originality of preserving the donor's anonymity by exchanging the donors recruited by the patients. It will be stressed that this kind of approach combines higher pregnancy chances for the patients, respect of ethical principles linked to gamete donation and gives satisfaction to the patients. The global normalized pregnancy cumulative curve shows that 60% of the couples entering IVF treatment will obtain a child within the first three pick-up cycles.

Assessing long-run economic benefits attributed to an IVF-conceived singleton based on projected lifetime net tax contributions in the UK.

PubMed

Connolly, M; Gallo, F; Hoorens, S; Ledger, W

2009-03-01

Over the past decade, demand for fertility treatments has increased as a result of delaying time to first pregnancy and growing awareness and acceptance of available treatment options. Despite increasing demand, health authorities often view infertility as a low health priority and consequently limit access to treatments by rationing and limiting funds. To assess the long-term economic benefits attributed to in vitro fertilization (IVF)-conceived children, we developed a health investment model to evaluate whether state-funded IVF programmes in the UK represent sound fiscal policies. Based on the average investment cost to conceive an IVF singleton, we describe the present value of net taxes derived from gross taxes paid minus direct government transfers received (e.g. education, health, pension) over the lifetime of the child. To establish the present value of investing in IVF, we have discounted all costs from benefits (i.e. lifetime taxes paid) using UK Treasury department rates based on a singleton delivery with similar characteristics for education, earnings, health and life expectancy to a naturally conceived child. The lifetime discounted value of net taxes from an IVF-conceived child with mother aged 35 is pound 109,939 compared with pound 122,127 for a naturally conceived child. The lifetime undiscounted net tax contribution for the IVF-conceived child and naturally conceived child are pound 603,000 and pound 616,000, respectively. An investment of pound 12,931 to achieve an IVF singleton is actually worth 8.5-times this amount to the UK Treasury in discounted future tax revenue. The analysis underscores that costs to the health sector are actually investments when a broader government perspective is considered over a longer period of time.

Improved embryo development in Japanese black cattle by in vitro fertilization using ovum pick-up plus intracytoplasmic sperm injection with dithiothreitol.

PubMed

Oikawa, Toshinori; Itahashi, Tomoko; Numabe, Takashi

2016-01-01

The purpose of this study was to determine whether dithiothreitol (DTT) treatment of sperm and ethanol activation improve embryo production by intracytoplasmic sperm injection (ICSI). Further, we compared ICSI with standard in vitro fertilization (IVF) in oocytes obtained from cattle. We demonstrated that DTT reduced the disulfide bond in the bovine sperm head. Using oocytes obtained from a slaughterhouse, ICSI-DTT treatment without ethanol showed the highest rate of blastocyst formation. We applied these results to fertilization using ovum pick-up (OPU). Eleven Japanese black cattle served as donors for OPU plus standard IVF (OPU-IVF). Of them, four donors with low embryo development rates were selected to determine whether embryo development was enhanced by OPU plus ICSI (OPU-ICSI). We assessed effects on embryo development following IVF and ICSI in oocytes obtained using OPU. Blastocyst rates were significantly higher for OPU-ICSI than for OPU-IVF. Our results suggest that OPU-ICSI improves the blastocyst development rate in donors with low embryo production compared with the standard OPU-IVF.

Improved embryo development in Japanese black cattle by in vitro fertilization using ovum pick-up plus intracytoplasmic sperm injection with dithiothreitol

PubMed Central

OIKAWA, Toshinori; ITAHASHI, Tomoko; NUMABE, Takashi

2015-01-01

The purpose of this study was to determine whether dithiothreitol (DTT) treatment of sperm and ethanol activation improve embryo production by intracytoplasmic sperm injection (ICSI). Further, we compared ICSI with standard in vitro fertilization (IVF) in oocytes obtained from cattle. We demonstrated that DTT reduced the disulfide bond in the bovine sperm head. Using oocytes obtained from a slaughterhouse, ICSI-DTT treatment without ethanol showed the highest rate of blastocyst formation. We applied these results to fertilization using ovum pick-up (OPU). Eleven Japanese black cattle served as donors for OPU plus standard IVF (OPU-IVF). Of them, four donors with low embryo development rates were selected to determine whether embryo development was enhanced by OPU plus ICSI (OPU-ICSI). We assessed effects on embryo development following IVF and ICSI in oocytes obtained using OPU. Blastocyst rates were significantly higher for OPU-ICSI than for OPU-IVF. Our results suggest that OPU-ICSI improves the blastocyst development rate in donors with low embryo production compared with the standard OPU-IVF. PMID:26460690

Estimating the chance of success in IVF treatment using a ranking algorithm.

PubMed

Güvenir, H Altay; Misirli, Gizem; Dilbaz, Serdar; Ozdegirmenci, Ozlem; Demir, Berfu; Dilbaz, Berna

2015-09-01

In medicine, estimating the chance of success for treatment is important in deciding whether to begin the treatment or not. This paper focuses on the domain of in vitro fertilization (IVF), where estimating the outcome of a treatment is very crucial in the decision to proceed with treatment for both the clinicians and the infertile couples. IVF treatment is a stressful and costly process. It is very stressful for couples who want to have a baby. If an initial evaluation indicates a low pregnancy rate, decision of the couple may change not to start the IVF treatment. The aim of this study is twofold, firstly, to develop a technique that can be used to estimate the chance of success for a couple who wants to have a baby and secondly, to determine the attributes and their particular values affecting the outcome in IVF treatment. We propose a new technique, called success estimation using a ranking algorithm (SERA), for estimating the success of a treatment using a ranking-based algorithm. The particular ranking algorithm used here is RIMARC. The performance of the new algorithm is compared with two well-known algorithms that assign class probabilities to query instances. The algorithms used in the comparison are Naïve Bayes Classifier and Random Forest. The comparison is done in terms of area under the ROC curve, accuracy and execution time, using tenfold stratified cross-validation. The results indicate that the proposed SERA algorithm has a potential to be used successfully to estimate the probability of success in medical treatment.

Full-sibling embryos created by anonymous gamete donation in unrelated recipients.

PubMed

Dicken, Cary L; Zapantis, Athena; Illions, Edward; Pollack, Staci; Lieman, Harry J; Bevilacqua, Kris; Jindal, Sangita K

2011-09-01

To report the rare occurrence of full-sibling embryos in unrelated women using independently chosen donor sperm and donor oocytes in two different cycles unintentionally created at our IVF program, and to discuss the concept of disclosure to the patients. Case report. Academic IVF program. Two women independently undergoing donor recipient cycles with anonymous donor oocytes and donor sperm. Both women received oocytes from the same donor several months apart and then by coincidence selected the same anonymous sperm donor to create anonymous full-sibling embryos. Clinical pregnancy after donor-recipient IVF cycle. Both women conceived using the same donor sperm and donor oocytes in independent cycles, resulting in simultaneous pregnancy of full siblings. As providers with the knowledge that anonymous full sibling embryos have been created, we may have an obligation to disclose this information to the patients. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Can a quality-of-life assessment assist in identifying women at risk of prematurely discontinuing IVF treatment? A prospective cohort study utilizing the FertiQoL questionnaire.

PubMed

Neumann, Kay; Kayser, Janna; Depenbusch, Marion; Schultze-Mosgau, Askan; Griesinger, Georg

2018-07-01

This study aimed at assessing quality of life (QoL) by means of a validated measurement tool (FertiQoL) in German infertile patients before a first IVF/ICSI cycle with ancillary assessment of changes in FertiQoL scores after a failed first cycle and the predictive capacity of FertiQoL scores for treatment discontinuation. The validated FertiQoL tool consisting of 24 questions regarding fertility-specific aspects of QoL was used for this prospective cohort study conducted at a university affiliated IVF center in Germany. Female patients (n = 119) filled out the FertiQoL form and questionnaire on sociodemographic variables on initiation of a first- and second-cycle IVF/ICSI treatment, respectively. On initiation of a first IVF/ICSI cycle, the mean scores (± standard deviation) for subscales emotional, mind-body, relational, and social items were 62 (± 19), 75 (± 17), 82 (± 13), and 78 (± 14), respectively; the total FertiQoL score was 73 (± 12). The mean total FertiQoL score at initiation of a first treatment cycle did not differ between patients who continued vs. discontinued treatment in case of no pregnancy achievement in the first cycle (73) (± 10) vs. 74 (± 14), p = 0.46). Furthermore, the mean total FertiQoL score did not change after an unsuccessful first IVF cycle (74 vs. 76, p = 0.46). There was no statistical difference in a small sample size for FertiQoL scores between all groups. In this study, FertiQoL scores were, therefore, not usable to predict withdrawal from infertility treatment.

Does prolonged pituitary down-regulation with gonadotropin-releasing hormone agonist improve the live-birth rate in in vitro fertilization treatment?

PubMed

Ren, Jianzhi; Sha, Aiguo; Han, Dongmei; Li, Ping; Geng, Jie; Ma, Chaihui

2014-07-01

To evaluate the effects of a prolonged duration of gonadotropin-releasing hormone agonist (GnRH-a) in pituitary down-regulation for controlled ovarian hyperstimulation (COH) on the live-birth rate in nonendometriotic women undergoing in vitro fertilization and embryo transfer (IVF-ET). Retrospective cohort study. University-affiliated hospital. Normogonadotropic women undergoing IVF. Three hundred seventy-eight patients receiving a prolonged pituitary down-regulation with GnRH-a before ovarian stimulation and 422 patients receiving a GnRH-a long protocol. Live-birth rate per fresh ET. In comparison with the long protocol, the prolonged down-regulation protocol required a higher total dose of gonadotropins. A lower serum luteinizing hormone (LH) level on the starting day of gonadotropin and the day of human chorionic gonadotropin (hCG) and a fewer number of oocytes and embryos were observed in the prolonged down-regulation protocol. However, the duration of stimulation and number of high-quality embryos were comparable between the two groups. A statistically significantly higher implantation rate (50.27% vs. 39.69%), clinical pregnancy rate (64.02% vs. 56.87%) and live-birth rate per fresh transfer cycle (55.56% vs. 45.73%) were observed in the prolonged protocol. Prolonged down-regulation in a GnRH-a protocol might increase the live-birth rates in normogonadotropic women. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Live birth rates in the first complete IVF cycle among 20 687 women using a freeze-all strategy.

PubMed

Zhu, Qianqian; Chen, Qiuju; Wang, Li; Lu, Xuefeng; Lyu, Qifeng; Wang, Yun; Kuang, Yanping

2018-05-01

What is the chance of having a child following one complete IVF cycle for patients using a freeze-all strategy? The chance of having a child after the first complete IVF cycle was 50.74% with the freeze-all strategy. Several studies have reported on live birth rates (LBRs) based on only the fresh embryo transfer cycle or fresh and frozen-thawed embryo transfer cycles. However, the LBR using a freeze-all strategy in IVF is unknown. This retrospective cohort study included 20 687 women who started their first IVF cycles using a freeze-all strategy during the period from 1 January 2007, through 31 March 2016, in China. Data on 20 687 women undergoing their first complete cycles using a freeze-all strategy from 2007 to 2016 were analyzed to estimate LBRs. The LBR in a complete cycle was defined as the chance of a live birth from an ovarian stimulation cycle including all subsequent frozen embryo transfers from this stimulation. The relationship between LBR and number of oocyte was explored. The LBR for the first complete cycle was 50.74% for patients using a freeze-all strategy. By age group, the LBR declined from 63.81% for women under 31 years old to 4.71% for women over 40 years old after the first complete cycle. The LBRs improved as the number of oocytes retrieved increased up to 25 in the freeze-all strategy. This was a retrospective study without a control group. Data on BMI and smoking status were not collected in this database. Our results showed that 50.74% of patients could achieve a live birth after the first complete cycle via a freeze-all strategy. In addition, the LBRs were positively correlated with the number of oocytes retrieved via the freeze-all strategy. These findings are critical for patients and clinicians in making an informed decision to embark on IVF treatment. This work was supported by grants from the National Natural Science Foundation of China (NSFC) (31770989 to Y.W.) and the Shanghai Ninth People's Hospital Foundation of China (JYLJ030 to Y.W.). None of the authors have any conflicts of interest to declare.

Evaluation of human sperm chromatin status after selection using a modified Diff-Quik stain indicates embryo quality and pregnancy outcomes following in vitro fertilization.

PubMed

Tavares, R S; Silva, A F; Lourenço, B; Almeida-Santos, T; Sousa, A P; Ramalho-Santos, J

2013-11-01

Sperm chromatin/DNA damage can be measured by a variety of assays. However, it has been reported that these tests may lose prognostic value in Assisted Reproductive Technology (ART) cycles when assessed in post-prepared samples, possibly due to the normalizing effect promoted by sperm preparation procedures. We have recently implemented a modified version of the Diff-Quik staining assay that allows for the evaluation of human sperm chromatin status in native samples, together with standard sperm morphology assessment. However, the value of this parameter in terms of predicting in vitro fertilization (IVF) and Intracytoplasmic sperm injection (ICSI) outcomes after sperm selection is unknown. In this study, data from 138 couples undergoing in vitro fertilization (IVF) or Intracytoplasmic sperm injection (ICSI) treatments showed that sperm chromatin integrity was significantly improved after density gradient centrifugation and swim up (p < 0.001), but no correlations were found with fertilization or embryo development rates (p > 0.05). However, sperm samples presenting lower percentages of damaged chromatin were associated with better quality (Grade I) embryos in both ART procedures (p < 0.05) and clinical pregnancy among IVF couples (p < 0.05). Furthermore, regression analysis confirmed the clinical value of Diff-Quik staining in predicting IVF (but not ICSI) clinical pregnancy (OR: 0.927, 95% CI: 0.871-0.985, p = 0.015), and a threshold value of 34.25% for this parameter was established. The proportion of IVF couples achieving a clinical pregnancy was reduced 1.9-fold when the percentage of abnormal dark staining was ≥34.25% (p = 0.05). In conclusion, the Diff-Quik staining assay provides useful information regarding ART success, particularly in IVF cycles, where some degree of 'natural' sperm selection may occur; but not in ICSI, where sperm selection is operator dependent. This quick and low-cost assay is suggested as an alternative method to detect sperm chromatin status in minimal clinical settings, when no other well-established and robust assays (e.g. Sperm chromatin structure assay, terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling) are available. © 2013 American Society of Andrology and European Academy of Andrology.

A qualitative study of women's decision-making at the end of IVF treatment.

PubMed

Peddie, V L; van Teijlingen, E; Bhattacharya, S

2005-07-01

The decision not to pursue further in vitro fertilization (IVF) after one or more unsuccessful attempts is an important and often difficult one for couples. Relatively little is known about the woman's perception of this decision-making process. The aim of this study was to examine patients' perspectives of decision-making, including circumstances influencing it and satisfaction with the decision-making process. Semi-structured interviews were conducted with a purposive sample of 25 women who had decided to end treatment after unsuccessful IVF treatment. Interviews were tape-recorded and transcribed by means of thematic analysis using the open coding technique. Women experienced difficulty in accepting that their infertility would remain unresolved. Many felt that they had started with unrealistic expectations of treatment success and felt vulnerable to the pressures of both the media and society. Although the decision to end treatment was difficult, it offered many women a way out of the emotional distress caused by IVF; however, the process of decision-making created a sense of 'confrontation' for the women in which they had to address issues they had previously avoided. Adoptive parents perceived less societal pressure than those who remained childless. Efforts to improve the psychological preparation of couples who decide to end IVF treatment should be directed towards examination of the existing system of consultation, which has certain limitations in terms of the quality of communication and the provision of post-treatment support. Further efforts to develop strategies, which facilitate the decision-making process, should be considered.

Pregnancy prediction by free sperm DNA and sperm DNA fragmentation in semen specimens of IVF/ICSI-ET patients.

PubMed

Bounartzi, Theofania; Dafopoulos, Konstantinos; Anifandis, George; Messini, Christina I; Koutsonikou, Chrysoula; Kouris, Spyros; Satra, Maria; Sotiriou, Sotirios; Vamvakopoulos, Nicholas; Messinis, Ioannis E

2016-04-01

The purpose of this study was to evaluate the predictive value of free sperm plasma DNA (f-spDNA) and sperm DNA fragmentation (SDF), in semen specimens from men undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) treatments. Fifty-five semen samples were evaluated during 55 consecutive IVF/ICSI-ET cycles. F-spDNA was determined by conventional quantitative real-time PCR-Sybr green detection approach, while evaluation of sperm DNA damage was performed using the sperm chromatin dispersion (SCD) assay. While f-spDNA only correlated with total sperm count, SDF correlated with many semen parameters (including sperm concentration, total sperm count and the per cent of non-progressive sperm). Neither SDF nor the proportion of sperm with small or no halos correlated with f-spDNA. Interestingly, smoking status correlated with f-spDNA but not with SDF. Although these two factors seem to interact for the prediction of pregnancy, receiver-operating characteristics (ROC) analysis revealed that SDF had a stronger predictive value (AUC = 0.7, p < 0.05) than f-spDNA (AUC = 0.6, p > 0.05). SDF and f-spDNA may not be associated together but they interact at a significant level in order to exert their actions on pregnancy outcome. Among the two markers, SDF appears to have stronger and significantly predictive value for pregnancy success.

The influence of body mass index to in-vitro fertilisation treatment outcome, risk of miscarriage and pregnancy outcome.

PubMed

Thum, M Y; El-Sheikhah, A; Faris, R; Parikh, J; Wren, M; Ogunyemi, T; Gafar, A; Abdalla, H

2007-10-01

The aim of this work was to evaluate the effects of extreme body mass index (BMI) on assisted reproductive treatment outcome and pregnancy outcome. This is a descriptive cohort study that evaluated 8,145 consecutive in-vitro fertilisation/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles in which BMI were known, from July 1997 to June 2005 in an inner London major fertility clinic. The data were collected prospectively and analysed retrospectively on women undergoing IVF/ICSI and ET. Patients' weight and height were established prior to treatment. IVF/ICSI treatment was then started using either a long or an antagonist protocol. Patients were divided into five groups: Group A (BMI < 19); Group B (BMI between 19 and 25.9); Group C (BMI between 26 and 30.9); Group D (BMI between 31 and 35.9); Group E (BMI > 36). The main outcomes measured were number of eggs collected, fertilisation rate, number of embryos available for transfer, pregnancy rate (PR), live-birth rate (LBR) and miscarriage rate (MR). The results showed no significant difference in the average number of days taking follicle stimulating hormone (FSH) for ovarian stimulation, the average amount of gonadotrophin used for stimulation, number of eggs collected and fertilisation rate. The pregnancy rate, miscarriage rate and the live-birth rate were not statistically different between all groups. However, in group E the miscarriage rate was significantly higher and the LBR was statistically lower compared with group B. We concluded that extreme BMI did not affect the super-ovulation outcome fertilisation rate and pregnancy rate. Women with a BMI > 35 had a higher miscarriage rate and hence a lower live-birth rate, but a reasonable pregnancy and live-birth rate can be achieved. For women with a BMI < 20 there was no difference in assisted reproduction treatment (ART) outcome and pregnancy outcome when compared with women with a normal BMI. This information should be used to advise patients who wish to embark on ART with extreme BMI.

Spontaneous pregnancies following discontinuation of IVF/ICSI treatment: an internet-based survey.

PubMed

Marcus, Adam P; Marcus, Diana M; Ayis, Salma; Johnson, Antoinette; Marcus, Samuel F

2016-06-01

The objective was to determine the likelihood of conceiving spontaneously following cessation of IVF/ICSI; how long does it take and what factors are associated with conception? The design was an internet-based survey. All registered users of www.ivf-infertility.com received an electronic questionnaire addressing issues relating to the duration and cause of infertility, number of IVF/ICSI cycles and outcome, whether they conceived following cessation of IVF/ICSI and the time taken to conceive and outcome. Four hundred and eighty four patients responded of whom 403 met the study criteria. The overall cumulative live birth rate over a 6-year period following cessation of IVF/ICSI was 29%. Eighty-two percent of conceptions occurred within 2 years. Positive factors associated with spontaneous conception were unexplained infertility (p = 0.02), ovulation dysfunction (p = 0.01), infertility less than four years prior to IVF/ICSI (p = 0.045) and 2 years or less since discontinuation of IVF/ICSI (p < 0.001) and up to four attempts at IVF/ICSI (p = 0.02). In conclusion, 29% of couples conceived spontaneously over a 6-year period following the cessation of IVF/ICSI. The findings of this study can be used to counsel and reassure women following IVF/ICSI.

Psychosocial Adjustment to Unsuccessful IVF and GIFT Treatment.

ERIC Educational Resources Information Center

Weaver, Susan M.; Clifford, Ellen; Hay, Douglas M.; Robinson, John

1997-01-01

Couples for whom in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) treatment failed (N=20) were followed up and compared with successful couples. Current mental-health status, quality of life, and marital adjustment were assessed via questionnaires; experiences were explored by interview. Results and recommendations for…

Measuring Sperm DNA Fragmentation and Clinical Outcomes of Medically Assisted Reproduction: A Systematic Review and Meta-Analysis.

PubMed

Cissen, Maartje; Wely, Madelon van; Scholten, Irma; Mansell, Steven; Bruin, Jan Peter de; Mol, Ben Willem; Braat, Didi; Repping, Sjoerd; Hamer, Geert

2016-01-01

Sperm DNA fragmentation has been associated with reduced fertilization rates, embryo quality, pregnancy rates and increased miscarriage rates. Various methods exist to test sperm DNA fragmentation such as the sperm chromatin structure assay (SCSA), the sperm chromatin dispersion (SCD) test, the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay and the single cell gel electrophoresis (Comet) assay. We performed a systematic review and meta-analysis to assess the value of measuring sperm DNA fragmentation in predicting chance of ongoing pregnancy with IVF or ICSI. Out of 658 unique studies, 30 had extractable data and were thus included in the meta-analysis. Overall, the sperm DNA fragmentation tests had a reasonable to good sensitivity. A wide variety of other factors may also affect the IVF/ICSI outcome, reflected by limited to very low specificity. The constructed hierarchical summary receiver operating characteristic (HSROC) curve indicated a fair discriminatory capacity of the TUNEL assay (area under the curve (AUC) of 0.71; 95% CI 0.66 to 0.74) and Comet assay (AUC of 0.73; 95% CI 0.19 to 0.97). The SCSA and the SCD test had poor predictive capacity. Importantly, for the TUNEL assay, SCD test and Comet assay, meta-regression showed no differences in predictive value between IVF and ICSI. For the SCSA meta-regression indicated the predictive values for IVF and ICSI were different. The present review suggests that current sperm DNA fragmentation tests have limited capacity to predict the chance of pregnancy in the context of MAR. Furthermore, sperm DNA fragmentation tests have little or no difference in predictive value between IVF and ICSI. At this moment, there is insufficient evidence to recommend the routine use of sperm DNA fragmentation tests in couples undergoing MAR both for the prediction of pregnancy and for the choice of treatment. Given the significant limitations of the evidence and the methodological weakness and design of the included studies, we do urge for further research on the predictive value of sperm DNA fragmentation for the chance of pregnancy after MAR, also in comparison with other predictors of pregnancy after MAR.

Hydrosalpinx: Tubal surgery or in vitro fertilisation? An everlasting dilemma nowadays; a narrative review.

PubMed

Daniilidis, A; Balaouras, D; Chitzios, D; Theodoridis, T; Assimakopoulos, E

2017-07-01

The decision on how to treat tubal diseases, specifically hydrosalpinx, is a difficult one. Ιt involves surgical, medical, social, emotional and economic factors. This narrative review aims to increase awareness of tubal disease diagnosis and treatment, to compare between tubal surgery and in vitro fertilisation (IVF) for tubal factor infertility, and to investigate the effect of the combination of both. This way, we can be more effective, safe and provide our patients with better treatment results. The review analysed randomised studies, trials and meta-analysis, which give new aspects on the treatment methods for tubal pathology before IVF. Recent papers published in English have been studied, alongside guidelines and committee opinions from previous years. Tubal surgery and IVF aim to exploit a woman's reproductive potential. IVF and endoscopic tubal surgery must be thought of as complementary, rather than competing techniques in tubal disease cases, in order to improve fertility outcome. The first-line treatment for young women less than 35 years old with minor tubal pathology, is tubal surgery. IVF should be offered if there are other factors in a couple's subfertility, if the patient is >38 years old, if moderate to severe tubal disease is present, and if it has been more than 12 months post-surgery.

In vitro fertilisation for unexplained subfertility.

PubMed

Pandian, Zabeena; Gibreel, Ahmed; Bhattacharya, Siladitya

2015-11-19

One-third of subfertile couples have no identifiable cause for their inability to conceive. In vitro fertilisation (IVF) is a widely accepted treatment for this condition; however, this treatment is invasive and expensive and is associated with risks. To evaluate the effectiveness and safety of IVF compared with expectant management, unstimulated intrauterine insemination (IUI) or intrauterine insemination along with ovarian stimulation with gonadotropins (IUI + gonadotropins) or clomiphene (IUI + CC) or letrozole (IUI + letrozole) in improving pregnancy outcomes. This review has drawn on the search strategy developed by the Cochrane Menstrual Disorders and Subfertility Group. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, first quarter), MEDLINE (1946 to May 2015), EMBASE (1985 to May 2015), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (May 2015) and reference lists of articles. We searched the following trial registries: clinicaltrials.gov (http://www.clinicaltrials.gov) and the World Health Organization International Trials Registry Platform search portal (http://www.who.int/trialsearch/Default.aspx). We searched the Web of Science (http://wokinfo.com/) as another source of trials and conference abstracts, OpenGrey (http://www.opengrey.eu/) for unpublished literature from Europe and the Latin American Caribbean Health Sciences Literature (LILACS) database (http://regional.bvsalud.org/php/index.php?lang=en). Moreover, we handsearched relevant conference proceedings and contacted study authors to ask about additional publications.Two review authors independently assessed trial eligibility, extracted data and assessed risk of bias. The primary review outcome was cumulative live birth rate. Multiple pregnancy and other adverse effects were secondary outcomes. We combined data to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity by using the I(2) statistic. We assessed the overall quality of evidence for the main comparisons using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methods. We included randomised controlled trials (RCTs) in which the effectiveness of IVF in couples with unexplained subfertility was compared with that of other treatments, including expectant management, unstimulated IUI and stimulated IUI using gonadotropins or clomiphene or letrozole.Live birth rate (LBR) per woman was the primary outcome. Two review authors independently assessed the eligibility and quality of trials and evaluated the quality of the evidence by using GRADE criteria. IVF versus expectant management (two RCTs):Live birth rate per woman was higher with IVF than with expectant management (odds ratio (OR) 22.00, 95% confidence interval (CI) 2.56 to 189.37, one RCT, 51 women, very low quality evidence). Multiple pregnancy rates (MPRs), ovarian hyperstimulation syndrome (OHSS) and miscarriage were not reported. IVF versus unstimulated IUI (two RCTs):Live birth rate was higher with IVF than with unstimulated IUI (OR 2.47, 95% CI 1.19 to 5.12, two RCTs, 156 women, I(2) = 60%, low quality evidence). There was no evidence of a difference between the groups in multiple pregnancy rates (OR 1.03, 95% CI 0.04 to 27.29, one RCT, 43 women, very low quality evidence) IVF versus IUI + ovarian stimulation with gonadotropins (three RCTs) or clomiphene (one RCT) or letrozole (no RCTs):Data from these trials could not be pooled because of high statistical heterogeneity (I(2) = 93.3%). Heterogeneity was eliminated when studies were stratified by pretreatment status.In trials comparing IVF versus IUI + gonadotropins among treatment-naive women, there was no conclusive evidence of a difference between the groups in live birth rates (OR 1.27, 95% CI 0.94 to 1.73, four RCTs, 745 women, I(2) = 8.0%, moderate-quality evidence). In women pretreated with IUI + clomiphene, a higher live birth rate was reported among those who underwent IVF than those given IUI + gonadotropins (OR 3.90, 95% CI 2.32 to 6.57, one RCT, 280 women, moderate-quality evidence).There was no conclusive evidence of a difference in live birth rates between IVF and IUI + CC in treatment-naive women (OR 2.51, 95% CI 0.96 to 6.55, one RCT, 103 women, low quality evidence).In treatment-naive women, there was no evidence of a difference in rates of multiple pregnancy between women who underwent IVF and those who received IUI + gonadotropins (OR 0.79, 95% CI 0.45 to 1.39, four RCTs, 745 women, I(2) = 0%, moderate quality evidence). There was no evidence of a difference in MPRs between women who underwent IVF compared with those given IUI + CC (OR 1.02, 95% CI 0.20 to 5.31, one RCT, 103 women, low-quality evidence).There was no evidence of a difference in ovarian hyperstimulation syndrome rate between treatment-naive women who underwent IVF and those given IUI + gonadotropins (OR 1.23, 95% CI 0.36 to 4.14, two RCTs, 221 women, low quality evidence). There was no evidence of a difference in OHSS rates between groups receiving IVF versus those receiving IUI + CC (OR 1.02, 95% CI 0.20 to 5.31, one RCT, 103 women, low-quality evidence).In treatment naive women, there was no evidence of a difference in miscarriage rates between IVF and IUI + CC (OR 1.16, 95% CI 0.44 to 3.02, one RCT, 103 women, low-quality evidence), nor between women treated with IVF versus those receiving IUI+ gonadotropins (OR 1.16, 95% CI 0.44 to 3.02, one RCT, 103 women).No studies compared IVF with IUI + letrozole.The quality of the evidence ranged from very low to moderate. The main limitation was serious imprecision resulting from small study numbers and low event rates. IVF may be associated with higher live birth rates than expectant management, but there is insufficient evidence to draw firm conclusions. IVF may also be associated with higher live birth rates than unstimulated IUI. In women pretreated with clomiphene + IUI, IVF appears to be associated with higher birth rates than IUI + gonadotropins. However in women who are treatment-naive there is no conclusive evidence of a difference in live birth rates between IVF and IUI + gonadotropins or between IVF and IUI + clomiphene. Adverse events associated with these interventions could not be adequately assessed owing to lack of evidence.

Cost-effectiveness of seven IVF strategies: results of a Markov decision-analytic model.

PubMed

Fiddelers, Audrey A A; Dirksen, Carmen D; Dumoulin, John C M; van Montfoort, Aafke P A; Land, Jolande A; Janssen, J Marij; Evers, Johannes L H; Severens, Johan L

2009-07-01

A selective switch to elective single embryo transfer (eSET) in IVF has been suggested to prevent complications of fertility treatment for both mother and infants. We compared seven IVF strategies concerning their cost-effectiveness using a Markov model. The model was based on a three IVF-attempts time horizon and a societal perspective using real world strategies and data, comparing seven IVF strategies, concerning costs, live births and incremental cost-effectiveness ratios (ICERs). In order to increase pregnancy probability, one cycle of eSET + one cycle of standard treatment policy [STP, i.e. eSET in patients <38 years of age with at least one good quality embryo and double embryo transfer (DET) in the remainder of patients] + one cycle of DET have an ICER of 16,593 euro compared with three cycles of eSET. Furthermore, three STP cycles have an ICER of 17,636 euro compared with one cycle of eSET + one cycle of STP + one cycle of DET, and three DET cycles have an ICER of 26,729 euro compared with three cycles STP. Our study shows that in patients qualifying for IVF treatment, combining several transfer policies was not cost-effective. A choice has to be made between three cycles of eSET, STP or DET. It depends, however, on society's willingness to pay which strategy is to be preferred from a cost-effectiveness point of view.

Premature progesterone rise on day of hCG negatively correlated with live birth rate in IVF cycles: An analysis of 1022 cycles.

PubMed

Lepage, Julien; Keromnes, Gwenola; Epelboin, Sylvie; Luton, Dominique; Yazbeck, Chadi

2018-05-18

To investigate the relationship between serum P levels on the day of hCG administration and pregnancy outcomes in patients undergoing IVF. Retrospective study. Teaching hospital. A total of 1022 IVF-ICSI cycles, frozen embryo transfer excluded. Patients-all types of responder - underwent IVF with agonist or antagonist protocols. Clinical outcomes of IVF were analyzed according to plasma P levels. Ongoing pregnancy rates. We proposed a serum P level of 1.57ng/ml on day of hCG as a threshold for all types of responders and all protocols combined. Ongoing implantation rates were not affected by elevated progesterone. Live birth rate was inversely associated with serum P levels on day of hCG and more miscarriages were associated with P>1.57ng/ml. We have not found the progesterone>1.57ng/ml on the day of hCG as a prognostic factor for pregnancy. Elevated P level on the day of hCG administration negatively influence live birth rate and is correlated to an increase of miscarriage. The detrimental effect of P elevation on pregnancy seems not to be related substantially to endometrium receptivity. Thus, despite a comparable clinical pregnancy rate and an initial implantation rate, we demonstrate more spontaneous abortion and it would seem that the effect of progesterone is later. Copyright © 2018. Published by Elsevier Masson SAS.

Costs of infertility treatment: Results from an 18-month prospective cohort study

PubMed Central

Katz, Patricia; Showstack, Jonathan; Smith, James F.; Nachtigall, Robert D.; Millstein, Susan G.; Wing, Holly; Eisenberg, Michael L.; Pasch, Lauri A.; Croughan, Mary S.; Adler, Nancy

2010-01-01

Objectives To examine resource use (costs) by women presenting for infertility evaluation and treatment over 18 months, regardless of treatment pursued. Design Prospective cohort study in which women were followed for 18 months. Setting Eight infertility practices. Patients 398 women recruited from infertility practices. Data collection Women completed interviews and questionnaires at baseline, and after 4, 10, and 18 months of follow-up. Medical records were abstracted after 18 months to obtain details of services used. Main outcome measures Per-person and per-successful-outcome costs Results Treatment groups were defined as highest intensity treatment use. 20% of women did not pursue cycle-based treatment; about half pursued in-vitro fertilization (IVF). Median per-person costs ranged from $1,182 for medications only, to $24,373 and $38,015 for IVF and IVF-donor egg groups, respectively. Estimates of costs of successful outcomes (delivery or ongoing pregnancy by 18 months) were higher – $61,377 for IVF, for example – reflecting treatment success rates. Within the timeframe of the study, costs were not significantly different for women who were successful and women who were not. Conclusions While individual patient costs vary, these cost estimates developed from actual patient treatment experiences may provide patients with realistic estimates to consider when initiating infertility treatment. PMID:21130988

Ovarian sensitivity index is strongly related to circulating AMH and may be used to predict ovarian response to exogenous gonadotropins in IVF

PubMed Central

2011-01-01

Background Serum anti-Mullerian hormone (AMH) is currently considered the best marker of ovarian reserve and of ovarian responsiveness to gonadotropins in in-vitro fertilization (IVF). AMH assay, however, is not available in all IVF Units and is quite expensive, a reason that limits its use in developing countries. The aim of this study is to assess whether the "ovarian sensitivity index" precisely reflects AMH so that this index may be used as a surrogate for AMH in prediction of ovarian response during an IVF cycle. Methods AMH serum levels were measured in 61 patients undergoing IVF with a "long" stimulation protocol including the GnRH agonist buserelin and recombinant follicle-stimulating hormone (rFSH). Patients were divided into four subgroups according to the percentile of serum AMH and their ovarian stimulation was prospectively followed. Ovarian sensitivity index (OSI) was calculated dividing the total administered FSH dose by the number of retrieved oocytes. Results AMH and OSI show a highly significant negative correlation (r = -0.67; p = 0.0001) that is stronger than the one between AMH and the total number of retrieved oocytes and than the one between AMH and the total FSH dose. Conclusions OSI reflects quite satisfactory the AMH level and may be proposed as a surrogate of AMH assay in predicting ovarian responsiveness to FSH in IVF. Being very easy to calculate and costless, its use could be proposed where AMH measurement is not available or in developing countries where limiting costs is of primary importance. PMID:21824441

[Do poor-responder patients benefit from increasing the daily gonadotropin dose from 300 to 450 IU during controlled ovarian hyperstimulation for IVF?].

PubMed

Haas, Jigal; Zilberberg, Eran; Kedem, Alon; Dar, Shir; Orvieto, Raoul

2015-02-01

We aim to evaluate the IVF-ET outcome in patients receiving a high daily dose (300 IU) of gonadotropins during controlled ovarian hyperstimulation (COH) for IVF and to assess the role of increasing the daily dose to 450 IU on improving outcome. All consecutive women admitted to our IVF unit during an 11 year period who underwent COH consisting of daily gonadotropin dose of 300 IU were included in the study. The ovarian stimulation characteristics, number of oocytes retrieved, number of embryo transferred and pregnancy rate were assessed. We also evaluated the subsequent cycle, using daily gonadotropin doses of 450 IU, among those patients who did not conceive using the 300 IU daily gonadotropin dose. Nine hundred and forty-nine consecutive IVF cycles were evaluated. Patients who conceived using the daily gonadotropin dose of 300 IU (n = 133, 14% pregnancy rate) had significantly longer stimulation, yielded higher numbers of oocytes retrieved, fertilization rate and number of embryos transferred, compared to those who did not conceive. Moreover, while comparing IVF cycles using daily gonadotropin doses of 300 IU to 450 IU (n = 117), no in-between group differences were observed, except for significantly higher yields of oocytes retrieved. Moreover, cycles using daily gonadotropin doses of 450 IU resulted in a 7.7 live-birth rate. In poor responders undergoing COH with a daily gonadotropin dose of 300 IU, increasing the dose to 450 IU resulted in significantly higher oocyte yields and a reasonable live birth rate.

Conversion to IUI versus continuance with IVF in low responder patients: A systematic review.

PubMed

Fujii, Dennis T; Quesnell, Jodi L; Heitmann, Ryan J

2018-06-01

Poor response to ovarian hyper-stimulation can be difficult to predict prior to stimulation even when factoring in patient age and ovarian reserve testing. When faced with the situation of poor response, patients and providers have the difficult decision to proceed with oocyte retrieval, convert to intrauterine insemination (IUI), or cancel the cycle. Although this is not an uncommon scenario, there is little data available to assist with the counseling of these patients. We performed a systematic review of published studies comparing clinical pregnancy and live births between those patients continuing with in-vitro fertilization (IVF) and those converting to IUI. PubMed and Ovid were searched for all retrospective and randomized studies using the Keywords 'in-vitro fertilization', 'intrauterine insemination', 'poor responders', 'clinical pregnancy' and 'live birth rates'. A total of seven retrospective studies and one randomized control trial were reviewed. When evaluating poor responders as a group, six studies reported higher overall clinical pregnancy rates and five studies reported overall increased live birth rates with continuance of IVF. When stratified by the number of follicles produced, continuance of IVF demonstrated higher clinical pregnancy and live birth rates with ≥ 2 follicles. When only one follicle developed there were no significant differences in clinical pregnancy or live birth rates between the two groups. In patients undergoing IVF with ≤4 follicles, continuance with IVF may lead to higher clinical pregnancy and live birth compared to conversion to IUI except in patients with monofollicular development, although additional randomized controlled trials are needed to confirm these findings. Published by Elsevier B.V.

Cumulative live-birth rates per total number of embryos needed to reach newborn in consecutive in vitro fertilization (IVF) cycles: a new approach to measuring the likelihood of IVF success.

PubMed

Garrido, Nicolás; Bellver, José; Remohí, José; Simón, Carlos; Pellicer, Antonio

2011-07-01

To report the use of cumulative live-birth rates (CLBRs) per ovarian stimulation cycle to measure the success of IVF is proving to be the most accurate method for advising couples who failed to conceive, although the accuracy yielded is relatively low, and cycle outcome is highly dependent on the number of embryos replaced. Our aim with this work is to report the CLBRs of IVF as a function of the number of embryos required to reach a live birth (EmbR), considering age, day of ET, and infertility etiology. Survival curves and Kaplan-Meier methods to analyze CLBR in a retrospective cohort with respect to the number of EmbR. University-affiliated infertility center. Infertile couples undergoing IVF using own oocytes. None. CLBR per embryo transferred. CLBRs increase rapidly between 1 and 5 EmbR, moderately between 5 and 15, and slowly thereafter. Live-birth rates rise more slowly when embryos are transferred on days 2-3 rather than on days 5-6, with comparable long-term results. Women's age is a negative factor from 35 to 37 years old, with a dramatic decrease in live-birth rates beyond age 40 years. In addition, there are significant worse results in endometriosis patients. The relationship between CLBR and number of EmbR provides realistic and precise information regarding IVF success and can be used to guide couples and practitioners. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Comparison of the efficacy of treating sperm with low hypoosmotic swelling test scores with chymotrypsin followed by intrauterine insemination vs in vitro fertilization with intracytoplasmic sperm injection.

PubMed

Bollendorf, A; Check, D; Check, J H; Hourani, W; McMonagle, K

2011-01-01

To compare the efficacy of two treatments for sperm with low hypoosmotic swelling (HOS) test scores - intrauterine insemination (IUI) with sperm pretreated with the protein digestive enzyme chymotrypsin versus in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). The choice of patient therapy was optional. The pregnancy rates following two IUI cycles vs one IVF cycle with ICSI were then compared. The data were further stratified and compared according to the severity of the HOS score defect. The more severe the HOS test defect the less likely for chymotrypsin therapy to work whereas the severity did not affect IVF with ICSI success. The use of IVF with ICSI was much more effective than IUI with chymotrypsin treatment. Though IVF with ICSI is much more effective, IUI is much less expensive. Couples should be presented with these data and be allowed to make their own choice considering risks and expense versus efficacy and speed of success.

[Management of assisted reproductive technology (ART) in case of endometriosis related infertility: CNGOF-HAS Endometriosis Guidelines].

PubMed

Santulli, P; Collinet, P; Fritel, X; Canis, M; d'Argent, E M; Chauffour, C; Cohen, J; Pouly, J L; Boujenah, J; Poncelet, C; Decanter, C; Borghese, B; Chapron, C

2018-03-01

The management of endometriosis related infertility requires a global approach. In this context, the prescription of an anti-gonadotropic hormonal treatment does not increase the rate of non-ART (assisted reproductive technologies) pregnancies and it is not recommended. In case of endometriosis related infertility, the results of IVF management in terms of pregnancy and birth rates are not negatively affected by the existence of endometriosis. Controlled ovarian stimulation during IVF does not increase the risk of endometriosis associated symptoms worsening, nor accelerate the intrinsic progression of endometriosis and does not increase the rate of recurrence. However, in the context of IVF management for women with endometriosis, pre-treatment with GnRH agonist or with oestrogen/progestin contraception improve IVF outcomes. There is currently no evidence of a positive or negative effect of endometriosis surgery on IVF outcomes. Information on the possibilities of preserving fertility should be considered, especially before surgery. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Fertility outcome of laparoscopic treatment in patients with severe endometriosis and repeated in vitro fertilization failures.

PubMed

Soriano, David; Adler, Iris; Bouaziz, Jerome; Zolti, Matti; Eisenberg, Vered H; Goldenberg, Mordechai; Seidman, Daniel S; Elizur, Shai E

2016-10-01

To evaluate fertility outcomes in infertile women with severe endometriosis (The revised American Fertility Society classification [AFS] 3-4) and repeated IVF failures, who underwent surgery due to exacerbation of endometriosis-related symptoms. Retrospective cohort study. University hospital. All women who failed IVF treatment before surgery and who underwent laparoscopic surgery for severe endometriosis between January 2006 and December 2014. All patients were operated by highly skilled surgeons specializing in laparoscopic surgery for advanced endometriosis. Only patients with evidence of endometriosis in the pathology specimens were included in this study. Delivery rate after surgery. Seventy-eight women were included in the present study. All women were diagnosed with severe endometriosis during surgery (AFS 3-4) and all women had experienced failed IVF treatments before surgery. All women were symptomatic before their surgery. After surgical treatment 33 women (42.3%) delivered. Three women (9%) conceived spontaneously and all other women conceived after IVF treatment. Women who delivered were younger (32.5 [±4.1] years vs. 35.5 [±3.8] years), were less often diagnosed with diminished ovarian reserve before surgery (6% vs. 28.8%), and were more often diagnosed with normal uterine anatomy (by preoperative transvaginal ultrasound and during operation). In addition, performing salpingectomy during surgery was associated with a trend of improvement in delivery rates after surgery (70% in women who delivered vs. 51% in women who failed to deliver). Symptomatic women with severe endometriosis and repeated IVF implantation failures may benefit from extensive laparoscopic surgery when performed by an experienced multidisciplinary surgical team to improve IVF outcome. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Proof of concept: preimplantation genetic screening without embryo biopsy through analysis of cell-free DNA in spent embryo culture media.

PubMed

Shamonki, Mousa I; Jin, Helen; Haimowitz, Zachary; Liu, Lian

2016-11-01

To assess whether preimplantation genetic screening (PGS) is possible by testing for free embryonic DNA in spent IVF media from embryos undergoing trophectoderm biopsy. Prospective cohort analysis. Academic fertility center. Seven patients undergoing IVF and 57 embryos undergoing trophectoderm biopsy for PGS. On day 3 of development, each embryo was placed in a separate media droplet. All biopsied embryos received a PGS result by array comparative genomic hybridization. Preimplantation genetic screening was performed on amplified DNA extracted from media and results were compared with PGS results for the corresponding biopsy. [1] Presence of DNA in spent IVF culture media. [2] Correlation between genetic screening result from spent media and corresponding biopsy. Fifty-five samples had detectable DNA ranging from 2-642 ng/μL after a 2-hour amplification. Six samples with the highest DNA levels underwent PGS, rendering one result with a derivative log ratio SD (DLRSD) of <0.85 (a quality control metric of oligonucleotide array comparative genomic hybridization). The fluid sample and trophectoderm results were identical demonstrating (45XY, -13). Three samples were reamplified 1 hour later and tested showing improving DLRSD. One of the three samples with a DLRSD of 0.85 demonstrated (46XY), consistent with the biopsy. Overnight DNA amplification showed DNA in all samples. We demonstrate two novel findings: the presence of free embryonic DNA in spent media and a result that is consistent with trophectoderm biopsy. Improvements in DNA collection, amplification, and testing may allow for PGS without biopsy in the future. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Effect of genistein added to bull semen after thawing on pronuclear and sperm quality.

PubMed

Silvestre, M A; Vicente-Fiel, S; Raga, E; Salvador, I; Soler, C; Yániz, J L

2015-12-01

The aim of this research was to study the effect of different genistein treatments on bull sperm after thawing on pronuclear formation after in vitro fertilization (IVF) and on different sperm quality variables. Three experiments were performed. In Experiment 1, three treatments (Control, sperm incubation for 1h at 37 °C with or without genistein) and two sperm concentrations during IVF (1 or 3 × 10(6)sperm/mL) were evaluated to study the influence of genistein on pronuclear formation (PNF). Sperm incubation for 1h before IVF reduced PNF regardless of sperm concentration. However, after sperm incubation and with 3 × 10(6)sperm/mL in IVF, the genistein treatment group had greater fertilization rates than the untreated group. In Experiment 2, six treatments plus the control group were performed to study the effect of genistein (presence or not) and incubation conditions (30 min at 37 °C, 1h at 27 °C or at 37 °C) on PNF using 3 × 10(6)sperm/mL for IVF. When incubation time was reduced to 30 min, PNF rate from the genistein treatment group was no different from either the control group or in the group in which incubation occurred for 1h at 27 °C. In Experiment 3, the effect of several genistein treatments (control; genistein treatment for 30 min of incubation at 37 °C; genistein treatment for 1h of incubation at 27 °C) on sperm motility, viability and DNA fragmentation were evaluated. Genistein did not improve sperm motility and, depending on the experimental group or time, it either reduced or had no effect on sperm motility. Genistein treatment did not improve sperm viability after 5h of incubation. However, genistein treatment for 1h at 27 °C decreased sperm DNA fragmentation compared with the control group after 5h of sperm incubation. In conclusion, the treatment of bull sperm with genistein for 1h at 27 °C could decrease sperm DNA fragmentation, although PNF rate after IVF and sperm motility were reduced. Copyright © 2015. Published by Elsevier B.V.

Correlation of serum anti-Müllerian hormone levels with positive in vitro fertilization outcome using a short agonist protocol.

PubMed

Mantzavinos, Spyridon D; Vlahos, Nikolaos P; Rizos, Demetrios; Botsis, Demetrios; Sergentanis, Theodoros N; Deligeoroglou, Efthimios; Mantzavinos, Themistoklis

2017-04-01

We examined the predictive ability of anti-Müllerian hormone (AMH) for clinical pregnancy in women who underwent in vitro fertilization (IVF) cycles in a short agonist protocol. This is a retrospective cohort study of 222 women undergoing their first IVF attempt between June 2010 and March 2016. Multivariate logistic regression analysis was performed to evaluate the independent associations between clinical pregnancy and its possible predictors. 14.9% of cycles were cancelled, >3 oocytes were retrieved in 55.4% of cycles and embryo transfer was performed in 70.7% of cases. Live birth was the final outcome in 19.8% of subjects, miscarriage occurred in 4.1%, whereas no pregnancy occurred in the remaining 76.1% of the study sample. The number of oocytes, number of embryos, embryo transfer rate and pregnancy rates were positively associated with serum AMH concentrations (p <0.001, for each association). When analyzed by age quartiles, the overall association between AMH and clinical pregnancy rates was evident across all age strata. Serum AMH levels are a strong predictive marker of clinical pregnancy in women undergoing a short agonist IVF protocol. There is also a strong association with cancellation rate, number of oocytes retrieved, poor response (≤3 oocytes), number of embryos, embryo transfer rate and live birth rates.

Elevated serum α-linolenic acid levels are associated with decreased chance of pregnancy after in vitro fertilization.

PubMed

Jungheim, Emily S; Macones, George A; Odem, Randall R; Patterson, Bruce W; Moley, Kelle H

2011-10-01

To analyze relationships between serum free fatty acid (FFA) concentrations and pregnancy. Prospective cohort. University hospital. Ninety-one women undergoing IVF. Serum was analyzed for total and specific serum FFAs, including myristic, palmitic, stearic, oleic, linoleic, and α-linolenic acids. Univariate analyses were used to identify specific FFAs and other factors associated with pregnancy after IVF. Logistic regression was performed modeling relationships between identified factors and chance of pregnancy. In unadjusted analyses, women with elevated serum α-linolenic acid (ALA) levels (highest quartile) demonstrated a decreased chance of pregnancy compared with women with the lowest levels (odds ratio 0.24, 95% confidence interval 0.052-0.792). No associations between other FFAs and pregnancy were identified. In a multivariable regression model, associations between elevated serum ALA levels and decreased chance of pregnancy remained after adjusting for patient age, body mass index, and history of endometriosis or previous live birth (adjusted odds ratio 0.139, 95% confidence interval 0.028-0.686). Elevated serum ALA levels are associated with decreased chance of pregnancy in women undergoing IVF. Further work is needed to determine whether ALA is involved in early reproductive processes and whether the relationship between ALA and pregnancy is associated with excess ALA intake, impaired ALA metabolism, or both. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

HYPERGLYCOSYLATED HUMAN CHORIONIC GONADOTROPIN AS AN EARLY PREDICTOR OF PREGNANCY OUTCOMES AFTER IN VITRO FERTILIZATION

PubMed Central

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H. Irene

2014-01-01

Objective To determine if hyperglycosylated hCG (hhCG), produced by invasive trophoblasts, measured as early as 9 days after egg retrieval can predict ongoing pregnancies (OP) after in vitro fertilization and fresh embryo transfer (IVF-ET). Design Cohort Setting Academic ART center Patients Consecutive patients undergoing IVF-ET Interventions Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Outcome Ongoing pregnancy (OP) beyond 9 weeks of gestation Results OP (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. D9 hhCG levels >110 pg/mL was 96% specific for OP, yielding a positive predictive value of 95%. Compared to D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67). Diagnostic test characteristics were similar between D16 hhCG and hCG levels. Conclusions In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable. HhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. At this early assessment, hhCG is superior to traditional hCG and highly predictive of ongoing pregnancies. PMID:24355054

Assessment of imaging parameters correlated with the effects of cryopreservation on embryo development

NASA Astrophysics Data System (ADS)

Zarnescu, Livia; Abeyta, Mike; Baer, Thomas M.; Behr, Barry; Ellerbee, Audrey K.

2014-03-01

Embryo cryopreservation is an increasingly common technique that allows patients to undergo multiple cycles of in vitro fertilization (IVF) without being subjected to repeated ovarian stimulation and oocyte retrieval. There are two types of cryopreservation commonly used in IVF clinics today: slow freezing and vitrification. Because vitrification has been shown to result in higher rates of embryo survival post-thaw compared to slow freezing, it is rapidly gaining popularity in clinics worldwide. However, several studies have shown that vitrification can still cause damage to embryos in the form of DNA fragmentation, altered mitochondrial distribution and changes in transcriptional activity, all of which are impossible to assess noninvasively. In this paper we demonstrate a new method of quantitatively and noninvasively assessing changes in embryo appearance due to vitrification. Using full-field optical coherence tomography (FF-OCT), we show that vitrification causes striking changes in the appearance of the cytoplasm that are not visible under conventional brightfield microscopy. Using an automated algorithm that extracts parameters to describe these changes, we show that these parameters can also predict viability in embryos that have undergone vitrification. An automated, noninvasive assessment of embryo viability after vitrification and thawing could have significant clinical impact: allowing clinicians to more accurately choose the most viable embryos to transfer back to patients could reduce the average number of IVF cycles that patients must undergo to achieve pregnancy.

Predicting the chance of live birth for women undergoing IVF: a novel pretreatment counselling tool.

PubMed

Dhillon, R K; McLernon, D J; Smith, P P; Fishel, S; Dowell, K; Deeks, J J; Bhattacharya, S; Coomarasamy, A

2016-01-01

Which pretreatment patient variables have an effect on live birth rates following assisted conception? The predictors in the final multivariate logistic regression model found to be significantly associated with reduced chances of IVF/ICSI success were increasing age (particularly above 36 years), tubal factor infertility, unexplained infertility and Asian or Black ethnicity. The two most widely recognized prediction models for live birth following IVF were developed on data from 1991 to 2007; pre-dating significant changes in clinical practice. These existing IVF outcome prediction models do not incorporate key pretreatment predictors, such as BMI, ethnicity and ovarian reserve, which are readily available now. In this cohort study a model to predict live birth was derived using data collected from 9915 women who underwent IVF/ICSI treatment at any CARE (Centres for Assisted Reproduction) clinic from 2008 to 2012. Model validation was performed on data collected from 2723 women who underwent treatment in 2013. The primary outcome for the model was live birth, which was defined as any birth event in which at least one baby was born alive and survived for more than 1 month. Data were collected from 12 fertility clinics within the CARE consortium in the UK. Multivariable logistic regression was used to develop the model. Discriminatory ability was assessed using the area under receiver operating characteristic (AUROC) curve, and calibration was assessed using calibration-in-the-large and the calibration slope test. The predictors in the final model were female age, BMI, ethnicity, antral follicle count (AFC), previous live birth, previous miscarriage, cause and duration of infertility. Upon assessing predictive ability, the AUROC curve for the final model and validation cohort was (0.62; 95% confidence interval (CI) 0.61-0.63) and (0.62; 95% CI 0.60-0.64) respectively. Calibration-in-the-large showed a systematic over-estimation of the predicted probability of live birth (Intercept (95% CI) = -0.168 (-0.252 to -0.084), P < 0.001). However, the calibration slope test was not significant (slope (95% CI) = 1.129 (0.893-1.365), P = 0.28). Due to the calibration-in-the-large test being significant we recalibrated the final model. The recalibrated model showed a much-improved calibration. Our model is unable to account for factors such as smoking and alcohol that can affect IVF/ICSI outcome and is somewhat restricted to representing the ethnic distribution and outcomes for the UK population only. We were unable to account for socioeconomic status and it may be that by having 75% of the population paying privately for their treatment, the results cannot be generalized to people of all socioeconomic backgrounds. In addition, patients and clinicians should understand this model is designed for use before treatment begins and does not include variables that become available (oocyte, embryo and endometrial) as treatment progresses. Finally, this model is also limited to use prior to first cycle only. To our knowledge, this is the first study to present a novel, up-to-date model encompassing three readily available prognostic factors; female BMI, ovarian reserve and ethnicity, which have not previously been used in prediction models for IVF outcome. Following geographical validation, the model can be used to build a user-friendly interface to aid decision-making for couples and their clinicians. Thereafter, a feasibility study of its implementation could focus on patient acceptability and quality of decision-making. None. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Total levels, localization patterns, and proportions of sperm exhibiting phospholipase C zeta are significantly correlated with fertilization rates after intracytoplasmic sperm injection.

PubMed

Yelumalai, Suseela; Yeste, Marc; Jones, Celine; Amdani, Siti N; Kashir, Junaid; Mounce, Ginny; Da Silva, Sarah J Martins; Barratt, Christopher L; McVeigh, Enda; Coward, Kevin

2015-09-01

To study the relationship of total levels, localization patterns, and proportions of sperm exhibiting phospholipase C zeta, with fertilization rates after in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Laboratory study; controls vs. patients after IVF (n = 27) or ICSI (n = 17) treatment. Fertility center. A total of 44 semen samples, subjected to either IVF or ICSI treatment. Oocyte collection, ICSI or IVF, determination of sperm concentration and motility, and immunocytochemical analyses of phospholipase C zeta (PLCζ). None. Percentages of sperm exhibiting PLCζ. Significant positive correlation between ICSI fertilization rates and total levels, localization patterns, and the proportion (percentage) of sperm exhibiting PLCζ. Total levels, localization patterns, and the proportion of sperm exhibiting PLCζ are correlated with fertilization rates for ICSI, but not for IVF. Evaluating total levels, localization patterns, and proportions of PLCζ may represent a useful diagnostic tool for clinical purposes in men for whom IVF is not advised or has previously failed. This clinical study further supports the fundamental role of PLCζ in the oocyte activation process. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Cost analysis of in vitro fertilization.

PubMed

Stern, Z; Laufer, N; Levy, R; Ben-Shushan, D; Mor-Yosef, S

1995-08-01

In vitro fertilization (IVF) has become a routine tool in the arsenal of infertility treatments. Assisted reproductive techniques are expensive, as reflected by the current "take home baby" rate of about 15% per cycle, implying the need for repeated attempts until success is achieved. Israel, today is facing a major change in its health care system, including the necessity to define a national package of health care benefits. The issue of infertility and whether its treatment should be part of the "health basket" is in dispute. Therefore an exact cost analysis of IVF is important. Since the cost of an IVF cycle varies dramatically between countries, we sought an exact breakdown of the different components of the costs involved in an IVF cycle and in achieving an IVF child in Israel. The key question is not how much we spend on IVF cycles but what is the cost of a successful outcome, i.e., a healthy child. This study intends to answer this question, and to give the policy makers, at various levels of the health care system, a crucial tool for their decision-making process. The cost analysis includes direct and indirect costs. The direct costs are divided into fixed costs (labor, equipment, maintenance, depreciation, and overhead) and variable costs (laboratory tests, chemicals, disposable supplies, medications, and loss of working days by the couples). The indirect costs are the costs of premature IVF babies, hospitalization of the IVF pregnant women in a high risk unit, and the cost of complications of the procedure. According to our economic analysis, an IVF cycle in Israel costs $2,560, of which fixed costs are about 50%. The cost of a "take home baby" is $19,267, including direct and indirect costs.

Impact of blood hypercoagulability on in vitro fertilization outcomes: a prospective longitudinal observational study.

PubMed

Gerotziafas, Grigoris T; Van Dreden, Patrick; Mathieu d'Argent, Emmanuelle; Lefkou, Eleftheria; Grusse, Matthieu; Comtet, Marjorie; Sangare, Rabiatou; Ketatni, Hela; Larsen, Annette K; Elalamy, Ismail

2017-01-01

Blood coagulation plays a crucial role in the blastocyst implantation process and its alteration may be related to in vitro fertilization (IVF) failure. We conducted a prospective observational longitudinal study in women eligible for IVF to explore the association between alterations of coagulation with the IVF outcome and to identify the biomarkers of hypercoagulability which are related with this outcome. Thirty-eight women eligible for IVF (IVF-group) and 30 healthy, age-matched women (control group) were included. In the IVF-group, blood was collected at baseline, 5-8 days after administration of gonadotropin-releasing hormone agonist (GnRH), before and two weeks after administration of human follicular stimulating hormone (FSH). Pregnancy was monitored by measurement of β HCG performed 15 days after embryo transfer. Thrombin generation (TG), minimal tissue factor-triggered whole blood thromboelastometry (ROTEM®), procoagulant phospholipid clotting time (Procoag-PPL®), thrombomodulin (TMa), tissue factor activity (TFa), factor VIII (FVIII), factor von Willebrand (FvW), D-Dimers and fibrinogen were assessed at each time point. Positive IVF occurred in 15 women (40%). At baseline, the IVF-group showed significantly increased TG, TFa and TMa and significantly shorter Procoag-PPL versus the control group. After initiation of hormone treatment TG was significantly higher in the IVF-positive as compared to the IVF-negative group. At all studied points, the Procoag-PPL was significantly shorter and the levels of TFa were significantly higher in the IVF-negative group compared to the IVF-positive one. The D-Dimers were higher in the IVF negative as compared to IVF positive group. Multivariate analysis retained the Procoag-PPL and TG as predictors for the IVF outcome. Diagnosis of women with hypercoagulability and their stratification to risk of IVF failure using a model based on the Procoag-PPL and TG is a feasible strategy for the optimization of IVF efficiency that needs to be validated in prospective trials.

Life after unsuccessful IVF treatment in an assisted reproduction unit: a qualitative analysis of gains through loss among Chinese persons in Hong Kong.

PubMed

Lee, Geok Ling; Hui Choi, W H; Chan, Celia H Y; Chan, Cecilia L W; Ng, Ernest H Y

2009-08-01

Previous studies examining experiences of infertility focused mainly on the aspect of loss but neglected the possible gains realized through surviving the experience of infertility. The success rate of IVF remains relatively low, and we used the strengths perspective to examine adjustment after unsuccessful treatment. This study aims to provide an in-depth description of the gains perceived by Chinese men and women and how they re-constructed their lives after unsuccessful IVF treatment. Four couples and another six women who experienced unsuccessful IVF treatment were recruited from an assisted reproduction clinic. Data were collected through in-depth interviews, using a grounded theory constructivist approach. Of the 10 women and 4 men interviewed, 9 remained childless, 3 had adopted a child and 2 had conceived naturally. They reported gains on a personal level, interpersonal level and transpersonal level through surviving the experience of infertility. All, regardless of the eventual outcome, reported at least one form of personal gain: in personality or knowledge gain. Interpersonal gains were perceived in relationships with their spouses, children, parents, friends, colleagues and fellow IVF service users. More than half of them reported spiritual growth and a change in identity through integrating their experiences and offering help to others. Despite the small sample size, this study makes a significant contribution by suggesting that while negative feelings provoked by the failure to conceive should be acknowledged, people in this situation should also be enabled to consolidate their negative experiences of IVF constructively, helping them to move on with their lives.

A retrospective evaluation of prognosis and cost-effectiveness of IVF in poor responders according to the Bologna criteria.

PubMed

Busnelli, Andrea; Papaleo, Enrico; Del Prato, Diana; La Vecchia, Irene; Iachini, Eleonora; Paffoni, Alessio; Candiani, Massimo; Somigliana, Edgardo

2015-02-01

Do the Bologna criteria for poor responders successfully identify women with poor IVF outcome? The Bologna criteria effectively identify a population with a uniformly low chance of success. Women undergoing IVF who respond poorly to ovarian hyper-stimulation have a low chance of success. Even if improving IVF outcome in this population represents a main priority, the lack of a unique definition of the condition has hampered research in this area. To overcome this impediment, a recent expert meeting in Bologna proposed a new definition of poor responders ('Bologna criteria'). However, data supporting the relevance of this definition in clinical practice are scanty. Retrospective study of women undergoing IVF-ICSI between January 2010 and December 2012 in two independent infertility units. Women could be included if they fulfilled the definition of poor ovarian response (POR) according to Bologna criteria prior to initiation of the cycle. Women were included only for one cycle. The main outcome was the live birth rate per started cycle. The perspective of the cost analysis was the one of the health provider. Three-hundred sixty-two women from two independent Infertility Units were selected. A binomial distribution model was used to calculate the 95% CI of the rate of success. Characteristics of women who did and did not obtain a live birth were compared. A logistic regression model was used to adjust for confounders. The economic analysis included costs for pharmacological compounds and for the IVF procedure. The benefits were estimated on quality-adjusted life years (QALY). To develop the model, we used the local life-expectancy tables, we applied a 3% discount of life years gained and we used a 0.07 improvement in quality of life associated with parenthood. Sensitivity analyses were performed varying the improvement of the quality of life and including/excluding the male partner. The reference values for cost-effectiveness were the Italian and the local (Lombardy) gross domestic product (GDP) pro capita per year in the studied period and the upper and lower limits suggested by NICE. Overall, 23 women had a live birth (6%, 95% CI: 4-9%), in line with the previous evidence. This proportion did not significantly differ in the different subgroups of poor responders. Positive predictive factors of success were previous deliveries (adjusted OR = 3.0, 95% CI: 1.1-8.7, P = 0.039) and previous chemotherapy (adjusted OR = 13.9, 95% CI: 2.5-77.2, P = 0.003). Age, serum AMH, serum FSH and antral follicle count were not significantly associated with live birth. The total cost per live birth was 87 748 Euros, corresponding to 49 919 Euros per QALY. This is above both the limits suggested by NICE for cost-effectiveness and the Italian and local GDP pro capita. Sensitivity analyses mainly support the robustness of the conclusion. We lack a control group and we cannot thus exclude that an alternative definition of poor responders may be equally if not more valid. Moreover, independent validations are warranted prior to concluding that IVF is not cost-effective. Women should thus not be denied treatment based on our findings. Noteworthy, there is also not yet a consensus on the most appropriate economic model to be used. We recommend the use of the Bologna criteria when designing future studies on poor responders. Large multi-centred international studies are now required to draw definite conclusions on the economic profile of IVF in this situation. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The pregnancy outcome of progestin-primed ovarian stimulation using 4 versus 10 mg of medroxyprogesterone acetate per day in infertile women undergoing in vitro fertilisation: a randomised controlled trial.

PubMed

Dong, J; Wang, Y; Chai, W R; Hong, Q Q; Wang, N L; Sun, L H; Long, H; Wang, L; Tian, H; Lyu, Q F; Lu, X F; Chen, Q J; Kuang, Y P

2017-06-01

To investigate the clinical outcome and endocrinological characteristics of progestin-primed ovarian stimulation (PPOS) using 4 versus 10 mg of medroxyprogesterone acetate (MPA) per day in infertile women with normal ovary reserve. A randomised parallel controlled trial. Tertiary-care academic medical centre. A cohort of 300 infertile women undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) treatment. Human menopausal gonadotropin (hMG; 225 iu per day) and MPA (group A, 10 mg per day; group B, 4 mg per day) were started simultaneously from cycle day 3 onwards. Ovulation was co-triggered by human chorionic gonadotropin (hCG; 1000 iu) and gonadotropin-releasing hormone agonist (GnRH agonist; 0.1 mg) when dominant follicles matured. Viable embryos were cryopreserved for later frozen embryo transfer (FET) in both groups. The primary outcome measure was the number of oocytes retrieved. Secondary outcomes included the incidence of a premature surge in luteinising hormone (LH), the number of viable embryos, and clinical pregnancy outcomes. The number of oocytes retrieved and viable embryos were similar between two groups (9.8 ± 6.3 versus 9.6 ± 5.9; 4.2 ± 2.6 versus 3.7 ± 3.0; P > 0.05). No significant difference was found in clinical pregnancy rate (58.0 versus 48.7%) and live birth rate per participant (48.7 versus 42.0%; P > 0.05). No premature LH surge and ovarian hyperstimulation syndrome (OHSS) occurred in either group. Progestin-primed ovarian stimulation (PPOS) using 4 or 10 mg of MPA per day was comparable in terms of the number of oocytes retrieved and pregnancy outcome after FET. The administration of 4 mg of MPA per day was sufficient to prevent an untimely LH rise in women undergoing IVF/ICSI treatment. An RCT confirmed similar pregnancy outcome in P-primed ovarian stimulation with a daily dose of 4 or 10 mg MPA. © 2017 Royal College of Obstetricians and Gynaecologists.

The success of assisted reproduction technologies in relation to composition of the total regulatory T cell (Treg) pool and different Treg subsets.

PubMed

Schlossberger, V; Schober, L; Rehnitz, J; Schaier, M; Zeier, M; Meuer, S; Schmitt, E; Toth, B; Strowitzki, T; Steinborn, A

2013-11-01

Are there differences in composition of the total regulatory T cell (Treg) pool and distinct Treg subsets (naïve CD45RA(+)-Tregs, HLA-DR(-)- and HLA-DR(+)-memory Tregs) between successfully and non-successfully IVF/ICSI-treated women? Non-successfully IVF/ICSI-treated women have a decreased percentage of naïve CD45RA(+)-Tregs and an increased percentage of HLA-DR(-)-memory Tregs within the total Treg pool. Immunosuppressive Tregs play a significant role in human reproduction and studies have shown that their number and function are reduced in reproductive failure and complications of pregnancy such as pre-eclampsia and preterm labor. However, no data exist concerning the importance of Tregs for a successful outcome following assisted reproduction technologies. Blood samples were obtained from 210 women undergoing IVF/ICSI treatment, where 14 patients were excluded due to biochemical pregnancy or missed abortion. Age control blood samples were collected from 20 neonates and 176 healthy female volunteers. The study was performed between October 2010 and March 2012. In this study, we determined prospectively the quantity and composition of the total CD4(+)CD127(low+/-)CD25(+)FoxP3(+)-Treg pool and three different Treg subsets (naïve CD45RA(+)-Tregs, HLA-DR(-)- and HLA-DR(+)-memory Tregs) in all women undergoing IVF/ICSI treatment. We examined whether there were differences between those who became pregnant (n = 36) and those who did not (n = 160). The blood samples were collected within 1 h before the embryo transfer and analyzed by six-color flow cytometry. In order to evaluate these results with regard to the normal age-related changes in composition of the total Treg pool, the same analysis was performed using samples of umbilical cord blood and from healthy female volunteers aged between 17 and 76 years. The composition of the total Treg pool was documented for successfully IVF/ICSI-treated women (n = 5) throughout their pregnancy and we assessed the suppressive activity of each Treg subset in pregnant (n = 10) compared with non-pregnant women (n = 10) using suppression assays. The percentage of CD4(+)CD127(low+/-)CD25(+)FoxP3(+)-Tregs within the total CD4(+)-T cell pool did not change with age and did not differ between IVF/ICSI-treated women who did or did not become pregnant. For the total Treg pool, the percentage of the naïve CD45RA(+)-Tregs decreased continuously, while the percentage of HLA-DR(-)- and HLA-DR(+)-memory Tregs increased with aging. From the age of about 40 years, the increase in HLA-DR(+)-memory Tregs in particular became less pronounced, indicating that conversion of naïve CD45RA(+)Tregs into HLA-DR(+)-memory Tregs decreases with age. Women who did not achieve a pregnancy with IVF/ICSI were older than those who did (P < 0.01). However, multiple logistic regression analysis revealed that irrespective of age, the percentage of naïve CD45RA(+)-Tregs within the total Treg pool was decreased (P < 0.05), while the percentage of HLA-DR(-)-memory Tregs was increased (P < 0.01) in women who did not become pregnant compared with those who did. At the beginning of pregnancy, naïve CD45RA(+)-Tregs showed a major decrease but increased again during pregnancy and these cells showed a higher suppressive activity (P < 0.0001) in pregnant compared with non-pregnant women. There was a large variation in the percentages of the Treg subsets within the total Treg pool between successfully and non-successfully IVF/ICSI-treated women. Therefore, their determination would not allow us to predict the IVF/ICSI outcome with sufficient specificity and sensitivity. We did not examine the antigen specificity of the Treg subsets and therefore could not discern whether the naïve CD45RA(+)-Tregs recognized maternal or paternal antigens. Our findings suggest that Tregs, especially the naïve CD45RA(+)-Treg subset, may play a role in determining the probability of both becoming pregnant and maintenance of the pregnancy. This work was supported by the German Research Council (DFG) grant STE 885/3-2 (to A.S.). All authors declare to have no conflict of interest.

The ISMAAR proposal on terminology for ovarian stimulation for IVF.

PubMed

Nargund, G; Fauser, B C J M; Macklon, N S; Ombelet, W; Nygren, K; Frydman, R

2007-11-01

IVF is performed with oocytes collected in natural and stimulated cycles. Different approaches to ovarian stimulation have been employed worldwide. Following the introduction of GnRH antagonists and strategies to reduce multiple births such as single embryo transfer, there is a genuine scientific interest in the revival of natural cycle and mild approaches to ovarian stimulation in IVF. Recent evidence suggests that application of natural and mild IVF is patient-centred, aimed at reducing the cost of treatment, patient discomfort and multiple pregnancies. However, there seems to be no consistency in the terminology used for definitions and protocols for ovarian stimulation in IVF cycles. Following the recent International Society for Mild Approaches in Assisted Reproduction (ISMAAR) meeting and communication with interested international experts, this article has recommended revised definitions and terminology for natural cycle IVF and different protocols used in ovarian stimulation for IVF. It is proposed that these terms are adopted internationally in order to achieve a consistency in clinical practice, research publications and communication with patients.

Risk of postpartum psychosis after IVF treatment: a nationwide case-control study.

PubMed

Vikström, Josefin; Josefsson, Ann; Hammar, Mats; Bladh, Marie; Sydsjö, Gunilla

2017-01-01

Is the risk of postpartum psychosis (PPP) increased in women who give birth after IVF treatment compared to after spontaneous conception? The risk of PPP is not higher in the group of women who give birth after IVF treatment compared with women who give birth after spontaneous conception. Women who conceive using IVF treatment can experience higher levels of pregnancy-specific distress and are at increased risk of pre-eclampsia, an immune-related condition which in turn has been linked to PPP, as well as other pregnancy and delivery complications, which also serve as PPP risk factors. It is not known whether the risk of PPP is increased in women who have conceived using IVF treatment. A nationwide, register-based, case-control study of all primiparous women who had given birth after IVF treatment between 1988 and 2012. Information about 10 412 women was collected from the Swedish IVF register. A control group of women who had given birth after spontaneous conception was selected from the Swedish Medical Birth Register (n = 18 624). PPP diagnoses, identified using ICD-10 diagnostic codes F20-31 and F531 the first year postpartum, were collected from the National Patient Register. Associations between PPP and IVF/spontaneous conception were evaluated using chi-square tests and logistic regression analyses while controlling for known risk factors of PPP. There were no differences in PPP prevalence between the IVF group and the control group (0.3%, n = 29 versus 0.4%, n = 77) in the chi-square analysis (P = 0.169) or the multiple logistic regression analyses (P = 0.646; odds ratio (OR): 1.178; 95% CI: 586-2.365). No associations between pregnancy or delivery complications and PPP were found. A history of any psychiatric disorder (P < 0.001; OR = 40.7; 95% CI = 23.9-69.5), or specifically a psychotic (P < 0.001; OR = 324.1; 95% CI = 131.3-800.0), bipolar (P < 0.001; OR = 516.1; 95% CI = 264.3-1008.1), depressive (P < 0.001; OR = 27.5; 95% CI = 16.2-46.5), anxiety (P < 0.001; OR = 12.9; 95% CI = 7.4-22.6) or personality disorder (P < 0.001; OR = 27.3; CI = 11.8-63.0), all significantly increased the risk of PPP. PPP is a rare condition, hence the number of individuals was small. Since all women for whom information was available from all registers were included, it was not possible to further increase the power of the study using this design. Since this study is the first to examine risk of PPP after IVF treatment, more studies are needed to verify these results. The generalizability is restricted to primiparous women in western countries. This study confirms the results of previous studies in showing a history of mental illness to be the major risk factor for PPP. None. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The practice gap in the care of women following successful infertility treatments: unasked research questions in midwifery and nursing.

PubMed

Allan, Helen; Finnerty, Gina

2007-06-01

The aim of this paper is to highlight the gap between existing research evidence and nursing and midwifery practices in caring for women following successful in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT), and to suggest directions for research within these disciplines. We argue that although the number of couples in the UK experiencing fertility problems has risen, 1.4% of all births in the UK are as the result of infertility treatments (HFEA, 2005/2006); yet there is little research into the experiences of motherhood for women who successfully achieve pregnancy following IVF or GIFT. Consequently, there is negligible research evidence for nurses and midwives practicing in this area, and British healthcare staff appear to be unaware of the specific needs of infertile women during pregnancy, birth and early motherhood. In this paper we review the existing literature on this group of women, which falls into three areas: studies into the psychosocial development of the child conceived via IVF/GIFT/donor insemination; comparative studies into experiences of women following successful infertility treatment and women who conceive naturally; and studies into the experiences of women following successful IVF treatment. We review this literature to argue for research into the needs of infertile women following successful IVF/GIFT, to inform evidence for practice.

Effect of metformin and oral contraceptives on polycystic ovary syndrome and IVF cycles.

PubMed

Kalem, M N; Kalem, Z; Gurgan, T

2017-07-01

The aim of this study is to investigate the effect of metformin and/or OC added to the treatment of PCOS patients at our clinic on IVF outcome. This study is a retrospective study that assesses the data of PCOS patients who received IVF between 2005 and 2015 at a private IVF center. The study included 496 PCOS cases aged between 24 and 40. Participants diagnosed with PCOS were divided into 4 groups according to the use of metformin and OC prior to the IVF cycle: 11.1% were in the metformin group, 31.3% in the OC group, 14.9% in the Metformin + OC group, and 42.7% in the control group. No difference was found in the total gonadotropin dose and duration of stimulation between the groups. Clinical pregnancy rates and implantation rates were similar in all groups, although the numbers of oocytes, mature oocytes, fertilized oocytes, and transferred embryos were lower in the treatment groups received metformin compared to the OC group and control group. There was no significant difference in the presence of OHSS and the singleton and multiple pregnancies between the four groups. The present study established no positive role of metformin and OC use in increasing the treatment success in IVF/ICSI cycles in PCOS patients. It would be appropriate to limit the use of these agents with special indications such as decreasing insulin resistance or synchronizing follicular cohort.

Social and private benefits of assisted reproductive technology: a national survey-based evaluation in Israel.

PubMed

Gonen, Limor Dina

2016-01-01

The objective of this paper was to measure the private and social benefits resulting from technological advances in fertility treatment. An empirical model investigates the willingness-to-pay (WTP) for advances in the medical technology of in vitro fertilization (IVF) among the general public and among IVF patients in Israel. The empirical model's findings demonstrate that IVF patients and the general public value medical technology advances and have a positive WTP for it. The average WTP for IVF technology advances, among IVF patients, is US $3116.9 whereas for the general public it is US$2284.4. Available evidence suggests that advances in medical technology have delivered substantial benefits and appear to have contributed to improved wellbeing.

Can we alter pregnancy outcome by adjusting progesterone treatment at mid-luteal phase: a randomized controlled trial.

PubMed

Aslih, Nardin; Ellenbogen, Adrian; Shavit, Tal; Michaeli, Medeia; Yakobi, Devora; Shalom-Paz, Einat

2017-08-01

Our study aimed to determine whether mid-luteal serum P concentrations can serve as a predictive factor for in vitro fertilization (IVF) outcomes and whether increasing P dosage for patients with low levels at mid-luteal phase may improve pregnancy rates. It was a prospective, randomized controlled study. A total of 146 patients undergoing IVF treatment were prospectively enrolled and received routine luteal phase support (LPS) regimen of Endometrin® (progesterone) 200 mg/day. Serum P levels were measured 7 days after embryo transfer (ET). Considering a cutoff level of 15 ng/ml on this day, patients with higher levels continued the same dosage until pregnancy test (control group). Patients with lower levels were randomly allocated to continue Endometrin® 200 mg/day (Group A) or to increase Endometrin® dosage to 300 mg/day (Group B). The Main Outcome Measures were pregnancy rates. Both biochemical and clinical pregnancy and live birth rates were comparable between all groups regardless of P level on day 7 of luteal phase and regardless of dose adjustment. ROC analysis determined that mid-luteal P levels of 17 ng/ml can be a better predictor of cycle outcome. In conclusion raising the P dose at mid-luteal phase to 300 mg daily did not improve cycle outcomes.

Ovarian response markers lead to appropriate and effective use of corifollitropin alpha in assisted reproduction.

PubMed

La Marca, Antonio; D'Ippolito, Giovanni

2014-02-01

Corifollitropin alpha is a highly effective gonadotrophin, which maintains multifollicular growth for a week. The advantages of its administration include ease of use of the drug, making the treatment more patient friendly, resulting in a lower level of distress for the patient. At the same time, the pregnancy rate resulting from its use in IVF/intracytoplasmic sperm injection cycles is similar to that found when daily recombinant FSH is administered. The ovarian response to corifollitropin alpha is dependent on clinically established predictors such as baseline FSH, antral follicle count (AFC) and age. There is a general trend towards a higher ovarian response with an increasing AFC and the number of oocytes per attempt decreased with increasing baseline FSH and age. Even if the risk of ovarian hyperstimulation syndrome following corifollitropin alpha is very similar to the rate reported in literature for young women undergoing IVF, the risk of overstimulation may be reduced by avoiding maximal ovarian stimulation in women anticipated to be hyperresponders. High basal anti-Müllerian hormone and/or AFC can identify women with enhanced functional ovarian reserve at risk of overstimulation, and the risk is even higher if maximally stimulated with corifollitropin alpha or high dose of daily recombinant FSH. Corifollitropin alpha is a highly effective gonadotrophin which maintains multifollicular growth for a week. The ovarian response to corifollitropin was demonstrated to be dependent on clinically established predictors such as baseline FSH, antral follicle count (AFC) and age. There was a general trend toward a higher ovarian response with an increasing AFC and the mean number of oocytes per attempt decreased with increasing baseline FSH and age. Even if the risk of ovarian hyperstimulation syndrome (OHSS) following corifollitropin alpha is very similar to the rate of OHSS reported in literature for young women undergoing IVF, the risk of overstimulation may be reduced by avoiding maximal ovarian stimulation in women anticipated to be hyperresponders. Increasing evidence demonstrates that anti-Müllerian hormone and AFC exhibit a very good diagnostic performance in the prediction of hyperresponse. High basal anti-Müllerian hormone and/or AFC can identify women with enhanced functional ovarian reserve who are at risk of overstimulation if stimulated in IVF cycles and the risk is even higher if maximally stimulated with corifollitropin alpha or high dose of daily recombinant FSH. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

A longitudinal study investigating the role of decisional conflicts and regret and short-term psychological adjustment after IVF treatment failure.

PubMed

Chan, Celia Hoi Yan; Lau, Hi Po Bobo; Tam, Michelle Yi Jun; Ng, Ernest Hung Yu

2016-12-01

What is the relationship between decisional conflict, decisional regret and psychological well-being in women following unsuccessful IVF cycles? The mediating effect of decisional regret on the relationship between decisional conflict and fertility-related quality of life (FRQOL) has been found to be moderated by the availability (versus absence) of frozen embryos after an unsuccessful IVF cycle. Infertility treatment is marked by its open-ended nature. Stresses in treatment decision-making could be aggravated by a culture which honours families through procreation. While studies have investigated treatment-related decision-making among infertile women, little is known about the mental health consequences of decisional conflict and decisional regret following an unsuccessful IVF cycle. A study was conducted over a 3-month period with infertile women who had recently experienced a failed IVF cycle (T 0 ). Decisional conflict when they decided on terminating or continuing treatment (T 1 ) and decisional regret 3 months later (T 2 ) were measured. Participants reported their levels of depression, anxiety and FRQOL at three time points. A total of 151 participants completed all time points (attrition rate: 39%). The average age of participants was 37.2 years, and they had had 1.1 cycles (range: 0-8) on average at the time of study intake. The duration of the study was 2 years. Participants were infertile women who were not pregnant following an IVF cycle recruited from a university-affiliated assisted reproduction centre. Following the notification of a negative pregnancy result, patients were invited to complete measures of FRQOL, depression and anxiety across three time points and decisional conflict and decisional regret at T 1 and T 2 respectively. Decisional regret partially mediated the effect of decisional conflict on overall and treatment-specific FRQOL (P < 0.05). The mediation by decisional regret was present only among participants who had no remaining frozen embryos after their unsuccessful IVF cycle (P < 0.05). Self-selection bias at recruitment remains a concern. Our results show for the first time how mental health implications of decisional conflict may vary among patients with different clinical characteristics (i.e. availability of frozen embryos), despite their common experience of an unsuccessful IVF cycle. Healthcare professionals should be aware of the psychological ramifications of treatment decision-making difficulties, as well as individual differences in adjustment to unsuccessful treatment. The study was funded by the Hong Kong University Grant Council-General Research Fund (HKU740613) and the authors have no conflicts of interest. HKU Clinical Trials Registry (Trial registration number: HKUCTR-1680). © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pregnancy Outcome Using General Anesthesia Versus Spinal Anesthesia for In Vitro Fertilization

PubMed Central

Azmude, Azra; Agha'amou, Shahrzad; Yousefshahi, Fardin; Berjis, Katayoun; Mirmohammad'khani, Majid; Sadaat'ahmadi, Farahnaz; Ghods, Kamran; Dabbagh, Ali

2013-01-01

Background There is a considerable rate of fertility failure and this causes a great burden of untoward effects for patients. Usually a considerable number of these patients undergo anesthesia for their treatment. Objectives This study was designed to compare the effects of general and spinal anesthesia on these patients. Patients and Methods In a randomized clinical trial, after taking informed written consent from the patients, 200 patients entered the study; 100 in each. During a 2 year period, women aged 20 to 40 years entered the study (one group receiving spinal anesthesia and the other, receiving general anesthesia). Ovum retrieval protocols were the same. Nonparametric and parametric analyses were used for data analysis. P value less than 0.05 was considered significant. Results There was no difference between the two groups regarding demographic variables. 15 of 100 patients (15%) in the general anesthesia group and 27 of 100 patients (27%) in the spinal anesthesia group had successful pregnancy after IVF; so, spinal anesthesia increased significantly the chance of IVF success (P value < 0.001; Chi Square). Conclusions The results of this study demonstrated that spinal anesthesia increased the chance of fertilization success. PMID:24282775

Prospective evaluation of basal stromal Doppler studies in women with good ovarian reserve and infertility undergoing in vitro fertilization-embryo transfer treatment: patients with polycystic ovary syndrome versus ovulatory patients.

PubMed

Younis, Johnny S; Jadaon, Jimmy E; Haddad, Sami; Izhaki, Ido; Ben-Ami, Moshe

2011-04-01

To gain insight into the ovarian stromal blood flow in women with polycystic ovary syndrome (PCOS) as compared with women with normal ovulation, good ovarian reserve, and infertility and to evaluate the role of stromal flow in these patients to predict clinical pregnancy in an assisted reproductive technologies setting. A prospective observational cohort study. A university-affiliated reproductive medicine unit. Eighteen consecutive patients with PCOS (study) compared with 101 patients with normal ovulation and infertility (control), undergoing their first IVF-ET treatment at our unit. Women with low ovarian reserve were excluded a priori from evaluation. Basal ovarian reserve parameters and stromal flow studies were conducted as routinely performed in our unit, in a natural cycle before starting treatment. None. Basal ovarian endocrine, sonographic, and stromal flow studies were compared between the groups. After completion of treatment, the stromal flow studies were compared between conception and nonconception cycles. Patients' characteristics and basal ovarian reserve, including endocrine and sonographic parameters, were similar between the PCOS and control groups. Only antral follicle count and LH/FSH ratio were higher in the PCOS as compared with the control group, corresponding to 15.11 ± 6.05 versus 9.05 ± 4.77 and 1.14 ± 0.64 versus 0.79 ± 0.37, respectively. Basal stromal flow indices were similar between the PCOS group and the group with normal ovulation and good ovarian reserve. Clinical pregnancy rate per initiated cycle was 50.0% and 39.6% in the PCOS and control groups, respectively, with no significant difference. Flow indices were similar between conception cycles in the PCOS and control groups. As well, the indices did not differ significantly between conception and nonconception cycles within the PCOS and control groups. Basal ovarian stromal blood flow does not differ between women with PCOS and women with normal ovulation, good ovarian reserve, and infertility. Moreover, stromal flow has no predictive value, in these patients, for clinical pregnancy achievement in an IVF-ET setting. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Economic Evaluation of Three Frequently Used Gonadotrophins in Assisted Reproduction Techniques in the Management of Infertility in the Netherlands.

PubMed

Fragoulakis, Vassilis; Pescott, Chris P; Smeenk, Jesper M J; van Santbrink, Evert J P; Oosterhuis, G Jur E; Broekmans, Frank J M; Maniadakis, Nikos

2016-12-01

Subfertility represents a multidimensional problem associated with significant distress and impaired social well-being. In the Netherlands, an estimated 50,000 couples visit their general practitioner and 30,000 couples seek medical specialist care for subfertility. We conducted an economic evaluation comparing recombinant human follicle-stimulating hormone (follitropin alfa, r-hFSH, Gonal-F ® ) with two classes of urinary gonadotrophins-highly purified human menopausal gonadotrophin (hp-HMG, Menopur ® ) and urinary follicle-stimulating hormone (uFSH, Fostimon ® )-for ovarian stimulation in women undergoing in vitro fertilization (IVF) treatment in the Netherlands. A pharmacoeconomic model was developed, simulating each step in the IVF protocol from the start of therapy until either a live birth, a new IVF treatment cycle or cessation of IVF, following a long down-regulation protocol. A decision tree combined with a Markov model details progress through each health state, including ovum pickup, fresh embryo transfer, up to two subsequent cryo-preserved embryo transfers, and (ongoing) pregnancy or miscarriage. A health insurer perspective was chosen, and the time horizon was set at a maximum of three consecutive treatment cycles, in accordance with Dutch reimbursement policy. Transition probabilities and costing data were derived from a real-world observational outcomes database (from Germany) and official tariff lists (from the Netherlands). Adverse events were considered equal among the comparators and were therefore excluded from the economic analysis. A Monte Carlo simulation of 5000 iterations was undertaken for each strategy to explore uncertainty and to construct uncertainty intervals (UIs). All cost data were valued in 2013 Euros. The model's structure, parameters and assumptions were assessed and confirmed by an external clinician with experience in health economics modelling, to inform on the appropriateness of the outcomes and the applicability of the model in the chosen setting. The mean total treatment costs were estimated as €5664 for follitropin alfa (95 % UI €5167-6151), €5990 for hp-HMG (95 % UI €5498-6488) and €5760 for uFSH (95 % UI €5256-6246). The probability of a live birth was estimated at 36.1 % (95 % UI 27.4-44.3 %), 33.9 % (95 % UI 26.2-41.5 %) and 34.1 % (95 % UI 25.9-41.8 %) for follitropin alfa, hp-HMG and uFSH, respectively. The costs per live birth estimates were €15,674 for follitropin alfa, €17,636 for hp-HMG and €16,878 for uFSH. Probabilistic sensitivity analysis indicated a probability of 72.5 % that follitropin alfa is cost effective at a willingness to pay of €20,000 per live birth. The probabilistic results remained constant under several analyses. The present analysis shows that follitropin alfa may represent a cost-effective option in comparison with uFSH and hp-HMG for IVF treatment in the Netherlands healthcare system.

Expensive but worth it: older parents' attitudes and opinions about the costs and insurance coverage for in vitro fertilization.

PubMed

Nachtigall, Robert D; MacDougall, Kirstin; Davis, Anne C; Beyene, Yewoubdar

2012-01-01

To describe older parents' attitudes and opinions about the costs and insurance coverage for IVF. Qualitative interview study. Two Northern California IVF practices. Sixty women and 35 male partners in which the woman had delivered her first child after the age of 40 years using IVF. Two in-depth interviews over 3 months. Thematic analysis of interview transcripts. We found that although the costs of IVF were perceived as high, even by those with insurance or who could afford them, the cost of IVF relative to other expenses in life was dwarfed by the value attributed to having a child. Women were twice as likely as men to support insurance coverage for IVF. Both men and women with complete or partial IVF insurance coverage were more likely to support insurance than those without coverage. There was a broad range of attitudes and opinions about the appropriateness of IVF insurance coverage, which addressed questions of age, gender equality, reproductive choice, whether infertility is a medical illness, and the role of personal and societal economic equity and responsibility. Despite a generally favorable opinion about the appropriateness of insurance coverage by those who have successfully undergone IVF treatment, the affordability of IVF remains an unresolved dilemma in the United States. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Expensive but worth it: older parents’ attitudes and opinions about the costs and insurance coverage for in vitro fertilization

PubMed Central

Nachtigall, Robert D.; MacDougall, Kirstin; Davis, Anne C.; Beyene, Yewoubdar

2011-01-01

Objective To describe older parents’ attitudes and opinions about the costs and insurance coverage for IVF. Design Qualitative interview study. Setting Two Northern California IVF practices. Patient(s) Sixty women and 35 male partners in which the woman had delivered her first child after the age of 40 years using IVF. Intervention(s) Two in-depth interviews over 3 months. Main Outcome Measure(s) Thematic analysis of interview transcripts. Result(s) We found that although the costs of IVF were perceived as high, even by those with insurance or who could afford them, the cost of IVF relative to other expenses in life was dwarfed by the value attributed to having a child. Women were twice as likely as men to support insurance coverage for IVF. Both men and women with complete or partial IVF insurance coverage were more likely to support insurance than those without coverage. There was a broad range of attitudes and opinions about the appropriateness of IVF insurance coverage, which addressed questions of age, gender equality, reproductive choice, whether infertility is a medical illness, and the role of personal and societal economic equity and responsibility. Conclusion(s) Despite a generally favorable opinion about the appropriateness of insurance coverage by those who have successfully undergone IVF treatment, the affordability of IVF remains an unresolved dilemma in the United States. PMID:22118993

Cumulative live birth rates after IVF in patients with polycystic ovaries: phenotype matters.

PubMed

De Vos, Michel; Pareyn, Stéphanie; Drakopoulos, Panagiotis; Raimundo, José M; Anckaert, Ellen; Santos-Ribeiro, Samuel; Polyzos, Nikolaos P; Tournaye, Herman; Blockeel, Christophe

2018-05-07

Do cumulative live birth rates (CLBR) vary among women with different polycystic ovary syndrome (PCOS) phenotypes who undergo IVF/intracytoplasmic sperm injection (ICSI) treatment? In this retrospective cohort study, data from 567 patients undergoing an assisted reproductive technology (ART) cycle between January 2010 and December 2015 were collected. Demographical traits, cycle characteristics and clinical and laboratory data were analysed. After conventional ovarian stimulation using a gonadotrophin-releasing hormone antagonist protocol, the median number of oocytes retrieved ranged between 11 and 13.5 and did not differ significantly among the studied groups. Live birth rate (LBR) after fresh embryo transfer and CLBR after transfer of all fresh and vitrified embryos were significantly lower in women with hyperandrogenic PCOS phenotypes A (LBR 16.7%, CLBR 25.8%) and C (LBR 18.5%, CLBR 27.8%) compared with women with normoandrogenic PCOS phenotype D (LBR 33.7%, CLBR 48%) (P-value for LBR 0.01 and 0.03, respectively; P-value for CLBR 0.002 and 0.01, respectively) and controls with a polycystic ovarian morphology (LBR 37.1%, CLBR 53.3%) (P-value for LBR 0.002 and 0.01, respectively; P-value for CLBR <0.001 and 0.001, respectively). Multivariate regression analysis indicated that after adjustment for relevant confounders, PCOS phenotype was an independent predictor for CLBR. Hyperandrogenic PCOS phenotypes confer significantly lower CLBR compared with their normoandrogenic counterparts. These findings may imply the need for adapted counselling and tailored approaches when treating PCOS patients with hyperandrogenism who require ART. Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

[Ten years of results of in-vitro fertilisation in the Netherlands 1996-2005].

PubMed

Kremer, J A M; Bots, R S G M; Cohlen, B; Crooij, M; van Dop, P A; Jansen, C A M; Land, J A; Laven, J S E; Kastrop, P M M; Naaktgeboren, N; Schats, R; Simons, A H M; van der Veen, F

2008-01-19

To present the numbers and results of Dutch IVF treatment from 1996-2005 and to describe trends and differences between centres. Retrospective data-collection, description and analysis. The annual statistics from all Dutch IVF centres covering the years 1996-2005 were collected, described and analysed. During this period 138,217 IVF or intracytoplasmic sperm injection (ICSI) cycles were started and 14,881 transfers of frozen-thawed embryos (cryo transfers) were performed. The number of ICSI treatments, in particular, increased to more than 6000 cycles during this period. These treatments resulted in 30,488 ongoing pregnancies (22.1% per cycle started; 19.1% for IVF and 23.4% for ICSI). The ongoing pregnancy rate per cycle increased from 17.6% in 1996 to 24.4% in 2005. The increase after cryo transfers was remarkable (from 9.4% to 17.6%). It is estimated that during this period, about 1 in 52 newborns in the Netherlands was an IVF or ICSI child (1996: 1 in 77, 2005: 1 in 43). There were differences between the individual centres regarding the ongoing pregnancy rate per cycle (range: 15.0-26.4%), the percentage of ICSI (range 20-58%), the percentage of cryo transfers per cycle (range: 4-22%) and the multiple pregnancy rate (range 5-27% in 2005). In the Netherlands the pregnancy rate has increased over the last 10 years as has the number of IVF treatments. Cryo transfers have become increasingly important and the multiple pregnancy rate has decreased. Although thanks to the collaboration of all centres, the current registry produces important data and works well, there are a number of limitations e.g. the retrospective nature with no validation, which must be tackled over the coming years.

The impact of introducing patient co-payments in Germany on the use of IVF and ICSI: a price-elasticity of demand assessment.

PubMed

Connolly, M P; Griesinger, G; Ledger, W; Postma, M J

2009-11-01

Authorities concerned by rising healthcare costs have a tendency to target reproductive treatments because of the perception that infertility is a low priority. In 2004 German health authorities introduced a 50% co-payment for patients, in an effort to save cost. We explored the impact of this pricing policy on the utilization of reproductive treatments in Germany. Using aggregated annual in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycle data in Germany, we evaluated the relationship between changes in the number of cycles in relation to changes in costs faced by consumers following the introduction of a patient co-payment from 'no fees' to 1500-2000 euros by estimating the short-run price-elasticity of demand. The impact of introducing patient co-payments for IVF/ICSI on the likelihood of switching to other low-cost fertility treatments was evaluated using the cross-price elasticity methodology. RESULTS The reduction in demand for IVF and ICSI cycles in the year following the introduction of patient co-payments resulted in elasticities of -0.41 and -0.34, respectively. The price-elasticity for the combined reduction of IVF/ICSI in relation to the co-payment was estimated to be -0.36. The cross-price elasticity for clomifene was close to zero (-0.01) suggesting that demand for these interventions are independent of each other and no substitution occurred. We report price elasticities for IVF and ICSI of -0.41 and -0.34 after introducing a 500-2000 euros co-payment. These findings likely represent short-run elasticities that are likely to vary over time as factors that influence the supply and demand for fertility treatments change.

In vitro maturation of human oocytes for assisted reproduction.

PubMed

Jurema, Marcus W; Nogueira, Daniela

2006-11-01

To describe and evaluate the current practice of in vitro maturation of oocytes for assisted reproduction. Review of the available and relevant literature regarding in vitro maturation of oocytes. In vitro maturation of human oocytes retrieved from antral ovarian follicles is an emerging procedure quickly being incorporated into the realm of assisted reproductive technologies. This new technology has several potential advantages over traditional controlled ovarian hyperstimulation for IVF, such as reduction of costs by minimizing gonadotropin and GnRH analogue use, elimination of ovarian hyperstimulation syndrome, and simplicity of protocol. In vitro maturation of oocytes for assisted reproduction in human beings still is undergoing refinement but currently is providing efficacy and safety outcome comparable to that of traditional IVF in recent selected studies. Implementing in vitro maturation into an established IVF practice is feasible and requires only a few simple adjustments. Crucial to the advancement and optimization of the technology is a better understanding of how to maximize immature oocyte developmental competence and endometrial receptivity.

Vascularization and VEGF expression altered in bovine yolk sacs from IVF and NT technologies.

PubMed

Mess, Andrea Maria; Carreira, Ana Claudia Oliveira; Marinovic de Oliveira, Cláudia; Fratini, Paula; Favaron, Phelipe Oliveira; Barreto, Rodrigo da Silva Nunes; Pfarrer, Christiane; Meirelles, Flávio Vieira; Miglino, Maria Angelica

2017-01-01

Reproductive technologies are widely used in cattle, although many are associated with high-embryonic mortality, especially during early gestation, when the yolk sac undergoes macroscopic changes in structure. We hypothesized that vasculogenesis and angiogenesis are affected, thereby affecting embryonic and placental differentiation. To test this, we studied yolk sac development and gene expression of the vascular endothelial growth factor system (VEGF-A, VEGFR-1/Flt-1, VEGFR-2/KDR). Samples from Days 25 to 40/41 of pregnancy from control cattle (n = 8) and from pregnancies established with IVF, (n = 7) or somatic cell nuclear transfer/clones (n = 5) were examined by histology, immunohistochemistry, and quantitative reverse transcriptase PCR. Yolk sacs in IVF- and nuclear transfer-derived pregnancies were immature. Development of villi was sparse in IVF yolk sacs, whereas vascularization was barely formed in clones and was associated, in part, with thin or interrupted endothelium. Transcript levels of the genes characterized exceed minimum detection limits for all groups, except in the mentioned clone with interrupted endothelium. Levels of mRNA for VEGF-A and VEGFR-2 were significantly higher in IVF yolk sacs. Clones had substantial individual variation in gene expression (both upregulation and downregulation). Our data confirmed the broad range in expression of VEGF genes. Furthermore, overexpression in IVF yolk sacs may compensate for an immature yolk sac structure, whereas in clones, patchy expression may cause structural alterations of blood vessels. In conclusion, we inferred that disturbances of yolk sac vasculature contributed to increased early embryonic mortality of bovine pregnancies established with reproductive technologies. Copyright © 2016 Elsevier Inc. All rights reserved.

How should we assess the safety of IVF technologies?

PubMed

Brison, Daniel R; Roberts, Stephen A; Kimber, Susan J

2013-12-01

Clinical IVF treatment was established over 30 years ago through pioneering work by Edwards and Steptoe and other teams around the world and is now considered routine treatment. However, the pace of scientific and technological advances means that IVF practitioners can now access an increasing array of new and invasive technologies. The examples are many but include: extended embryo culture, development of media to include growth factors, developments in genetic screening, use of time-lapse technology and the advent of vitrification of embryos and oocytes. In parallel, wider scientific and medical advances are raising our awareness of the potential impact of assisted reproduction technology on areas such as embryonic development, gene expression and genomic imprinting and the developmental origins of health and disease. A recently suggested paradigm for assessing new technologies in IVF includes development in animal models such as rodents and large animals, preclinical research with human gametes and embryos donated to research, prospective clinical trials in IVF and, finally, follow-up studies of IVF children. In this paper, we describe efforts to address key areas of this pathway, namely preclinical research using human gametes/embryos and long-term, follow-up studies of the health of assisted reproduction children. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Cost analysis of singleton versus twin pregnancies after in vitro fertilization.

PubMed

Lukassen, H G Marieke; Schönbeck, Yvonne; Adang, Eddy M M; Braat, Didi D M; Zielhuis, Gerhard A; Kremer, Jan A M

2004-05-01

To determine the difference in costs between singleton and twin pregnancies after IVF treatment from pregnancy to 6 weeks after delivery from a health care perspective. Retrospective cost analysis. IVF department at the University Medical Center Nijmegen, The Netherlands. A representative sample of singleton and twin pregnancies after IVF treatment between 1995 and 2001 at the University Medical Center Nijmegen. IVF with or without intracytoplasmic sperm injection and with or without cryopreservation. Medical costs per singleton and twin pregnancy after IVF. In patients pregnant with twins, the incidence of hospital antenatal care, complicated vaginal deliveries, and cesarean sections was higher and was associated with more frequent and longer maternal and neonatal hospital admissions. Maternal and neonatal hospital admissions were the major cost drivers. The medical cost per twin pregnancy was found to be more than five times higher than per singleton pregnancy, 13,469 and 2,550, respectively. The medical cost per twin pregnancy was more than 10,000 higher than per singleton pregnancy. A reduction in the number of twin pregnancies by elective single ET will save substantial amounts of money. This money might be used for the additional IVF cycles that will probably be needed to achieve similar success rates between single ET and two-embryo transfer.

An international survey of the health economics of IVF and ICSI.

PubMed

Collins, JohnA

2002-01-01

The health economics of IVF and ICSI involve assessments of utilization, cost, cost-effectiveness and ability to pay. In 48 countries, utilization averaged 289 IVF/ICSI cycles per million of population per annum, ranging from two in Kazachstan, to 1657 in Israel. Higher national utilization of IVF/ICSI was associated with higher quality of health services, as indicated by lower infant mortality rates. IVF and ICSI are scientifically demanding and personnel-intensive, and are therefore expensive procedures. The average cost per IVF/ICSI cycle in 2002 would be US$9547 in the USA, and US$3518 in 25 other countries. Price elasticity estimates suggest that a 10% decrease in IVF/ICSI cost would generate a 30% increase in utilization. The average cost-effectiveness ratios in 2002 would be US$58,394 per live birth in the USA, and US$22,048 in other countries. In three randomized controlled trials, incremental costs per additional live birth with IVF compared with conventional therapy were US$ -26,586, $79,472 and $47,749. The national costs of IVF/ICSI treatment would be US$1.00 per capita in one current model, but the costs to individual couples range from 10% of annual household expenditures in European countries to 25% in Canada and the USA.

Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice.

PubMed

Escoffier, Jessica; Jemel, Ikram; Tanemoto, Akemi; Taketomi, Yoshitaka; Payre, Christine; Coatrieux, Christelle; Sato, Hiroyasu; Yamamoto, Kei; Masuda, Seiko; Pernet-Gallay, Karin; Pierre, Virginie; Hara, Shuntaro; Murakami, Makoto; De Waard, Michel; Lambeau, Gérard; Arnoult, Christophe

2010-05-01

Ejaculated mammalian sperm must undergo a maturation process called capacitation before they are able to fertilize an egg. Several studies have suggested a role for members of the secreted phospholipase A2 (sPLA2) family in capacitation, acrosome reaction (AR), and fertilization, but the molecular nature of these enzymes and their specific roles have remained elusive. Here, we have demonstrated that mouse group X sPLA2 (mGX) is the major enzyme present in the acrosome of spermatozoa and that it is released in an active form during capacitation through spontaneous AR. mGX-deficient male mice produced smaller litters than wild-type male siblings when crossed with mGX-deficient females. Further analysis revealed that spermatozoa from mGX-deficient mice exhibited lower rates of spontaneous AR and that this was associated with decreased in vitro fertilization (IVF) efficiency due to a drop in the fertilization potential of the sperm and an increased rate of aborted embryos. Treatment of sperm with sPLA2 inhibitors and antibodies specific for mGX blocked spontaneous AR of wild-type sperm and reduced IVF success. Addition of lysophosphatidylcholine, a catalytic product of mGX, overcame these deficiencies. Finally, recombinant mGX triggered AR and improved IVF outcome. Taken together, our results highlight a paracrine role for mGX during capacitation in which the enzyme primes sperm for efficient fertilization and boosts premature AR of a likely phospholipid-damaged sperm subpopulation to eliminate suboptimal sperm from the pool available for fertilization.

Group X phospholipase A2 is released during sperm acrosome reaction and controls fertility outcome in mice

PubMed Central

Escoffier, Jessica; Jemel, Ikram; Tanemoto, Akemi; Taketomi, Yoshitaka; Payre, Christine; Coatrieux, Christelle; Sato, Hiroyasu; Yamamoto, Kei; Masuda, Seiko; Pernet-Gallay, Karin; Pierre, Virginie; Hara, Shuntaro; Murakami, Makoto; De Waard, Michel; Lambeau, Gérard; Arnoult, Christophe

2010-01-01

Ejaculated mammalian sperm must undergo a maturation process called capacitation before they are able to fertilize an egg. Several studies have suggested a role for members of the secreted phospholipase A2 (sPLA2) family in capacitation, acrosome reaction (AR), and fertilization, but the molecular nature of these enzymes and their specific roles have remained elusive. Here, we have demonstrated that mouse group X sPLA2 (mGX) is the major enzyme present in the acrosome of spermatozoa and that it is released in an active form during capacitation through spontaneous AR. mGX-deficient male mice produced smaller litters than wild-type male siblings when crossed with mGX-deficient females. Further analysis revealed that spermatozoa from mGX-deficient mice exhibited lower rates of spontaneous AR and that this was associated with decreased in vitro fertilization (IVF) efficiency due to a drop in the fertilization potential of the sperm and an increased rate of aborted embryos. Treatment of sperm with sPLA2 inhibitors and antibodies specific for mGX blocked spontaneous AR of wild-type sperm and reduced IVF success. Addition of lysophosphatidylcholine, a catalytic product of mGX, overcame these deficiencies. Finally, recombinant mGX triggered AR and improved IVF outcome. Taken together, our results highlight a paracrine role for mGX during capacitation in which the enzyme primes sperm for efficient fertilization and boosts premature AR of a likely phospholipid-damaged sperm subpopulation to eliminate suboptimal sperm from the pool available for fertilization. PMID:20424324

External validation of anti-Müllerian hormone based prediction of live birth in assisted conception

PubMed Central

2013-01-01

Background Chronological age and oocyte yield are independent determinants of live birth in assisted conception. Anti-Müllerian hormone (AMH) is strongly associated with oocyte yield after controlled ovarian stimulation. We have previously assessed the ability of AMH and age to independently predict live birth in an Italian assisted conception cohort. Herein we report the external validation of the nomogram in 822 UK first in vitro fertilization (IVF) cycles. Methods Retrospective cohort consisting of 822 patients undergoing their first IVF treatment cycle at Glasgow Centre for Reproductive Medicine. Analyses were restricted to women aged between 25 and 42 years of age. All women had an AMH measured prior to commencing their first IVF cycle. The performance of the model was assessed; discrimination by the area under the receiver operator curve (ROCAUC) and model calibration by the predicted probability versus observed probability. Results Live births occurred in 29.4% of the cohort. The observed and predicted outcomes showed no evidence of miscalibration (p = 0.188). The ROCAUC was 0.64 (95% CI: 0.60, 0.68), suggesting moderate and similar discrimination to the original model. The ROCAUC for a continuous model of age and AMH was 0.65 (95% CI 0.61, 0.69), suggesting that the original categories of AMH were appropriate. Conclusions We confirm by external validation that AMH and age are independent predictors of live birth. Although the confidence intervals for each category are wide, our results support the assessment of AMH in larger cohorts with detailed baseline phenotyping for live birth prediction. PMID:23294733

Glycosaminoglycan and transforming growth factor beta1 changes in human plasma and urine during the menstrual cycle, in vitro fertilization treatment, and pregnancy.

PubMed

De Muro, Pierina; Capobianco, Giampiero; Formato, Marilena; Lepedda, Antonio Junior; Cherchi, Gian Mario; Gordini, Laila; Dessole, Salvatore

2009-07-01

To evaluate transforming growth factor beta1 (TGF-beta1) and glycosaminoglycans (GAG) changes in human plasma and urine during the menstrual cycle, IVF-ET, and pregnancy. Prospective clinical study. University hospital. Thirteen women with apparently normal menstrual cycle (group 1); 18 women undergoing IVF-ET (group 2); and 14 low-risk pregnant women (group 3). We assayed plasma and urine concentrations of TGF-beta1, urine content, and distribution of GAG. Blood and urine samples were collected during days 2 to 3, 12 to 13, and 23 to 24 in group 1; in group 2, samples were obtained at menstrual phase, oocyte pick-up day, and 15 days after ET; in group 3, samples were obtained during gestational weeks 10-12, 22-24, and 30-32 and 1 month after delivery. Changes in TGF-beta1 and GAG content. The mean value of total urinary trypsin inhibitor/chondroitin sulfate (UTI/CS) showed a distinct peak at day 12 of the menstrual cycle in the fertile women in whom we monitored the ovulatory period. In the IVF-ET group, GAG distribution and TGF-beta1 levels showed significant differences during the cycle. We observed increased levels of plasma TGF-beta1 15 days after ET. A significant increase of total UTI/CS value with increasing gestation was detected. Transforming growth factor beta1 and GAG levels could represent an additional tool to monitor reproductive events and could be useful, noninvasive markers of ovulation and ongoing pregnancy.

Abdominal ectopic pregnancy after in vitro fertilization and single embryo transfer: a case report and systematic review.

PubMed

Yoder, Nicole; Tal, Reshef; Martin, J Ryan

2016-10-19

Ectopic pregnancy is the leading cause of maternal morbidity and mortality during the first trimester and the incidence increases dramatically with assisted-reproductive technology (ART), occurring in approximately 1.5-2.1 % of patients undergoing in-vitro fertilization (IVF). Abdominal ectopic pregnancy is a rare yet clinically significant form of ectopic pregnancy due to potentially high maternal morbidity. While risk factors for ectopic pregnancy after IVF have been studied, very little is known about risk factors specific for abdominal ectopic pregnancy. We present a case of a 30 year-old woman who had an abdominal ectopic pregnancy following IVF and elective single embryo transfer, which was diagnosed and managed by laparoscopy. We performed a systematic literature search to identify case reports of abdominal or heterotopic abdominal ectopic pregnancies after IVF. A total of 28 cases were identified. Patients' ages ranged from 23 to 38 (Mean 33.2, S.D. = 3.2). Infertility causes included tubal factor (46 %), endometriosis (14 %), male factor (14 %), pelvic adhesive disease (7 %), structural/DES exposure (7 %), and unexplained infertility (14 %). A history of ectopic pregnancy was identified in 39 % of cases. A history of tubal surgery was identified in 50 % of cases, 32 % cases having had bilateral salpingectomy. Transfer of two embryos or more (79 %) and fresh embryo transfer (71 %) were reported in the majority of cases. Heterotopic abdominal pregnancy occurred in 46 % of cases while 54 % were abdominal ectopic pregnancies. Our systematic review has revealed several trends in reported cases of abdominal ectopic pregnancy after IVF including tubal factor infertility, history of tubal ectopic and tubal surgery, higher number of embryos transferred, and fresh embryo transfers. These are consistent with known risk factors for ectopic pregnancy following IVF. Further research focusing on more homogenous population may help in better characterizing this rare IVF complication and its risks.

Effect of air quality on assisted human reproduction.

PubMed

Legro, Richard S; Sauer, Mark V; Mottla, Gilbert L; Richter, Kevin S; Li, Xian; Dodson, William C; Liao, Duanping

2010-05-01

Air pollution has been associated with reproductive complications. We hypothesized that declining air quality during in vitro fertilization (IVF) would adversely affect live birth rates. Data from US Environmental Protection Agency air quality monitors and an established national-scale, log-normal kriging method were used to spatially estimate daily mean concentrations of criteria pollutants at addresses of 7403 females undergoing their first IVF cycle and at the their IVF labs from 2000 to 2007 in the Northeastern USA. These data were related to pregnancy outcomes. Increases in nitrogen dioxide (NO(2)) concentration both at the patient's address and at the IVF lab were significantly associated with a lower chance of pregnancy and live birth during all phases of an IVF cycle from medication start to pregnancy test [most significantly after embryo transfer, odds ratio (OR) 0.76, 95% confidence interval (CI) 0.66-0.86, per 0.01 ppm increase]. Increasing ozone (O(3)) concentration at the patient's address was significantly associated with an increased chance of live birth during ovulation induction (OR 1.26, 95% CI 1.10-1.44, per 0.02 ppm increase), but with decreased odds of live birth when exposed from embryo transfer to live birth (OR 0.62, 95% CI 0.48-0.81, per 0.02 ppm increase). After modeling for interactions of NO(2) and O(3) at the IVF lab, NO(2) remained negatively and significantly associated with live birth (OR 0.86, 95% CI 0.78-0.96), whereas O(3) was non-significant. Fine particulate matter (PM(2.5)) at the IVF lab during embryo culture was associated with decreased conception rates (OR 0.90, 95% CI 0.82-0.99, per 8 microg/m(3) increase), but not with live birth rates. No associations were noted with sulfur dioxide or larger particulate matter (PM(10)). The effects of declining air quality on reproductive outcomes after IVF are variable, cycle-dependent and complex, though increased NO(2) is consistently associated with lower live birth rates. Our findings are limited by the lack of direct measure of pollutants at homes and lab sites.

Review of Research Shows, Overall, Acupuncture Did Not Increase Pregnancy Rates with IVF

MedlinePlus

... X Y Z Review of Research Shows, Overall, Acupuncture Did Not Increase Pregnancy Rates With IVF Share: An analysis of research conducted on acupuncture as an adjuvant (booster) treatment to in vitro ...

Autism and mental retardation among offspring born after in vitro fertilization.

PubMed

Sandin, Sven; Nygren, Karl-Gösta; Iliadou, Anastasia; Hultman, Christina M; Reichenberg, Abraham

2013-07-03

Between 1978 and 2010, approximately 5 million infants were born after in vitro fertilization (IVF) treatments. Yet limited information on neurodevelopment after IVF exists, especially after the first year of life. To examine the association between use of any IVF and different IVF procedures and the risk of autistic disorder and mental retardation in the offspring. A population-based, prospective cohort study using Swedish national health registers. Offspring born between 1982 and 2007 were followed up for a clinical diagnosis of autistic disorder or mental retardation until December 31, 2009. The exposure of interest was IVF, categorized according to whether intracytoplasmic sperm injection (ICSI) for male infertility was used and whether embryos were fresh or frozen. For ICSI, whether sperm were ejaculated or surgically extracted was also considered. Relative risks (RRs) for autistic disorder and mental retardation and rates per 100,000 person-years, comparing spontaneously conceived offspring with those born after an IVF procedure and comparing 5 IVF procedures used in Sweden vs IVF without ICSI with fresh embryo transfer, the most common treatment. We also analyzed the subgroup restricted to singletons. Of the more than 2.5 million infants born, 30,959 (1.2%) were conceived by IVF and were followed up for a mean 10 (SD, 6) years. Overall, 103 of 6959 children (1.5%) with autistic disorder and 180 of 15,830 (1.1%) with mental retardation were conceived by IVF. The RR for autistic disorder after any procedure compared with spontaneous conception was 1.14 (95% CI, 0.94-1.39; 19.0 vs 15.6 per 100,000 person-years). The RR for mental retardation was 1.18 (95% CI, 1.01-1.36; 46.3 vs 39.8 per 100,000 person-years). For both outcomes, there was no statistically significant association when restricting analysis to singletons. Compared with IVF without ICSI with fresh embryo transfer, there were statistically significantly increased risks of autistic disorder following ICSI using surgically extracted sperm and fresh embryos (RR, 4.60 [95% CI, 2.14-9.88]; 135.7 vs 29.3 per 100,000 person-years); for mental retardation following ICSI using surgically extracted sperm and fresh embryos (RR, 2.35 [95% CI, 1.01-5.45]; 144.1 vs 60.8 per 100,000 person-years); and following ICSI using ejaculated sperm and fresh embryos (RR, 1.47 [95% CI, 1.03-2.09]; 90.6 vs 60.8 per 100,000 person-years). When restricting the analysis to singletons, the risks of autistic disorder associated with ICSI using surgically extracted sperm were not statistically significant, but the risks associated with ICSI using frozen embryos were significant for mental retardation (with frozen embryos, RR, 2.36 [95% CI, 1.04-5.36], 118.4 vs 50.6 per 100,000 person-years]; with fresh embryos, RR, 1.60 [95% CI, 1.00-2.57], 80.0 vs 50.6 per 100,000 person-years). Compared with spontaneous conception, IVF treatment overall was not associated with autistic disorder but was associated with a small but statistically significantly increased risk of mental retardation. For specific procedures, IVF with ICSI for paternal infertility was associated with a small increase in the RR for autistic disorder and mental retardation compared with IVF without ICSI. The prevalence of these disorders was low, and the increase in absolute risk associated with IVF was small.

Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization.

PubMed

Chuan, Sandy; Homer, Michael; Pandian, Raj; Conway, Deirdre; Garzo, Gabriel; Yeo, Lisa; Su, H Irene

2014-02-01

To determine whether serum hyperglycosylated human chorionic gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF-ET). Cohort Academic assisted reproduction center. Consecutive patients undergoing IVF-ET INTERVENTION(S): Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Ongoing pregnancy beyond 9 weeks of gestation. Ongoing pregnancy (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG. However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67, respectively). The diagnostic test characteristics were similar between the D16 hhCG and hCG levels. In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. In this early assessment, hhCG was superior to traditional hCG and highly predictive of ongoing pregnancies. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

In vitro fertilization outcomes after fresh and frozen blastocyst transfer in South Asian compared with Caucasian women.

PubMed

Shah, Meera Sridhar; Caballes, Marissa; Lathi, Ruth Bunker; Baker, Valerie Lynn; Westphal, Lynn Marie; Milki, Amin A

2016-06-01

To study pregnancy outcomes between South Asian and Caucasian women undergoing frozen blastocyst transfer cycles. Retrospective cohort study. Not applicable. Caucasian and South Asian patients undergoing frozen blastocyst transfer between January 2011 and December 2014. Not applicable. Live birth rate. A total of 196 Caucasian and 117 South Asian women were included in our study. Indians were on average 2.2 years younger than Caucasian women (34.9 vs. 37.1 years), and were more likely to be nulliparous (59% vs. 43%). All other baseline characteristics were similar. In women undergoing their first frozen ET cycle, implantation rate (49% vs. 47%), clinical pregnancy rate (PR; 54% vs. 49%), and live birth rate (43% vs. 43%) were similar between South Asians and Caucasians, respectively. In patients who underwent a prior fresh blastocyst transfer, the live birth rate was significantly lower in South Asian versus Caucasian women (21% vs. 37%). Our data demonstrate that IVF outcomes are better in frozen versus fresh cycles among South Asian women. The IVF clinics may wish to consider these findings when counseling South Asian patients about the timing of ET. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Estradiol and Antagonist Pretreatment Prior to Microdose Leuprolide in in Vitro Fertilization. Does It Improve IVF Outcomes in Poor Responders as Compared to Oral Contraceptive Pill?

PubMed

Elassar, Alyaa; Nulsen, John; Engmann, Lawrence; Benadiva, Claudio

2015-01-01

To compare in vitro fertilization (IVF) outcomes in low responders stimulated with microdose leuprolide protocol (ML) following pretreatment with either oral contraceptive pill (OCP) or luteal estradiol (E2) + GnRH antagonist (E2 + antag) for follicular synchronization prior to controlled ovarian hyperstimulation (COH). This was a retrospective study of 130 women, who were poor responders, undergoing IVF with either OCP/ML or E2+ antag/ML protocols. The main outcome measures were ongoing pregnancy rates, number of oocytes retrieved, and cancellation rate. Both groups were similar in baseline characteristics. There were no significant differences in gonadotropin requirement, cancellation rate, and number of embryos transferred. Ongoing pregnancy rates (40% vs. 15%) were significantly higher in the OCP/ML group. Trends toward greater number of oocytes retrieved (7.7 ± 3.4 vs. 5.9 ± 4.2) and improved implantation rates (20% vs. 12%) were also noted, but these did not reach statistical significance. E2+antag pretreatment does not appear to improve IVF outcomes in ML protocol when compared to the standard OCP in poor responders. Randomized trials with adequate power to study the optimal method of steroid pretreatments appear justified.

Semen Levels of Spermatid-Specific Thioredoxin-3 Correlate with Pregnancy Rates in ART Couples

PubMed Central

Qiu, Jing; Sutovsky, Miriam; Rawe, Vanesa Y.; Manandhar, Gaurishankar; Miranda-Vizuete, Antonio; Sutovsky, Peter

2013-01-01

Spermatid specific thioredoxin-3 (SPTRX3 or TXNDC8) is a testis/male germ line specific member of thioredoxin family that accumulates in the superfluous cytoplasm of defective human spermatozoa. We hypothesized that semen levels of SPTRX3 are reflective of treatment outcome in assisted reproductive therapy (ART) couples treated by in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Relationship between SPTRX3 and treatment outcome was investigated in 239 couples undergoing ART at an infertility clinic. Sperm content of SPTRX3 was evaluated by flow cytometry and epifluorescence microscopy, and correlated with clinical semen analysis parameters, and data on embryo development and pregnancy establishment. High SPTRX3 levels (>15% SPTRX3-positive spermatozoa) were found in 51% of male infertility patients (n = 72), in 20% of men from couples with unexplained, idiopathic infertility (n = 61) and in 14% of men from couples previously diagnosed with female-only infertility (n = 85). Couples with high SPTRX3 produced fewer two-pronuclear zygotes and had a reduced pregnancy rate (19.2% pregnant with >15% SPTRX3-positive spermatozoa vs. 41.2% pregnant with <5% SPTRX3-positive sperm; one-sided p<0.05). The average pregnancy rate of all 239 couples was 25.1%. Live birth rate was 19.2% and lowest average SPTRX3 levels were found in couples that delivered twins. Men with >15% of SPTRX3-positive spermatozoa, a cutoff value established by ROC analysis, had their chance of fathering children by IVF or ICSI reduced by nearly two-thirds. The percentage of SPTRX3-positive spermatozoa had predictive value for pregnancy after ART. Gradient purification and sperm swim-up failed to remove all SPTRX3-positive spermatozoa from semen prepared for ART. In summary, the elevated semen content of SPTRX3 in men from ART couples coincided with reduced incidence of pregnancy by IVF or ICSI, identifying SPTRX3 as a candidate biomarker reflective of ART outcome. PMID:23734172

Neurodevelopmental and cardiometabolic outcome in 4-year-old twins and singletons born after IVF.

PubMed

Kuiper, Derk; Bennema, Anne; la Bastide-van Gemert, Sacha; Seggers, Jorien; Schendelaar, Pamela; Haadsma, Maaike; Hoek, Annemieke; Heineman, Maas-Jan; Hadders-Algra, Mijna

2017-06-01

This prospective cohort study evaluated whether the cognitive development, neurological condition, anthropometrics and blood pressure of 4-year-old IVF twins differed from those of 4-year-old IVF singletons; 103 IVF singletons and 48 IVF twins born after conventional IVF treatment were included. Primary outcome was total intelligence quotient (IQ). Secondary outcomes were minor neurological dysfunction, anthropometrics and blood pressure. Unadjusted analyses found that the total IQ score of twins was lower than that of singletons, with a mean difference of -5.4 (-9.7 to -1.0). Weight (singletons: 18.6 [18.1 to 19.1] kg; twins: 16.9 [16.0 to 17.9] kg) and height (singletons: 108.8 [107.9 to 109.8] cm; twins: 105.9 [104.0 to 107.7] cm) of twins were lower than those of singletons (mean values [95% CI]). All differences disappeared after adjusting for mediators and confounders. Neurological outcome, systolic and diastolic blood pressure of twins and singletons were similar. Four-year-old IVF twins had a lower total IQ (-5.4 points), lowerbodyweight (-1.7 kg) and were shorter (-2.9 cm) than 4-year-old IVF singletons. After adjustment, the adverse twin effect disappeared, implying that increased risk for impaired health and development in twins also holds true for IVF twins, and is not altered by IVF. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Associations between Individual and Combined Polymorphisms of the TNF and VEGF Genes and the Embryo Implantation Rate in Patients Undergoing In Vitro Fertilization (IVF) Programs

PubMed Central

Boudjenah, Radia; Molina-Gomes, Denise; Torre, Antoine; Boitrelle, Florence; Taieb, Stéphane; Dos Santos, Esther; Wainer, Robert; de Mazancourt, Philippe; Selva, Jacqueline; Vialard, François

2014-01-01

Background A multiple pregnancy is now considered to be the most common adverse outcome associated with in vitro fertilization (IVF). As a consequence, the identification of women with the best chances of embryo implantation is a challenge in IVF program, in which the objective is to offer elective single-embryo transfer (eSET) without decreasing the pregnancy rate. To date, a range of hormonal and clinical parameters have been used to optimize eSET but none have significant predictive value. This variability could be due to genetic predispositions related to single-nucleotide polymorphisms (SNPs). Here, we assessed the individual and combined impacts of thirteen SNPs that reportedly influence the outcome of in vitro fertilisation (IVF) on the embryo implantation rate for patients undergoing intracytoplasmic sperm injection program (ICSI). Materials and Methods A 13 gene polymorphisms: FSHR(Asn680Ser), p53(Arg72Pro), AMH(Ile49Ser), ESR2(+1730G>A), ESR1(−397T>C), BMP15(−9C>G), MTHFR1(677C>T), MTHFR2(1298A>C), HLA-G(−725C>G), VEGF(+405G>C), TNFα(−308A>G), AMHR(−482A>G), PAI-1(4G/5G), multiplex PCR assay was designed to genotype women undergoing ICSI program. We analyzed the total patients population (n = 428) and a subgroup with homogeneous characteristics (n = 112). Results Only the VEGF(+405G>C) and TNFα(−308A>G) polymorphisms impacted fertilization, embryo implantation and pregnancy rates. Moreover, the combined VEGF+405.GG and TNFα-308.AG or AA genotype occurred significantly more frequently in women with high implantation potential. In contrast, the VEGF+405.CC and TNFα-308.GG combination was associated with a low implantation rate. Conclusion We identified associations between VEGF(+405G>C) and TNFα(−308A>G) polymorphisms (when considered singly or as combinations) and the embryo implantation rate. These associations may be predictive of embryo implantation and could help to define populations in which elective single-embryo transfer should be recommended (or, conversely, ruled out). However, the mechanism underlying the function of these polymorphisms in embryo implantation remains to be determined and the associations observed here must be confirmed in a larger, more heterogeneous cohort. PMID:25247819

A preliminary evaluation of influence of body mass index on in vitro fertilization outcome in non-obese endometriosis patients.

PubMed

Garalejic, Eliana; Arsic, Biljana; Radakovic, Jovana; Bojovic Jovic, Dragana; Lekic, Dragana; Macanovic, Biljana; Soldatovic, Ivan; Perovic, Milan

2017-11-16

Obese and overweight women experience a lower probability for pregnancy after IVF. However, despite the increasing prevalence of obesity, the large majority of infertile women are non-obese. One of the most common indications for IVF is endometriosis. Thought-provoking inverse correlation has been established between BMI and endometriosis. Lower BMI is a risk factor for development of endometriosis and a predictive factor for severe endometriosis. Since severe endometriosis carries lower reproductive chances, even after IVF, we preliminary tested a hypothesis that higher BMI among non-obese endometriosis patients improves IVF outcomes. Preliminary retrospective observational cross-sectional study was performed in women with endometriosis as a sole infertility cause who underwent IVF. During analyzed period we performed 2782 IVF procedures. In order to achieve highly homogenous study sample and to eliminate almost all confound factors that could lead to bias, we implemented strict study criteria. The number of eligible subjects was 156 and they were divided into underweight, normal weight and overweight groups. Primary outcomes were number of retrieved oocytes, good quality oocytes, embryos, and the rates of biochemical, clinical and ongoing pregnancies. For group comparisons, we used parametric test, analysis of variance, and non-parametric tests (Kruskal-Wallis test, Chi-square test). Logistic regression and General linear model was used to assess correlation between BMI and dependent variables (outcome and stimulation duration) when adjusted for age. Endometriosis as a single infertility factor among IVF couples had prevalence of 5.61%. Underweight women accounted for 10.26%, normal weight 71.15% and overweight 18.59% of study population. Significant differences were not found in number of retrieved oocytes (p = 0.880), good quality oocytes (p = 0.476), obtained embryos (p = 0.706), and biochemical (p = 0.298), clinical (p = 0.770) and ongoing (p = 0.822) pregnancy rates between study groups. Although preliminary results do not support our hypothesis, increase in BMI did not adversely affect the outcome of IVF in non-obese endometriosis patients, which is in contrast to literature data as regards general population of infertile women undergoing IVF. Prospective studies with large number of patients with endometriosis or prospective case-control studies should address these issues and provide more comprehensive counseling of infertile endometriosis patients regarding achievement of optimal BMI prior to IVF with the intention of achievement higher pregnancy rates.

Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatory infertility (WHO group 2).

PubMed

Eijkemans, Marinus J C; Polinder, Suzanne; Mulders, Annemarie G M G J; Laven, Joop S E; Habbema, J Dik F; Fauser, Bart C J M

2005-10-01

Conventional treatment in normogonadotrophic anovulatory infertility (WHO 2) consists of clomiphene citrate (CC), followed by exogenous gonadotrophins (FSH) and IVF. Response to these treatments may be predicted on the basis of individual patient characteristics. We aimed to devise a patient-tailored, cost-effective treatment algorithm involving the above-mentioned treatment modalities, based on individual patient characteristics. Sixteen prognostic groups are defined, according to the presence or absence of: age >30 years, amenorrhea, elevated androgen levels and obesity. The chances of response with each of the three treatments were calculated using prediction models. Treatment costs were based on the data of 240 patients visiting a specialist academic fertility unit. Outcome was an ongoing pregnancy within 12 months after initiation of treatment. The costs per pregnancy of three different strategies were compared, with a threshold for cost-effectiveness of 10 000. The strategy CC + FSH + IVF compared with FSH + IVF generated more pregnancies against lower costs. Compared with CC + IVF, it also produced more pregnancies, but at higher costs. For <30 years of age with normal androgen levels, costs per pregnancy were less than 10 000. For women >30 years old, costs per pregnancy were 25 000 and over 200 000, when presenting with normal or elevated androgen levels, respectively. The conventional treatment protocol is efficient for women aged <30 years with normal androgen levels. For women >30 years old with elevated androgen levels, FSH may be skipped.

The use of serum anti-Mullerian hormone (AMH) levels and antral follicle count (AFC) to predict the number of oocytes collected and availability of embryos for cryopreservation in IVF.

PubMed

Kotanidis, L; Nikolettos, K; Petousis, S; Asimakopoulos, B; Chatzimitrou, E; Kolios, G; Nikolettos, N

2016-12-01

To investigate the predictive value of anti-Mullerian hormone (AMH) and antral follicle count (AFC) on the final number of oocytes retrieved and the availability of embryos for cryopreservation in in vitro fertilization (IVF) cycles. In this prospective study, one hundred and twenty women in their first IVF treatment were enrolled. The short stimulation agonist protocol was used for controlled ovarian hyperstimulation in all cases. Serum AMH levels were measured during the menstrual cycle preceding treatment. AFC was measured in cycle day 2, just before starting ovarian stimulation. A strong, positive correlation between AMH, AFC and the number of collected oocytes was found. The patients with available and suitable supplementary embryos for cryopreservation had higher levels of AMH and larger numbers of AFC. AMH and AFC appear to be valuable markers mainly for ovarian reserve and response to IVF treatment. Serum AMH levels and AFC are significantly associated with the number of retrieved oocytes. Also, a positive correlation with the availability of supernumerary embryos suitable for cryopreservation was observed.

A cost-effectiveness analysis of in-vitro fertilization by maternal age and number of treatment attempts.

PubMed

Griffiths, Alison; Dyer, Suzanne M; Lord, Sarah J; Pardy, Chris; Fraser, Ian S; Eckermann, Simon

2010-04-01

The increase in use and costs of assisted reproductive therapies including in-vitro fertilization (IVF) has led to debate over public funding. A decision analytic model was designed to estimate the incremental cost-effectiveness of IVF by additional treatment programmes and maternal age. Data from the Australian and New Zealand Assisted Reproductive Database were used to estimate incremental effects (live birth and other pregnancy outcomes) and costs for cohorts of women attempting up to three treatment programmes. A treatment programme included one fresh cycle and a variable number of frozen cycles dependent on maternal age. The incremental cost per live birth ranged from AU dollars 27 373 and AU dollars 31 986 for women aged 30-33 on their first and third programmes to AU dollars 130 951 and AU dollars 187 515 for 42-45-year-old women on their first and second attempts. Overall, these trends were not affected by inclusions of costs associated with ovarian hyperstimulation syndrome or multiple births. This study suggests that cost per live birth from IVF increases with maternal age and treatment programme number and indicates that maternal age has the much greater effect. This evidence may help decisionmakers target the use of IVF services conditional on societal willingness to pay for live births and equity considerations.

Eight years' experience with an IVF surrogate gestational pregnancy programme.

PubMed

Raziel, Arieh; Schachter, Morey; Strassburger, Deborah; Komarovsky, Dafna; Ron-El, Raphael; Friedler, Shevach

2005-08-01

The aim of this study was to retrospectively audit eight years' experience of an IVF surrogate gestational programme and to compare the outcome of surrogacy due to absence of the uterus with surrogacy indicated for repeated IVF failure and recurrent abortions. A total of 60 cycles of IVF surrogate pregnancy were initiated in 19 treated couples. Absence of the uterus was the indication for surrogacy in 10 cases: Rokitansky syndrome (eight cases) and post-hysterectomy (two cases) designated as group A. The indications in the remaining nine patients (group B) were: IVF implantation failure (three cases), habitual abortions (four cases) and deteriorating maternal diseases (two cases). IVF performance and subsequent pregnancy outcome of groups A and B were compared. There was no difference in ovarian stimulation parameters and in IVF performance between the groups A and B. The overall pregnancy rate per transfer was 10/60 (17%). The pregnancy rates per patient and per transfer were 7/10 (70%) and 7/35 (20%) in group A compared with 3/9 (33%) and 3/25 (12%) in group B. A median number of three treatment cycles were needed to achieve pregnancy. In conclusion, the existence or absence of the uterus in the commissioning mothers is irrelevant for their IVF performance and conception rates. In patients who conceived after more than three IVF cycles, an additional 'oocyte factor' might be present.

Direct peritoneal resuscitation improves inflammation, liver blood flow, and pulmonary edema in a rat model of acute brain death.

PubMed

Smith, Jason W; Ghazi, Cameron A; Cain, Brandon C; Hurt, Ryan T; Garrison, R Neal; Matheson, Paul J

2014-07-01

Brain death in organ donors alters central hemodynamic performance, impairs physiology, exaggerates inflammation, and causes end-organ microcirculatory dysfunction and hypoxia. A new treatment, direct peritoneal resuscitation (DPR), might improve these derangements in acute brain death (ABD). We studied a standardized rodent model of brain death with matched controls to assess the efficacy of DPR as a resuscitation strategy after ABD. Anesthetized Sprague-Dawley rats were randomized as follows: ABD (supradural balloon inflation) with minimal IV fluid (IVF; 2 mL/h, n = 12); ABD + adequate IVF (5 mL/h, n = 12); ABD with aggressive IVF (goal: mean arterial pressure [MAP] >80 mmHg, n = 15); or ABD + IVF + DPR (goal: MAP >80 mmHg, n = 12). Ventilation support, IVF, and DPR were started at loss of reflexes, and MAP, heart rate, and effective hepatic blood flow were recorded. High IVF and DPR prevented mortality (0%) compared with low IVF (81.8%) or mid IVF (16.7%). Effective hepatic blood flow was decreased in low and mid IVF (2.8 ± 0.3 mL/min/g body weight and 4.0 ± 0.5 mL/min/g body weight, respectively) vs baseline, but was stable in high IVF (6.2 ± 0.5 mL/min/g body weight; NS) or improved with DPR (8.6 ± 0.7 mL/min/g body weight). The high-IVF group had significant organ edema, which was prevented in the DPR group. The mid-IVF and low-IVF groups had higher serum markers of organ injury compared with high-IVF or DPR groups. The high-IVF group had elevated inflammatory cytokines compared with the DPR group. Direct peritoneal resuscitation improved survival and effective hepatic blood flow, required less IVF to stabilize blood pressure, prevented organ edema, and normalized fluid electrolyte balance compared with IVF-alone groups. Direct peritoneal resuscitation in animals reduced inflammatory response after ABD compared with IVF-alone controls. These data suggest a potential role for DPR in organ donors to stabilize donors and possibly increase the number of organs suitable for transplantation per donor. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Natural cycle IVF reduces the risk of low birthweight infants compared with conventional stimulated IVF.

PubMed

Mak, Winifred; Kondapalli, Laxmi A; Celia, Gerard; Gordon, John; DiMattina, Michael; Payson, Mark

2016-04-01

Are perinatal outcomes improved in singleton pregnancies resulting from fresh embryo transfers performed following unstimulated/natural cycle IVF (NCIVF) compared with stimulated IVF? Infants conceived by unstimulated/NCIVF have a lower risk of being low birthweight than infants conceived by stimulated IVF; however, this risk did not remain significant after adjusting for gestation age. Previous studies have shown that infants born after modified NCIVF have a higher average birthweight and are less likely to be low birthweight than those infants conceived with conventional stimulated IVF. Retrospective cohort study of singleton live births in non-smoking women undergoing fresh IVF-embryo transfer cycles from 2007 to 2013 in a single IVF center. The women were stratified by stimulated (n = 174) or unstimulated (n = 190) IVF exposure status. Unstimulated/NCIVF is defined as IVF without the use of exogenous gonadotrophins, and only includes the use of HCG to time oocyte retrieval. Demographic data including maternal age, BMI, infertility diagnosis and IVF cycle characteristics were collected. The perinatal outcomes used for comparison between the two study groups were length of gestation, birthweight, preterm delivery, very preterm delivery, low birthweight, small for gestational age and large for gestational age. Although women in the NCIVF group were older than those in the stimulated group (35.0 versus 34.2 years, P < 0.05), parity and history of prior ART cycles were comparable between the groups. The mean birthweight was significantly higher in the NCIVF group by 163 g than in the stimulated group (3436 ± 420 g versus 3273 ± 574 g, P < 0.05). Consistent with this finding, there were also less low birthweight (<2500 g) infants in the NCIVF group versus stimulated group (1 versus 8.6%, P < 0.005). The reduction in risk for low birthweight in the NCIVF group remained significant after adjustment for maternal age, infertility diagnosis, ICSI, number of embryos transferred and blastocyst transfer (odds ratio (OR) 0.07; 95% CI 0.014-0.35). As NCIVF group had less preterm infants, additional adjustment for gestational age was performed and this showed a tendency towards lower risk of low birthweight in NCIVF (OR 0.11; 95% CI 0.01-1.0). While gestational age at delivery was comparable between the groups, both preterm births (<37 weeks gestation) (31 versus 42%, P < 0.05) and very preterm births (<32 weeks gestation) (0.52 versus 6.3%, P < 0.005) were significantly reduced in the NCIVF group. However, after adjustment for potential confounders, the reduction in risk of preterm and very preterm delivery associated with the NCIVF group was no longer significant (OR 1.1; 95% CI 0.48-2.5). Limitations of this study are the retrospective nature of the data collection and the lack of information about parental characteristics associated with birthweight. The improved perinatal outcomes following successful unstimulated/NCIVF suggest that this treatment should be considered as a viable option for infertile couples. NCIVF could reduce potential adverse perinatal outcomes such as low birthweight related to fresh embryo transfers performed following ovarian stimulation. The etiology of the improved perinatal outcomes following NCIVF needs to be explored further to determine if the improvement is derived from endometrial factors versus follicular/oocyte factors. The study was supported by the following grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NICHD K12HD047018 (W.M.), NICHD K12HD001271 (L.A.K.). The authors have no competing interests. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Partnership and Coping Enhancement Programme for couples undergoing in vitro fertilization treatment: the development of a complex intervention in China.

PubMed

Ying, Liying; Chen, Xiaomin; Wu, Lai Har; Shu, Jing; Wu, Xiangli; Loke, Alice Yuen

2017-01-01

Couples as dyads suffer from the diagnosis of infertility and related treatment. These couples commonly experience emotional and physical pain and tension in their marital lives. The purpose of this study is to report on the process of developing a potentially feasible and effective complex intervention for couples undergoing in vitro fertilization treatment in China. The Medical Research Council (MRC) framework for developing and evaluating the complex intervention was adopted to guide the development of the Partnership and Coping Enhancement Programme (PCEP). In developing the PCEP, three steps were taken, namely, (1) identifying evidence by conducting literature reviews, a concept analysis and a qualitative study; (2) identifying/developing a theory-in this case, a preliminary Endurance with Partnership Conceptual Framework (P-EPCF) was proposed; and (3) modelling the process and outcomes of the PCEP. The PCEP that was developed is targeted mainly at the domains of the partnership mediators of stress in the P-EPCF. It consists of two sections-partnership and coping-and will be delivered to infertile couples on the day of embryo transfer. The main focuses of the programme are to facilitate mutual sharing and support in infertile couples, and to improve their individual and dyadic coping strategies while undergoing IVF treatment, especially in the period when they are waiting for the results of a pregnancy test and after the disclosure of a negative treatment outcome. The programme is couple-based, consisting of experience sharing, psychoeducation, meditation exercise, skill practise and supplemental written materials. The Partnership and Coping Enhancement Programme (PCEP) for couples undergoing in vitro fertilization treatment was developed according to the guideline of the MRC framework. It is recommended that a pilot study be conducted to evaluate its feasibility and to model the process and outcomes of the programme.

Predicting the chances of a live birth after one or more complete cycles of in vitro fertilisation: population based study of linked cycle data from 113 873 women.

PubMed

McLernon, David J; Steyerberg, Ewout W; Te Velde, Egbert R; Lee, Amanda J; Bhattacharya, Siladitya

2016-11-16

 To develop a prediction model to estimate the chances of a live birth over multiple complete cycles of in vitro fertilisation (IVF) based on a couple's specific characteristics and treatment information.  Population based cohort study.  All licensed IVF clinics in the UK. National data from the Human Fertilisation and Embryology Authority register.  All 253 417 women who started IVF (including intracytoplasmic sperm injection) treatment in the UK from 1999 to 2008 using their own eggs and partner's sperm.  Two clinical prediction models were developed to estimate the individualised cumulative chance of a first live birth over a maximum of six complete cycles of IVF-one model using information available before starting treatment and the other based on additional information collected during the first IVF attempt. A complete cycle is defined as all fresh and frozen-thawed embryo transfers arising from one episode of ovarian stimulation.  After exclusions, 113 873 women with 184 269 complete cycles were included, of whom 33 154 (29.1%) had a live birth after their first complete cycle and 48 925 (43.0%) after six complete cycles. Key pretreatment predictors of live birth were the woman's age (31 v 37 years; adjusted odds ratio 1.66, 95% confidence interval 1.62 to 1.71) and duration of infertility (3 v 6 years; 1.09, 1.08 to 1.10). Post-treatment predictors included number of eggs collected (13 v 5 eggs; 1.29, 1.27 to 1.32), cryopreservation of embryos (1.91, 1.86 to 1.96), the woman's age (1.53, 1.49 to 1.58), and stage of embryos transferred (eg, double blastocyst v double cleavage; 1.79, 1.67 to 1.91). Pretreatment, a 30 year old woman with two years of unexplained primary infertility has a 46% chance of having a live birth from the first complete cycle of IVF and a 79% chance over three complete cycles. If she then has five eggs collected in her first complete cycle followed by a single cleavage stage embryo transfer (with no embryos left for freezing) her chances change to 28% and 56%, respectively.  This study provides an individualised estimate of a couple's cumulative chances of having a baby over a complete package of IVF both before treatment and after the first fresh embryo transfer. This novel resource may help couples plan their treatment and prepare emotionally and financially for their IVF journey. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Dynamic integrated analysis of DNA methylation and gene expression profiles in in vivo and in vitro fertilized mouse post-implantation extraembryonic and placental tissues.

PubMed

Tan, Kun; Zhang, Zhenni; Miao, Kai; Yu, Yong; Sui, Linlin; Tian, Jianhui; An, Lei

2016-07-01

How does in vitro fertilization (IVF) alter promoter DNA methylation patterns and its subsequent effects on gene expression profiles during placentation in mice? IVF-induced alterations in promoter DNA methylation might have functional consequences in a number of biological processes and functions during IVF placentation, including actin cytoskeleton organization, hematopoiesis, vasculogenesis, energy metabolism and nutrient transport. During post-implantation embryonic development, both embryonic and extraembryonic tissues undergo de novo DNA methylation, thereby establishing a global DNA methylation pattern, and influencing gene expression profiles. Embryonic and placental tissues of IVF conceptuses can have aberrant morphology and functions, resulting in adverse pregnancy outcomes such as pregnancy loss, low birthweight, and long-term health effects. To date, the IVF-induced global profiling of DNA methylation alterations, and their functional consequences on aberrant gene expression profiles in IVF placentas have not been systematically studied. Institute for Cancer Research mice (6 week-old females and 8-9 week-old males) were used to generate in vivo fertilization (IVO) and IVF blastocysts. After either IVO and development (IVO group as control) or in vitro fertilization and culture (IVF group), blastocysts were collected and transferred to pseudo-pregnant recipient mice. Extraembryonic (ectoplacental cone and extraembryonic ectoderm) and placental tissues from both groups were sampled at embryonic day (E) 7.5 (IVO, n = 822; IVF, n = 795) and E10.5 (IVO, n = 324; IVF, n = 278), respectively. The collected extraembryonic (E7.5) and placental tissues (E10.5) were then used for high-throughput RNA sequencing (RNA-seq) and methylated DNA immunoprecipitation sequencing (MeDIP-seq). The main dysfunctions indicated by bioinformatic analyses were further validated using molecular detection, and morphometric and phenotypic analyses. Dynamic functional profiling of high-throughput data, together with molecular detection, and morphometric and phenotypic analyses, showed that differentially expressed genes dysregulated by DNA methylation were functionally involved in: (i) actin cytoskeleton disorganization in IVF extraembryonic tissues, which may impair allantois or chorion formation, and chorioallantoic fusion; (ii) disturbed hematopoiesis and vasculogenesis, which may lead to abnormal placenta labyrinth formation and thereby impairing nutrition transport in IVF placentas; (iii) dysregulated energy and amino acid metabolism, which may cause placental dysfunctions, leading to delayed embryonic development or even lethality; (iv) disrupted genetic information processing, which can further influence gene transcriptional and translational processes. Findings in mouse placental tissues may not be fully representative of human placentas. Further studies are necessary to confirm these findings and determine their clinical significance. Our study is the first to provide the genome-wide analysis of gene expression dysregulation caused by DNA methylation during IVF placentation. Systematic understanding of the molecular mechanisms implicated in IVF placentation can be useful for the improvement of existing assisted conception systems to prevent these IVF-associated safety concerns. This work was supported by grants from the National Natural Science Foundation of China (No. 31472092), and the National High-Tech R&D Program (Nos. 2011|AA100303, 2013AA102506). There was no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The economic impact of assisted reproductive technology: a review of selected developed countries.

PubMed

Chambers, Georgina M; Sullivan, Elizabeth A; Ishihara, Osamu; Chapman, Michael G; Adamson, G David

2009-06-01

To compare regulatory and economic aspects of assisted reproductive technologies (ART) in developed countries. Comparative policy and economic analysis. Couples undergoing ART treatment in the United States, Canada, United Kingdom, Scandinavia, Japan, and Australia. Description of regulatory and financing arrangements, cycle costs, cost-effectiveness ratios, total expenditure, utilization, and price elasticity. Regulation and financing of ART share few general characteristics in developed countries. The cost of treatment reflects the costliness of the underlying healthcare system rather than the regulatory or funding environment. The cost (in 2006 United States dollars) of a standard IVF cycle ranged from $12,513 in the United States to $3,956 in Japan. The cost per live birth was highest in the United States and United Kingdom ($41,132 and $40,364, respectively) and lowest in Scandinavia and Japan ($24,485 and $24,329, respectively). The cost of an IVF cycle after government subsidization ranged from 50% of annual disposable income in the United States to 6% in Australia. The cost of ART treatment did not exceed 0.25% of total healthcare expenditure in any country. Australia and Scandinavia were the only country/region to reach levels of utilization approximating demand, with North America meeting only 24% of estimated demand. Demand displayed variable price elasticity. Assisted reproductive technology is expensive from a patient perspective but not from a societal perspective. Only countries with funding arrangements that minimize out-of-pocket expenses met expected demand. Funding mechanisms should maximize efficiency and equity of access while minimizing the potential harm from multiple births.

Paving the way for a gold standard of care for infertility treatment: improving outcomes through standardization of laboratory procedures.

PubMed

Schoolcraft, William; Meseguer, Marcos

2017-10-01

Infertility affects over 70 million couples globally. Access to, and interest in, assisted reproductive technologies is growing worldwide, with more couples seeking medical intervention to conceive, in particular by IVF. Despite numerous advances in IVF techniques since its first success in 1978, almost half of the patients treated remain childless. The multifactorial nature of IVF treatment means that success is dependent on many variables. Therefore, it is important to examine how each variable can be optimized to achieve the best possible outcomes for patients. The current approach to IVF is fragmented, with various protocols in use. A systematic approach to establishing optimum best practices may improve IVF success and live birth rates. Our vision of the future is that technological advancements in the laboratory setting are standardized and universally adopted to enable a gold standard of care. Implementation of best practices for laboratory procedures will enable clinicians to generate high-quality gametes, and to produce and identify gametes and embryos of maximum viability and implantation potential, which should contribute to improving take-home healthy baby rates. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Association between preconception maternal beverage intake and in vitro fertilization outcomes.

PubMed

Machtinger, Ronit; Gaskins, Audrey J; Mansur, Abdallah; Adir, Michal; Racowsky, Catherine; Baccarelli, Andrea A; Hauser, Russ; Chavarro, Jorge E

2017-12-01

To study whether maternal intake of beverage type affects IVF outcomes. A prospective study. Tertiary, university-affiliated center. Three hundred forty women undergoing IVF from 2014 through 2016 for infertility as well as for pregenetic diagnosis for autosomal recessive diseases were enrolled during ovarian stimulation and completed a questionnaire describing their usual beverage consumption. None. IVF outcomes were abstracted from medical records. Total caffeine intake was estimated by summing the caffeine content for specific beverages multiplied by frequency of intake. Associations between specific types of beverages and IVF outcomes were analyzed using Poisson and logistic regression models adjusting for possible confounders. Higher intake of sugared soda was associated with lower total, mature, and fertilized oocytes and top-quality embryos after ovarian stimulation. Women who consumed sugared soda had, on average, 1.1 fewer oocytes retrieved, 1.2 fewer mature oocytes retrieved, 0.6 fewer fertilized oocytes, and 0.6 fewer top-quality embryos compared with women who did not consume sugared soda. Furthermore, compared with women who did not drink sugared soda, the adjusted difference in percent of cycles resulting in live birth for women consuming 0.1-1 cups/day and >1 cup/day were -12% and -16%, respectively. No associations were found between consumption of coffee, caffeine, or diet sodas and IVF outcome. Sugared beverages, independent of their caffeine content, may be a bigger threat to reproductive success than caffeine and caffeinated beverages without added sugar. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Maternal whole grain intake and outcomes of in vitro fertilization.

PubMed

Gaskins, Audrey J; Chiu, Yu-Han; Williams, Paige L; Keller, Myra G; Toth, Thomas L; Hauser, Russ; Chavarro, Jorge E

2016-06-01

To evaluate the relationship between pretreatment intake of whole grains and outcomes of IVF. Prospective cohort study. Academic medical center. A total of 273 women who collectively underwent 438 IVF cycles. Whole grain intake was assessed with a validated food frequency questionnaire at enrollment. Intermediate and clinical end points of IVF were abstracted from medical records. Women had a median whole grain intake of 34.2 g per day (∼1.2 servings/day). Higher pretreatment whole grain intake was associated with higher probability of implantation and live birth. The adjusted percentage of cycles resulting in live birth for women in the highest quartile of whole grain intake (>52.4 g/day) was 53% (95% confidence interval [CI] 41%, 65%) compared with 35% (95% CI 25%, 46%) for women in the lowest quartile (<21.4 g/day). This association was largely driven by intake of bran as opposed to germ. When intermediate end points of IVF were examined, only endometrial thickness on the day of ET was associated with whole grain intake. A 28-g per day (∼1 serving/day) increase in whole grain intake was associated with a 0.4-mm (95% CI 0.1, 0.7 mm) increase in endometrial thickness. Higher pretreatment whole grain intake was related to higher probability of live birth among women undergoing IVF. The higher probability of live birth may result from increased endometrial thickness on the day of ET and improved embryo receptivity manifested in a higher probability of implantation. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Associations between IVF outcomes and essential trace elements measured in follicular fluid and urine: a pilot study.

PubMed

Ingle, Mary E; Bloom, Michael S; Parsons, Patrick J; Steuerwald, Amy J; Kruger, Pamela; Fujimoto, Victor Y

2017-02-01

A hypothesis-generating pilot study exploring associations between essential trace elements measured in follicular fluid (FF) and urine and in vitro fertilization (IVF) endpoints. We recruited 58 women undergoing IVF between 2007 and 2008, and measured cobalt, chromium, copper, manganese, molybdenum, and zinc in FF (n = 46) and urine (n = 45) by inductively coupled plasma mass spectrometry (ICP-MS). We used multivariable regression models to assess the impact of FF and urine trace elements on IVF outcomes, adjusted for age, body mass index, race, and cigarette smoking. Trace elements were mostly present at lower concentrations in FF than in urine. The average number of oocytes retrieved was positively associated with higher urine cobalt, chromium, copper, and molybdenum concentrations. FF chromium and manganese were negatively associated with the proportion of mature oocytes, yet urine manganese had a positive association. FF zinc was inversely associated with average oocyte fertilization. Urine trace elements were significant positive predictors for the total number of embryos generated. FF copper predicted lower embryo fragmentation while urine copper was associated with higher embryo cell number and urine manganese with higher embryo fragmentation. No associations were detected for implantation, pregnancy, or live birth. Our results suggest the importance of trace elements in both FF and urine for intermediate, although not necessarily clinical, IVF endpoints. The results differed using FF or urine biomarkers of exposure, which may have implications for the design of clinical and epidemiologic investigations. These initial findings will form the basis of a more definitive future study.

Embryonic development in human oocytes fertilized by split insemination

PubMed Central

Kim, Myo Sun; Kim, Jayeon; Youm, Hye Won; Park, Jung Yeon; Choi, Hwa Young

2015-01-01

Objective To compare the laboratory outcomes of intracytoplasmic sperm injection (ICSI) and conventional insemination using sibling oocytes in poor prognosis IVF cycles where ICSI is not indicated. Methods Couples undergoing IVF with following conditions were enrolled: history of more than 3 years of unexplained infertility, history of ≥3 failed intrauterine insemination, leukocytospermia or wide variation in semen analysis, poor oocyte quality, or ≥50% of embryos had poor quality in previous IVF cycle(s). Couples with severe male factor requiring ICSI were excluded. Oocytes were randomly assigned to the conventional insemination (conventional group) or ICSI (ICSI group). Fertilization rate (FR), total fertilization failure, and embryonic development at day 3 and day 5 were assessed. Results A total of 309 mature oocytes from 37 IVF cycles (32 couples) were obtained: 161 were assigned to conventional group and 148 to ICSI group. FR was significantly higher in the ICSI group compared to the conventional group (90.5% vs. 72.7%, P<0.001). Total fertilization failure occurred in only one cycle in conventional group. On day 3, the percentage of cleavage stage embryos was higher in ICSI group however the difference was marginally significant (P=0.055). In 11 cycles in which day 5 culture was attempted, the percentage of blastocyst (per cleaved embryo) was significantly higher in the ICSI group than the conventional group (55.9% vs. 25.9%, P=0.029). Conclusion Higher FR and more blastocyst could be achieved by ICSI in specific circumstances. Fertilization method can be tailored accordingly to improve IVF outcomes. PMID:26023671

[Effect of luteal-phase gonadotropin-releasing hormone agonist administration on pregnancy outcome in IVF/ICSI cycles: a systematic review and Meta-analysis].

PubMed

Yu, L P; Liu, N; Liu, Y

2016-11-25

Objective: To evaluate the potential efficacy and safety of gonadotropin-releasing hormone agonist(GnRH-a) administration in the luteal-phase on in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles in assisted reproductive technology (ART). Methods: The relevant papers published before November 2015 were electronically searched in PubMed, EMBASE, Cochrane Library, WHO ICTRP, ClinicalTrials.gov, CNKI, CBM and WanFang database to collect randomized controlled trial (RCT) involving GnRH-a administration in the luteal-phase on IVF/ICSI cycles in ART. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality according to the Cochrane Handbook. Then, Meta-analysis was performed using Stata 13.0. Results: A total of 3 406 patients, 3 280 IVF/ICSI cycles from 11 RCT were subjected to Meta-analysis. All cycles presented statistically significantly higher rates of live birth/ongoing pregnancy ( RR= 1.29, 95% CI: 1.11-1.51), clinical pregnancy ( RR= 1.24, 95% CI: 1.08-1.43) and multiple pregnancy ( RR= 1.95, 95% CI: 1.21-3.14) in patients who received luteal-phase GnRH-a administration compared with those who did not. Conclusions: These findings demonstrate that the luteal-phase GnRH-a administration could increase birth/ongoing pregnancy rate, clinical pregnancy rate and multiple pregnancy rate in all cycles, so it may be an ideal choice for luteal phase support in patients undergoing IVF/ICSI therapy.

Prediction of different ovarian responses using anti-Müllerian hormone following a long agonist treatment protocol for IVF.

PubMed

Heidar, Z; Bakhtiyari, M; Mirzamoradi, M; Zadehmodarres, S; Sarfjoo, F S; Mansournia, M A

2015-09-01

The purpose of this study was to predict the poor and excessive ovarian response using anti-Müllerian hormone (AMH) levels following a long agonist protocol in IVF candidates. Through a prospective cohort study, the type of relationship and appropriate scale for AMH were determined using the fractional polynomial regression. To determine the effect of AMH on the outcomes of ovarian stimulation and different ovarian responses, the multi-nominal and negative binomial regression models were fitted using backward stepwise method. The ovarian response of study subject who entered a standard long-term treatment cycle with GnRH agonist was evaluated using prediction model, separately and in combined models with (ROC) curves. The use of standard long-term treatments with GnRH agonist led to positive pregnancy test results in 30% of treated patients. With each unit increase in the log of AMH, the odds ratio of having poor response compared to normal response decreases by 64% (OR 0.36, 95% CI 0.19-0.68). Also the results of negative binomial regression model indicated that for one unit increase in the log of AMH blood levels, the odds of releasing an oocyte increased 24% (OR 1.24, 95% CI 1.14-1.35). The optimal cut-off points of AMH for predicting excessive and poor ovarian responses were 3.4 and 1.2 ng/ml, respectively, with area under curves of 0.69 (0.60-0.77) and 0.76 (0.66-0.86), respectively. By considering the age of the patient undergoing infertility treatment as a variable affecting ovulation, use of AMH levels showed to be a good test to discriminate between different ovarian responses.

Long-term economic benefits attributed to IVF-conceived children: a lifetime tax calculation.

PubMed

Connolly, Mark P; Pollard, Michael S; Hoorens, Stijn; Kaplan, Brian R; Oskowitz, Selwyn P; Silber, Sherman J

2008-09-01

To evaluate whether lifetime future net tax revenues from an in vitro fertilization (IVF)-conceived child are substantial enough to warrant public subsidy relative to the mean IVF treatment costs required to obtain 1 live birth. Mathematical generational accounting model. The model estimates direct financial interactions between the IVF-conceived child and the government during the child's projected lifetime. In the model, we accrue IVF costs required to conceive the child to the government, and then we estimate future net tax revenue to the federal and state governments from this individual, offset by direct financial transfers from the government (eg, child allowances, education, Medicare, and Social Security). We discount lifetime costs and gross tax payments at Treasury Department rates to establish the present value of investing in IVF. We applied US Congressional Budget Office projected changes in tax rates over the course of the model. An IVF-conceived child, average in every respect (eg, future earnings, healthcare consumption, and life expectancy), represents a net positive return to the government. Based on an average employed individual born in 2005, the projected net lifetime tax contribution is US $606,200. Taking into consideration IVF costs and all direct financial interactions, the net present value is US $155,870. Lifetime net taxes paid from a child relative to the child's initial IVF investment represent a 700% net return to the government in discounted US dollars from fully employed individuals. This suggests that removing barriers to IVF would have positive tax benefits for the government, notwithstanding its beneficial effect on overall economic growth.

Embryonic aneuploidy does not differ among genetic ancestry according to continental origin as determined by ancestry informative markers.

PubMed

Franasiak, Jason M; Olcha, Meir; Shastri, Shefali; Molinaro, Thomas A; Congdon, Haley; Treff, Nathan R; Scott, Richard T

2016-10-01

Is embryonic aneuploidy, as determined by comprehensive chromosome screening (CCS), related to genetic ancestry, as determined by ancestry informative markers (AIMs)? In this study, when determining continental ancestry utilizing AIMs, genetic ancestry does not have an impact on embryonic aneuploidy. Aneuploidy is one of the best-characterized barriers to ART success and little information exists regarding ethnicity and whole chromosome aneuploidy in IVF. Classifying continental ancestry utilizing genetic profiles from a selected group of single nucleotide polymorphisms, termed AIMs, can determine ancestral origin with more accuracy than self-reported data. This is a retrospective cohort study of patients undergoing their first cycle of IVF with CCS at a single center from 2008 to 2014. There were 2328 patients identified whom had undergone IVF/CCS and AIM genotyping. All patients underwent IVF/ICSI and CCS after trophectoderm biopsy. Patients' serum was genotyped using 32 custom AIMs to identify continental origin. Admixture proportions were determined using Bayesian clustering algorithms. Patients were assigned to the population (European, African, East Asian or Central/South Asian) corresponding to their greatest admixture proportion. The mean number of embryos tested was 5.3 (range = 1-40) and the mode was 1. Patients' ethnic classifications revealed European (n = 1698), African (n = 103), East Asian (n = 206) or Central/South Asian (n = 321). When controlling for age and BMI, aneuploidy rate did not differ by genetic ancestry (P = 0.28). The study type (retrospective) and the ability to classify patients by continental rather than sub-continental origin as well as the predominantly European patient mix may impact generalizability. Post hoc power calculation revealed power to detect a 16.8% difference in embryonic aneuploidy between the two smallest sample size groups. These data do not support differences in embryonic aneuploidy among various genetic ancestry groups in patients undergoing IVF/CCS. We used a novel approach of determining continental origin using a validated panel of AIMs as opposed to patient self-reported ethnicities. It does not appear that specific recommendations for aneuploidy screening should be made based upon continental heritage. None. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cost effectiveness of ovarian reserve testing in in vitro fertilization: a Markov decision-analytic model.

PubMed

Moolenaar, Lobke M; Broekmans, Frank J M; van Disseldorp, Jeroen; Fauser, Bart C J M; Eijkemans, Marinus J C; Hompes, Peter G A; van der Veen, Fulco; Mol, Ben Willem J

2011-10-01

To compare the cost effectiveness of ovarian reserve testing in in vitro fertilization (IVF). A Markov decision model based on data from the literature and original patient data. Decision analytic framework. Computer-simulated cohort of subfertile women aged 20 to 45 years who are eligible for IVF. [1] No treatment, [2] up to three cycles of IVF limited to women under 41 years and no ovarian reserve testing, [3] up to three cycles of IVF with dose individualization of gonadotropins according to ovarian reserve, and [4] up to three cycles of IVF with ovarian reserve testing and exclusion of expected poor responders after the first cycle, with no treatment scenario as the reference scenario. Cumulative live birth over 1 year, total costs, and incremental cost-effectiveness ratios. The cumulative live birth was 9.0% in the no treatment scenario, 54.8% for scenario 2, 70.6% for scenario 3 and 51.9% for scenario 4. Absolute costs per woman for these scenarios were €0, €6,917, €6,678, and €5,892 for scenarios 1, 2, 3, and 4, respectively. Incremental cost-effectiveness ratios (ICER) for scenarios 2, 3, and 4 were €15,166, €10,837, and €13,743 per additional live birth. Sensitivity analysis showed the model to be robust over a wide range of values. Individualization of the follicle-stimulating hormone dose according to ovarian reserve is likely to be cost effective in women who are eligible for IVF, but this effectiveness needs to be confirmed in randomized clinical trials. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

In vitro fertilization in Japan — Early days of in vitro fertilization and embryo transfer and future prospects for assisted reproductive technology —

PubMed Central

SUZUKI, Masakuni

2014-01-01

Assisted reproductive technology (ART) such as in vitro fertilization (IVF) and embryo transfer (ET) has been essential in the treatment of infertility. The world’s first IVF-ET baby was born in 1978 based on the technique developed by Dr. Robert Edwards and Dr. Patrick Steptoe.1) In Japan, the first IVF-ET birth was reported in 1983 by Prof. Masakuni Suzuki at Tohoku University School of Medicine.2,3) IVF-ET is a procedure used to achieve pregnancy that consists of extracting oocytes from an infertile woman, fertilizing them in vitro, and transferring fertilized eggs into the patient’s uterine cavity (Fig. 1). Since the first report of successful IVF-ET, numerous techniques related to ART, such as cryopreservation of oocytes and embryos, gamete intrafallopian transfer (GIFT), and microinsemination, have been developed and refined (Table 1). Herein we describe the history of basic research in IVF-ET that led to human applications, how the birth of the first IVF-ET baby was achieved in Japan, the current status of ART in Japan, issues related to ART, and future prospects for ART. PMID:24814992

Women's perspectives regarding subcutaneous injections, costs and live birth rates in IVF.

PubMed

Musters, A M; de Bekker-Grob, E W; Mochtar, M H; van der Veen, F; van Mello, N M

2011-09-01

The addition of recombinant LH (rLH) to controlled ovarian hyperstimulation (COH) shows a beneficial effect on ongoing pregnancy rates in poor responder women, with an increase of ongoing pregnancy rate. Next to this possible beneficial effect, there are two potential drawbacks of adding rLH to COH; women have to administer extra injections, and daily rLH injections generate additional costs. We therefore investigated women's perspectives on an additional injection of rLH with respect to live birth rates (LBR) and out-of-pocket costs in a discrete choice experiment. Women eligible for IVF were asked to choose between treatments that differed in LBR after one IVF cycle, the amount of self-administered injections and out-of-pocket costs or reimbursement. The relative weights that women place on these attributes were estimated with a logistic regression model. To test for heterogeneity of preferences among women, patient characteristics were included in the model. Two-hundred and thirty-four women were asked to participate in the study. In total, 223 women responded (response rate 95%) and 206 questionnaires were analysed. An increase of one daily injection did not alter women's treatment preference. LBR and costs did have a significant (P < 0.001) impact on women's choice of IVF treatment. Patient characteristics significantly influenced the effect of costs on women's preferences. One extra daily injection will not cause a woman to refrain from a certain IVF treatment. However, to compensate for the out-of-pocket costs of this extra daily injection, the expected LBR should at least be 6%.

HP-HMG versus rFSH in treatments combining fresh and frozen IVF cycles: success rates and economic evaluation.

PubMed

Wex-Wechowski, Jaro; Abou-Setta, Ahmed M; Kildegaard Nielsen, Sandy; Kennedy, Richard

2010-08-01

The economic implications of the choice of gonadotrophin influence decision making but their cost-effectiveness in frozen-embryo transfer cycles has not been adequately studied. An economic evaluation was performed comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) using individual patient data (n=986) from two large randomized controlled trials using a long agonist IVF protocol. The simulation model incorporated live birth data and published UK costs of IVF-related medical resources. After treatment for up-to-three cycles (one fresh and up to two subsequent fresh or frozen cycles conditional on availability of cryopreserved embryos), the cumulative live birth rate was 53.7% (95% CI 49.3-58.1%) for HP-HMG and 44.6% (40.2-49.0%) for rFSH (OR 1.44, 95% CI 1.12-1.85; P<0.005). The mean costs per IVF treatment for HP-HMG and rFSH were pound5393 ( pound5341-5449) and pound6269 ( pound6210-6324), respectively (number needed to treat to fund one additional treatment was seven; P<0.001). With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound11,157 ( pound11,089-11,129) and pound14,227 ( pound14,183-14,222) with rFSH (P<0.001). The cost saving using HP-HMG remained after varying model parameters in a probabilistic sensitivity analysis. 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients.

PubMed

Haahr, T; Jensen, J S; Thomsen, L; Duus, L; Rygaard, K; Humaidan, P

2016-04-01

What is the diagnostic performance of qPCR assays compared with Nugent scoring for abnormal vaginal microbiota and for predicting the success rate of IVF treatment? The vaginal microbiota of IVF patients can be characterized with qPCR tests which may be promising tools for diagnosing abnormal vaginal microbiota and for prediction of clinical pregnancy in IVF treatment. Bacterial vaginosis (BV) is a common genital disorder with a prevalence of approximately 19% in the infertile population. BV is often sub-clinical with a change of the vaginal microbiota from being Lactobacillus spp. dominated to a more heterogeneous environment with anaerobic bacteria, such as Gardnerella vaginalis and Atopobium vaginae. Few studies have been conducted in infertile women, and some have suggested a negative impact on fecundity in the presence of BV. A cohort of 130 infertile patients, 90% Caucasians, attending two Danish fertility clinics for in vitro fertilization (IVF) treatment from April 2014-December 2014 were prospectively enrolled in the trial. Vaginal swabs from IVF patients were obtained from the posterior fornix. Gram stained slides were assessed according to Nugent's criteria. PCR primers were specific for four common Lactobacillus spp., G. vaginalis and A. vaginae. Threshold levels were established using ROC curve analysis. The prevalence of BV defined by Nugent score was 21% (27/130), whereas the prevalence of an abnormal vaginal microbiota was 28% (36/130) defined by qPCR with high concentrations of Gardnerella vaginalis and/or Atopobium vaginae. The qPCR diagnostic approach had a sensitivity and specificity of respectively 93% and 93% for Nugent-defined BV. Furthermore, qPCR enabled the stratification of Nugent intermediate flora. Eighty-four patients completed IVF treatment. The overall clinical pregnancy rate was 35% (29/84). Interestingly, only 9% (2/22) with qPCR defined abnormal vaginal microbiota obtained a clinical pregnancy (P = 0.004). Although a total of 130 IVF patients were included in the study, a larger sample size is needed to draw firm conclusions regarding the possible adverse effect of an abnormal vaginal microbiota in relation to the clinical pregnancy rate and other reproductive outcomes. Abnormal vaginal microbiota may negatively affect the clinical pregnancy rate in IVF patients. If a negative correlation between abnormal vaginal microbiota and the clinical pregnancy rate is corroborated, patients could be screened and subsequently treated for abnormal vaginal microbiota prior to fertility treatment. This study was funded by The AP Møller Maersk Foundation for the advancement of Medical Science and Hospital of Central Jutland Research Fund, Denmark. No competing interests. The project was registered at clinicaltrials.gov (file number NCT02042352). © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Building resilience: A preliminary exploration of women's perceptions of the use of acupuncture as an adjunct to In Vitro Fertilisation

PubMed Central

2009-01-01

Background In Vitro Fertilisation (IVF) is now an accepted and effective treatment for infertility, however IVF is acknowledged as contributing to, rather than lessening, the overall psychosocial effects of infertility. Psychological and counselling interventions have previously been widely recommended in parallel with infertility treatments but whilst in many jurisdictions counselling is recommended or mandatory, it may not be widely used. Acupuncture is increasingly used as an adjunct to IVF, in this preliminary study we sought to investigate the experience of infertile women who had used acupuncture to improve their fertility. Methods A sample of 20 women was drawn from a cohort of women who had attended for a minimum of four acupuncture sessions in the practices of two acupuncturists in South Australia. Eight women were interviewed using a semi-structured questionnaire. Six had sought acupuncture during IVF treatment and two had begun acupuncture to enhance their fertility and had later progressed to IVF. Descriptive content analysis was employed to analyse the data. Results Four major categories of perceptions about acupuncture in relation to reproductive health were identified: (a) Awareness of, and perceived benefits of acupuncture; (b) perceptions of the body and the impact of acupuncture upon it; (c) perceptions of stress and the impact of acupuncture on resilience; and (d) perceptions of the intersection of medical treatment and acupuncture. Conclusion This preliminary exploration, whilst confined to a small sample of women, confirms that acupuncture is indeed perceived by infertile women to have an impact to their health. All findings outlined here are reported cautiously because they are limited by the size of the sample. They suggest that further studies of acupuncture as an adjunct to IVF should systematically explore the issues of wellbeing, anxiety, personal and social resilience and women's identity in relation to sexuality and reproduction. PMID:20003370

The Impact of Psycho-Education on in Vitro Fertilisation Treatment Efficiency.

PubMed

Belevska, Jana

2015-01-01

The aim of the study was to examine the efficiency of psycho-education of candidates for the IVF in stress, anxiety and depression decreasing, and the impact of the psycho educative techniques on the successfulness of the treatment. A random sample of 64 candidates for IVF treatment is divided in two groups: control group without psycho-education (32 candidates) and intervention group of 32 candidates included in psycho-education. Depression, anxiety and stress scale (DASS) was used as a psychometric test. It's a multiple choice, self-reported inventory for measuring the levels of stress, anxiety and severity of depression. For statistic evaluation SPSS software was used. The study shows that the intervention group included in psycho-education has a signifycantly lower scores on stress (t = 3.201, p < 0.05) and anxiety (t = 2.311, p < 0.05). The scale of depression did not show differences in the two compared groups. However, the success of the IVF treatment is more common among candidates that were included in psycho-education. In our country, psycho-education of candidates for in vitro fertilization is not systematically integrated in the treatment. The study showed the efficiency of psycho-education in anxiety and stress decreasing, as well as significant impact in the successfulness of the treatment. It was pointed out that psychological support of candidates for IVF is important for the lessening of the negative emotional reactions of candidates as well as for the successfulness of the treatment.

Predicting IVF Outcome: A Proposed Web-based System Using Artificial Intelligence.

PubMed

Siristatidis, Charalampos; Vogiatzi, Paraskevi; Pouliakis, Abraham; Trivella, Marialenna; Papantoniou, Nikolaos; Bettocchi, Stefano

2016-01-01

To propose a functional in vitro fertilization (IVF) prediction model to assist clinicians in tailoring personalized treatment of subfertile couples and improve assisted reproduction outcome. Construction and evaluation of an enhanced web-based system with a novel Artificial Neural Network (ANN) architecture and conformed input and output parameters according to the clinical and bibliographical standards, driven by a complete data set and "trained" by a network expert in an IVF setting. The system is capable to act as a routine information technology platform for the IVF unit and is capable of recalling and evaluating a vast amount of information in a rapid and automated manner to provide an objective indication on the outcome of an artificial reproductive cycle. ANNs are an exceptional candidate in providing the fertility specialist with numerical estimates to promote personalization of healthcare and adaptation of the course of treatment according to the indications. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study.

PubMed

Tarlatzis, B; Tavmergen, E; Szamatowicz, M; Barash, A; Amit, A; Levitas, E; Shoham, Z

2006-01-01

The effect of recombinant human LH (r-hLH; lutropin alfa) in women undergoing controlled ovarian stimulation with recombinant human FSH (r-hFSH) prior to IVF was investigated. After down-regulation with the GnRH agonist, buserelin, 114 normo-ovulatory women (aged 18-37 years) received r-hFSH alone until the lead follicle reached a diameter of 14 mm. Patients were then randomized in a double-blind fashion to receive r-hFSH in addition to r-hLH, 75 IU s.c., or placebo daily for a maximum of 10 days prior to oocyte retrieval and IVF. The primary end-point was the number of metaphase II oocytes. There were no significant differences between treatment groups for the primary end-point. Serum estradiol concentrations on the day of HCG administration were significantly higher in the group receiving r-hLH plus r-hFSH than in the group receiving r-hFSH alone (P = 0.0001), but there were no significant differences between the groups in dose and duration of r-hFSH treatment required, oocyte maturation, fertilization rate, pregnancy rate and live birth rate. In this patient population, the addition of r-hLH during the late follicular phase of a long GnRH agonist and r-hFSH stimulation cycle provides no further benefit in terms of oocyte maturation or other end-points.

A prospective study using Hatha Yoga for stress reduction among women waiting for IVF treatment.

PubMed

Oron, Galia; Allnutt, Erica; Lackman, Tasha; Sokal-Arnon, Tamar; Holzer, Hananel; Takefman, Janet

2015-05-01

Yoga has been found to be effective in treating anxiety and depression, reducing stress and improving the overall quality of life in the general population. Minimal research is available on the effect of stress-management programmes with IVF patients. Owing to the diversity of conditions treated, the poor quality of most studies, and the different assessment tools used to evaluate the psychological state, it is difficult to draw definite conclusions. Previous studies have used different mind-body interventions and general measures of stress without evaluation of specific stresses known to result from infertility and its treatment using standardized measures. In this single-centre study, 49 infertile women were recruited to participate in a 6-week Yoga class during 2013 while awaiting their IVF treatment. Study participants were asked to complete standardized questionnaires assessing fertility-related quality of life (FertiQoL), marital harmony (Dyadic Adjustment Scale [DAS]), state and trait anxiety (State-Trait Anxiety Inventory [STAI]) and depression (Beck Depression Inventory [BDI]) before commencing and after completing the Yoga workshops. Anxiety, depression and fertility-specific quality of life showed improvement over time in association with participation in a 6-week Yoga programme in women awaiting their treatment with IVF. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Duration of luteal support after IVF is important, so why is there no consistency in practice? The results of a dynamic survey of practice in the United Kingdom.

PubMed

Russell, Richard; Kingsland, Charles; Alfirevic, Zarko; Gazvani, Rafet

2015-03-01

Luteal support is considered as an essential component of IVF treatment following ovarian stimulation and embryo transfer. Several studies have consistently demonstrated a benefit of luteal support compared with no treatment and whilst a number of preparations are available, no product has been demonstrated as superior. There is an emerging body of evidence which suggests that extension of luteal support beyond biochemical pregnancy does not confer a benefit in terms of successful pregnancy outcome. We performed two surveys separated by 5 years of practice evolution, with the latter reporting on the use of luteal support in all IVF clinics in the UK. All clinics reported utilising luteal support with the majority favouring the use of Cyclogest 400 mg twice daily. In contrast, there was no consensus on the optimal duration of luteal support. Whilst 24% of clinics withdrew luteal support at biochemical confirmation of pregnancy, 40% continued treatment until 12 weeks gestation. Several clinics even extended luteal support beyond 12 weeks gestation. We observed no difference in practice based on the size of the IVF unit or treatment funding source. Although there was some change in practice between surveys in many clinics, there was no uniformity in the direction of change.

Comparison of fertilization outcome between microdrop and open insemination methods in non-male factor IVF patients.

PubMed

Li, Yubin; Li, Tao; Mai, Qingyun; Long, Lingli; Ou, Jianping

2014-06-01

Both microdrop and open methods are commonly used for in vitro fertilization (IVF) protocols for embryo culture as well as oocyte insemination. However, few comparative studies evaluating the microdrop or open method of insemination on the fertilization outcome and subsequent embryo development have been performed. A randomized study was conducted to compare microdrop and open fertilization with respect to fertilization rate and embryo development among non-male factor patients undergoing in vitro fertilization and embryo transfer (IVF-ET). The results presented in this study demonstrate that the fertilization failure rate [total fertilization failure rate (TFF) plus low fertilization rate (<25% oocytes fertilized)] in the microdrop insemination group was higher than in the open insemination group (11.9% versus 3.3%, p < 0.001), while the good quality embryo rate and pregnancy rate did not differ significantly between the groups. As a highly complicated process involving many extrinsic and intrinsic factors, further studies are needed to confirm the effects of these insemination methods on the rate of fertilization failure.

[THROMBOPHILIC GENETIC MUTATIONS AND POLYMORPHISMS IN WOMEN WITH INFERTILITY AND FAILED IN VITRO FERTILIZATION].

PubMed

Abrahamyan, G

2017-01-01

Occurrence of pregnancy after in vitro fertilization depends of two components: functional adequacy of the embryo at the blastocyst stage and receptivity of endometrium, which, according to modern perception, are determinate in achieving optimal conditions of implantation. From the pregnancy occurrence point of view, as well as in regard to its further development , implantation is the most crucial phase of IVF/ICSI and ET. As the same time, this phase is also the most vulnerable. Multiple researches have proven the role of mother thrombophilia for genesis of gestation complications and early embryo losses, but in relation to this problem i the context of IVF there is still a lot to be detailed. The objective of this work was to increase the efficiency of IVF and to research the causes of IVF failures, related to thrombophilic genetic mutations and polymorphisms. In order to achieve the set goal 354 women with infertility, who turned to the department of aided reproductive technologies (ART) for infertility treatment by means of IVF, were examined. 237 (66,9%) of women had primary infertility, 117 (33,1%) - secondary infertility. To 228 of these women the IVF (in vitro fertilization) program was introduced for the first time (study group 1), 126 patients had failed IVF history (1 to 9 failed attempts). Patients were 23 to 43 years of age. Obtained results confirm the relation between hemostasis defects, change of hemostasis system activity and efficiency of IVF. One of the main reason of IVF failure and, probably, of infertility is the hemostasis system disturbance of thrombophilic nature. High correlation is established between the hemostasis system disturbance of thrombophilic nature, preconditioned by genetic mutations and polymorphisms, as well as failed IVFs. Failure of IVF is the indication for expanded examination of genetically determined factors of hemostasis system. In case of presence of genetic defects of thrombophilic nature in hemostasis system the risk of failure in IVF program is 2 and more times higher.

Impact of subserosal and intramural uterine fibroids that do not distort the endometrial cavity on the outcome of in vitro fertilization-intracytoplasmic sperm injection.

PubMed

Oliveira, Flávio Garcia; Abdelmassih, Vicente G; Diamond, Michael P; Dozortsev, Dimitri; Melo, Nilson R; Abdelmassih, Roger

2004-03-01

To further evaluate the effects of intramural and subserosal uterine fibroids on the outcome of IVF-ET, when there is no compression of the endometrial cavity. Retrospective, matched-control study from January 2000 to October 2001. Private IVF center. Two hundred forty-five women with subserosal and/or intramural fibroids that did not compress the uterine cavity (fibroid group) and 245 women with no evidence of fibroids anywhere in the uterus (control group). In vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) cycles. The type of fibroid (intramural, subserosal), number, size (cm), and location of intramural leiomyomas (fundal, corpus) were recorded. Outcomes of IVF-ICSI cycles were compared between the two groups. There was no correlation between location and number of uterine fibroids and the outcomes of IVF-ICSI. Patients with subserosal or intramural fibroids <4 cm had IVF-ICSI outcomes (pregnancy, implantation, and abortion rates) similar to those of controls. Patients with intramural fibroids >4.0 cm had lower pregnancy rates than patients with intramural fibroids 4 cm and that such patients be submitted to treatment before they are enrolled in IVF-ICSI cycles. Whether or not women with fibroids > 4 cm would benefit from fibroid treatment remains to be determined.

Influence of intracervical and intravaginal seminal plasma on the endometrium in assisted reproduction: a double-blind, placebo-controlled, randomized study.

PubMed

Mayer, R B; Ebner, T; Yaman, C; Hartl, J; Sir, A; Krain, V; Oppelt, P; Shebl, O

2015-02-01

To investigate the effect of intracervical and intravaginal application of seminal plasma on the endometrium, as assessed by endometrial/subendometrial vascularization and endometrial volume between the day of oocyte retrieval and the day of embryo transfer in an in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle. This was a double-blind, placebo-controlled, randomized study including patients undergoing a first or second IVF/ICSI cycle. Homologous seminal plasma or placebo (sodium chloride) was injected into the cervix and posterior vaginal fornix just after follicle aspiration. Three-dimensional power Doppler examination was performed 30 min before oocyte retrieval and 30 min before embryo transfer. Main outcome measures were changes in vascularization flow index (VFI), flow index (FI) and vascularization index (VI) of the endometrium/subendometrium using VOCAL™ (Virtual Organ Computer-aided AnaLysis) and endometrial volume. One hundred patients agreed to participate in the study. Twenty-three patients were excluded, mainly as a result of canceled embryo transfer. Data were analyzed from 40 patients receiving seminal plasma and 37 receiving placebo. No significant differences between the two groups were seen in VFI, FI or VI of the endometrium or subendometrium or in endometrial volume on the day of oocyte pick-up and on the day of embryo transfer. Neither endometrial/subendometrial vascularization parameters nor endometrial volume seem to be affected by the application of seminal plasma in patients undergoing their first or second IVF/ICSI cycle. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Practical evolution and application of direct intracytoplasmic sperm injection for male factor and idiopathic fertilization failure infertilities.

PubMed

Tucker, M J; Wright, G; Morton, P C; Mayer, M P; Ingargiola, P E; Jones, A E

1995-04-01

To analyze the introduction of a new assisted fertilization technique for the treatment of severe male factor and idiopathic fertilization failure infertilities. Retrospective analysis of 16-month clinical application of IVF-ET where insemination was performed solely by direct intracytoplasmic sperm injection. Clinical IVF-ET program. Ninety-two couples undergoing 105 cycles of sperm injection. One hundred embryo transfers yielded 28 viable pregnancies (28%) from which eight normal deliveries have occurred to date. Complete cleavage arrest or fertilization failure occurred in four cycles, and one couple had all embryos cryopreserved. One thousand one hundred forty-three eggs were injected of which 173 (15%) degenerated. Four hundred seventy-nine of the surviving 970 eggs became normally fertilized (49%), and 381 of these zygotes (79.5%) developed suitably for cryopreservation or for transfer. Thirty-four of 310 embryos transferred implanted, yielding an implantation rate of 11%. Both testicular and epididymal sperm were used successfully to achieve fertilization and pregnancies, as was sperm retrieved by electroejaculation. Older women and couples suffering from prior idiopathic fertilization failure had a markedly poorer outcome. These results confirm that the intracytoplasmic sperm injection technique is a successful form of assisted fertilization that can be applied to a wide range of couples at significant risk from fertilization failure.

Reverse traffic: intersecting inequalities in human egg donation.

PubMed

Nahman, Michal

2011-11-01

The paper examines a case of cross-border reproductive care that happens in reverse by looking at Israeli--Romanian transnational ova traffic. The state of Israel claims to have the most IVF clinics per capita in the world, some of the highest success rates in the use of assisted reproductive technology, very liberal regulation of these technologies and the most heavily subsidized IVF in the world. This support and the government's demographic policies are designed to encourage the growth of the Jewish population in its demographic race against Palestinians. Yet transnational egg donation is very costly and reimbursement to patients a slow and involved process. Hence, while transnational ova donation is increasing in Israel, only a few can afford to participate in this border crossing. Further, new laws are meant to forbid cross-religious donation in Israel, hardening the borders of the Jewish State. Romanian ova donors are part of the global majority, exploited by markets' incursions into new niches in bodies. The history of Romanian oppression of women's reproduction makes today's women willing to undergo invasive treatment for very little compensation, even when there is the possibility of injury. This paper documents reverse traffic reproduction, which maintains, rather than addresses, inequalities. Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice.

PubMed

La Marca, Antonio; Sunkara, Sesh Kamal

2014-01-01

The main objective of individualization of treatment in IVF is to offer every single woman the best treatment tailored to her own unique characteristics, thus maximizing the chances of pregnancy and eliminating the iatrogenic and avoidable risks resulting from ovarian stimulation. Personalization of treatment in IVF should be based on the prediction of ovarian response for every individual. The starting point is to identify if a woman is likely to have a normal, poor or a hyper response and choose the ideal treatment protocol tailored to this prediction. The objective of this review is to summarize the predictive ability of ovarian reserve markers, such as antral follicle count (AFC) and anti-Mullerian hormone (AMH), and the therapeutic strategies that have been proposed in IVF after this prediction. A systematic review of the existing literature was performed by searching Medline, EMBASE, Cochrane library and Web of Science for publications in the English language related to AFC, AMH and their incorporation into controlled ovarian stimulation (COS) protocols in IVF. Literature available to May 2013 was included. The search generated 305 citations of which 41 and 25 studies, respectively, reporting the ability of AMH and AFC to predict response to COS were included in this review. The literature review demonstrated that AFC and AMH, the most sensitive markers of ovarian reserve identified to date, are ideal in planning personalized COS protocols. These sensitive markers permit prediction of the whole spectrum of ovarian response with reliable accuracy and clinicians may use either of the two markers as they can be considered interchangeable. Following the categorization of expected ovarian response to stimulation clinicians can adopt tailored therapeutic strategies for each patient. Current scientific trend suggests the elective use of the GnRH antagonist based regimen for hyper-responders, and probably also poor responders, as likely to be beneficial. The selection of the appropriate and individualized gonadotrophin dose is also of paramount importance for effective COS and subsequent IVF outcomes. Personalized IVF offers several benefits; it enables clinicians to give women more accurate information on their prognosis thus facilitating counselling especially in cases of extremes of ovarian response. The deployment of therapeutic strategies based on selective use of GnRH analogues and the fine tuning of the gonadotrophin dose on the basis of potential ovarian response in every single woman can allow for a safer and more effective IVF practice.

Stress and marital satisfaction among women before and after their first cycle of in vitro fertilization and intracytoplasmic sperm injection.

PubMed

Verhaak, C M; Smeenk, J M; Eugster, A; van Minnen, A; Kremer, J A; Kraaimaat, F W

2001-09-01

To determine differences in emotional status (anxiety and depression) and marital satisfaction in pregnant and nonpregnant women before and after their first cycle of IVF and intracytoplasmic sperm injection (ICSI). Repeated measurement. Fertility department at a university and a regional hospital. Women entering their first treatment cycle of IVF or ICSI. Questionnaires on psychological factors were administered 3 to 12 days before the start of their first treatment cycle and repeated 3 weeks after the pregnancy test. State anxiety, depression, mood, and marital satisfaction. At pretreatment, the women who became pregnant showed lower levels of depression than those who did not. Higher levels of depression in the pregnant women after the first cycle were due to higher scores on vital aspects of depression, related to signs of early pregnancy. Higher levels of depression in the nonpregnant women were due to a higher score on cognitive aspects of depression. Differences in emotional status between pregnant and nonpregnant women were present before treatment and became more apparent after the first IVF and ICSI cycle. There were no differences in emotional status between the women who underwent IVF and those who underwent ICSI.

Comparison of IVF and ICSI when only few oocytes are available for insemination.

PubMed

Borini, Andrea; Gambardella, Alessia; Bonu, Maria Antonietta; Dal Prato, Luca; Sciajno, Raffaella; Bianchi, Liana; Cattoli, Monica

2009-08-01

The aim of this work was to evaluate the efficiency of IVF and intracytoplasmic sperm injection (ICSI) when few eggs available for insemination. A total of 601 women (group A, mean age 31.2 +/- 2.8 years) who were undergoing a total of 671 assisted reproduction cycles donated their excess oocytes to 694 patients (group B, mean age 41.0 +/- 0.2) for 1606 replacement cycles. Each recipient received three to five eggs. The recipients were divided into two groups depending on the insemination method used (IVF, group B1; or ICSI, group B2); ICSI patients were then subdivided into two further groups based on the semen parameters: B2A adequate for IVF and B2B only suitable for ICSI. The results showed that, when comparing A versus B and B1 versus B2, no significant differences were found in terms of pregnancy (28.0 versus 24.1% and 25.5 versus 21.4%), implantation (15.6 versus 14.9% and 15.9 versus 13.1%) and miscarriage (15.4 versus 20.5% and 17.9 versus 26.3) rates respectively. Comparing subgroups B2A and B2B, no significant differences were found in terms of pregnancy (20.0 versus 21.9%), implantation (14.4 versus 12.7%) and miscarriage rates (18.2 versus 28.6%) respectively. In conclusion, ICSI does not seem to yield better outcomes.

Correlation of Site of Embryo Transfer with IVF Outcome: Analysis of 743 Cycles from a Single Center

PubMed Central

Singh, Neeta; Lata, Kusum; Malhotra, Neena; Vanamail, P.

2017-01-01

Objective: To investigate the influence of site of embryo transfer (ET) on reproductive outcome. Materials and Methods: A retrospective analysis of 743 ultrasound-guided ET in fresh in vitro fertilization (IVF) cycles from a single center over a period of 4 years was conducted. The distance between the fundal endometrial surface and the air bubble was measured, and accordingly, patients were divided into four groups (≤10 mm; >10 and ≤15 mm; >15 and 20 mm; >20 and <25 mm). Setting: Tertiary Assisted Reproductive Technology (ART) center. Patient(s): All patients enrolled in the IVF program undergoing ET. Intervention(s): Controlled ovarian hyperstimulation (OS), IVF, and ET. Main Outcome Measure(s): Cleavage rate and clinical pregnancy rate. Result(s): Clinical pregnancy rate was significantly more in groups 2 and 3 compared to the other groups. Logistic regression analysis showed that one unit increase in embryos transfer will enhance the pregnancy outcome about 3.7 (adjusted odds ratio) times with 95% confidence limits 2.6 to 5.4. Similarly, pregnancy outcome will be 3.1 (95% confidence limits: 1.5–6.4) times higher for distance group >15 and <20 mm compared to less than 10-mm distance group. Ectopic pregnancy rates were similar in all the four groups. Conclusion: The present study demonstrates that site of ET has significant difference on reproductive outcome. PMID:28904498

Comparison of a Web-Based Teaching Tool and Traditional Didactic Learning for In Vitro Fertilization Patients: A Preliminary Randomized Controlled Trial.

PubMed

Vause, Tannys Dawn Reiko; Allison, David J; Vause, Tricia; Tekok-Kilic, Ayda; Ditor, David S; Min, Jason K

2018-05-01

The objective of this prospective RCT was to compare the efficacy of a web-based teaching tool to traditional didactic teaching in IVF patients. Forty women undergoing their first IVF cycle were randomly allocated to an interactive web-based teaching session or a nurse-led didactic teaching session. The primary outcome measure was participant knowledge regarding the IVF process, risks, and logistics assessed before and after the respective teaching session. Secondary outcomes included patient stress, assessed before and after the respective teaching session, and patient satisfaction, assessed following the respective teaching session and on the day of embryo transfer (following implementation of the teaching protocol). Both groups demonstrated similar and significant improvements in knowledge and stress after exposure to their respective teaching sessions. The web-based group was significantly more satisfied than the didactic teaching group. Web-based teaching was also shown to be equally effective for participants of high versus low income and education status for knowledge, stress, and satisfaction. This study provides preliminary support for the use of web-based teaching as an equally effective tool for increasing knowledge and reducing stress compared to traditional didactic teaching in IVF patients, with the added benefit of increased patient satisfaction. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

Association of physical activity in the past year and immediately after in vitro fertilization on pregnancy.

PubMed

Evenson, Kelly R; Calhoun, Kathryn C; Herring, Amy H; Pritchard, David; Wen, Fang; Steiner, Anne Z

2014-04-01

To estimate the association of physical activity on in vitro fertilization (IVF). Prospective cohort study. Academic infertility clinic. Women (n = 121) undergoing nondonor IVF embryo transfer (fresh or frozen). The women completed a questionnaire on past year physical activity and wore an accelerometer from embryo transfer to serum pregnancy testing. Implantation, intrauterine gestation, and live birth. Based on self-reported past year physical activity, the adjusted odds of intrauterine gestation was higher among those that had higher continuous active living (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.09-3.50), sports/exercise (OR 1.48, CI 1.02-2.15), and total activity (OR 1.52, 95%CI 1.15-2.01) indices. After embryo transfer, women did almost no vigorous activity (median 0 min/d) as measured by the accelerometer. More of their time was spent in light activity (median 3.0 h/d) and sedentary behaviors (median 9.3 h/d). Accelerometer-measured physical activity and sedentary behavior after embryo transfer were not associated with any IVF outcome. An active lifestyle in the preceding year favorably impacted the IVF outcome. After embryo transfer, women engaged in mostly light physical activity and sedentary behaviors; therefore, the impact of vigorous physical activity on implantation could not be determined. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The role of ovarian reserve markers in prediction of clinical pregnancy.

PubMed

Zebitay, Ali G; Cetin, Orkun; Verit, Fatma F; Keskin, Seda; Sakar, M Nafi; Karahuseyinoglu, Sercin; Ilhan, Gulsah; Sahmay, Sezai

2017-05-01

To evaluate the role of ovarian reserve markers in the prediction of clinical pregnancy and embryo transfer accomplishment among poor responder IVF applicants. 304 female poor responder IVF applicants were included in this prospective cohort study conducted at the IVF-unit. Antral follicle count, FSH, LH, E2, AMH and IVF outcomes were compared in pregnant and non-pregnant groups as well as in ET vs. non-ET groups. The number of retrieved oocytes was significantly correlated positively with AMH and AFC, and negatively with FSH and age. Quartiles of FSH and AFC were similar to the rate of pregnancy. Quartiles of AMH (<25%/25-75% and <25%/>75%) were statistically significant. Mean serum levels for AMH were significantly lower in the non-ET group. Our findings seem to indicate that day 3 AMH values can predict ET accomplishment with a sensitivity of 96% and a specificity of 35%. Quartiles of AMH <25% (< 0.21 ng/mL) can predict the IVF results among poor responder IVF applicants. Impact statement Various cut-off values have been determined for day 3 serum AMH values. These values help to determine the groups that are expected to give normal, high or low response to stimulation and decide the treatment options. In contrast to other groups of patients, poor responders cannot reach the embryo transfer stage for several reasons. These are; absence of a mature oocyte after oocyte pick-up, fertilisation failure without male factor or poor embryo quality. In the present study; a cut-off value of 0.33 ng/mL for the prediction of ET accomplishment in poor responder patients was determined with a sensitivity of 96%. Additionally, clinical pregnancy could not be achieved under the value of 0.21 ng/mL day 3 AMH values. It is important to clarify the embryo transfer success of poor responder patients prior to expected treatment success. Pre-treatment counselling for these patients would lessen the disappointment that may develop after treatment. The cost-effectiveness of treatments below these AMH values can be determined by further studies.

An economic assessment of embryo diagnostics (Dx) - the costs of introducing non-invasive embryo diagnostics into IVF standard treatment practices.

PubMed

Fugel, Hans-Joerg; Connolly, Mark; Nuijten, Mark

2014-10-09

New techniques in assessing oocytes and embryo quality are currently explored to improve pregnancy and delivery rates per embryo transfer. While a better understanding of embryo quality could help optimize the existing "in vitro fertilization" (IVF) therapy schemes, it is essential to address the economic viability of such technologies in the healthcare setting. An Embryo-Dx economic model was constructed to assess the cost-effectiveness of 3 different IVF strategies from a payer's perspective; it compares Embryo-Dx with single embryo transfer (SET) to elective single embryo transfer (eSET) and to double embryo transfer (DET) treatment practices. The introduction of a new non-invasive embryo technology (Embryo-Dx) associated with a cost up to €460 is cost-effective compared to eSET and DET based on the cost per live birth. The model assumed that Embryo-Dx will improve ongoing pregnancy rate/realize an absolute improvement in live births of 9% in this case. This study shows that improved embryo diagnosis combined with SET may have the potential to reduce the cost per live birth per couple treated in IVF treatment practices. The results of this study are likely more sensitive to changes in the ongoing pregnancy rate and consequently the live birth rate than the diagnosis costs. The introduction of a validated Embryo-Dx technology will further support a move towards increased eSET procedures in IVF clinical practice and vice versa.

Opportunities for reproductive tourism: cost and quality advantages of Turkey in the provision of in-vitro Fertilization (IVF) services.

PubMed

Yildiz, M Said; Khan, M Mahmud

2016-08-12

The scale and scope of medical tourism have expanded rapidly over the last few decades. Turkey is becoming an important player in this market because of its relatively better service quality and large comparative cost advantage. This paper compares cost, quality and effectiveness of in-vitro fertilization (IVF) in the USA and in Turkey. The data from Turkey were obtained from a hospital specializing in IVF services and the US data came from secondary sources. Package price offered by the dominant IVF-service provider to international patients in Turkey was used as a measure of cost for Turkey while IVF-specific service prices were used to estimate the cost for USA. To compare quality and effectiveness of IVF services, a number of general clinical quality indicators and IVF success rate were used. Indicators of quality, cost and success rate in the Turkish hospital were found to be better than the corresponding indicators in US hospitals. The cost difference of IVF services between USA and Turkey is so significant that the overall cost of obtaining the service from Turkey remains lower even with additional expenses for travel and accommodation. Cost-effectiveness ratio of IVF treatment per successful clinical pregnancy was much lower in Turkey than in the USA. It appears that cost and quality are the two most important factors affecting demand for health care services by international patients in Turkey. Like other important players in the medical tourism market, Turkey should be able to take advantage of its success in IVF, a highly specialized niche market, to transform its health system into an important exporter of general health services.

Gestational surrogacy.

PubMed

Brinsden, Peter R

2003-01-01

Gestational surrogacy is a treatment option available to women with certain clearly defined medical problems, usually an absent uterus, to help them have their own genetic children. IVF allows the creation of embryos from the gametes of the commissioning couple and subsequent transfer of these embryos to the uterus of a surrogate host. The indications for treatment include absent uterus, recurrent miscarriage, repeated failure of IVF and certain medical conditions. Treatment by gestational surrogacy is straightforward and follows routine IVF procedures for the commissioning mother, with the transfer of fresh or frozen-thawed embryos to the surrogate host. The results of treatment are good, as would be expected from the transfer of embryos derived from young women and transferred to fit, fertile women who are also young. Clinical pregnancy rates achieved in large series are up to 40% per transfer and series have reported 60% of hosts achieving live births. The majority of ethical or legal problems that have arisen out of surrogacy have been from natural or partial surrogacy arrangements. The experience of gestational surrogacy has been largely complication-free and early results of the follow-up of children, commissioning couples and surrogates are reassuring. In conclusion, gestational surrogacy arrangements are carried out in a few European countries and in the USA. The results of treatment are satisfactory and the incidence of major ethical or legal complications has been limited. IVF surrogacy is therefore a successful treatment for a small group of women who would otherwise not be able to have their own genetic children.

Cost-effective treatment for the couple with infertility.

PubMed

Van Voorhis, B J; Syrop, C H

2000-12-01

Although the evaluation of cost-effective approaches to infertility treatment remains in its infancy, several important principles have emerged from the initial studies in this field. Currently, in treating couples with infertility without tubal disease or severe male-factor infertility, the most cost-effective approach is to start with IUI or superovulation-IUI treatments before resorting to IVF procedures. The woman's age and number of sperm present for insemination are significant factors influencing cost-effectiveness. The influence of certain diagnoses on the cost-effectiveness of infertility treatments requires further study. Even when accounting for the costs associated with multiple gestations and premature deliveries, the cost of IVF decreases within the range of other cost-effective medical procedures and decreases to less than the willingness to pay for these procedures. Indeed, for patients with severe tubal disease, IVF has been found to be more cost-effective than surgical repair. The cost-effectiveness of IVF will likely improve as success rates show continued improvements over the course of time. In addition, usefulness of embryo selection and practices to reduce the likelihood of high-order multiple pregnancies, without reductions in pregnancy rates, will significantly impact cost-effectiveness. The exclusion of infertility treatments from insurance plans is unfortunate and accentuates the importance of physicians understanding the economics of infertility treatment with costs that are often passed directly to the patient. The erroneous economic policies and judgments that have led to inequities in access to infertility health care should not be tolerated.

First births with a simplified culture system for clinical IVF and embryo transfer.

PubMed

Van Blerkom, Jonathan; Ombelet, Willem; Klerkx, Elke; Janssen, Mia; Dhont, Nathalie; Nargund, Geeta; Campo, Rudi

2014-03-01

This study reports the outcome results from a pilot clinical trial using a simplified laboratory method for human IVF. This system reproducibly generates de novo the atmospheric and culture conditions that support normal fertilization and preimplantation embryogenesis to the hatched blastocyst stage without the need for specialized medical-grade gases or equipment. Development from insemination to the hatched blastocyst stage occurs undisturbed in a completely closed system that enables timed performance assessments for embryo selection in situ that, in this study, involved single-embryo transfers on day 3. With the simplified culture system, 8/23 embryos implanted, one miscarried at 8weeks of gestation and seven healthy babies have been born. The methodology and results are discussed with regard to how this simplified system can be adopted worldwide to meet the growing need for accessible and affordable IVF. A common notion concerning the demographics of infertility is that it is largely a phenomenon associated with developed countries, where infertility treatments are commonplace. In fact, most infertile couples reside in developing/low-resource countries where infertility diagnosis and treatment is nonexistent, inaccessible or unaffordable by the vast majority of young men and women in need. The irony of this situation is that bilateral tubal occlusions, for which IVF was originally indicated and is the most effective treatment, is by far the most common cause of their infertility. We have addressed one aspect of this issue, the IVF laboratory, as part of a wider effort by the Walking Egg Project to design and establish small, dedicated centres in developing countries to provide assisted reproduction technologies that are affordable and accessible to a wider proportion of the population in need. The methods for conventional IVF designed to addresses tubal obstructions are relatively simple and free of complex instrumentation and the highly developed infrastructure common to high-resource centres. This simplified IVF system self-generates culture conditions in a closed system. After prolonged preclinical testing, a pilot clinical study was initiated in 2012 in Genk, Belgium. The findings suggest that a significant first step has been achieved in the effort to bring advanced assisted reproduction to developed countries using a low-resource but highly effective IVF system capable of bringing modern reproductive medicine to infertile couples in low-resource societies. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Inositol Treatment and ART Outcomes in Women with PCOS.

PubMed

Garg, Deepika; Tal, Reshef

2016-01-01

Polycystic ovary syndrome (PCOS) affects 5-10% of women in reproductive age and is characterized by oligo/amenorrhea, androgen excess, insulin resistance, and typical polycystic ovarian morphology. It is the most common cause of infertility secondary to ovulatory dysfunction. The underlying etiology is still unknown but is believed to be multifactorial. Insulin-sensitizing compounds such as inositol, a B-complex vitamin, and its stereoisomers (myo-inositol and D-chiro-inositol) have been studied as an effective treatment of PCOS. Administration of inositol in PCOS has been shown to improve not only the metabolic and hormonal parameters but also ovarian function and the response to assisted-reproductive technology (ART). Accumulating evidence suggests that it is also capable of improving folliculogenesis and embryo quality and increasing the mature oocyte yield following ovarian stimulation for ART in women with PCOS. In the current review, we collate the evidence and summarize our current knowledge on ovarian stimulation and ART outcomes following inositol treatment in women with PCOS undergoing in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI).

Adjuncts in the IVF laboratory: where is the evidence for 'add-on' interventions?

PubMed

Harper, Joyce; Jackson, Emily; Sermon, Karen; Aitken, Robert John; Harbottle, Stephen; Mocanu, Edgar; Hardarson, Thorir; Mathur, Raj; Viville, Stephane; Vail, Andy; Lundin, Kersti

2017-03-01

Globally, IVF patients are routinely offered and charged for a selection of adjunct treatments and tests or 'add-ons' that they are told may improve their chance of a live birth, despite there being no clinical evidence supporting the efficacy of the add-on. Any new IVF technology claiming to improve live birth rates (LBR) should, in most cases, first be tested in an appropriate animal model, then in clinical trials, to ensure safety, and finally in a randomized controlled trial (RCT) to provide high-quality evidence that the procedure is safe and effective. Only then should the technique be considered as 'routine' and only when applied to the similar patient population as those studied in the RCT. Even then, further pediatric and long-term follow-up studies will need to be undertaken to examine the long-term safety of the procedure. Alarmingly, there are currently numerous examples where adjunct treatments are used in the absence of evidence-based medicine and often at an additional fee. In some cases, when RCTs have shown the technique to be ineffective, it is eventually withdrawn from the clinic. In this paper, we discuss some of the adjunct treatments currently being offered globally in IVF laboratories, including embryo glue and adherence compounds, sperm DNA fragmentation, time-lapse imaging, preimplantation genetic screening, mitochondria DNA load measurement and assisted hatching. We examine the evidence for their safety and efficacy in increasing LBRs. We conclude that robust studies are needed to confirm the safety and efficacy of any adjunct treatment or test before they are offered routinely to IVF patients. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

IVF outcome is optimized when embryos are replaced between 5 and 15 mm from the fundal endometrial surface: a prospective analysis on 1184 IVF cycles

PubMed Central

2013-01-01

Background Some data suggest that the results of human in vitro fertilization (IVF) may be affected by the site of the uterine cavity where embryos are released. It is not yet clear if there is an optimal range of embryo-fundus distance (EFD) within which embryos should be transferred to optimize IVF outcome. Methods The present study included 1184 patients undergoing a blind, clinical-touch ET of 1–2 fresh embryos loaded in a soft catheter with a low amount of culture medium. We measured the EFD using transvaginal US performed immediately after ET, with the aim to assess (a) if EFD affects pregnancy and implantation rates, and (b) if an optimal EFD range can be identified. Results Despite comparable patients’ clinical characteristics, embryo morphological quality, and endometrial thickness, an EFD between 5 and 15 mm allowed to obtain significantly higher pregnancy and implantation rates than an EFD above 15 mm. The abortion rate was much higher (although not significantly) when EFD was below 5 mm than when it was between 5 and 15 mm. Combined together, these results produced an overall higher ongoing pregnancy rate in the group of patients whose embryos were released between 5 and 15 mm from the fundal endometrial surface. Conclusions The site at which embryos are released affects IVF outcome and an optimal EFD range exists; this observations suggest that US-guided ET could be advantageous vs. clinical-touch ET, as it allows to be more accurate in releasing embryos within the optimal EFD range. PMID:24341917

First intention IVF protocol for polycystic ovaries: does oral contraceptive pill pretreatment influence COH outcome?

PubMed

Decanter, Christine; Robin, Geoffroy; Thomas, Patricia; Leroy, Maryse; Lefebvre, Catherine; Soudan, Benoit; Lefebvre-Khalil, Valerie; Leroy-Martin, Brigitte; Dewailly, Didier

2013-06-19

Morphological aspect of polycystic ovaries (PCO) is a very common finding in an IVF center population: this includes PCOS patients identified in 18-25% of the couples presenting with infertility and so called "sonographic PCO only" the prevalence of which has been estimated as high as 33% in asymptomatic patients. Finding the optimal first intention IVF protocol for polycystic ovaries patients is still challenging in order to improve the controlled ovarian hyperstimulation (COH) outcome while avoiding ovarian hyperstimulation syndrome (OHSS). It has been suggested that women with PCO would benefit from a longer period of pituitary down-regulation. The purpose of this study was to compare an extended duration of OCP pretreatment with a classic GnRH agonist protocol. A single center prospective non-randomized study was performed from January 2009 to December 2010 in the Lille University Hospital including 113 women diagnosed with PCO(S) according to the Rotterdam ultrasonographic criteria and undergoing their first IVF attempt. Comprehensive hormonal and ultra-sonographic assessments were collected during COH in these patients. LH and androgen suppression and dynamics of follicular growth were compared between the two protocols as well as the COH outcome in terms of oocyte/embryo number and quality, implantation and pregnancy rates. No significant difference was observed between the two groups concerning dynamics of follicular growth and hormonal values. Clinical and ongoing pregnancy rates were significantly lower in the OCP group despite same oocyte and embryo quality. Nevertheless, the cumulative pregnancy rate did not differ between the two groups. The incidence of OHSS was not statistically significant. Extended duration of OCP pretreatment, as a first intention IVF protocol for PCO patients, does not improve the pattern of follicular growth nor the oocyte and embryo quality.

[Prognosis of the IVF ICSI/ET procedure efficiency with the use of artificial neural networks among patients of the Department of Reproduction and Gynecological Endocrinology].

PubMed

Milewski, Robert; Jamiołkowski, Jacek; Milewska Anna, Justyna; Domitrz, Jan; Szamatowicz, Jacek; Wołczyński, Sławomir

2009-12-01

Prognosis of pregnancy for patients treated with IVF ICSI/ET methods, using artificial neural networks. Retrospective study of 1007 cycles of infertility treatment of 899 patients of Department of Reproduction and Gynecological Endocrinology in Bialystok. The subjects were treated with IVF ICSI/ET method from August 2005 to September 2008. Classifying artificial neural network is described in the paper Architecture of the network is three-layered perceptron consisting of 45 neurons in the input layer 14 neurons in the hidden layer and a single output neuron. The source data for the network are 36 variables. 24 of them are nominal variables and the rest are quantitative variables. Among non-pregnancy cases only 59 prognosis of the network were incorrect. The results of treatment were correctly forecast in 68.5% of cases. The pregnancy was accurately confirmed in 49.1% of cases and lack of pregnancy in 86.5% of cases. Treatment of infertility with the use of in vitro fertilization methods continues to have too low efficiency per one treatment cycle. To improve this indicator it is necessary to find dependencies, which describe the model of IVF treatment. The application of advanced methods of bioinformatics allows to predict the result of the treatment more effectively With the help of artificial neural networks, we are able to forecast the failure of the treatment using IFV ICSI/ET procedure with almost 90% probability of certainty These possibilities can be used to predict negative cases.

Predicting the success of IVF: external validation of the van Loendersloot's model.

PubMed

Sarais, Veronica; Reschini, Marco; Busnelli, Andrea; Biancardi, Rossella; Paffoni, Alessio; Somigliana, Edgardo

2016-06-01

Is the predictive model for IVF success proposed by van Loendersloot et al. valid in a different geographical and cultural context? The model discriminates well but was less accurate than in the original context where it was developed. Several independent groups have developed models that combine different variables with the aim of estimating the chance of pregnancy with IVF but only four of them have been externally validated. One of these four, the van Loendersloot's model, deserves particular attention and further investigation for at least three reasons; (i) the reported area under the receiver operating characteristics curve (c-statistics) in the temporal validation setting was the highest reported to date (0.68), (ii) the perspective of the model is clinically wise since it includes variables obtained from previous failed cycles, if any, so it can be applied to any women entering an IVF cycle, (iii) the model lacks external validation in a geographically different center. Retrospective cohort study of women undergoing oocyte retrieval for IVF between January 2013 and December 2013 at the infertility unit of the Fondazione Ca' Granda, Ospedale Maggiore Policlinico of Milan, Italy. Only the first oocyte retrieval cycle performed during the study period was included in the study. Women with previous IVF cycles were excluded if the last one before the study cycle was in another center. The main outcome was the cumulative live birth rate per oocytes retrieval. Seven hundred seventy-two women were selected. Variables included in the van Loendersloot's model and the relative weights (beta) were used. The variable resulting from this combination (Y) was transformed into a probability. The discriminatory capacity was assessed using the c-statistics. Calibration was made using a logistic regression that included Y as the unique variable and live birth as the outcome. Data are presented using both the original and the calibrated models. Performance was evaluated correlating the mean predicted chances of live births in the five quintiles and the observed rates. Two-hundred-eleven live births (27%) were obtained. The c-statistic was 0.64 (95% CI: 0.61-0.67, P < 0.001). The slope of the linear predictor (calibration slope) expressed as an Odds Ratio was 1.81 (95% CI: 1.46-2.24, P < 0.001), corresponding to a beta of 0.630. The calibration intercept was +0.349 (P = 0.13). While a clear discrepancy exists using the original model, data appear properly distributed with the calibrated model. The Pearson coefficient of the correlation between the mean predicted chances of live births in the five quintiles and the observed rates was 0.99 (P = 0.002). Data were collected retrospectively, thus exposing them to potential inaccuracies. The selection criteria for access to IVF adopted in our center might be too stringent, leading to the exclusion of women with a poor, yet acceptable chance of live birth. Therefore, the validity of the model in women with a very low chance of live birth could not be tested. The van Loendersloot's model can be used in other contexts but it is important that it has local calibration. It may help in counseling couples about their chance of success but it cannot be used to exclude treatments. Further research is needed to improve the discriminatory performance of IVF predictive models. None. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A short course of metformin does not reduce OHSS in a GnRH antagonist cycle for women with PCOS undergoing IVF: a randomised placebo-controlled trial.

PubMed

Jacob, S L; Brewer, C; Tang, T; Picton, H M; Barth, J H; Balen, A H

2016-12-01

Does 'metformin' reduce the incidence of ovarian hyperstimulation syndrome (OHSS) for women with polycystic ovary syndrome (PCOS) undergoing a GnRH antagonist assisted conception treatment cycle? A short course of metformin does not reduce the incidence of OHSS for women with PCOS undergoing a GnRH antagonist treatment cycle. Metformin does reduce the incidence of OHSS in a GnRH-agonist treatment cycle. A randomised placebo-controlled trial (RCT) using metformin or placebo. Randomisation was blinded to both patient and investigator, using a random permuted blocks method with a 50:50 allocation ratio. The study was completed over 5 years (2009-2014) with 153 randomised patients. A sample size calculation based on the incidence of OHSS was completed prospectively suggesting a minimum of 146 recruits was required for the trial with a power of 80% and a type 1 error of 0.05. All patients met the Rotterdam criteria for PCOS and were treated with a standard GnRH antagonist IVF/ICSI treatment cycle in a tertiary infertility clinic. The study medication was started prior to stimulation and continued to oocyte retrieval. Of the 153 patients, 77 received metformin and 76 placebo. There was no reduction in the incidence of moderate-severe OHSS (Placebo (PLA) 12.2%, metformin (MET) = 16%, 95% CI -0.08-0.16, P = 0.66). There was no difference in total gonadotrophin dose (PLA = 1200, MET = 1200, 95% CI -118.67-118.67, P = 0.75), oocytes retrieved (PLA = 15, MET = 14, 95% CI -2.37-4.37, P = 0.66) or fertilisation rate (PLA = 60.7%, MET = 53.3%, 95% CI -0.96-14.94, P = 0.07). However, using metformin resulted in a reduced clinical pregnancy rate (CPR) per cycle started (PLA = 48.7%, MET = 28.6%, 95% CI 0.04-0.35, P = 0.02) and live birth rate (PLA = 51.6%, MET = 27.6%, 95% CI 0.05-0.40, P = 0.02). Furthermore, when ethnicity was taken into account there was a significant reduction in pregnancy outcome for the South Asian population irrespective of metformin or placebo use (CPR per cycle started, White Caucasian = 44.4%, South Asian = 19.4%; 95% CI 0.06-0.39, P = 0.01). This study was only undertaken on an infertility population with PCOS with a limited duration of study medication use. This is the first adequately powered RCT to assess the impact of metformin on OHSS in a high-risk group (women with PCOS) undergoing a GnRH antagonist cycle. It does not support the empirical prescribing of metformin as an adjunct to a GnRH antagonist treatment cycle. None. EudraCT number 2009-010952-81. 21 September 2009. 30 October 2009. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[RESULTS OF PREPARATION AND IMPLEMENTATION OF IVF PROGRAM IN PATIENTS WITH THROMBOPHILIA AND HISTORY OF FAILED IVF].

PubMed

Abrahamyan, G

2017-01-01

The problem of infertility and reproductive losses maintains its urgency, as well as medical and social significance. Frequency of infertility in overall population, according to the data from different authors, varies from 9 to 18 per cent. Methods of aided reproductive technologies (ART) opened a new era in the field of correction of infertile marriage. As a result, more and more couples choose to solve this problem by means of aided reproductive technologies (ART): in-vitro fertilization (IVF) and embryo transfer (ET). However, despite of all achievements, the frequency of pregnancy development remains relatively low and makes 25-30% per treatment cycle, furthermore, during the last decade this value did not change to any significant extent. Analysis of literature sources revealed that genetic, acquired and combined forms of thrombophilia, which often cause severe complications at ART, are among main causes of IVF failures. The aim of the research was to develop and to introduce main principles of prophylaxis of repeated IVF failures in women with thrombophilia and history of failed IVF. In order to achieve the goal we have examined 80 patients (main group) with genetic, acquired or combined thrombophilia, identified on the first stage of standard examination. One of the main reasons of IVF failure is genetic, acquired or combined thrombophilia. Delivery of pathogenetically justified antithrombotic prophylaxis (75 mg. of aspirin and low molecular heparin - enoxaparinum) in patients with thrombophilia and history of failed IVFs allowed improvement of hemostasiogram profile and efficiency of IVF. Frequency of pregnancy in patients with history of failed IVF after the therapy made 31,3% in the first cycle of simulation (in 25 women), 20,0% in the second cycle of simulation (in 16 women) and 11,3% (9 women) in the third cycle. Due to justified antithrombotic prophylaxis 50 cases of pregnancy was registered (62,5%). Introduction of long-term therapy with application of antithrombotic preparations and vitamins in continuous mode promoted successful course of pregnancy, occurred as a result of IVF in patients with history of failed IVF.

Replacing single frozen-thawed euploid embryos in a natural cycle in ovulatory women may increase live birth rates compared to medicated cycles in anovulatory women.

PubMed

Melnick, Alexis P; Setton, Robert; Stone, Logan D; Pereira, Nigel; Xu, Kangpu; Rosenwaks, Zev; Spandorfer, Steven D

2017-10-01

The goal of this study was to compare pregnancy outcomes between natural frozen embryo transfer (FET) cycles in ovulatory women and programmed FET cycles in anovulatory women after undergoing in vitro fertilization with preimplantation genetic screening (IVF-PGS). This was a retrospective cohort study performed at an academic medical center. Patients undergoing single FET IVF-PGS cycles between October 2011 and December 2014 were included. Patients were stratified by type of endometrial replacement: programmed cycles with estrogen/progesterone replacement and natural cycles. IVF-PGS with 24-chromosome screening was performed on all included patients. Those patients with euploid embryos had single embryo transfer in a subsequent FET. The primary study outcome was live birth/ongoing pregnancy rate. Secondary outcomes included implantation, biochemical pregnancy, and miscarriage rates. One hundred thirteen cycles met inclusion criteria: 65 natural cycles and 48 programmed cycles. The programmed FET group was younger (35.9 ± 4.5 vs. 37.5 ± 3.7, P = 0.03) and had a higher AMH (3.95 ± 4.2 vs. 2.37 ± 2.4, P = 0.045). The groups were similar for BMI, gravidity, parity, history of uterine surgery, and incidence of Asherman's syndrome. There was also no difference in embryo grade at biopsy or transfer, and proportion of day 5 and day 6 transfers. Implantation rates were higher in the natural FET group (0.66 ± 0.48 vs. 0.44 ± 0.50, P = 0.02). There was no difference in the rates of biochemical pregnancy or miscarriage. After controlling for age, live birth/ongoing pregnancy rate was higher in natural FETs with an adjusted odds ratio of 2.68 (95% CI 1.22-5.87). Natural FET in ovulatory women after IVF-PGS is associated with increased implantation and live birth rates compared to programmed FET in anovulatory women. Further investigation is needed to determine whether these findings hold true in other patient cohorts.

Stakeholders' views on ethical issues in the practice of in-vitro fertilisation and embryo transfer in Nigeria.

PubMed

Ajayi, R A; Dibosa-Osadolor, O J

2011-09-01

The provision of IVF for the specialized treatment of infertility has grown very rapidly in Nigeria in recent times, especially within the private sector. The objective of this study was to document the views of key stakeholders regarding salient ethical issues relating to the practice of in-vitro fertilisation (IVF) in Nigeria. A think-tank session was convened with participants drawn from different backgrounds and disciplines to deliberate on ethical issues in IVF. Ten key issues were discussed at this inaugural session. It was unanimously agreed that there are no right or wrong answers when considering the ethics and morality of IVF as these are principally dependent on choice and circumstances. However within the legal and socio-cultural dictates of the Nigerian society, right and wrong may be clearly determined on some issues. With the expansion of the IVF industry and technology in Nigeria, the need to address related ethical issues have become paramount. The forum recommended that it is important that regulatory guidelines are put in place to regulate the practice of IVF in Nigeria and to protect patients' rights and safety.

Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial.

PubMed

Einarsson, Snorri; Bergh, Christina; Friberg, Britt; Pinborg, Anja; Klajnbard, Anna; Karlström, Per-Olof; Kluge, Linda; Larsson, Ingrid; Loft, Anne; Mikkelsen-Englund, Anne-Lis; Stenlöf, Kaj; Wistrand, Anna; Thurin-Kjellberg, Ann

2017-08-01

Does an intensive weight reduction programme prior to IVF increase live birth rates for infertile obese women? An intensive weight reduction programme resulted in a large weight loss but did not substantially affect live birth rates in obese women scheduled for IVF. Among obese women, fertility and obstetric outcomes are influenced negatively with increased risk of miscarriage and a higher risk of maternal and neonatal complications. A recent large randomized controlled trial found no effect of lifestyle intervention on live birth in infertile obese women. A prospective, multicentre, randomized controlled trial was performed between 2010 and 2016 in the Nordic countries. In total, 962 women were assessed for eligibility and 317 women were randomized. Computerized randomization with concealed allocation was performed in the proportions 1:1 to one of two groups: weight reduction intervention followed by IVF-treatment or IVF-treatment only. One cycle per patient was included. Nine infertility clinics in Sweden, Denmark and Iceland participated. Women under 38 years of age planning IVF, and having a BMI ≥30 and <35 kg/m2 were randomized to two groups: an intervention group (160 patients) with weight reduction before IVF, starting with 12 weeks of a low calorie liquid formula diet (LCD) of 880 kcal/day and thereafter weight stabilization for 2-5 weeks, or a control group (157 patients) with IVF only. In the full analysis set (FAS), the live birth rate was 29.6% (45/152) in the weight reduction and IVF group and 27.5% (42/153) in the IVF only group. The difference was not statistically significant (difference 2.2%, 95% CI: 12.9 to -8.6, P = 0.77). The mean weight change was -9.44 (6.57) kg in the weight reduction and IVF group as compared to +1.19 (1.95) kg in the IVF only group, being highly significant (P < 0.0001). Significantly more live births were achieved through spontaneous pregnancies in the weight reduction and IVF group, 10.5% (16) as compared to the IVF only group 2.6% (4) (P = 0.009). Miscarriage rates and gonadotropin dose used for IVF stimulation did not differ between groups. Two subgroup analyses were performed. The first compared women with PCOS in the two randomized groups, and the second compared women in the weight reduction group reaching BMI ≤ 25 kg/m2 or reaching a weight loss of at least five BMI units to the IVF only group. No statistical differences in live birth rates between the groups in either subgroup analysis were found. The study was not powered to detect a small increase in live births due to weight reduction and was not blinded for the patients or physician. Further, the intervention group had a longer time to achieve a spontaneous pregnancy, but were therefore slightly older than the control group at IVF. The study only included women with a BMI lower than 35 kg/m2. The study suggests that weight loss for obese women (BMI: 30-34.9 kg/m2) may not rectify the outcome in IVF cycles, although a significant higher number of spontaneous conceptions occurred in the weight loss group. Also, the study suggests that intensive weight reduction with LCD treatment does not negatively affects the results. The study was funded by Sahlgrenska University Hospital (ALFGBG-70 940), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Impolin AB, Hjalmar Svensson Foundation and Jane and Dan Olsson Foundation. Dr Thurin-Kjellberg reports grants from Merck, non-financial support from Impolin AB, during the conduct of the study, and personal fees from Merck outside the submitted work. Dr Friberg reports personal fees from Ferring, Merck, MSD, Finox and personal fees from Studentlitteratur, outside the submitted work. Dr Englund reports personal fees from Ferring, and non-financial support from Merck, outside the submitted work. Dr Bergh reports and has been reimbursed for: writing a newsletter twice a year (Ferring), lectures (Ferring, MSD, Merck), and Nordic working group meetings (Finox). Dr Karlström reports lectures (Ferring, Finox, Merck, MSD) and Nordic working group meetings (Ferring). Ms Kluge, Dr Einarsson, Dr Pinborg, Dr Klajnbard, Dr Stenlöf, Dr Larsson, Dr Loft and Dr Wistrand have nothing to disclose. ClinicalTrials.gov number, NCT01566929. 23-03-2012. 05-10-2010. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Experiences of physical activity during pregnancy resulting from in vitro fertilisation: an interpretative phenomenological analysis.

PubMed

Walker, Chloe; Mills, Hayley; Gilchrist, Angela

2017-09-01

To explore the qualitative experiences and decision-making processes surrounding physical activity (PA) for women who have undergone IVF treatment. PA during pregnancy is safe for both mother and fetus in the majority of cases, including for women who have undergone in vitro fertilisation (IVF) treatment; however, there is a paucity of research into decision-making and PA in this population. Eight women, who had undergone successful IVF treatment and were currently pregnant or had given birth within the last two years, participated in semi-structured interviews about their experiences of infertility and PA during pregnancy. Interview transcripts were analysed using interpretative phenomenological analysis. Three superordinate themes emerged from the data: 'navigating away from childlessness and towards motherhood', 'negotiating a safe passage' and 'balancing the challenges of pregnancy with the needs of the self'. Ten subthemes indicated the processes adopted to navigate experiences of infertility, the IVF process, and subsequent decision-making about PA during pregnancy. PA during pregnancy was experienced as a way to soothe the self and control the experience of pregnancy; however, this was mediated by concerns about safety and physical limitations on PA. Limitations of the study are considered, as well as implications for clinical practice and directions for future research.

Modified natural cycle versus controlled ovarian hyperstimulation IVF: a cost-effectiveness evaluation of three simulated treatment scenarios.

PubMed

Groen, Henk; Tonch, Nino; Simons, Arnold H M; van der Veen, Fulco; Hoek, Annemieke; Land, Jolande A

2013-12-01

Can modified natural cycle IVF or ICSI (MNC) be a cost-effective alternative for controlled ovarian hyperstimulation IVF or ICSI (COH)? The comparison of simulated scenarios indicates that a strategy of three to six cycles of MNC with minimized medication is a cost-effective alternative for one cycle of COH with strict application of single embryo transfer (SET). MNC is cheaper per cycle than COH but also less effective in terms of live birth rate (LBR). However, strict application of SET in COH cycles reduces effectiveness and up to three MNC cycles can be performed at the same costs as one COH cycle. The cost-effectiveness of MNC versus COH was evaluated in three simulated treatment scenarios: three cycles of MNC versus one cycle of COH with SET or double embryo transfer (DET) and subsequent transfer of cryopreserved embryos (Scenario 1); six cycles of MNC versus one cycle of COH with strictly SET and subsequent transfer of cryopreserved embryos (Scenario 2); six cycles of MNC with minimized medication (hCG ovulation trigger only) versus one cycle of COH with SET or DET and subsequent transfer of cryopreserved embryos (Scenario 3). We used baseline data obtained from two retrospective cohorts of consecutive patients (2005-2008) undergoing MNC in the University Medical Center Groningen (n = 499, maximum six cycles per patient) or their first COH cycle with subsequent transfer of cryopreserved embryos in the Academic Medical Center Amsterdam (n = 392). Data from 1994 MNC cycles (958 MNC-IVF and 1036 MNC-ICSI) and 392 fresh COH cycles (one per patient, 196 COH-IVF and 196 COH-ICSI) with subsequent transfer of cryopreserved embryos (n = 72 and n = 94 in MNC and COH cycles, respectively) in ovulatory, subfertile women <36 years of age served as baseline for the three simulated scenarios. To compare the scenarios, the incremental cost-effectiveness ratio (ICER) was calculated, defined as the ratio of the difference in IVF costs up to 6 weeks postpartum to the difference in LBR. Live birth was the primary outcome measure and was defined as the birth of at least one living child after a gestation of ≥25 weeks. In the baseline data, MNC was not cost-effective, as COH dominated MNC with a higher cumulative LBR (27.0 versus 24.0%) and lower cost per patient (€3694 versus €5254). The simulations showed that in scenario 1 three instead of six cycles lowered the costs of MNC to below the level of COH (€3390 versus €3694, respectively), but also lowered the LBR per patient (from 24.0 to 16.2%, respectively); Scenario 2: COH with strict SET was less effective than six cycles MNC (LBR 17.5 versus 24.0%, respectively), but also less expensive per patient (€2908) than MNC (€5254); Scenario 3: improved the cost-effectiveness of MNC but COH still dominated MNC when medication was minimized in terms of costs, i.e. €855 difference in favor of COH and 3% difference in LBR in favor of COH (ICER: €855/-3.0%). Owing to the retrospective nature of the study, the analyses required some assumptions, for example regarding the costs of pregnancy and delivery, which had to be based on the literature rather than on individual data. Furthermore, costs of IVF treatment were based on tariffs and not on actual costs. Although this may limit the external generalizability of the results, the limitations will influence both treatments equally, and would therefore not bias the comparison of MNC versus COH. The combined results suggest that MNC with minimized medication might be a cost-effective alternative for COH with strict SET. The scenarios reflect realistic alternatives for daily clinical practice. A preference for MNC depends on the willingness to trade off effectiveness in terms of LBR against the benefits of a milder stimulation regimen, including a very low rate of multiple pregnancies and hyperstimulation syndrome and ensuing lower costs per live birth. The study was supported by research grants from Merck Serono and Ferring Pharmaceuticals. The authors declare no conflicts of interest. Not applicable.

Recurrent implantation failure in IVF: features of cycles that eventually ended in conception.

PubMed

Bord, Ilia; Tamir, Belle; Harlev, Avraham; Har-Vardi, Iris; Lunenfeld, Eitan; Friger, Michael; Levitas, Eliahu

2016-04-01

To evaluate the characteristics of patients and IVF cycles with recurrent implantation failure who eventually succeeded to conceive compared to those who failed to do so. In a retrospective study, we explored our database for patients younger than 35 years old who underwent at least three unsuccessful fresh IVF cycles. The following parameters were analyzed: cause of infertility, FSH level, stimulation cycle characteristics, fertilization rate, the type of luteal support, and cycle outcome. Uterine cavity assessment was also included. The relationship between endometrial scratching and the outcome of the following IVF cycle was assessed for the subsequent pregnancy rate. The study included 184 patients who underwent 854 IVF cycles. There were no statistically significant differences between patients who eventually conceived and those who did not in terms of ovarian reserve and response to gonadotropin treatment. IVF cycles that eventually ended with conception were characterized by shorter stimulation (10.87 ± 2.17 versus 11.34 ± 2.33 days, p < 0.05), higher estrogen level on the day of hCG administration (1661 ± 667 versus 1472 ± 633 pg/ml, p = 0.009), more fertilized oocytes via ICSI (5.04 ± 4.29 versus 3.85 ± 3.45, p = 0.002), and more embryos available for transfer (5.98 ± 3.89 versus 5.12 ± 3.31, p = 0.002). Combined estrogen and progesterone luteal support combined with endometrial scratching prior to the subsequent IVF cycle has been positively related to increased pregnancy rates. Young patients with RIF having a normal ovarian reserve and satisfactory ovarian response to superovulation should be encouraged to pursue IVF, even though the probability to conceive is relatively low compared to the general IVF population.

Association of in vitro fertilization with global and IGF2/H19 methylation variation in newborn twins.

PubMed

Loke, Y J; Galati, J C; Saffery, R; Craig, J M

2015-04-01

In vitro fertilization (IVF) and its subset intracytoplasmic sperm injection (ICSI), are widely used medical treatments for conception. There has been controversy over whether IVF is associated with adverse short- and long-term health outcomes of offspring. As with other prenatal factors, epigenetic change is thought to be a molecular mediator of any in utero programming effects. Most studies focused on DNA methylation at gene-specific and genomic level, with only a few on associations between DNA methylation and IVF. Using buccal epithelium from 208 twin pairs from the Peri/Postnatal Epigenetic Twin Study (PETS), we investigated associations between IVF and DNA methylation on a global level, using the proxies of Alu and LINE-1 interspersed repeats in addition to two locus-specific regulatory regions within IGF2/H19, controlling for 13 potentially confounding factors. Using multiple correction testing, we found strong evidence that IVF-conceived twins have lower DNA methylation in Alu, and weak evidence of lower methylation in one of the two IGF2/H19 regulatory regions and LINE-1, compared with naturally conceived twins. Weak evidence of a relationship between ICSI and DNA methylation within IGF2/H19 regulatory region was found, suggesting that one or more of the processes associated with IVF/ICSI may contribute to these methylation differences. Lower within- and between-pair DNA methylation variation was also found in IVF-conceived twins for LINE-1, Alu and one IGF2/H19 regulatory region. Although larger sample sizes are needed, our results provide additional insight to the possible influence of IVF and ICSI on DNA methylation. To our knowledge, this is the largest study to date investigating the association of IVF and DNA methylation.

Cycle scheduling for in vitro fertilization with oral contraceptive pills versus oral estradiol valerate: a randomized, controlled trial

PubMed Central

2013-01-01

Background Both oral contraceptive pills (OCPs) and estradiol (E2) valerate have been used to schedule gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles and, consequently, laboratory activities. However, there are no studies comparing treatment outcomes directly between these two pretreatment methods. This randomized controlled trial was aimed at finding differences in ongoing pregnancy rates between GnRH antagonist IVF cycles scheduled with OCPs or E2 valerate. Methods Between January and May 2012, one hundred consecutive patients (nonobese, regularly cycling women 18–38 years with normal day 3 hormone levels and <3 previous IVF/ICSI attempts) undergoing IVF with the GnRH antagonist protocol were randomized to either the OCP or E2 pretreatment arms, with no restrictions such as blocking or stratification. Authors involved in data collection and analysis were blinded to group assignment. Fifty patients received OCP (30 μg ethinyl E2/150 μg levonorgestrel) for 12–16 days from day 1 or 2, and stimulation was started 5 days after stopping OCP. Similarly, 50 patients received 4 mg/day oral E2 valerate from day 20 for 5–12 days, until the day before starting stimulation. Results Pretreatment with OCP (mean±SD, 14.5±1.7 days) was significantly longer than with E2 (7.8±1.9 days). Stimulation and embryological characteristics were similar. Ongoing pregnancy rates (46.0% vs. 44.0%; risk difference, –2.0% [95% CI –21.2% to 17.3%]), as well as implantation (43.5% vs. 47.4%), clinical pregnancy (50.0% vs. 48.0%), clinical miscarriage (7.1% vs. 7.7%), and live birth (42.0% vs. 40.0%) rates were comparable between groups. Conclusions This is the first study to directly compare these two methods of cycle scheduling in GnRH antagonist cycles. Our results fail to show statistically significant differences in ongoing pregnancy rates between pretreatment with OCP and E2 for IVF with the GnRH antagonist protocol. Although the study is limited by its sample size, our results may contribute to a future meta-analysis. An interesting future direction would be to extend our study to women with decreased ovarian reserve, as these are the patients in whom an increase in oocyte yield—due to the hypothetical beneficial effect of steroid pretreatment on follicular synchronization—could more easily be demonstrated. Trial registration ClinicalTrials.gov http://NCT01501448. PMID:24074027

Observational Study to Assess the Therapeutic Value of Four Ovarian Hyperstimulation Protocols in IVF After Pituitary Suppression with GnRH Antagonists in Normally Responding Women.

PubMed

Ana, Monzó; Vicente, Montañana; María, Rubio José; Trinidad, García-Gimeno; Alberto, Romeu

2011-02-22

To compare the clinical results of four different protocols of COH for IVF-ICSI in normovulatory women, using in all cases pituitary suppression with GnRH antagonists. A single center, open label, parallel-controlled, prospective, post-authorization study under the approved conditions for use where 305 normal responders women who were candidates to COH were assigned to r-FSH +hp-hMG (n = 51, Group I), hp-hMG (n = 61, Group II), fixed-dose r-FSH (n = 118, Group III), and r-FSH with potential dose adjustment (n = 75, Group IV) to subsequently undergo IVF-ICSI. During stimulation, Group IV needed significantly more days of stimulation as compared to Group II [8.09 ± 1.25 vs. 7.62 ± 1.17; P < 0.05], but was the group in which more oocytes were recovered [Group I: 9.43 ± 4.99 vs. Group II: 8.96 ± 4.82 vs. Group III: 8.78 ± 3.72 vs. Group IV: 11.62 ± 5.80; P < 0.05]. No significant differences were seen between the groups in terms of clinical and ongoing pregnancy, but among patients in whom two embryos with similar quality parameters (ASEBIR) were transferred, the group treated with hp-hMG alone achieved a significantly greater clinical pregnancy rate as compared to all other groups [Group I: 31.6%, Group II: 56.4%, Group III: 28.7%, Group IV: 32.7%; P < 0.05]. Although randomized clinical trials should be conducted to achieve a more reliable conclusion, these observations support the concept that stimulation with hp-hMG could be beneficial in normal responders women undergoing pituitary suppression with GnRH antagonists.

The “graying” of infertility services: an impending revolution nobody is ready for

PubMed Central

2014-01-01

Background As demand for infertility services by older women continues to grow, because achievable in vitro fertilization (IVF) outcomes are widely underestimated, most fertility centers do not offer maximal treatment options with use of autologous oocytes. Limited data suggest that clinical IVF outcomes in excess of what the American Society for Reproductive Medicine (ASRM) considers “futile” can, likely, be achieved up to at least age 45 years. Methods In an attempt to point out an evolving demographic trend in IVF, we here report our center’s IVF data for 2010-2012 and national U.S. data for 1997-2010. Though our center’s data are representative of only one IVF center’s patients, they, likely, are unique since they probably represent the most adversely selected IVF patient population ever reported and, thus, are predictive of future demographic trends. In addition we performed a systematic review of the literature on the subject based on PubMed, Medline and Google Scholar searches till year-end 2013. The literature search was performed using key words and phrases relevant to fertility treatments in older women. Results As demonstrated by our center’s patient demographics and national U.S. data, IVF centers are destined to treat increasingly adversely selected patients. Despite our center’s already extremely adversely selected patient population, age-specific IVF cycle outcomes in women above age 40 years, nevertheless, exceeded criteria for “futility” by the ASRM and widely quoted outcome expectations in the literature for patient ages. Age 43 discriminates between better and poorer clinical pregnancy and live birth rates. Conclusions “Graying” of the infertility populations in the developed world, a problem with potentially far-reaching medical and societal consequences, has so far been only insufficiently addressed in the literature. As women’s postmenopausal life spans already exceed postmenarcheal life spans at the start of the 20th century, the “graying” of infertility services can be expected to further accelerate, no longer as in recent decades bringing only women in their 40s into maternity wards but also women in their 50s and 60s. Medicine and society better get ready for this revolution. PMID:25012752

The duration of gonadotropin stimulation does not alter the clinical pregnancy rate in IVF or ICSI cycles.

PubMed

Purandare, N; Emerson, G; Kirkham, C; Harrity, C; Walsh, D; Mocanu, E

2017-08-01

Ovarian stimulation is an essential part of assisted reproduction treatments. Research on whether the duration of stimulation alters the success in assisted reproduction has not been conclusive. The purpose of the study was to establish whether the duration of ovarian stimulation alters the success in assisted reproduction treatments. All fresh (non-donor) stimulation cycles performed in an academic tertiary referral ART centre over a period of 18 years, between 1st January 1997 and 31st December 2014, were identified. Data were prospectively and electronically collected. IVF and ICSI cycles were analysed independently. Each category was then subdivided into assisted reproduction cycles where the antagonist, long (down regulation) and flare protocol were used. Clinical pregnancy was the main outcome measured. A total of 10,478 stimulation cycles (6011 fresh IVF and 4467 fresh ICSI) reaching egg collection were included. We showed no significant difference in CP rates in IVF cycles for the long (p = 0.082), antagonist (p = 0.217) or flare (p = 0.741) protocol cycles or in ICSI cycles with the long (p = 0.223), antagonist (p = 0.766) or the flare (p = 0.690) protocol with regards the duration of stimulation. The duration of stimulation does not alter the CP rate in ICSI or IVF cycles using the long, antagonist or flare stimulation protocol.

Overt leptin response to controlled ovarian hyperstimulation negatively correlates with pregnancy outcome in in vitro fertilization--embryo transfer cycle.

PubMed

Chakrabarti, Jana; Chatterjee, Ratna; Goswami, Sourendrakanta; Chakravarty, Baidyanath; Kabir, Syed Nazrul

2012-05-01

A critical body mass of adipose tissue is essential for the normal development of female reproductive functions. Leptin, an adipocyte-derived hormone encoded by the 'Ob' gene has been proposed as a peripheral signal indicating the adequacy of nutritional status for reproductive functions. It is reported as a direct regulator of gametogenic and steroidogenic potential of ovary. Though leptin is widely present in reproductive tissues, its relationship to reproductive hormones is still poorly understood. Present investigation attempts to explore ovarian response to secretory profile of leptin and its impact on pregnancy outcome in women undergoing controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer (IVF-ET). Patients enrolled for IVF-ET underwent pituitary-ovarian suppression by 'Long Protocol' GnRH-agonist downregulation followed by ovarian stimulation. Sera were procured at different phases of IVF-ET for the assay of estradiol, progesterone, human chorionic gonadotropin, and for leptin. Ovarian follicular fluids were also assayed for leptin. Luteinized granulosa cells were cultured in vitro to evaluate their steroidogenic potential. Statistical analyses were done by student's t-test, ANOVA, and Chi-square tests as applicable. All results were expressed as Mean ± SE. P values < 0.05 were considered significant. Positive correlation was observed between serum and ovarian follicular fluid leptin. A negative correlation was noted between the serum leptin levels and endometrial thickness. Elevated leptin response may exert adverse impacts on pregnancy success during IVF-ET possibly by modulating uterine receptivity.

Effects of female increased body mass index on in vitro fertilization cycles outcome.

PubMed

Caillon, Hélène; Fréour, Thomas; Bach-Ngohou, Kalyane; Colombel, Agnès; Denis, Marc G; Barrière, Paul; Masson, Damien

2015-01-01

As being overweight can impair female spontaneous fertility or after assisted reproductive technology (ART) cycles, the aim of this study was to compare in vitro fertilization (IVF) outcome according to women's body mass index (BMI). Retrospective study conducted from 2006 to 2009 in the IVF unit of Nantes University Hospital, France. 582 patients undergoing standard infertility workup and controlled ovarian stimulation were categorized according to BMI into two groups: group 1: normal weight (20-24.9 kg/m(2); n=409) and group 2: overweight and obese (≥25 kg/m(2); n=149). Basal hormonal status, smoking habitus, infertility duration, IVF cycle parameters and outcome were recorded. Basal LH, FSH and estradiol levels were higher in group 1 than group 2, but ovarian reserve markers were comparable across the two BMI groups. Higher doses of gonadotropins were required in group 2 to obtain equivalent ovarian response than in group 1. No difference was observed on ovarian response and embryonic parameters. Cycle outcome were not significantly different between both groups, but we found a strong trend towards increasing transfer cancellation and miscarriage rates in group 2. Although overweight and obesity do not compromise ovarian stimulation results whenever adaptation of recombinant FSH doses is made, our data suggest an increased risk of cancellation transfer and miscarriage rate, leading to poorer IVF outcome. Copyright © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Thicker endometrial linings are associated with better IVF outcomes: a cohort of 6331 women.

PubMed

Holden, Emily C; Dodge, Laura E; Sneeringer, Rita; Moragianni, Vasiliki A; Penzias, Alan S; Hacker, Michele R

2017-06-18

Our objective was to determine if a correlation exists between endometrial thickness measured on the day of ovulation trigger during an in vitro fertilization (IVF) cycle and pregnancy outcomes among non-cancelled cycles. We performed a retrospective cohort study looking at 6331 women undergoing their first, fresh autologous IVF cycle from 1 May 2004 to 31 December 2012 at Boston IVF (Waltham, MA). Our primary outcome was the risk ratio (RR) of live birth and positive β-hCG. We found that thicker endometrial linings were associated with positive β-hCG and live birth rates. For each additional millimetre of endometrial thickness, we found a statistically significant increased risk of positive β-hCG (adjusted RR: 1.14; 95% CI: 1.09-1.18) and live birth (RR: 1.08; 95% CI: 1.05-1.11). There was no association between endometrial thickness and miscarriage (RR: 0.99; 95% CI: 0.91-1.07). Similar results were seen when categorizing endometrial thickness. Compared with an endometrial thickness >7 to <11 mm, the likelihood of a live birth was significantly higher for an endometrial thickness ≥11 mm (adjusted RR: 1.23; 95% CI: 1.11-1.37) and significantly lower for the ≤7 mm group (adjusted RR: 0.64; 95% CI: 0.45-0.90). In conclusion, thicker endometrial linings were associated with increased pregnancy and live birth rates.

Minimising twins in in vitro fertilisation: a modelling study assessing the costs, consequences and cost-utility of elective single versus double embryo transfer over a 20-year time horizon.

PubMed

Scotland, G S; McLernon, D; Kurinczuk, J J; McNamee, P; Harrild, K; Lyall, H; Rajkhowa, M; Hamilton, M; Bhattacharya, S

2011-08-01

To assess the cumulative costs and consequences of double embryo transfer (DET) or elective single embryo transfer (eSET) in women commencing in vitro fertilisation (IVF) treatment aged 32, 36 and 39 years. Microsimulation model. Three assisted reproduction centres in Scotland. A total of 6153 women undergoing treatment at one of three Scottish IVF clinics, between January 1997 and June 2007. A microsimulation model, populated using data inputs derived from a large clinical data set and published literature, was developed to compare the costs and consequences of using eSET or DET over multiple treatment cycles. Disability-free live births; twin pregnancy rate; women's quality-adjusted life-years (QALYs); health service costs. Not only did DET produce a higher cumulative live birth rate compared with eSET for women of all three ages, but also a higher twin pregnancy rate. Compared with eSET, DET ranged from costing an additional £ 27,356 per extra live birth in women commencing treatment aged 32 years, to costing £ 15,539 per extra live birth in 39-year-old women. DET cost ∼ £ 28,300 and ∼ £ 20,300 per additional QALY in women commencing treatment aged 32 and 39 years, respectively. Considering the high twin pregnancy rate associated with DET, coupled with uncertainty surrounding QALY gains, eSET is likely to be the preferred option for most women aged ≤ 36 years. The cost-effectiveness of DET improves with age, and may be considered cost-effective in some groups of older women. The decision may best be considered on a case-by-case basis for women aged 37-39 years. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

Endometrial fluid associated with Essure implants placed before in vitro fertilization: Considerations for patient counseling and surgical management

PubMed Central

Walsh, David J; Jones, Christopher A; Wood, Samuel H

2015-01-01

Essure (Bayer) received approval from the U.S. Food and Drugs Administration as a permanent non-hormonal contraceptive implant in November 2002. While the use of Essure in the management of hydrosalpinx prior to in vitro fertilization (IVF) remains off-label, it has been used specifically for this purpose since at least 2007. Although most published reports on Essure placement before IVF have been reassuring, clinical experience remains limited, and no randomized studies have demonstrated the safety or efficacy of Essure in this context. In fact, no published guidelines deal with patient selection or counseling regarding the Essure procedure specifically in the context of IVF. Although Essure is an irreversible birth control option, some patients request the surgical removal of the implants for various reasons. While these patients could eventually undergo hysterectomy, at present no standardized technique exists for simple Essure removal with conservation of the uterus. This article emphasizes new aspects of the Essure procedure, as we describe the first known association between the placement of Essure implants and the subsequent development of fluid within the uterine cavity, which resolved after the surgical removal of both devices. PMID:26473113

Management of women with PCOS using myo-inositol and folic acid. New clinical data and review of the literature.

PubMed

Regidor, Pedro-Antonio; Schindler, Adolf Eduard; Lesoine, Bernd; Druckman, Rene

2018-03-02

Introduction The use of 2 × 2000 mg myo-inositol +2 × 200 μg folic acid per day is a safe and promising tool in the effective improvement of symptoms and infertility for patients with polycystic ovary syndrome (PCOS). In addition, PCOS is one of the pathological factors involved in the failure of in vitro fertilization (IVF). Typically, PCOS patients suffer of poor quality oocytes. Patients and methods In an open, prospective, non-blinded, non-comparative observational study, 3602 infertile women used myo-inositol and folic acid between 2 and 3 months in a dosage of 2 × 2000 mg myo-inositol +2 × 200 μg folic acid per day. In a subgroup of 32 patients, hormonal values for testosterone, free testosterone and progesterone were analyzed before and after 12 weeks of treatment. The mean time of use was 10.2 weeks. In the second part of this trial it was investigated if the combination of myo-inositol + folic acid was able to improve the oocyte quality, the ratio between follicles and retrieved oocytes, the fertilization rate and the embryo quality in PCOS patients undergoing IVF treatments. Twenty-nine patients with PCOS, underwent IVF protocols for infertility treatment and were randomized prospectively into two groups. Group A (placebo) with 15 patients and group B (4000 mg myo-inositol +400 μg folic acid per day) with 14 patients were evaluated. The patients of group B used 2 months' myo-inositol + folic acid before starting the IVF protocol. For statistically analyses Student's t-test was performed. Results Seventy percent of the women had a restored ovulation, and 545 pregnancies were observed. This means a pregnancy rate of 15.1% of all the myo-inositol and folic acid users. In 19 cases a concomitant medication with clomiphene or dexamethasone was used. One twin pregnancy was documented. Testosterone levels changed from 96.6 ng/mL to 43.3 ng/mL and progesterone from 2.1 ng/mL to 12.3 ng/mL in the mean after 12 weeks of treatment (p < 0.05) Student's t-test. No relevant side effects were present among the patients. The women in the IVF treatment the group A showed a higher number of retrieved oocytes than group B. Nevertheless, the ratio follicle/retrieved oocyte was clearly better in the myo-inositol group (= group B). Out of the 233 oocytes collected in the myo-inositol group, 136 where fertilized whereas only 128 out of 300 oocytes were fertilized in the placebo group. With regards to the oocytes quality, better data were obtained in the myo-inositol group. More metaphase II and I oocytes were retrieved in relation to the total number of oocytes, when compared with the placebo group. Also, more embryos of grade I quality were observed in the myo-inositol group than in the placebo group. The duration of stimulation was 9.7 days (±3.3) in the myo-inositol group and 11.2 (±1.8) days in the placebo group and the number of used follicle-stimulating hormone (FSH) units was lower in the myo-inositol group in comparison to the placebo group: 1850 FSH units (mean) versus 1850 units (mean). Discussion Myo-inositol has proven to be a new treatment option for patients with PCOS and infertility. The achieved pregnancy rates are at least in an equivalent or even superior range than those reported using metformin as an insulin sensitizer. No moderate to severe side effects were observed when myo-inositol was used at a dosage of 4000 mg per day. In addition, our evidence suggests that a myo-inositol therapy in women with PCOS results in better fertilization rates and a clear trend to a better embryo quality. As by the same way the number of retrieved oocytes was smaller in the myo-inositol group, the risk of a hyperstimulation syndrome in these patients can be reduced. Therefore, myo-inositol also represents an improvement in IVF protocols for patients with PCOS.

IVF versus ICSI for the fertilization of in-vitro matured human oocytes.

PubMed

Walls, M; Junk, S; Ryan, J P; Hart, R

2012-12-01

Traditional dogma suggests that intracytoplasmic sperm injection (ICSI) should be performed to ensure successful oocyte fertilization in an in-vitro maturation (IVM) cycle. This study postulated that there would be no difference in the fertilization rate when ICSI was compared with IVF. This hypothesis was tested in a randomized trial of IVF versus ICSI in IVM. A total of 150 immature oocytes were collected in eight cycles of IVM for patients diagnosed with polycystic ovarian syndrome (PCOS). Patients were primed with minimal FSH before transvaginal oocyte aspiration. Sibling oocytes were inseminated by 50% IVF and 50% ICSI. There was no significant difference in fertilization, useable or total blastocyst development between the two insemination technique groups. Clinical pregnancy results for combined fresh and cryopreserved transfers were identical between the two insemination techniques with a total of two fresh and five cryopreserved IVF-inseminated embryos resulting in three clinical pregnancies (42.9%) and five fresh and two cryopreserved ICSI-derived embryos resulting in three clinical pregnancies (42.9%). This research has shown IVF to be a legitimate fertilization technique for IVM oocytes in PCOS patients and provides a greater awareness of the use of a fertilization method previously not utilized with IVM. In-vitro maturation (IVM) is an alternative treatment method to traditional IVF. Due to the minimal use of stimulating hormones in this treatment, IVM has a lower risk of ovarian hyperstimulation syndrome, it can be used for fertility preservation in cancer patients and it is more cost conservative. Early research into the effects of IVM showed a hardening effect on the membrane surrounding the egg (the zona pellucida). It was initially believed that, to overcome this hardening in order to allow the egg to be fertilized, spermatozoa would need to be injected into the egg using intracytoplasmic sperm injection. Due to recent advances in hormonal stimulation protocols (FSH priming) and culture conditions, we postulated that, for patients suffering from polycystic ovarian syndrome (PCOS), fertilization, embryo development and clinical pregnancy would not be superior in the injected oocytes compared with those inseminated by IVF. We found that by using the two insemination techniques on sibling oocytes from eight PCOS patients, there was no significant difference in fertilization, useable or total blastocyst development (day 5 or 6 embryos) and that clinical pregnancy results were identical. This research provides a greater awareness of a fertilization technique which is not normally utilized for IVM treatment, providing a less invasive, more cost-effective approach for the patient. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

In vitro fertilization in women under 35: counseling should differ by age.

PubMed

Humm, K C; Dodge, L E; Wu, L H; Penzias, A S; Malizia, B A; Sakkas, D; Hacker, M R

2015-10-01

The aim of this study is to evaluate the outcomes of in vitro fertilization (IVF), including cumulative live birth rate, among women <25 years, 25 to <30 years, and 30 to <35 years. A retrospective cohort study of all women 18 to <35 years of age at their first fresh-embryo, non-donor IVF cycle from January 1995 through December 2012 at a single center was conducted. A competing-risk regression model was used to estimate the cumulative probability and 95 % confidence interval (CI) of the first live birth in up to 6 cycles during the study period with IVF cycle number as the time metric. Among 7243 women who underwent 16,792 cycles, there were 163 (2.3 %) women <25 years, 1691 (23.3 %) women 25 to <30 years, and 5389 (74.4 %) women 30 to <35 years. Women <25 years had the lowest cumulative live birth rate after each cycle, followed by women 30 to <35 years. In both groups, the cumulative live birth rate after 6 cycles was significantly lower than that of women 25 to <30 years; these rates were 58 % (95 % CI 0.51-0.66) among women <25 years, 69 % (95 % CI 0.67-0.71) among women 25 to <30 years, and 64 % (95 % CI 0.63-0.65) among women 30 to <35 years. Our findings are consistent with other reports of less favorable IVF treatment outcomes in women <25 years of age following their first IVF cycle. This indicates that there are underlying factors in couples with a female <25 years of age that should lead to different treatment counseling when they attempt IVF.

A Focus on Maternal Health Before Assisted Reproduction: Results From a Pilot Survey of Canadian IVF Medical Directors.

PubMed

Dayan, Natalie; Spitzer, Karen; Laskin, Carl A

2015-07-01

To describe current physician practice patterns in Canada with regard to performing in vitro fertilization in high-risk patients. All medical directors of IVF clinics registered with the Canadian Fertility and Andrology Society (n=35) were invited to participate in an online survey between January and May 2014. We carried out descriptive analyses of participants' responses regarding implementation of local restrictive policies for access to IVF. Whether practice patterns differed in hospital versus community-based clinics was assessed using chi-square testing with significance set at alpha<0.05. The response rate was 77.1%. More than one half of clinics (55.6%) were university-affiliated, and 29.6% were hospital-based. The majority of respondents (70.4%) used an upper age limit for permitting IVF (median 50 years, IQR 44 to 50), mostly because of lower pregnancy and live birth rates. Approximately one half of respondents limited treatment according to BMI (median upper permitted BMI 38 kg/m2, IQR 35 to 40 kg/m2) to minimize complications during pregnancy. Most respondents (77.8%) believed that routine pre-IVF medical assessment would be useful in their daily practice. There was a non-significant trend towards more restrictive policies in hospital-based clinics compared with community-based clinics. Our findings confirm that Canadian reproductive medicine physicians are taking maternal health factors into consideration when assessing patients' suitability for IVF. Nevertheless, there is between-clinic variability in the parameters used to assess eligibility for treatment. In light of the changing maternal demographic, more research is needed on assisted reproductive technology and perinatal outcomes in women who are at risk for pregnancy complications.

The effect of cigarette smoking, alcohol consumption and fruit and vegetable consumption on IVF outcomes: a review and presentation of original data.

PubMed

Firns, Sarah; Cruzat, Vinicius Fernandes; Keane, Kevin Noel; Joesbury, Karen A; Lee, Andy H; Newsholme, Philip; Yovich, John L

2015-12-16

Lifestyle factors including cigarette smoking, alcohol consumption and nutritional habits impact on health, wellness, and the risk of chronic diseases. In the areas of in-vitro fertilization (IVF) and pregnancy, lifestyle factors influence oocyte production, fertilization rates, pregnancy and pregnancy loss, while chronic, low-grade oxidative stress may underlie poor outcomes for some IVF cases. Here, we review the current literature and present some original, previously unpublished data, obtained from couples attending the PIVET Medical Centre in Western Australia. During the study, 80 % of females and 70 % of male partners completed a 1-week diary documenting their smoking, alcohol and fruit and vegetable intake. The subsequent clinical outcomes of their IVF treatment such as quantity of oocytes collected, fertilization rates, pregnancy and pregnancy loss were submitted to multiple regression analysis, in order to investigate the relationship between patients, treatment and the recorded lifestyle factors. Of significance, it was found that male smoking caused an increased risk of pregnancy loss (p = 0.029), while female smoking caused an adverse effect on ovarian reserve. Both alcohol consumption (β = 0.074, p < 0.001) and fruit and vegetable consumption (β = 0.034, p < 0.001) had positive effects on fertilization. Based on our results and the current literature, there is an important impact of lifestyle factors on IVF clinical outcomes. Currently, there are conflicting results regarding other lifestyle factors such as nutritional habits and alcohol consumption, but it is apparent that chronic oxidative stress induced by lifestyle factors and poor nutritional habits associate with a lower rate of IVF success.

Predicting Implantation Outcome of In Vitro Fertilization and Intracytoplasmic Sperm Injection Using Data Mining Techniques.

PubMed

Hafiz, Pegah; Nematollahi, Mohtaram; Boostani, Reza; Namavar Jahromi, Bahia

2017-10-01

In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are two important subsets of the assisted reproductive techniques, used for the treatment of infertility. Predicting implantation outcome of IVF/ICSI or the chance of pregnancy is essential for infertile couples, since these treatments are complex and expensive with a low probability of conception. In this cross-sectional study, the data of 486 patients were collected using census method. The IVF/ICSI dataset contains 29 variables along with an identifier for each patient that is either negative or positive. Mean accuracy and mean area under the receiver operating characteristic (ROC) curve are calculated for the classifiers. Sensitivity, specificity, positive and negative predictive values, and likelihood ratios of classifiers are employed as indicators of performance. The state-of-art classifiers which are candidates for this study include support vector machines, recursive partitioning (RPART), random forest (RF), adaptive boosting, and one-nearest neighbor. RF and RPART outperform the other comparable methods. The results revealed the areas under the ROC curve (AUC) as 84.23 and 82.05%, respectively. The importance of IVF/ICSI features was extracted from the output of RPART. Our findings demonstrate that the probability of pregnancy is low for women aged above 38. Classifiers RF and RPART are better at predicting IVF/ICSI cases compared to other decision makers that were tested in our study. Elicited decision rules of RPART determine useful predictive features of IVF/ICSI. Out of 20 factors, the age of woman, number of developed embryos, and serum estradiol level on the day of human chorionic gonadotropin administration are the three best features for such prediction. Copyright© by Royan Institute. All rights reserved.

An ICSI rate of 90% minimizes complete failed fertilization and provides satisfactory implantation rates without elevating fetal abnormalities.

PubMed

Yovich, John L; Conceicao, Jason L; Marjanovich, Nicole; Ye, Yun; Hinchliffe, Peter M; Dhaliwal, Satvinder S; Keane, Kevin N

2018-05-22

IVF cycles utilizing the ICSI technique for fertilization have been rising over the 25 years since its introduction, with indications now extending beyond male factor infertility. We have performed ICSI for 87% of cases compared with the ANZARD average of 67%. This retrospective study reports on the outcomes of 1547 autologous ART treatments undertaken over a recent 3-year period. Based on various indications, cases were managed within 3 groupings - IVF Only, ICSI Only or IVF-ICSI Split insemination where oocytes were randomly allocated. Overall 567 pregnancies arose from mostly single embryo transfer procedures up to December 2016, with 402 live births, comprising 415 infants and a low fetal abnormality rate (1.9%) was recorded. When the data was adjusted for confounders such as maternal age, measures of ovarian reserve and sperm quality, it appeared that IVF-generated and ICSI-generated embryos had a similar chance of both pregnancy and live birth. In the IVF-ICSI Split model, significantly more ICSI-generated embryos were utilised (2.5 vs 1.8; p < 0.003) with productivity rates of 67.8% for pregnancy and 43.4% for livebirths per OPU for this group. We conclude that ART clinics should apply the insemination method which will maximize embryo numbers and the first treatment for unexplained infertility should be undertaken within the IVF-ICSI Split model. Whilst ICSI-generated pregnancies are reported to have a higher rate of fetal abnormalities, our data is consistent with the view that the finding is not due to the ICSI technique per se. Copyright © 2018 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.

Enough is enough! Patients who do not conceive on 600IU/day of gonadotropins show no improvement from an additional 150IU of LH activity

PubMed Central

Maguire, Marcy; Csokmay, John; Segars, James; Payson, Mark; Armstrong, Alicia

2010-01-01

Studies have suggested that supplemental LH improves outcomes in ART cycles. In this retrospective review, an additional 150IU of LH activity did not improve ART outcomes in women undergoing a second round of IVF/ICSI following an initial failed cycle employing 600IU of gonadotropins. PMID:20850732

Extremities of body mass index and their association with pregnancy outcomes in women undergoing in vitro fertilization in the United States.

PubMed

Kawwass, Jennifer F; Kulkarni, Aniket D; Hipp, Heather S; Crawford, Sara; Kissin, Dmitry M; Jamieson, Denise J

2016-12-01

To investigate the associations among underweight body mass index (BMI), pregnancy, and obstetric outcomes among women using assisted reproductive technology (ART). Retrospective cohort study using national data and log binomial regression. Not applicable. Women undergoing IVF in the United States from 2008 to 2013. None. Pregnancy outcomes (intrauterine pregnancy, live birth rates) per transfer, miscarriage rate per pregnancy, and low birth weight and preterm delivery rates among singleton and twin pregnancies. For all fresh autologous in vitro fertilization (IVF) cycles in the United States from 2008 to 2013 (n = 494,097 cycles, n = 402,742 transfers, n = 180,855 pregnancies) reported to the national ART Surveillance System, compared with normal weight women, underweight women had a statistically significant decreased chance of intrauterine pregnancy (adjusted risk ratio [aRR] 0.97; 95% confidence interval [CI], 0.96-0.99) and live birth (aRR 0.95; 95% CI, 0.93-0.98) per transfer. Obese women also had a statistically decreased likelihood of both (aRR 0.94; 95% CI, 0.94-0.95; aRR 0.87; 95% CI, 0.86-0.88, respectively). Among cycles resulting in singleton pregnancy, both underweight and obese statuses were associated with increased risk of low birth weight (aRR 1.39; 95% CI, 1.25-1.54, aRR 1.26; 95% CI, 1.20-1.33, respectively) and preterm delivery (aRR 1.12; 95% CI, 1.01-1.23, aRR 1.42; 95% CI, 1.36-1.48, respectively). The association between underweight status and miscarriage was not statistically significant (aRR 1.04; 95% CI, 0.98-1.11). In contrast, obesity was associated with a statistically significantly increased miscarriage risk (aRR 1.23; 95% CI, 1.20-1.26). Among women undergoing IVF, prepregnancy BMI affects pregnancy and obstetric outcomes. Underweight status may have a limited impact on pregnancy and live-birth rates, but it is associated with increased preterm and low-birth-weight delivery risk. Obesity negatively impacts all ART and obstetric outcomes investigated. Copyright © 2016 American Society for Reproductive Medicine. All rights reserved.

The periconception maternal cardiovascular risk profile influences human embryonic growth trajectories in IVF/ICSI pregnancies.

PubMed

Wijnands, K P J; van Uitert, E M; Roeters van Lennep, J E; Koning, A H J; Mulders, A G M G J; Laven, J S E; Steegers, E A P; Steegers-Theunissen, R P M

2016-06-01

Is the maternal cardiovascular (CV) risk profile associated with human embryonic growth trajectories and does the mode of conception affect this association? This small study suggests that the maternal CV risk profile is inversely associated with first trimester embryonic growth trajectories in in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) pregnancies, but not in spontaneously conceived pregnancies. Maternal high-blood pressure and smoking affect placental function, accompanied by increased risk of fetal growth restriction and low-birthweight. Mothers who experience pregnancies complicated by fetal growth restriction are at increased risk of CV disease in later life. In a prospective periconception birth cohort conducted in a tertiary hospital, 111 singleton ongoing pregnancies with reliable pregnancy dating, no pre-existing maternal disease and no malformed live borns were investigated. Spontaneously conceived pregnancies with a reliable first day of the last menstrual period and a regular menstrual cycle of 25-31 days only (n = 66) and IVF/ICSI pregnancies (n = 45) were included. Women underwent weekly three-dimensional ultrasound scans (3D US) from 6- to 13-week gestational age. To estimate embryonic growth, serial crown-rump length (CRL) measurements were performed using the V-Scope software in a BARCO I-Space. Maternal characteristics and CV risk factors were collected by self-administered questionnaires. The CV risk profile was created based on a score of risk factors, including maternal age, body-mass index, CV disease in the family, diet and smoking. Quartiles of the CV risk score were calculated. Associations between the CV risk score and embryonic growth were assessed using square root transformed CRL in multivariable linear mixed model analyses. From the 111 included pregnancies, 696 3D US data sets were obtained of which 637 (91.5%) CRLs could be measured. In the total group, The CV risk score was inversely, but not significantly associated with embryonic growth (-0.03√mm; P = 0.291). Stratified by mode of conception, the CV risk score was inversely and significantly associated with embryonic growth (β = -0.04√mm; P = 0.025, adjusted for possible confounders) in the IVF/ICSI group. Compared with the first quartile, embryos in the upper quartile were 10.4% smaller at 6(+0) weeks (4.4 versus 4.9 mm) and 3.1% smaller at 12(+0) weeks (56.5 versus 58.4 mm) of gestation. Although the CV risk score was slightly, but significantly, higher in women conceiving spontaneously compared with those undergoing IVF/ICSI treatment [CV risk score = 2.06 (SD: 1.23) and 1.60 (SD: 1.15), respectively], no association was established with embryonic growth in that particular group. Participants included in the present cohort are women with a singleton ongoing pregnancy without any pre-existing disease and selected from a tertiary hospital. Hence, they represent a selected group of women. Larger and population-based periconception birth cohort studies are recommended to demonstrate external validity. Differences in embryonic growth between pregnancies conceived spontaneously and after IVF/ICSI treatment in relation with CV risk factors substantiate the importance of more investigation into differences in sensitivity of endometrial, endothelial, placental and embryonic tissues. Funded by the Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands. The authors declare no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Reproductive potential of mature oocytes after conventional ovarian hyperstimulation for in vitro fertilization.

PubMed

Zhang, John J; Yang, Mingxue; Merhi, Zaher

2016-05-01

To compare cumulative live birth rate according to the rate of use of metaphase II (MII) oocytes in conventional ovarian stimulation protocols for in vitro fertilization (IVF) or intracytoplasmic sperm injection. In a cohort study, patients aged 18-38 years undergoing their first IVF treatment at one US center were enrolled between February 1, 2009, and August 31, 2013. Ovarian response was categorized by the yield of MII oocytes (low: 1-2; intermediate: 3-6; high: ≥7). The main outcome measure was cumulative live birth rate over a 6-month period. Among 250 participants, 3240 oocytes (mean±SEM 12.96±0.50) were retrieved and there were 152 (60.8%) live births. Overall, 172 (68.8%) participants had a high oocyte yield, 61 (24.4%) an intermediate yield, and 17 (6.8%) a low yield. The cumulative live birth rate was 58.8% (10/17) in the low-yield group, 55.7% (34/61) in the intermediate-yield group, and 62.8% (108/172) in the high-yield group (P=0.35). In conventional ovarian stimulation, live birth rate is not affected by the ovarian response. Whether oocytes produced from a low ovarian response are biologically more effective than oocytes obtained from a high ovarian response remains to be determined. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Should obese women's access to assisted fertility treatment be limited? A scientific and ethical analysis.

PubMed

Tremellen, Kelton; Wilkinson, Dominic; Savulescu, Julian

2017-10-01

Obesity is associated with a reduction in fertility treatment success and increased risks to mother and child. Therefore guidelines of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) suggest that a body mass index exceeding 35 kg/m 2 should be an absolute contraindication to assisted fertility treatment such as in vitro fertilisation IVF. In this paper we challenge the ethical and scientific basis for such a ban. Livebirth rates for severely obese women are reduced by up to 30%, but this result is still far better than that observed for many older women who are allowed access to IVF. This prohibition is particularly unjust when IVF is the only treatment capable of producing a pregnancy, such as bilateral tubal blockage or severe male factor infertility. Furthermore, the absolute magnitude of risks to mother or child is relatively small, and while a woman has a right to be educated about these risks, she alone should be allowed to make a decision on proceeding with treatment. We do not prohibit adults from engaging in dangerous sports, nor do we force parents to vaccinate their children, despite the risks. Similarly, we should not prohibit obese women from becoming parents because of increased risk to themselves or their child. Finally, prohibiting obese women's access to IVF to prevent potential harms such as 'fetal programing' is questionable, especially when compared to that child never being born at all. As such, we believe the RANZCOG ban on severely obese women's access to assisted reproductive treatment is unwarranted and should be revised. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Fertility in Women of Reproductive Age After Breast Cancer Treatment: Practice Patterns and Outcomes.

PubMed

McCray, Devina K S; Simpson, Ashley B; Flyckt, Rebecca; Liu, Yitian; O'Rourke, Colin; Crowe, Joseph P; Grobmyer, Stephen R; Moore, Halle C; Valente, Stephanie A

2016-10-01

Breast cancer is the most frequently occurring cancer in women of reproductive age, and systemic treatments may adversely affect childbearing plans. Use of assisted reproductive technologies and therapies for ovarian protection improve fertility prospects. We evaluated whether patients had a documented fertility discussion (FD) with their oncology physician prior to therapy, what options were chosen, and if pregnancy was achieved. A retrospective chart review from 2006 to 2014 was performed to evaluate women aged 40 years and younger who were diagnosed with breast cancer and treated with chemotherapy and/or antihormonal therapy. Patient demographics, treatment regimens, presence or absence of FD, in vitro fertilization (IVF) consultation, gonadotropin-releasing hormone (GnRH) agonist use, and subsequent successful pregnancy were analyzed. Among 303 patients meeting the inclusion criteria, 80 (26 %) had an FD with their physician documented; 71 of these 80 women (89 %) sought further fertility consultation and options. Sixteen (20 %) women were prescribed a GnRH agonist only for ovarian protection during chemotherapy, 50 (63 %) underwent IVF consultation only, and 5 (6 %) had both a GnRH agonist prescribed and an IVF consultation. The overall pregnancy rate was 7 % at a mean of 3 years post breast cancer treatment. Pregnancy after treatment was more common among those pursuing IVF consultation or prescribed a GnRH agonist. In treating young breast cancer patients, it is important to assess fertility desire, discuss treatment risks relating to fertility, and discuss preservation options. Although not every woman in this group desired pregnancy, 71/80 (89 %) women having a documented FD sought further fertility consultation and options.

Laparoscopic ovarian cystectomy of endometriomas does not affect the ovarian response to gonadotropin stimulation.

PubMed

Marconi, Guillermo; Vilela, Martín; Quintana, Ramiro; Sueldo, Carlos

2002-10-01

To evaluate the ovarian response cycles of IVF-ET in patients who previously underwent laparoscopic cystectomy for endometriomas. Retrospective study with prospective selection of participants and controls. Instituto de Ginecología y Fertilidad Buenos Aires, Argentina. Thirty-nine patients underwent an operation for ovarian endometriomas by atraumatic removal of the pseudocapsule with minimal bipolar cauterization of small bleeders and an IVF-ET cycle (group A) and 39 control patients of similar age underwent an IVF-ET cycle for tubal factor infertility (group B). Laparoscopic endometrioma cystectomy, IVF-ET cycle. E(2) levels, number of gonadotropin ampoules, follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate. There were no differences in all the parameters studied (E(2) levels, number of follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate) except for the number of gonadotropin ampoules needed for ovarian hyperstimulation, which was significantly higher in group A than in group B. Our results indicate that laparoscopic cystectomy for endometriomas is an appropriate treatment since it did not negatively affect the ovarian response for IVF-ET.

Failure mode and effects analysis of witnessing protocols for ensuring traceability during IVF.

PubMed

Rienzi, Laura; Bariani, Fiorenza; Dalla Zorza, Michela; Romano, Stefania; Scarica, Catello; Maggiulli, Roberta; Nanni Costa, Alessandro; Ubaldi, Filippo Maria

2015-10-01

Traceability of cells during IVF is a fundamental aspect of treatment, and involves witnessing protocols. Failure mode and effects analysis (FMEA) is a method of identifying real or potential breakdowns in processes, and allows strategies to mitigate risks to be developed. To examine the risks associated with witnessing protocols, an FMEA was carried out in a busy IVF centre, before and after implementation of an electronic witnessing system (EWS). A multidisciplinary team was formed and moderated by human factors specialists. Possible causes of failures, and their potential effects, were identified and risk priority number (RPN) for each failure calculated. A second FMEA analysis was carried out after implementation of an EWS. The IVF team identified seven main process phases, 19 associated process steps and 32 possible failure modes. The highest RPN was 30, confirming the relatively low risk that mismatches may occur in IVF when a manual witnessing system is used. The introduction of the EWS allowed a reduction in the moderate-risk failure mode by two-thirds (highest RPN = 10). In our experience, FMEA is effective in supporting multidisciplinary IVF groups to understand the witnessing process, identifying critical steps and planning changes in practice to enable safety to be enhanced. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

[Effects of a yoga-focused prenatal program on stress, anxiety, self confidence and labor pain in pregnant women with in vitro fertilization treatment].

PubMed

Shim, Chung Sin; Lee, Young-Sook

2012-06-01

The purpose of this study was to identify the effects of a Yoga-focused prenatal program on the stress, anxiety, self confidence and labor pain of pregnant women who had in vitro fertilization (IVF) treatment. A quasi experimental study with a non-equivalent control group pretest-posttest design was used. The data collection period and meditation program were between January 9 and August 31, 2009. Forty-six women who were pregnant following IVF, and were between 12-20 weeks gestation, participated in the study (23 experimental group, 23 control group). Data were analyzed using Chi-square test, Mann-Whitney U Test, ANCOVA, and Cronbach's alpha coefficients with the SPSS 12.0 for Windows Program. Although the sample size was limited, women who participated in the program showed statistically significant improvements in stress, anxiety, labor pain, and labor confidence for women pregnant after IVF. The result indicate that this 12-week Yoga-focused educational program can be utilized for women pregnant following IVF to reduce their stress, anxiety, and labor pain, and to increase delivery confidence. It is suggested that the Yoga-focused educational program be offered to every pregnant woman.

A practical blueprint to systematically study life-long health consequences of novel medically assisted reproductive treatments

PubMed Central

Mulder, Callista L; Serrano, Joana B; Catsburg, Lisa A E; Roseboom, Tessa J; Repping, Sjoerd; van Pelt, Ans M M

2018-01-01

Abstract In medicine, safety and efficacy are the two pillars on which the implementation of novel treatments rest. To protect the patient from unnecessary or unsafe treatments, usually, a stringent path of (pre) clinical testing is followed before a treatment is introduced into routine patient care. However, in reproductive medicine several techniques have been clinically introduced without elaborate preclinical studies. Moreover, novel reproductive techniques may harbor safety risks not only for the patients undergoing treatment, but also for the offspring conceived through these techniques. If preclinical (animal) studies were performed, efficacy and functionality the upper hand. When a new medically assisted reproduction (MAR) treatment was proven effective (i.e. if it resulted in live birth) the treatment was often rapidly implemented in the clinic. For IVF, the first study on the long-term health of IVF children was published a decade after its clinical implementation. In more recent years, prospective follow-up studies have been conducted that provided the opportunity to study the health of large groups of children derived from different reproductive techniques. Although such studies have indicated differences between children conceived through MAR and children conceived naturally, results are often difficult to interpret due to the observational nature of these studies (and the associated risk of confounding factors, e.g. subfertility of the parents), differences in definitions of clinical outcome measures, lack of uniformity in assessment protocols and heterogeneity of the underlying reasons for fertility treatment. With more novel MARs waiting at the horizon, there is a need for a framework on how to assess safety of novel reproductive techniques in a preclinical (animal) setting before they are clinically implemented. In this article, we provide a blueprint for preclinical testing of safety and health of offspring generated by novel MARs using a mouse model involving an array of tests that comprise the entire lifespan. We urge scientists to perform the proposed extensive preclinical tests for novel reproductive techniques with the goal to acquire knowledge on efficacy and the possible health effects of to-be implemented reproductive techniques to safeguard quality of novel MARs. PMID:29635479

Add-ons in IVF programme – Hype or Hope?

PubMed Central

Datta, AK; Campbell, S; Deval, B; Nargund, G

2015-01-01

A series of new technologies and adjuvant therapies have been advocated in order to improve the success of IVF treatment. Dehydro-epiandrostenedione, growth hormones, Coenzyme Q 10, calcium ionosphores, immune therapy, heparin, low-dose aspirin, and vasodilators are among commonly prescribed pharmacological adjuvants. New technologies that are proposed to improve IVF outcomes include advanced sperm selection procedures, time- lapse embryo monitoring, preimplantation genetic screening, assisted hatching endometrial injury or embryo-glue. This review looked into current evidence to justify the use of these co-interventions and whether some of them can still be offered while awaiting more robust evidence to con rm or refute their role. PMID:27729969

Surrogate pregnancy in a patient who underwent radical hysterectomy and bilateral transposition of ovaries.

PubMed

Azem, Foad; Yovel, Israel; Wagman, Israel; Kapostiansky, Rita; Lessing, Joseph B; Amit, Ami

2003-05-01

To evaluate IVF-surrogate pregnancy in a patient with ovarian transposition after radical hysterectomy for carcinoma of the cervix. Case report. A maternity hospital in Tel Aviv that is a major tertiary care and referral center. A 29-year-old woman who underwent Wertheim's hysterectomy for carcinoma of the uterine cervix and ovarian transposition before total pelvic irradiation. Standard IVF treatment, transabdominal oocyte retrieval, and transfer to surrogate mother. Outcome of IVF cycle. A twin pregnancy in the first cycle. This is the second reported case of controlled ovarian stimulation and oocyte retrieval performed on a transposed ovary.

Association between induced abortion history and later in vitro fertilization outcomes.

PubMed

Wang, Yao; Sun, Yun; Di, Wen; Kuang, Yan-Ping; Xu, Bing

2018-06-01

To establish an effective and safe clinical fertility strategy by investigating the relationship between abortion history and pregnancy outcomes of in vitro fertilization (IVF) treatment. In the present retrospective cohort study, data from IVF treatment cycles performed at a reproductive center in China between October 1, 2014, and October 31, 2015, were assessed. Outcomes were compared between women with a history of induced abortion and those without. There were 1532 IVF treatment cycles included; 454 patients had a history of induced abortion and 1078 did not. The spontaneous abortion rate was significantly higher (30/170 [17.6%] vs 41/420 [9.8%]; P=0.002) and the endometrium was significantly thinner (8.8 ± 1.8 vs 9.7 ± 1.8 cm; P=0.001) among patients with a history of induced abortion compared with those without. In a subgroup analysis of patients with a history of induced abortion, women who had undergone surgical abortions had a lower live delivery rate compared with medical abortions (29/76 [38%] vs 101/378 [27%]; P=0.039). Further, women who had a history of more than two surgical abortions had lower live delivery and clinical pregnancy rates (both P<0.05). A history of induced abortion was associated with worse IVF outcomes, especially a history of more than two surgical abortions. © 2018 International Federation of Gynecology and Obstetrics.

[Health economic consequences of the choice of follicle stimulating hormone alternatives in IVF treatment].

PubMed

Poulsen, Peter Bo; Højgaard, Astrid; Quartarolo, Jens Piero

2007-04-02

There is a choice between two types of hormones for stimulation of the follicles in IVF treatment - recombinant FSH and the urine-derived menotrophin. A literature review by NICE (2004) in the United Kingdom documented that the two types of hormones were equally effective and safe, which is why it was recommended to use the cheaper urine-derived hormone. Based on the EISG study (European and Israeli Study Group), the aim was to analyse the health economic consequences of the choice between the two types of hormone in IVF treatment in Denmark. In a prospective cost-effectiveness analysis (health care sector perspective), menotrophin and recombinant FSH (Gonal-F) were compared. Differences in costs were compared with differences in effects of the two alternatives. The total costs for the average patient are lower when using menotrophin compared with recombinant FSH. Furthermore, the cost per clinical pregnancy was lower with menotrophin compared with recombinant FSH hormone. Menotrophin is therefore less expensive both for the patient as well as for the health care sector. The use of menotrophin instead of recombinant FSH can result in savings of up to DKK 16 million on the drug budget--savings that could finance 1,400 additional IVF cycles. The analysis shows that urine-derived menotrophin is a cost-effective alternative to recombinant FSH with a potential for considerable savings for patients as well as the public drug budget.

High-risk of preterm birth and low birth weight after oocyte donation IVF: analysis of 133,785 live births.

PubMed

Kamath, Mohan Shashikant; Antonisamy, Belavendra; Mascarenhas, Mariano; Sunkara, Sesh Kamal

2017-09-01

A higher risk of pregnancy complications occurs after assisted reproductive techniques compared with spontaneously conceived pregnancies. This is attributed to the underlying infertility and assisted reproduction technique procedures involved during treatment. It is a matter of interest whether use of donor oocytes affects perinatal outcomes compared with pregnancies after autologous IVF. Anonymized data were obtained from the Human Fertilization and Embryology Authority. The analysis included 5929 oocyte donation and 127,856 autologous IVF live births. Data from all women who underwent donor oocyte recipient or autologous IVF cycles, both followed with fresh embryo transfer, were analysed to compare perinatal outcomes of preterm birth (PTB) and low birthweight (LBW) after singleton and multiple live births. The risk of adverse perinatal outcomes after oocyte donation was increased: adjusted OR (aOR) 1.56, 99.5% CI 1.34 to 1.80 for PTB and aOR 1.43, 99.5% CI 1.24 to 1.66 for LBW were significantly higher after oocyte donation compared with autologous IVF singletons. The adjusted odds PTB (aOR 1.21, 99.5% CI 1.02 to 1.43) was significantly higher after oocyte donation compared with autologous IVF multiple births. Analysis of this large dataset suggests significantly higher risk of PTB and LBW after ooctye donation compared with autologous IVF pregnancies. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Spontaneous abortion in IVF couples--a role of male welding exposure.

PubMed

Hjollund, N H; Bonde, J P; Ernst, E; Lindenberg, S; Andersen, A N; Olsen, J

2005-07-01

Fume from welding of stainless steel contains hexavalent chromium, which in animal studies can induce paternally mediated spontaneous abortion. Human studies have shown conflicting results. The best studies include early pregnancy experience, but these are expensive to conduct. In vitro fertilization (IVF) provides new design opportunities. Our aim was to study pregnancy survival in IVF treated women with respect to paternal welding exposure. We mailed a questionnaire to 5879 couples from the Danish IVF register that covers all IVF treatments after 1993 (response ratio 68.2%). A subgroup of male metal workers received a second questionnaire on exposure to welding (n = 319 men, response ratio 77%). Information on outcome was collected from national health registers. Survival of the first hCG-positive pregnancy was analysed using Cox regression. The proportion of pregnancies terminated by spontaneous abortion before 28 gestational weeks was 18% (n = 91 pregnancies) and 25% (n = 128) in pregnancies with paternal exposure to stainless steel welding and mild steel welding, respectively. In the reference group of 2925 pregnancies the abortion ratio was 28%. The risk ratio for pregnancies with paternal exposure to stainless steel was 0.6 (95% CI 0.4-1.0). We found no increased risk of spontaneous abortion in IVF treated women, who became pregnant by a man exposed to welding of any sort. Since the process of fertilization and selection of IVF pregnancies differs from natural pregnancies the negative results need not apply to other pregnancies.

[Management by assisted reproductive technology in women with endometriosis: CNGOF-HAS Endometriosis Guidelines].

PubMed

Chauffour, C; Pouly, J-L; Gremeau, A-S

2018-03-01

Should the presence of endometriosis change the management of assisted reproductive technology? There is no difference in pregnancy rate after IVF between an agonist or antagonist protocol in patients with endometriosis, so the choice between one or the other of these protocols is free. But the review of the literature has shown an improvement in the chances of pregnancy in case of prolonged ovulation suppression before stimulation for IVF with a GnRH agonist analogue or with oral contraception, especially in cases of severe endometriosis. Endometriosis, regardless of the stage and type of lesions, would have no effect on the IVF results in terms of pregnancy rate and live birth rate, but with a lower number of oocytes collected, especially in cases of severe endometriosis. In a context of superficial endometriosis without pain and of infertility, surgical treatment of superficial endometriosis is not recommended just to increase the chances of pregnancy in IVF. Surgery may have a place in case of failure of IVF to improve the results of the ART. In case of recurrence of endometriosis, surgery is not better than IVF, a medico-surgical concertation is recommended. In addition, studies on ovulation stimulation for IVF do not show any aggravation of the symptoms associated with endometriosis lesions, or an acceleration of its progression, or an increase in the rate of recurrence of the disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Is ovarian hyperstimulation associated with higher blood pressure in 4-year-old IVF offspring? Part I: multivariable regression analysis.

PubMed

Seggers, Jorien; Haadsma, Maaike L; La Bastide-Van Gemert, Sacha; Heineman, Maas Jan; Middelburg, Karin J; Roseboom, Tessa J; Schendelaar, Pamela; Van den Heuvel, Edwin R; Hadders-Algra, Mijna

2014-03-01

Does ovarian hyperstimulation, the in vitro procedure, or a combination of these two negatively influence blood pressure (BP) and anthropometrics of 4-year-old children born following IVF? Higher systolic blood pressure (SBP) percentiles were found in 4-year-old children born following conventional IVF with ovarian hyperstimulation compared with children born following IVF without ovarian hyperstimulation. Increasing evidence suggests that IVF, which has an increased incidence of preterm birth and low birthweight, is associated with higher BP and altered body fat distribution in offspring but the underlying mechanisms are largely unknown. We performed a prospective, assessor-blinded follow-up study in which 194 children were assessed. The attrition rate up until the 4-year-old assessment was 10%. We measured BP and anthropometrics of 4-year-old singletons born following conventional IVF with controlled ovarian hyperstimulation (COH-IVF, n = 63), or born following modified natural cycle IV (MNC-IVF, n = 52), or born to subfertile couples who conceived naturally (Sub-NC, n = 79). Both IVF and ICSI were performed. Primary outcome measures were the SBP percentiles and diastolic BP (DBP) percentiles. Anthropometric measures included triceps and subscapular skinfold thickness. Several multivariable regression analyses were applied in order to correct for subsets of confounders. The value 'B' is the unstandardized regression coefficient. SBP percentiles were significantly lower in the MNC-IVF group (mean 59, SD 24) than in the COH-IVF (mean 68, SD 22) and Sub-NC groups (mean 70, SD 16). The difference in SBP between COH-IVF and MNC-IVF remained significant after correction for current, early life and parental characteristics (B: 14.09; 95% confidence interval (CI): 5.39-22.79), whereas the difference between MNC-IVF and Sub-NC did not. DBP percentiles did not differ between groups. After correction for early life factors, subscapular skinfold thickness was thicker in the COH-IVF group than in the Sub-NC group (B: 0.28; 95% CI: 0.03-0.53). Larger study groups are necessary to draw firm conclusions. An effect of gender or ICSI could not be properly investigated as stratifying would further reduce the sample size. We corrected for the known differences between MNC-IVF and COH-IVF but it is possible that the groups differ in additional, more subtle parental characteristics. In addition, we measured BP on 1 day only, had no control group of children born to fertile couples (precluding investigating effects of the underlying subfertility) and included singletons only. As COH-IVF is associated with multiple births we may have underestimated cardiometabolic problems after COH-IVF. Finally, multivariable regression analysis does not provide clear insight in the causal mechanisms and we have performed further explorative analyses. Our findings are in line with other studies describing adverse effects of IVF on cardiometabolic outcome but this is the first study suggesting that ovarian hyperstimulation, as used in IVF treatments, could be a causative mechanism. Perhaps ovarian hyperstimulation negatively influences cardiometabolic outcome via changes in the early environment of the oocyte and/or embryo that result in epigenetic modifications of key metabolic systems that are involved in BP regulation. Future research needs to assess further the role of ovarian hyperstimulation in poorer cardiometabolic outcome and investigate the underlying mechanisms. The findings emphasize the importance of cardiometabolic monitoring of the growing number of children born following IVF. The authors have no conflicts of interest to declare. The study was supported by the University Medical Center Groningen, the Cornelia Foundation and the school for Behavioral- and Cognitive Neurosciences. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report.

The fiscal outcome of artificial conception in Brazil--creating citizens in developing countries.

PubMed

Kröger, G B; Ejzenberg, D

2012-01-01

Infertility is an important health issue, but only a small fraction of the affected population receives treatment in Brazil, because it is not covered by the government or private health insurance plans. We developed a generational accounting-based mathematical model to assess the direct economic result of creating a citizen through IVF in different economic scenarios, and the potential economic benefit generated by the individual and his/her future offspring. A mathematical model analyzes the revenues and expenses of an IVF-conceived individual over his lifetime. We calculated the net present value (NPV) of an IVF-conceived citizen, and this value corresponds to the fiscal contribution to the government by an individual, from birth through his predicted life expectancy. The calculation used discount rates of 4.0 and 7.0% to depreciate the money value by time. A 4.0% discount rate represents the most favorable economic scenario in Brazil, and it results in an NPV of US$ 61 428. A 7.0% discount rate represents a less favorable economic reality, and it results in a debit of U$ 563, but this debt may be compensated by his/her future offspring. The fiscal contribution generated by each IVF-conceived citizen can justify an initial government investment in infertility treatment. Poor economic times in Brazil can sometimes result in a fiscal debt from each new IVF-conceived child, but this initial expenditure may be compensated by the fiscal contribution in the next generation.

From Embryos to Adults: A DOHaD Perspective on In Vitro Fertilization and Other Assisted Reproductive Technologies

PubMed Central

Feuer, Sky; Rinaudo, Paolo

2016-01-01

Human in vitro fertilization (IVF) as a treatment for infertility is regarded as one of the most outstanding accomplishments of the 20th century, and its use has grown dramatically since the late 1970s. Although IVF is considered safe and the majority of children appear healthy, reproductive technologies have been viewed with some skepticism since the in vitro environment deviates substantially from that in vivo. This is increasingly significant because the Developmental Origins of Health and Disease (DOHaD) hypothesis has illuminated the sensitivity of an organism to its environment at critical stages during development, including how suboptimal exposures restricted specifically to gamete maturation or the preimplantation period can affect postnatal growth, glucose metabolism, fat deposition, and vascular function. Today, some of the physiological metabolic phenotypes present in animal models of IVF have begun to emerge in human IVF children, but it remains unclear whether or not in vitro embryo manipulation will have lasting health consequences in the offspring. Our expanding knowledge of the DOHaD field is fueling a paradigm shift in how disease susceptibility is viewed across the life course, with particular emphasis on the importance of collecting detailed exposure information, identifying biomarkers of health, and performing longitudinal studies for any medical treatment occurring during a developmentally vulnerable period. As IVF use continues to rise, it will be highly valuable to incorporate DOHaD concepts into the clinical arena and future approaches to public health policy. PMID:27517965

Sperm function and assisted reproduction technology

PubMed Central

MAAß, GESA; BÖDEKER, ROLF‐HASSO; SCHEIBELHUT, CHRISTINE; STALF, THOMAS; MEHNERT, CLAAS; SCHUPPE, HANS‐CHRISTIAN; JUNG, ANDREAS; SCHILL, WOLF‐BERNHARD

2005-01-01

The evaluation of different functional sperm parameters has become a tool in andrological diagnosis. These assays determine the sperm's capability to fertilize an oocyte. It also appears that sperm functions and semen parameters are interrelated and interdependent. Therefore, the question arose whether a given laboratory test or a battery of tests can predict the outcome in in vitro fertilization (IVF). One‐hundred and sixty‐one patients who underwent an IVF treatment were selected from a database of 4178 patients who had been examined for male infertility 3 months before or after IVF. Sperm concentration, motility, acrosin activity, acrosome reaction, sperm morphology, maternal age, number of transferred embryos, embryo score, fertilization rate and pregnancy rate were determined. In addition, logistic regression models to describe fertilization rate and pregnancy were developed. All the parameters in the models were dichotomized and intra‐ and interindividual variability of the parameters were assessed. Although the sperm parameters showed good correlations with IVF when correlated separately, the only essential parameter in the multivariate model was morphology. The enormous intra‐ and interindividual variability of the values was striking. In conclusion, our data indicate that the andrological status at the end of the respective treatment does not necessarily represent the status at the time of IVF. Despite a relatively low correlation coefficient in the logistic regression model, it appears that among the parameters tested, the most reliable parameter to predict fertilization is normal sperm morphology. (Reprod Med Biol 2005; 4: 7–30) PMID:29699207

[Increased risk of relapse in multiple sclerosis patients after ovarian stimulation for in vitro fertilization].

PubMed

Laplaud, D-A; Lefrère, F; Leray, E; Barrière, P; Wiertlewski, S

2007-10-01

In this preliminary study we analysed the impact of ovarian stimulations and the different protocols used for in vitro fertilizations (IVF) on the clinical activity of multiple sclerosis (MS). By matching the databases on MS and IVF of the past 10 years at the university hospital of Nantes, six patients have been found and, for five of them MS relapse rate seemed to be increased in the three-month period following IVF as compared to the previous three months and to two other control periods of three months (P<0.05, Friedman test). The increased relapse rate mainly concerned patients treated by GnRH agonists but not the patients treated by GnRH antagonists. This preliminary work suggests a possible impact of the treatments used for IVF on MS relapse rate. Further studies are now underway to validate these results on a larger scale, by including all cases reported in France.

Public financing of IVF: a review of policy rationales.

PubMed

Mladovsky, Philipa; Sorenson, Corinna

2010-06-01

There is great diversity in in vitro fertilization (IVF) funding and reimbursement policies and practice throughout Europe and the rest of the world. While many existing reimbursement and regulatory frameworks address safety and legal concerns, economic factors also assume a central role. However, there are several problems with the evidence that is available on the economics of IVF. This suggests there is a need for more robust cost-effectiveness studies. It also indicates the need for alternative rationales to justify the reimbursement of IVF, which might more fully account for the social, political, ethical, and philosophical considerations embedded in notions of infertility and technology-driven reproductive treatments. The merits and limitations of five alternative rationales are discussed. The review suggests that while no existing single rationale provides a complete framework with which to support funding decisions, taken together they provide guideposts which signal important issues for consideration and highlight where further research, action, and debate are needed.

[Deeply infiltrating endometriosis and infertility: CNGOF-HAS Endometriosis Guidelines].

PubMed

Mathieu d'Argent, E; Cohen, J; Chauffour, C; Pouly, J L; Boujenah, J; Poncelet, C; Decanter, C; Santulli, P

2018-03-01

Deeply infiltrating endometriosis is a severe form of the disease, defined by endometriotic tissue peritoneal infiltration. The disease may involve the rectovaginal septum, uterosacral ligaments, digestive tract or bladder. Deeply infiltrating endometriosis is responsible for disabling pain and infertility. The purpose of these recommendations is to answer the following question: in case of deeply infiltrating endometriosis associated infertility, what is the best therapeutic strategy? First-line surgery and then in vitro fertilization (IVF) in case of persistent infertility or first-line IVF, without surgery? After exhaustive literature analysis, we suggest the following recommendations: studies focusing on spontaneous fertility of infertile patients with deeply infiltrating endometriosis found spontaneous pregnancy rates about 10%. Treatment should be considered in infertile women with deeply infiltrating endometriosis when they wish to conceive. First-line IVF is a good option in case of no operated deeply infiltrating endometriosis associated infertility. Pregnancy rates (spontaneous and following assisted reproductive techniques) after surgery (deep lesions without colorectal involvement) varie from 40 to 85%. After colorectal endometriosis resection, pregnancy rates vary from 47 to 59%. The studies comparing the pregnancy rates after IVF, whether or not preceded by surgery, are contradictory and do not allow, to date, to conclude on the interest of any surgical management of deep lesions before IVF. In case of alteration of ovarian reserve parameters (age, AMH, antral follicle count), there is no argument to recommend first-line surgery or IVF. The study of the literature does not identify any prognostic factors, allowing to chose between surgical management or IVF. The use of IVF in the indication "deep infiltrating endometriosis" allows satisfactory pregnancy rates without significant risk, regarding disease progression or oocyte retrieval procedure morbidity. Copyright © 2018. Published by Elsevier Masson SAS.

Public health implications of a North American publicly funded in vitro fertilization program; lessons to learn.

PubMed

Shaulov, Talya; Belisle, Serge; Dahan, Michael H

2015-09-01

A retrospective study was conducted to determine trends in practice and outcomes that occurred since the implementation of the publicly funded in vitro fertilization (IVF) and single embryo transfer (SET) program in Quebec, in August, 2010. Data presented was extracted from an advisory report by the Health and Welfare Commissioner, and from a report by the Ministry of Health and Social Services published in June 2014 and October 2013, respectively. This data is publicly available, and was collected from all six private and three public-assisted reproduction centers in Quebec providing IVF services. Data pertains to all IVF cycles performed from the 2009-2010 to 2012-2013 fiscal years. SET was performed in 71 % of cycles in 2012. The number of children born from IVF was 1057 in 2009-2010 and 1723 in 2012-2013 (p < 0.0001). Multiple birth rates from IVF were 24 % in 2009-2010 (before the program began) and 9.45 % in 2012-2013 (p < 0.0001). The proportions of IVF babies that were premature, that were the result of multiple births, or that required neonatal intensive care unit admission (NICU) all decreased by 35.5 % (p < 0.0001), 55 % (p < 0.0001), and 37 % (p < 0.0001), respectively, from 2009-2010 to 2012-2013. The cost per NICU admission for an IVF baby increased from $19,990 to $28,418 from 2009-2010 to 2011-2012. This first North American publicly funded IVF program with a SET policy shows that such a program contributes substantially to number of births. It has also succeeded in increasing access to treatment and decreasing perinatal morbidity by decreasing multiple birth rates from IVF. A substantial increase in global public health care costs occurred as well.

Oocyte-triggering day progesterone levels and endometrial appearance in normoresponders undergoing IVF/ICSI cycles: a hypothesis and a study protocol.

PubMed

Siristatidis, Charalampos; Drakopoulos, Panagiotis; Vogiatzi, Paraskevi; Karageorgiou, Vasilios; Daskalakis, George

2018-05-16

In this report, we propose a study protocol capable of improving IVF outcomes in subfertile women with expected normal ovarian response. This proposal derives from conflicting published data and observations in our daily practice, concerning the negative impact of progesterone (P4) elevation at the day of oocyte triggering on pregnancy outcomes. Our hypothesis points to the combination of two previous "suspects" of reduced success after assisted reproduction techniques (ART) - the endometrium ultrasonographic parameters and P4 elevation at the day of oocyte triggering on their impact on pregnancy outcomes. Up-to-the minute data show that, there is a different impact of elevated P4 in fresh, frozen and donor cycles, whereas there are plenty of reports pointing to a different endometrial gene expression on different P4 measurements. Gaps in the literature are linked with a variation of the measurements of P4, its cycle-to-cycle reproducibility, the different cut-off levels used, the impact of various protocols of ovarian stimulation and the limitations of systematic reviews originating from the initial studies. Our hypothesis states that the combination of P4 values and endometrial ultrasound parameters at the day of oocyte triggering can affect clinical pregnancy rates in normal responders undergoing ART.

Beta endorphin in serum and follicular fluid of PCOS- and non-PCOS women.

PubMed

Jaschke, Nikolai; Lunger, Fabian; Wildt, Ludwig; Seeber, Beata

2018-07-01

To compare the concentrations of beta endorphin in serum and follicular fluid (FF) of PCOS- and non-PCOS women. Secondarily, to investigate associations between beta endorphin and other parameters. Fifty-nine women undergoing in vitro fertilization (IVF) were included in the study. Sixteen were stratified to the PCOS group using the Rotterdam criteria. The remaining 43 women served as controls. Follicular fluid was collected during oocyte retrieval and peripheral blood sampling was performed on the same day. Beta endorphin concentrations in serum and follicular fluid, serum levels of insulin, glucose, LH, estradiol and progesterone were measured. Additionally, testosterone was measured before starting the stimulation protocol. There was no difference in beta endorphin levels between PCOS- and non-PCOS women. The concentration of the peptide was higher in serum than in FF, likely due to collection of FF after ovulation induction and corresponding to the early luteal phase. We found a significant correlation between the number of mature Metaphase II (MII) oocytes retrieved and beta endorphin concentration in FF. In women with biochemical hyperandrogenemia, beta endorphin levels in FF correlated with testosterone levels. Beta Endorphin concentrations in serum and FF do not differ between PCOS- and non PCOS-women undergoing IVF. However, together with sex hormones, beta endorphin might play a key role in oocyte maturation.

The Impact of Progesterone Level on Day Of hCG Injection in IVF Cycles on Clinical Pregnancy Rate.

PubMed

Ashmita, Jawa; Vikas, Swarankar; Swati, Garg

2017-01-01

Premature progesterone rise (PPR) has long been implicated as contributing to implantation failure. Despite the use of gonadotropin-releasing hormone (GnRH) analogues, subtle increases in serum progesterone ( P 4 ) levels beyond a threshold progesterone concentration were observed on the day of trigger in controlled ovarian hyperstimulation cycles. The purpose of the study was to evaluate the incidence of PPR on the day of trigger in conventional IVF/ICSI cycles and its impact on clinical pregnancy rate. A total of 235 patients undergoing conventional IVF/IVF-ICSI by fresh embryo transfer cycles from January 2016 to December 2016 at the infertility unit of a tertiary care hospital were prospectively analyzed. Patients included in the study were subjected to GnRH agonist long/antagonist protocol. Ovulation induction was given with rFSH and/or HMG in both the protocols. The cutoff for defining PPR was P 4 ≥ 1.5 ng/ml, and an analysis of the role of P 4 on clinical pregnancy rate was performed. Statistical analysis was performed with the Statistical Package for the Social Sciences trial version 23.0 software for Windows and Primer software. The overall clinical pregnancy rate per embryo transfer was 30.6%. The clinical pregnancy rate in the patients with P 4 <1.5 ng/ml was significantly higher than those with elevated levels, P 4 ≥ 1.5 ng/ml (33.3% vs. 12.9%; P = 0.037). Premature progesterone elevation in ART cycles is possibly associated with lower clinical pregnancy rates.

Cytokine expression in the seminal plasma and its effects on fertilisation rates in an IVF cycle.

PubMed

Seshadri, S; Bates, M; Vince, G; Jones, D I Lewis

2011-12-01

Cytokines are released by various immunocompetent cell subsets in the male urogenital tract and are thought to affect sperm cell function and reproductive process. The aim of the study was to evaluate the levels and a possible role of seven seminal plasma cytokines with fertilisation rates in men attending an in vitro fertilisation (IVF) programme. A total of 36 men of couples who were undergoing traditional IVF in a regional reproductive medicine unit were recruited into this prospective study. Cytokines such as interleukin (IL)-6, IL-8, IL-10, IL-11, IL-12, tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) in the seminal plasma were determined using enzyme linked immunosorbent assay. IL-6, IL-8, IL-10, IL-11 and IFN-γ were detected in all samples. IL-12, and TNF-α were detected in most samples. Levels of IL-11 were significantly higher in the good fertiliser group (P ≤ 0.05). Positive correlation between cytokines such as IL-6 and IL-8 (P < 0.03), IL-10 and IL-11 (P < 0.001) and IFN-γ and IL-10 and IL-11 (P < 0.04 and P < 0.0001 respectively) were found. Our study confirms that the six cytokines other than IL-11 do not affect spermatozoon-oocyte interaction and fertilisation rates in IVF. IL-11 could have a role in the fertilising capacity of the spermatozoa. Significant correlation exists among these cytokines which shows that cytokines rarely act in isolation but rather in a network. © 2011 Blackwell Verlag GmbH.

Oocyte vitrification for elective fertility preservation: the past, present, and future.

PubMed

Gunnala, Vinay; Schattman, Glenn

2017-02-01

Oocyte cryopreservation is no longer experimental and one of its rapidly growing indications is elective fertility preservation. Currently there is no sufficient evidence to support its practice and therefore its place in IVF remains uncertain. Vitrification has superior post-thaw survival and fertilization outcomes compared with oocytes that were frozen with the slow-freeze technique. Oocyte vitrification produces similar IVF outcomes compared with fresh oocytes and is not associated with further obstetrical or perinatal morbidity. Undergoing elective oocyte cryopreservation between ages 35 and 37 will optimize live birth rates as well as cost effectiveness from mathematical models. In women who delay child bearing, elective oocyte cryopreservation in the mid 30s may be beneficial in terms of live birth rates and cost effectiveness. Prospective studies of women who have undergone oocyte cryopreservation and are now attempting conception are needed before official recommendations can be made regarding elective egg freezing.

Multivariate analysis identifies the estradiol level at ovulation triggering as an independent predictor of the first trimester pregnancy-associated plasma protein-A level in IVF/ICSI pregnancies.

PubMed

Giorgetti, C; Vanden Meerschaut, F; De Roo, C; Saunier, O; Quarello, E; Hairion, D; Penaranda, G; Chabert-Orsini, V; De Sutter, P

2013-10-01

Can independent predictors of pregnancy-associated plasma protein-A (PAPP-A) levels be identified in a group of women who conceived following IVF/ICSI? The significantly decreased PAPP-A level in IVF and ICSI pregnancies compared with non-IVF/ICSI pregnancies was correlated strongly with the serum estradiol (E2) level at ovulation triggering. The first trimester prenatal combined screening test for fetal aneuploidies in pregnancies conceived following assisted reproduction techniques (ART) is complicated by an alteration of the maternal biomarkers free β-hCG and PAPP-A, causing a higher false-positive rate compared with pregnancies which are conceived naturally. The use of controlled ovarian stimulation prior to IVF/ICSI is suggested to be the principle reason for these alterations of biomarkers in ART pregnancies. Between January 2010 and December 2011, 1474 women who conceived naturally and 374 women who conceived following IVF (n = 89), ICSI (n = 204) or intrauterine insemination (IUI, n = 81) were included in this retrospective study. Only singleton pregnancies were eligible for this study. For all women, serum analysis was performed in the same clinical laboratory. Measurement of nuchal translucency (NT) thickness was performed by four physicians belonging to the same infertility centre. First-trimester combined screening test of aneuploidy parameters (maternal age, PAPP-A and free β-hCG, NT thickness) were compared between non-ART and ART (IVF, ICSI and IUI) singleton pregnancies. Next, a minimal threshold E2 level at ovulation triggering was suggested for IVF/ICSI pregnancies above which the PAPP-A levels were significantly decreased compared with non-ART pregnancies. Finally, a multivariate analysis was performed to reveal independent predictors of PAPP-A level in IVF/ICSI pregnancies. We showed a decrease of the multiple of the median (MoM) PAPP-A level in IVF and ICSI singleton pregnancies compared with non-ART singleton pregnancies (P < 0.001), with MoM values of 0.74 (0.16-3.16) and 0.81 (0.12-4.61) versus 0.98 (0.14-5.76), respectively. Analysis of variance of the overall model was highly significant (Fisher test 3.76, P = 0.01), indicating that the model explains a significant portion of the variation in the data. No difference in PAPP-A level was found between non-ART and IUI pregnancies. The free β-hCG level and NT thickness did not differ between ART and non-ART pregnancies. PAPP-A levels in IVF and ICSI pregnancies were strongly correlated with the E2 level at ovulation triggering. We showed by multivariate analysis that an E2 cut-off level of 1300 pg/ml at the time of ovulation could predict a significantly lower PAPP-A level at first trimester combined screening (β -0.239 ± 0.088, P < 0.005). The measures of biochemical markers can differ between laboratories and with the used equipment; therefore, extrapolation of the E2 cut-off level to other infertility centres should be undertaken with caution. One should be careful when using correction factors for ART patients undergoing the first trimester combined screening test. The proposed E2 cut-off level may help to identify a subgroup of women within the population of ART patients for whom use of a correction factor is justified. None.

Assisted reproductive technology and intrauterine inseminations in Europe, 2005: results generated from European registers by ESHRE: ESHRE. The European IVF Monitoring Programme (EIM), for the European Society of Human Reproduction and Embryology (ESHRE).

PubMed

Nyboe Andersen, A; Goossens, V; Bhattacharya, S; Ferraretti, A P; Kupka, M S; de Mouzon, J; Nygren, K G

2009-06-01

Results of assisted reproductive techniques from treatments initiated in Europe during 2005 are presented in this ninth report. Data were mainly collected from existing national registers. From 30 countries, 923 clinics reported 418 111 treatment cycles including: IVF (118 074), ICSI (203 329), frozen embryo replacement (79 140), oocyte donation (ED, 11 475), preimplantation genetic diagnosis/screening (5846) and in vitro maturation (247). Overall, this represents a 13.6% increase since 2004, partly due to inclusion of 28 417 cycles from Turkey. European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 21 countries and included 128 908 IUI-H and 20 568 IUI-D cycles. In 16 countries where all clinics reported to the IVF register, 1115 cycles were performed per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 26.9% and 30.3%, respectively. For ICSI, the corresponding rates were 28.5% and 30.9%. After IUI-H, the clinical pregnancy rate was 12.6% per insemination in women <40. After IVF and ICSI, the distribution of transfer of one, two, three and four or more embryos was 20.0%, 56.1%, 21.5% and 2.3%, respectively. Huge differences exist between countries. The distribution of singleton, twin and triplet deliveries after IVF and ICSI was 78.2%, 21.0% and 0.8%, respectively. This gives a total multiple delivery rate of 21.8% compared with 22.7% in 2004 and 23.1% in 2003. In women <40 years of age, IUI-H was associated with a twin and triplet pregnancy rate of 11.0% and 1.1%, respectively. Compared with earlier years, there was an increase in the reported number of ART cycles in Europe. Although fewer embryos were transferred per treatment, there was a marginal increase in pregnancy rates and a reduction in multiple deliveries.

The effects of cetrorelix and triptorelin on the viability and steroidogenesis of cultured human granulosa luteinized cells.

PubMed

Metallinou, Chryssa; Köster, Frank; Diedrich, Klaus; Nikolettos, Nikos; Asimakopoulos, Byron

2012-01-01

We investigated the effects of the gonadotropin-releasing hormone (GnRH) agonist triptorelin as well the GnRH antagonist cetrorelix those of on the viability and steroidogenesis in human granulosa luteinized (hGL) cell cultures. The hGL cells were obtained from 34 women undergoing ovarian stimulation for IVF treatment. The cells were cultured for 48 h with or without 1 nM or 3 nM of cetrorelix or triptorelin in serum-free media. The cell viability was evaluated by the MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay. The concentrations of estradiol and progesterone in culture supernatants were measured by ELISA. Treatment with triptorelin slightly increased cell viability, whereas treatment with 3 nM cetrorelix led to a significant decrease. Estradiol concentrations were reduced with 3 nM triptorelin. Cultures treated with high-dose of either cetrorelix or triptorelin tended to secrete less progesterone than controls. Cetrorelix significantly reduces the viability of hGL cells. Triptorelin and cetrorelix may have minor effects on steroidogenesis. These results suggest that GnRH analogues may influence ovarian functions.

Balancing selected medication costs with total number of daily injections: a preference analysis of GnRH-agonist and antagonist protocols by IVF patients.

PubMed

Sills, E Scott; Collins, Gary S; Salem, Shala A; Jones, Christopher A; Peck, Alison C; Salem, Rifaat D

2012-08-30

During in vitro fertilization (IVF), fertility patients are expected to self-administer many injections as part of this treatment. While newer medications have been developed to substantially reduce the number of these injections, such agents are typically much more expensive. Considering these differences in both cost and number of injections, this study compared patient preferences between GnRH-agonist and GnRH-antagonist based protocols in IVF. Data were collected by voluntary, anonymous questionnaire at first consultation appointment. Patient opinion concerning total number of s.c. injections as a function of non-reimbursed patient cost associated with GnRH-agonist [A] and GnRH-antagonist [B] protocols in IVF was studied. Completed questionnaires (n = 71) revealed a mean +/- SD patient age of 34 +/- 4.1 yrs. Most (83.1%) had no prior IVF experience; 2.8% reported another medical condition requiring self-administration of subcutaneous medication(s). When out-of-pocket cost for [A] and [B] were identical, preference for [B] was registered by 50.7% patients. The tendency to favor protocol [B] was weaker among patients with a health occupation. Estimated patient costs for [A] and [B] were $259.82 +/- 11.75 and $654.55 +/- 106.34, respectively (p < 0.005). Measured patient preference for [B] diminished as the cost difference increased. This investigation found consistently higher non-reimbursed direct medication costs for GnRH-antagonist IVF vs. GnRH-agonist IVF protocols. A conditional preference to minimize downregulation (using GnRH-antagonist) was noted among some, but not all, IVF patient sub-groups. Compared to IVF patients with a health occupation, the preference for GnRH-antagonist was weaker than for other patients. While reducing total number of injections by using GnRH-antagonist is a desirable goal, it appears this advantage is not perceived equally by all IVF patients and its utility is likely discounted heavily by patients when nonreimbursed medication costs reach a critical level.

Balancing selected medication costs with total number of daily injections: a preference analysis of GnRH-agonist and antagonist protocols by IVF patients

PubMed Central

2012-01-01

Background During in vitro fertilization (IVF), fertility patients are expected to self-administer many injections as part of this treatment. While newer medications have been developed to substantially reduce the number of these injections, such agents are typically much more expensive. Considering these differences in both cost and number of injections, this study compared patient preferences between GnRH-agonist and GnRH-antagonist based protocols in IVF. Methods Data were collected by voluntary, anonymous questionnaire at first consultation appointment. Patient opinion concerning total number of s.c. injections as a function of non-reimbursed patient cost associated with GnRH-agonist [A] and GnRH-antagonist [B] protocols in IVF was studied. Results Completed questionnaires (n = 71) revealed a mean +/− SD patient age of 34 +/− 4.1 yrs. Most (83.1%) had no prior IVF experience; 2.8% reported another medical condition requiring self-administration of subcutaneous medication(s). When out-of-pocket cost for [A] and [B] were identical, preference for [B] was registered by 50.7% patients. The tendency to favor protocol [B] was weaker among patients with a health occupation. Estimated patient costs for [A] and [B] were $259.82 +/− 11.75 and $654.55 +/− 106.34, respectively (p < 0.005). Measured patient preference for [B] diminished as the cost difference increased. Conclusions This investigation found consistently higher non-reimbursed direct medication costs for GnRH-antagonist IVF vs. GnRH-agonist IVF protocols. A conditional preference to minimize downregulation (using GnRH-antagonist) was noted among some, but not all, IVF patient sub-groups. Compared to IVF patients with a health occupation, the preference for GnRH-antagonist was weaker than for other patients. While reducing total number of injections by using GnRH-antagonist is a desirable goal, it appears this advantage is not perceived equally by all IVF patients and its utility is likely discounted heavily by patients when nonreimbursed medication costs reach a critical level. PMID:22935199

Selection of euploid blastocysts for cryopreservation with array comparative genomic hybridization (aCGH) results in increased implantation rates in subsequent frozen and thawed embryo transfer cycles

PubMed Central

2013-01-01

Background In assisted reproductive treatments, embryos remaining after fresh embryo transfer are usually selected for cryopreservation based on traditional morphology assessment. Our previous report has demonstrated that array comparative genomic hybridization (aCGH) screening for IVF patients with good prognosis significantly improves clinical and ongoing pregnancy rates in fresh embryo transfer cycles. The current study further investigates the efficiency of applying aCGH in the selection of euploid embryos for cryopreservation as related to pregnancy and implantation outcomes in subsequent frozen embryo transfer (FET) cycles. Methods First-time IVF patients with good prognosis undergoing fresh single embryo transfer and having at least one remaining blastocyst for cryopreservation were prospectively randomized into two groups: 1) Group A patients had embryos assessed by morphology first and then by aCGH screening of trophectoderm cells and 2) Group B patients had embryos evaluated by morphology alone. All patients had at least one blastocyst available for cryopreservation after fresh embryo transfer. There were 15 patients in Group A and 23 patients in Group B who failed to conceive after fresh embryo transfer and completed the FET cycles. Blastocyst survival and implantation rates were compared between the two groups. Results There were no significant differences in blastocyst survival rates between Group A and Group B (90.9% vs. 91.3%, respectively; p >0.05). However, a significantly higher implantation rate was observed in the morphology assessment plus aCGH screening group compared to the morphology assessment alone group (65.0% vs. 33.3%, respectively; p = 0.038). There was no miscarriage observed in Group A while a 16.7% miscarriage rate was recorded in Group B (0% vs. 16.7%, respectively; p >0.05). Conclusions While aCGH screening has been recently applied to select euploid blastocysts for fresh transfer in young, low-risk IVF patients, this is the first prospective study on the impact of aCGH specifically on blastocyst survival and implantation outcomes in the subsequent FET cycles of IVF patients with good prognosis. The present study demonstrates that aCGH screening of blastocysts prior to cryopreservation significantly improves implantation rates and may reduce the risk of miscarriage in subsequent FET cycles. Further randomized clinical studies with a larger sample size are needed to validate these preliminary findings. PMID:23937723

Intrauterine instillation of diluted seminal plasma at oocyte pick-up does not increase the IVF pregnancy rate: a double-blind, placebo controlled, randomized study.

PubMed

von Wolff, M; Rösner, S; Germeyer, A; Jauckus, J; Griesinger, G; Strowitzki, T

2013-12-01

Does intrauterine application of diluted seminal plasma (SP) at the time of ovum pick-up improve the pregnancy rate by ≥14% in IVF treatment? Intrauterine instillation of diluted SP at the time of ovum pick-up is unlikely to increase the pregnancy rate by ≥14% in IVF. SP modulates endometrial function, and sexual intercourse around the time of embryo transfer has been suggested to increase the likelihood of pregnancy. A previous randomized double-blind pilot study demonstrated a strong trend towards increased pregnancy rates following the intracervical application of undiluted SP. As this study was not conclusive and as the finding could have been confounded by sexual intercourse, the intrauterine application of diluted SP was investigated in the present trial. A single-centre, prospective, double-blind, placebo-controlled, randomized, superiority trial on women undergoing IVF was conducted from April 2007 until February 2012 at the University Department of Gynaecological Endocrinology and Reproductive Medicine, Heidelberg, Germany. The study was powered to detect an 14% increase in the clinical pregnancy rate and two sequential tests were planned using the Pocock spending function. At the first interim analysis, 279 women had been randomly assigned to intrauterine diluted SP (20% SP in saline from the patients' partner) (n = 138) or placebo (n = 141) at the time of ovum pick-up. The clinical pregnancy rate per randomized patient was 37/138 (26.8%) in the SP group and 41/141 (29.1%) in the placebo group (difference: -2.3%, 95% confidence interval of the difference: -12.7 to +8.2%; P = 0.69). The live birth rate per randomized patient was 28/138 (20.3%) in the SP group and 33/141 (23.4%) in the placebo group (difference: -3.1%, 95% confidence interval of the difference: -12.7 to +6.6%; P = 0.56). It was decided to terminate the trial due to futility at the first interim analysis, at a conditional power of 62%. The confidence interval of the difference remains wide, thus clinically relevant differences cannot reliably be excluded based on this single study. The results of this study cast doubt on the validity of the concept that SP increases endometrial receptivity and thus implantation in humans. Funding was provided by the department's own research facilities. DRKS00004615.

Disparities in Assisted Reproductive Technology Utilization by Race and Ethnicity, United States, 2014: A Commentary.

PubMed

Dieke, Ada C; Zhang, Yujia; Kissin, Dmitry M; Barfield, Wanda D; Boulet, Sheree L

2017-06-01

Disparities in infertility and access to infertility treatments, such as assisted reproductive technology (ART), by race/ethnicity, have been reported. However, identifying disparities in ART usage may have been hampered by missing race/ethnicity information in ART surveillance. We review infertility prevalence and treatment disparities, use recent data to examine ART use in the United States by race/ethnicity and residency in states with mandated insurance coverage for in vitro fertilization (IVF), and discuss approaches for reducing disparities. We used 2014 National ART Surveillance System (NASS) data to calculate rates of ART procedures per million women 15-44 years of age, a proxy measure of ART utilization, for Census-defined racial/ethnic groups in the United States; rates were further stratified by the presence of insurance mandates for IVF treatment. Missing race/ethnicity data (35.6% of cycles) were imputed. Asian/Pacific Islander (A/PI) women had the highest rates of ART utilization at 5883 ART procedures per million women 15-44 years of age in 2014, whereas American Indian/Alaska Native non-Hispanic women had the lowest rates at 807 per million, compared with other racial/ethnic groups. In each racial/ethnic category, ART utilization rates were higher for women in states with an insurance mandate for IVF treatment versus those without. In 2014, A/PI women had the highest rates of ART utilization. ART utilization for all racial/ethnic groups was higher in states with insurance mandates for IVF than those without, although disparities were still evident. Although mandates may increase access to infertility treatments, they are not sufficient to eliminate these disparities.

Circulating basal anti-Müllerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization.

PubMed

Nardo, Luciano G; Gelbaya, Tarek A; Wilkinson, Hannah; Roberts, Stephen A; Yates, Allen; Pemberton, Phil; Laing, Ian

2009-11-01

To evaluate the clinical value of basal anti-Müllerian hormone (AMH) measurements compared with other available determinants, apart from chronologic age, in the prediction of ovarian response to gonadotrophin stimulation. Prospective cohort study. Tertiary referral center for reproductive medicine and an IVF unit. Women undergoing their first cycle of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Basal levels of FSH and AMH as well as antral follicle count (AFC) were measured in 165 subjects. All patients were followed prospectively and their cycle outcomes recorded. Predictive value of FSH, AMH, and AFC for extremes of ovarian response to stimulation. Out of the 165 women, 134 were defined as normal responders, 15 as poor responders, and 16 as high responders. Subjects in the poor response group were significantly older then those in the other two groups. Anti-Müllerian hormone levels and AFC were markedly raised in the high responders and decreased in the poor responders. Compared with FSH and AFC, AMH performed better in the prediction of excessive response to ovarian stimulation-AMH area under receiver operating characteristic curve (ROC(AUC)) 0.81, FSH ROC(AUC) 0.66, AFC ROC(AUC) 0.69. For poor response, AMH (ROC(AUC) 0.88) was a significantly better predictor than FSH (ROC(AUC) 0.63) but not AFC (ROC(AUC) 0.81). AMH prediction of ovarian response was independent of age and PCOS. Anti-Müllerian hormone cutoffs of >3.75 ng/mL and <1.0 ng/mL would have modest sensitivity and specificity in predicting the extremes of response. Circulating AMH has the ability to predict excessive and poor response to stimulation with exogenous gonadotrophins. Overall, this biomarker is superior to basal FSH and AFC, and has the potential to be incorporated in to work-up protocols to predict patient's ovarian response to treatment and to individualize strategies aiming at reducing the cancellation rate and the iatrogenic complications of COH.

[In vitro fertilization at our department. A decade's work in figures and facts (1994-2003)].

PubMed

Urbancsek, János; Fancsovits, Péter; Akos, Murber; Tóthné Gilán, Zsuzsa; Hauzman, Erik; Papp, Zoltán

2006-01-08

We report here on the first decade of in vitro fertilization (IVF) treatments performed at a newly established clinical infertility and assisted reproductive unit. We present the number of treatment cycles, the distribution of treatment modalities ("classical" IVF and intracytoplasmic sperm injection, ICSI) and success rates, and relate them to national and international data. During the last decade, ICSI was introduced gradually and is now used routinely at our department. In certain cases of azoospermia, testicular sperm extraction (TESE) is used to retrieve male gametes for ICSI. Embryo cryopreservation, which is also part of the routine, provides the chance to establish pregnancy in subsequent cycles without the need to repeat hormonal stimulation. Preimplantation genetic diagnosis helps us to avoid transferring embryos carrying certain hereditary diseases. 1517 IVF cycles were started in the past ten years. Oocyte pickup and IVF were performed in 1423 cases. In the end of the described period, ICSI was used in more than two thirds of treatment cycles. Pregnancy rates were 39.0% per embryo transfer (ET), 36.3% per oocyte pickup, and 34.0% per started cycle. Clinical pregnancy was achieved in 34.2% per ET, and the delivery rate was 27.9% per ET. These success rates have exceeded the national average every year since 1996. Pregnancy rates in frozen-thawed ET cycles and in cryo-TESE-ICSI cycles are in the range of international data. We attribute the gradual and continuous improvement in our success rates to rigorous and well-coordinated clinical and laboratory work and to judicious adoption of the latest assisted reproductive techniques.

Unexplained infertility: overall ongoing pregnancy rate and mode of conception.

PubMed

Brandes, M; Hamilton, C J C M; van der Steen, J O M; de Bruin, J P; Bots, R S G M; Nelen, W L D M; Kremer, J A M

2011-02-01

Unexplained infertility is one of the most common diagnoses in fertility care. The aim of this study was to evaluate the outcome of current fertility management in unexplained infertility. In an observational, longitudinal, multicentre cohort study, 437 couples were diagnosed with unexplained infertility and were available for analysis. They were treated according to their prognosis using standing national treatment protocols: (i) expectant management-IUI-IVF (main treatment route), (ii) IUI-IVF and (iii) directly IVF. Primary outcome measures were: ongoing pregnancy rate, patient flow over the strategies, numbers of protocol violation and drop out rates. A secondary outcome measure was the prediction of ongoing pregnancy and mode of conception. Of all couples 81.5% (356/437) achieved an ongoing pregnancy and 73.9% (263/356) of the pregnancies were conceived spontaneously. There were 408 couples (93.4%) in strategy-1, 21 (5.0%) in strategy-2 and 8 (1.8%) in strategy-3. In total, 33 (7.6%) couples entered the wrong strategy. There were 104 couples (23.8%) who discontinued fertility treatment prematurely: 26 on doctor's advice (with 4 still becoming pregnant) and 78 on their own initiative (with 33 still achieving a pregnancy). Predictors for overall pregnancy chance and mode of conception were duration of infertility, female age and obstetrical history. Overall success rate in couples with unexplained infertility is high. Most pregnancies are conceived spontaneously. We recommend that if the pregnancy prognosis is good, expectant management should be suggested. The prognosis criteria for treatment with IUI or IVF needs to be investigated in randomized controlled trials.

Long term costs and effects of reducing the number of twin pregnancies in IVF by single embryo transfer: the TwinSing study

PubMed Central

2010-01-01

Background Pregnancies induced by in vitro fertilisation (IVF) often result in twin gestations, which are associated with both maternal and perinatal complications. An effective way to reduce the number of IVF twin pregnancies is to decrease the number of embryos transferred from two to one. The interpretation of current studies is limited because they used live birth as outcome measure and because they applied limited time horizons. So far, research on long-term outcomes of IVF twins and singletons is scarce and inconclusive. The objective of this study is to investigate the short (1-year) and long-term (5 and 18-year) costs and health outcomes of IVF singleton and twin children and to consider these in estimating the cost-effectiveness of single embryo transfer compared with double embryo transfer, from a societal and a healthcare perspective. Methods/Design A multi-centre cohort study will be performed, in which IVF singletons and IVF twin children born between 2003 and 2005 of whom parents received IVF treatment in one of the five participating Dutch IVF centres, will be compared. Data collection will focus on children at risk of health problems and children in whom health problems actually occurred. First year of life data will be collected in approximately 1,278 children (619 singletons and 659 twin children). Data up to the fifth year of life will be collected in approximately 488 children (200 singletons and 288 twin children). Outcome measures are health status, health-related quality of life and costs. Data will be obtained from hospital information systems, a parent questionnaire and existing registries. Furthermore, a prognostic model will be developed that reflects the short and long-term costs and health outcomes of IVF singleton and twin children. This model will be linked to a Markov model of the short-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies to enable the calculation of the long-term cost-effectiveness. Discussion This is, to our knowledge, the first study that investigates the long-term costs and health outcomes of IVF singleton and twin children and the long-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies. PMID:20961411

Long term costs and effects of reducing the number of twin pregnancies in IVF by single embryo transfer: the TwinSing study.

PubMed

van Heesch, Mirjam M J; Bonsel, Gouke J; Dumoulin, John C M; Evers, Johannes L H; van der Hoeven, Mark Ahbm; Severens, Johan L; Dykgraaf, Ramon H M; van der Veen, Fulco; Tonch, Nino; Nelen, Willianne L D M; van Zonneveld, Piet; van Goudoever, Johannes B; Tamminga, Pieter; Steiner, Katerina; Koopman-Esseboom, Corine; van Beijsterveldt, Catharina E M; Boomsma, Dorret I; Snellen, Diana; Dirksen, Carmen D

2010-10-20

Pregnancies induced by in vitro fertilisation (IVF) often result in twin gestations, which are associated with both maternal and perinatal complications. An effective way to reduce the number of IVF twin pregnancies is to decrease the number of embryos transferred from two to one. The interpretation of current studies is limited because they used live birth as outcome measure and because they applied limited time horizons. So far, research on long-term outcomes of IVF twins and singletons is scarce and inconclusive. The objective of this study is to investigate the short (1-year) and long-term (5 and 18-year) costs and health outcomes of IVF singleton and twin children and to consider these in estimating the cost-effectiveness of single embryo transfer compared with double embryo transfer, from a societal and a healthcare perspective. A multi-centre cohort study will be performed, in which IVF singletons and IVF twin children born between 2003 and 2005 of whom parents received IVF treatment in one of the five participating Dutch IVF centres, will be compared. Data collection will focus on children at risk of health problems and children in whom health problems actually occurred. First year of life data will be collected in approximately 1,278 children (619 singletons and 659 twin children). Data up to the fifth year of life will be collected in approximately 488 children (200 singletons and 288 twin children). Outcome measures are health status, health-related quality of life and costs. Data will be obtained from hospital information systems, a parent questionnaire and existing registries. Furthermore, a prognostic model will be developed that reflects the short and long-term costs and health outcomes of IVF singleton and twin children. This model will be linked to a Markov model of the short-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies to enable the calculation of the long-term cost-effectiveness. This is, to our knowledge, the first study that investigates the long-term costs and health outcomes of IVF singleton and twin children and the long-term cost-effectiveness of single embryo transfer strategies versus double embryo transfer strategies.

Obstetric and perinatal outcomes in IVF versus ICSI-conceived pregnancies at a tertiary care center--a pilot study.

PubMed

Nouri, Kazem; Ott, Johannes; Stoegbauer, Lucia; Pietrowski, Detlef; Frantal, Sophie; Walch, Katharina

2013-08-31

Although most pregnancies after IVF result in normal healthy outcomes, an increased risk for a number of obstetric and neonatal complications, compared to naturally conceived pregnancies, has been reported. While there are many studies that compare pregnancies after assisted reproductive techniques with spontaneously conceived pregnancies, fewer data are available that evaluate the differences between IVF and ICSI-conceived pregnancies. The aim of our present study was, therefore, to compare obstetric and perinatal outcomes in pregnancies conceived after in vitro fertilization (IVF) versus intracytoplasmatic sperm injection (ICSI). Three-hundred thirty four women who had become pregnant after an IVF or ICSI procedure resulted in a total of 530 children referred between 2003 und 2009 to the Department of Obstetrics and Gynecology of the Medical University of Vienna, a tertiary care center, and were included in this retrospective cohort study. We assessed maternal and fetal parameters in both groups (IVF and ICSI). The main study outcomes were preterm delivery, the need for neonatal intensive care, and congenital malformations. Moreover, we compared the course of pregnancy between both groups and the occurrence of complications that led to maternal hospitalization during pregnancy. There were 80 children conceived via ICSI and 450 children conceived via IVF.Mean gestational age was significantly lower in the ICSI group (p = 0.001). After ICSI, the birth weight (p = 0.008) and the mean APGAR values after 1 minute and after 10 minutes were lower compared to that of the IVF group (p = 0.016 and p = 0.047, respectively). Moreover, ICSI-conceived children had to be hospitalized more often at a neonatal intensive care unit (p = 0.004). There was no difference in pH of the umbilical artery or in major congenital malformations between the two groups. Pregnancy complications (i.e., premature rupture of membranes, cervical insufficiency, and premature uterine contractions) and the need for maternal hospitalization during pregnancy were found significantly more often after IVF (p = 0.0016 and p = 0.0095, respectively), compared to the ICSI group. When comparing IVF versus ICSI-conceived pregnancies at a tertiary care center, we found the course of pregnancy to be more complicated after IVF, whereas the primary fetal outcome seemed to be better in this group than after ICSI treatment.

Obstetric and perinatal outcomes in IVF versus ICSI-conceived pregnancies at a tertiary care center - a pilot study

PubMed Central

2013-01-01

Background Although most pregnancies after IVF result in normal healthy outcomes, an increased risk for a number of obstetric and neonatal complications, compared to naturally conceived pregnancies, has been reported. While there are many studies that compare pregnancies after assisted reproductive techniques with spontaneously conceived pregnancies, fewer data are available that evaluate the differences between IVF and ICSI-conceived pregnancies. The aim of our present study was, therefore, to compare obstetric and perinatal outcomes in pregnancies conceived after in vitro fertilization (IVF) versus intracytoplasmatic sperm injection (ICSI). Methods Three-hundred thirty four women who had become pregnant after an IVF or ICSI procedure resulted in a total of 530 children referred between 2003 und 2009 to the Department of Obstetrics and Gynecology of the Medical University of Vienna, a tertiary care center, and were included in this retrospective cohort study. We assessed maternal and fetal parameters in both groups (IVF and ICSI). The main study outcomes were preterm delivery, the need for neonatal intensive care, and congenital malformations. Moreover, we compared the course of pregnancy between both groups and the occurrence of complications that led to maternal hospitalization during pregnancy. Results There were 80 children conceived via ICSI and 450 children conceived via IVF. Mean gestational age was significantly lower in the ICSI group (p = 0.001). After ICSI, the birth weight (p = 0.008) and the mean APGAR values after 1 minute and after 10 minutes were lower compared to that of the IVF group (p = 0.016 and p = 0.047, respectively). Moreover, ICSI-conceived children had to be hospitalized more often at a neonatal intensive care unit (p = 0.004). There was no difference in pH of the umbilical artery or in major congenital malformations between the two groups. Pregnancy complications (i.e., premature rupture of membranes, cervical insufficiency, and premature uterine contractions) and the need for maternal hospitalization during pregnancy were found significantly more often after IVF (p = 0.0016 and p = 0.0095, respectively), compared to the ICSI group. Conclusions When comparing IVF versus ICSI-conceived pregnancies at a tertiary care center, we found the course of pregnancy to be more complicated after IVF, whereas the primary fetal outcome seemed to be better in this group than after ICSI treatment. PMID:24004836

Dual triggering with GnRH agonist plus hCG versus triggering with hCG alone for IVF/ICSI outcome in GnRH antagonist cycles: a systematic review and meta-analysis.

PubMed

Chen, Chi-Huang; Tzeng, Chii-Ruey; Wang, Peng-Hui; Liu, Wei-Min; Chang, Heng-Yu; Chen, Huang-Hui; Chen, Ching-Hui

2018-03-29

To summarize available evidence from randomized-controlled trials which have evaluated triggering of final oocyte maturation with concomitant GnRH agonists and hCG in patients undergoing IVF, and to analyze whether dual triggering is as efficacious as hCG triggering in terms of oocyte and pregnancy outcomes. A comprehensive literature search was performed to identify randomized-controlled trials comparing IVF outcomes between women receiving combined administration of hCG with GnRH agonists and those receiving hCG alone for triggering of final oocyte maturation. Four studies including 527 patients eligible for inclusion in meta-analysis were identified. No significant difference in the number of mature oocytes or fertilized oocytes retrieved was found between groups. Clinical pregnancy rate with dual triggering was significantly higher as compared with hCG-alone triggering (pooled OR = 0.48, 95% CI 0.31-0.77, P = 0.002), but there was no significant difference in the ongoing pregnancy rate between groups. Results of meta-analysis indicate comparable or significantly improved outcomes with the use of GnRH agonists plus hCG as compared with hCG alone for triggering of final oocyte maturation.

Body mass index is an independent risk factor for the development of endometrial polyps in patients undergoing in vitro fertilization.

PubMed

Onalan, Reside; Onalan, Gogsen; Tonguc, Esra; Ozdener, Tulin; Dogan, Muammer; Mollamahmutoglu, Leyla

2009-04-01

To determine the subgroup of patients in whom office hysteroscopy should be routinely performed before an in vitro fertilization (IVF) program. Retrospective cohort analysis. Tertiary education and research hospital. Two hundred twenty-three patients who underwent a uterine evaluation by office hysteroscopy before the IVF and embryo transfer cycle. The office hysteroscopy was performed in the follicular phase of the menstrual cycle before the IVF cycle. The office findings: number of polyps, number of multiple polyps, and polyp size. Patients with polycystic ovary syndrome (PCOS) had a higher number of endometrial polyps, but the difference was not statistically significant (28.9% vs. 18.3%). When comparing the patients according to BMI, patients with BMI >or=30 had a statistically significantly higher number of endometrial polyps versus BMI <30 (52% vs. 15%). On the other hand, obesity was positively correlated with the occurrence of polyps, size of the polyps, and occurrence of multiple number of polyps in the correlation analysis. In addition, logistic regression analysis using age, obesity, duration of infertility, and estradiol levels revealed that obesity was an independent prognostic factor for the development of endometrial polyps. Office hysteroscopy should be performed in patients with BMI >or=30 because obesity may act as an initiator for the pathogenesis of endometrial polyps.

Proteomic analysis of human follicular fluid associated with successful in vitro fertilization.

PubMed

Shen, Xiaofang; Liu, Xin; Zhu, Peng; Zhang, Yuhua; Wang, Jiahui; Wang, Yanwei; Wang, Wenting; Liu, Juan; Li, Ning; Liu, Fujun

2017-07-27

Human follicular fluid (HFF) provides a key environment for follicle development and oocyte maturation, and contributes to oocyte quality and in vitro fertilization (IVF) outcome. To better understand folliculogenesis in the ovary, a proteomic strategy based on dual reverse phase high performance liquid chromatography (RP-HPLC) coupled to matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (LC-MALDI TOF/TOF MS) was used to investigate the protein profile of HFF from women undergoing successful IVF. A total of 219 unique high-confidence (False Discovery Rate (FDR) < 0.01) HFF proteins were identified by searching the reviewed Swiss-Prot human database (20,183 sequences), and MS data were further verified by western blot. PANTHER showed HFF proteins were involved in complement and coagulation cascade, growth factor and hormone, immunity, and transportation, KEGG indicated their pathway, and STRING demonstrated their interaction networks. In comparison, 32% and 50% of proteins have not been reported in previous human follicular fluid and plasma. Our HFF proteome research provided a new complementary high-confidence dataset of folliculogenesis and oocyte maturation environment. Those proteins associated with innate immunity, complement cascade, blood coagulation, and angiogenesis might serve as the biomarkers of female infertility and IVF outcome, and their pathways facilitated a complete exhibition of reproductive process.

In Vitro Fertilization in 37 Women with Systemic Lupus Erythematosus or Antiphospholipid Syndrome: A Series of 97 Procedures.

PubMed

Orquevaux, Pauline; Masseau, Agathe; Le Guern, Véronique; Gayet, Vanessa; Vauthier, Danièle; Guettrot-Imbert, Gaelle; Huong, Du Le Thi; Wechsler, Bertrand; Morel, Nathalie; Cacoub, Patrice; Pennaforte, Jean-Loup; Piette, Jean-Charles; Costedoat-Chalumeau, Nathalie

2017-05-01

To compile and assess data about complication and success rates for in vitro fertilization (IVF) of women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). To date, such data are sparse. This retrospective study described women with SLE and/or APS who have had at least 1 IVF cycle. Thirty-seven women with SLE (n = 23, including 8 with antiphospholipid antibodies), SLE with APS (n = 4), or primary APS (n = 10) underwent 97 IVF procedures. For 43% of cases, the infertility was female in origin, for 19% male, 14% mixed, and 24% unexplained. No women had premature ovarian insufficiency because of cyclophosphamide. Median age at IVF was 34 years (range 26-46). The median number of IVF cycles was 2.6 (1-8). Patients were treated with hydroxychloroquine (72%), steroids (70%), azathioprine (3%), aspirin (92%), and/or low molecular weight heparin (62%). There were 27 (28%) pregnancies, 23 live births among 26 neonates (3 twin pregnancies), 2 miscarriages, and 2 terminations for trisomy 13 and 21. Six spontaneous pregnancies occurred during the followup. Finally, 26 women (70%) delivered at least 1 healthy child. Complications occurred in or after 8 IVF cycles (8%): SLE flares in 4 (polyarthritis in 3 and lupus enteritis in 1) and thromboembolic events in 4 others. One SLE flare was the first sign of previously undiagnosed SLE. Poor treatment adherence was obvious in 2 other flares and 2 thromboses. No ovarian hyperstimulation syndrome was reported. These preliminary results confirm that IVF can be safely and successfully performed in women with SLE and/or APS.

PGD for all cystic fibrosis carrier couples: novel strategy for preventive medicine and cost analysis.

PubMed

Tur-Kaspa, I; Aljadeff, G; Rechitsky, S; Grotjan, H E; Verlinsky, Y

2010-08-01

Over 1000 children affected with cystic fibrosis (CF) are born annually in the USA. Since IVF with preimplantation genetic diagnosis (PGD) is an alternative to raising a sick child or to aborting an affected fetus, a cost-benefit analysis was performed for a national IVF-PGD program for preventing CF. The amount spent to deliver healthy children for all CF carrier-couples by IVF-PGD was compared with the average annual and lifetime direct medical costs per CF patient avoided. Treating annually about 4000 CF carrier-couples with IVF-PGD would result in 3715 deliveries of non-affected children at a cost of $57,467 per baby. Because the average annual direct medical cost per CF patient was $63,127 and life expectancy is 37 years, savings would be $2.3 million per patient and $2.2 billion for all new CF patients annually in lifetime treatment costs. Cumulated net saving of an IVF-PGD program for all carrier-couples for 37 years would be $33.3 billion. A total of 618,714 cumulative years of patients suffering because of CF and thousands of abortions could be prevented. A national IVF-PGD program is a highly cost-effective novel modality of preventive medicine and would avoid most births of individuals affected with debilitating genetic disease. 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Hyper-activated motility in sperm capacitation is mediated by phospholipase D-dependent actin polymerization.

PubMed

Itach, Sarit Bar-Sheshet; Finklestein, Maya; Etkovitz, Nir; Breitbart, Haim

2012-02-15

In order to fertilize the oocyte, sperm must undergo a series of biochemical changes in the female reproductive tract, known as capacitation. Once capacitated, spermatozoon can bind to the zona pellucida of the egg and undergo the acrosome reaction (AR), a process that enables its penetration and fertilization of the oocyte. Important processes that characterize sperm capacitation are actin polymerization and the development of hyper-activated motility (HAM). Previously, we showed that Phospholipase D (PLD)-dependent actin polymerization occurs during sperm capacitation, however the role of this process in sperm capacitation is not yet known. In the present study, we showed for the first time the involvement of PLD-dependent actin polymerization in sperm motility during mouse and human capacitation. Sperm incubated under capacitation conditions revealed a time dependent increase in actin polymerization and HAM. Inhibition of Phosphatidic Acid (PA) formation by PLD using butan-1-ol, inhibited actin polymerization and motility, as well as in vitro fertilization (IVF) and the ability of the sperm to undergo the AR. The inhibition of sperm HAM by low concentration of butan-1-ol is completely restored by adding PA, further indicating the involvement of PLD in these processes. Furthermore, exogenous PA enhanced rapid actin polymerization that was followed by a rise in the HAM, as well as an increased in IVF rate. In conclusion, our results demonstrate that PLD-dependent actin polymerization is a critical step needed for the development of HAM during mouse and human sperm capacitation. Copyright © 2011 Elsevier Inc. All rights reserved.

Analysis of follicular fluid retinoids in women undergoing in vitro fertilization: retinoic acid influences embryo quality and is reduced in women with endometriosis.

PubMed

Pauli, Samuel A; Session, Donna R; Shang, Weirong; Easley, Kirk; Wieser, Friedrich; Taylor, Robert N; Pierzchalski, Keely; Napoli, Joseph L; Kane, Maureen A; Sidell, Neil

2013-09-01

Retinol (ROL) and its biologically active metabolite, all-trans retinoic acid (ATRA), are essential for a number of reproductive processes. However, there is a paucity of information regarding their roles in ovarian folliculogenesis, oocyte maturation, and early embryogenesis. The objectives of this study were to quantify and compare peripheral plasma (PP) and follicular fluid (FF) retinoid levels, including ATRA in women undergoing in vitro fertilization (IVF) and to investigate the relationship between retinoid levels and embryo quality. Retinoid levels were evaluated in PP and FF from 79 women undergoing IVF at the time of oocyte retrieval and corresponding embryo quality assessed on a daily basis after retrieval for 3 days until uterine transfer. Analysis compared the retinoid levels with day 3 embryo grades and between endometriosis versus control patients. Results demonstrated distinctive levels of retinoid metabolites and isomers in FF versus PP. There was a significantly larger percentage of high-quality grade I embryos derived from the largest versus smallest follicles. An increase in follicle size also correlated with a >50% increase in FF ROL and ATRA concentrations. Independent of follicle size, FF yielding grade I versus nongrade I embryos showed higher mean levels of ATRA but not ROL. In a nested case-control analysis, control participants had 50% higher mean levels of ATRA in their FF and PP than women with endometriosis. These findings strongly support the proposition that ATRA plays a fundamental role in oocyte development and quality, and that reduced ATRA synthesis may contribute to decreased fecundity of participants with endometriosis.

Analysis of Follicular Fluid Retinoids in Women Undergoing In Vitro Fertilization

PubMed Central

Pauli, Samuel A.; Session, Donna R.; Shang, Weirong; Easley, Kirk; Wieser, Friedrich; Taylor, Robert N.; Pierzchalski, Keely; Napoli, Joseph L.; Kane, Maureen A.

2013-01-01

Retinol (ROL) and its biologically active metabolite, all-trans retinoic acid (ATRA), are essential for a number of reproductive processes. However, there is a paucity of information regarding their roles in ovarian folliculogenesis, oocyte maturation, and early embryogenesis. The objectives of this study were to quantify and compare peripheral plasma (PP) and follicular fluid (FF) retinoid levels, including ATRA in women undergoing in vitro fertilization (IVF) and to investigate the relationship between retinoid levels and embryo quality. Retinoid levels were evaluated in PP and FF from 79 women undergoing IVF at the time of oocyte retrieval and corresponding embryo quality assessed on a daily basis after retrieval for 3 days until uterine transfer. Analysis compared the retinoid levels with day 3 embryo grades and between endometriosis versus control patients. Results demonstrated distinctive levels of retinoid metabolites and isomers in FF versus PP. There was a significantly larger percentage of high-quality grade I embryos derived from the largest versus smallest follicles. An increase in follicle size also correlated with a >50% increase in FF ROL and ATRA concentrations. Independent of follicle size, FF yielding grade I versus nongrade I embryos showed higher mean levels of ATRA but not ROL. In a nested case–control analysis, control participants had 50% higher mean levels of ATRA in their FF and PP than women with endometriosis. These findings strongly support the proposition that ATRA plays a fundamental role in oocyte development and quality, and that reduced ATRA synthesis may contribute to decreased fecundity of participants with endometriosis. PMID:23427183

Massage therapy improves in vitro fertilization outcome in patients undergoing blastocyst transfer in a cryo-cycle.

PubMed

Okhowat, Jasmin; Murtinger, Maximilian; Schuff, Maximilian; Wogatzky, Johannes; Spitzer, Dietmar; Vanderzwalmen, Pierre; Wirleitner, Barbara; Zech, Nicolas Herbert

2015-01-01

Massage therapy is increasingly used to relieve physical and mental discomfort and is suggested as a safe therapeutic modality, without any significant risks or any known side effects. Although a multitude of complementary therapies, such as acupuncture, are applied in reproductive medicine, no information is available with regard to the application of massage as an adjuvant therapy in assisted-reproduction techniques (ARTs). This study was intended to assess the effectiveness of a deep relaxation (andullation) therapy based on oscillating vibrations when used prior to embryo transfer (ET) in in vitro fertilization (IVF) cryo-cycles. The research team designed a retrospective, observational study. Participants willing to undergo the massage treatment were allocated to the intervention (andullation) group. The study was performed at the IVF Centers Prof. Zech-Bregenz in Bregenz, Austria. A total of 267 IVF patients, with a mean age of 36.3 y, participated in this single-center study. All patients receiving a transfer of vitrified and warmed blastocysts between January and December 2012 were included in the evaluation. Prior to ET, the andullation group received a standardized program of therapy-a 30-min, deep relaxation massage on an oscillating (vibrating) device, whereas the control group did not. To determine efficacy, the primary outcomes that the study measured were (1) pregnancy rates (PRs), by testing urine and obtaining a positive β-human chorionic gonadotropin (β-hCG); and (2) ongoing, pregnancies (oPR), by observation of fetal heartbeat and birth rates (BR) as well as miscarriage rates. The patients' medical histories and types of infertility as well as the quality of the embryo transfers (ETs) were evaluated. In patients using the massage therapy prior to ET, significantly higher PRs, oPRs, and BRs were observed compared with the control group-PR: 58.9% vs 41.7%, P<.05; oPR: 53.6% vs 33.2%, P<.01; and BR: 32.0% vs 20.3%, P<.05. No differences were detected among groups for patients' ages, hormonal substitution protocols, endometrium structures and buildups, quality of transferred embryos, or quality of transfers. No adverse effects were noted in the massage group. The research team's results suggested that andullation therapy prior to blastocyst transfer in a cryo-cycle improves embryo implantation, most likely due to a reduction in stress (ie, a relaxation effect on patients), a reduction in uterine contractions, and, probably, an enhancement of the blood flow in the abdominal region. These findings provide support for use of andullation as a complementary therapy for ART.

Paternal urinary concentrations of organophosphate flame retardant metabolites, fertility measures, and pregnancy outcomes among couples undergoing in vitro fertilization.

PubMed

Carignan, Courtney C; Mínguez-Alarcón, Lidia; Williams, Paige L; Meeker, John D; Stapleton, Heather M; Butt, Craig M; Toth, Thomas L; Ford, Jennifer B; Hauser, Russ

2018-02-01

Use of organophosphate flame retardants (PFRs) has increased over the past decade following the phase out of some brominated flame retardants, leading to increased human exposure. We recently reported that increasing maternal PFR exposure is associated with poorer pregnancy outcomes among women from a fertility clinic. Because a small epidemiologic study previously reported an inverse association between male PFR exposures and sperm motility, we sought to examine associations of paternal urinary concentrations of PFR metabolites and their partner's pregnancy outcomes. This analysis included 201 couples enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2005-2015) who provided one or two urine samples per IVF cycle. In both the male and female partner, we measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). The sum of the molar concentrations of the urinary PFR metabolites was calculated. We used multivariable generalized linear mixed models to evaluate the association of urinary concentrations of paternal PFR metabolites with IVF outcomes, accounting for multiple in vitro fertilization (IVF) cycles per couple. Models were adjusted for year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity. Detection rates were high for paternal urinary concentrations of BDCIPP (84%), DPHP (87%) and ip-PPP (76%) but low for tb-PPP (12%) and zero for BCIPP (0%). We observed a significant 12% decline in the proportion of fertilized oocytes from the first to second quartile of male urinary ΣPFR and a 47% decline in the number of best quality embryos from the first to third quartile of male urinary BDCIPP in our adjusted models. An 8% decline in fertilization was observed for the highest compared to lowest quartile of urinary BDCIPP concentrations (95% CI: 0.01, 0.12, p-trend=0.06). Using IVF as a model to investigate human reproduction and pregnancy outcomes, we found that paternal urinary concentrations of BDCIPP were associated with reduced fertilization. In contrast to previously reported findings for the female partners, the paternal urinary PFR metabolites were not associated with the proportion of cycles resulting in successful implantation, clinical pregnancy, and live birth. These results indicate that paternal preconception exposure to TDCIPP may adversely impact successful oocyte fertilization, whereas female preconception exposure to ΣPFRs may be more relevant to adverse pregnancy outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Seeking conception: experiences of urban Indian women with in vitro fertilisation.

PubMed

Widge, Anjali

2005-12-01

This paper reports on a study of involuntarily childless Indian women/couples seeking in vitro fertilisation (IVF). The focus is on the social context of infertility and on women's perceptions of and experiences with IVF. Twenty-two childless women/couples who sought IVF. The sample was drawn from consenting clients of clinics in two major Indian cities, viz. New Delhi and Mumbai. In-depth interviews revealed that infertility is deeply feared, women's status and security are affected, and they experience stigmatisation and isolation. IVF was pursued after less intrusive avenues had been exhausted. Inadequate information/counselling is provided, success rates are low, IVF is commercialised and the process is physiologically, emotionally and financially stressful. In Indian society fertility defines womanhood and motherhood, and infertility is stigmatised. Women faced a lot of pressures to produce a biological child, and go through all kinds of treatments, including the expensive ARTs, to have a child. Integration of infertility services into the state's reproductive health programme and disseminate information on infertility and to offer other appropriate choices, such as adoption. Effective counselling on coping with psychosocial/sexual problems. Monitoring of the prevalence of sex preselection.

Influence of embryo culture medium (G5 and HTF) on pregnancy and perinatal outcome after IVF: a multicenter RCT.

PubMed

Kleijkers, Sander H M; Mantikou, Eleni; Slappendel, Els; Consten, Dimitri; van Echten-Arends, Jannie; Wetzels, Alex M; van Wely, Madelon; Smits, Luc J M; van Montfoort, Aafke P A; Repping, Sjoerd; Dumoulin, John C M; Mastenbroek, Sebastiaan

2016-10-01

Does embryo culture medium influence pregnancy and perinatal outcome in IVF? Embryo culture media used in IVF affect treatment efficacy and the birthweight of newborns. A wide variety of culture media for human preimplantation embryos in IVF/ICSI treatments currently exists. It is unknown which medium is best in terms of clinical outcomes. Furthermore, it has been suggested that the culture medium used for the in vitro culture of embryos affects birthweight, but this has never been demonstrated by large randomized trials. We conducted a multicenter, double-blind RCT comparing the use of HTF and G5 embryo culture media in IVF. Between July 2010 and May 2012, 836 couples (419 in the HTF group and 417 in the G5 group) were included. The allocated medium (1:1 allocation) was used in all treatment cycles a couple received within 1 year after randomization, including possible transfers with frozen-thawed embryos. The primary outcome was live birth rate. Couples that were scheduled for an IVF or an ICSI treatment at one of the six participating centers in the Netherlands or their affiliated clinics. The live birth rate was higher, albeit nonsignificantly, in couples assigned to G5 than in couples assigned to HTF (44.1% (184/417) versus 37.9% (159/419); RR: 1.2; 95% confidence interval (CI): 0.99-1.37; P = 0.08). Number of utilizable embryos per cycle (2.8 ± 2.3 versus 2.3 ± 1.8; P < 0.001), implantation rate after fresh embryo transfer (20.2 versus 15.3%; P < 0.001) and clinical pregnancy rate (47.7 versus 40.1%; RR: 1.2; 95% CI: 1.02-1.39; P = 0.03) were significantly higher for couples assigned to G5 compared with those assigned to HTF. Of the 383 live born children in this trial, birthweight data from 380 children (300 singletons (G5: 163, HTF: 137) and 80 twin children (G5: 38, HTF: 42)) were retrieved. Birthweight was significantly lower in the G5 group compared with the HTF group, with a mean difference of 158 g (95% CI: 42-275 g; P = 0.008). More singletons were born preterm in the G5 group (8.6% (14/163) versus 2.2% (3/137), but singleton birthweight adjusted for gestational age and gender (z-score) was also lower in the G5 than in the HTF group (-0.13 ± 0.08 versus 0.17 ± 0.08; P = 0.008). This study was powered to detect a 10% difference in live births while a smaller difference could still be clinically relevant. The effect of other culture media on perinatal outcome remains to be determined. Embryo culture media used in IVF affect not only treatment efficacy but also perinatal outcome. This suggests that the millions of human embryos that are cultured in vitro each year are sensitive to their environment. These findings should lead to increased awareness, mechanistic studies and legislative adaptations to protect IVF offspring during the first few days of their existence. This project was partly funded by The NutsOhra foundation (Grant 1203-061) and March of Dimes (Grant 6-FY13-153). The authors declare no conflict of interest. NTR1979 (Netherlands Trial Registry). 1 September 2009. 18 July 2010. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Desire for a child and desired children--possibilities and limits of reproductive biomedicine].

PubMed

Krones, Tanja; Neuwohner, Elke; El Ansari, Susan; Wissner, Thomas; Richter, Gerd

2006-03-01

Definition of problem: Reproductive Biomedicine and new reproductive technologies (ART) belong to the fields of medicine that initiated most of the discussion on enhancement and desire fulfilling medicine in bioethics during the last years. One of the crucial questions to be answered is the definition of the right to procreate/right for a genetically related child. Closely connected are controversial opinions in regard to the definition of sterility as a disease/illness, or a mere fate, or malfunction, which does not have to be medically cured. Arguments: After a cursory description of the national and international debate, we introduce some results of our 'bioethical field studies', exploring and comparing the views of experts (human geneticists, ethicists, pediatricians, obstetricians and midwifes) and couples/patients (IVF couples, high genetic risk couples and couples with no known risk for an inherited disease or infertility problem) on sterility, the right to procreate, possibilities and appropriate limits of IVF in Germany. According to the WHO, sterility has to be defined as an illness, if the respective couples have a desire for a child. IVF can be a means for a cure. Since 2004, Germany does no longer supply a thoroughly insurer financed IVF treatment. Our surveys indicate that this change, though supported by many experts, is hard to accept for couples concerned. Only obstetricians share the WHO's view that sterility should count as an illness. Many ethicists see a proclaimed human right to procreate as merely negative right, although many support free IVF treatment for poor couples. We challenge the expert majority view on the basis of the capability approach (Amartya Sen) and functional liberalism (Herlinde Pauer Studer) and with a view to the international state of the art in IVF. The desire to have children cannot be reduced to a non-authoritative preference whose fulfillment is optional, but has to be conceptualized as a normative need that ought to be met.

Transcriptional regulators TRIM28, SETDB1, and TP53 are aberrantly expressed in porcine embryos produced by in vitro fertilization in comparison to in vivo- and somatic-cell nuclear transfer-derived embryos

PubMed Central

Hamm, Jennifer; Tessanne, Kim; Murphy, Clifton N; Prather, Randall S

2014-01-01

In vitro embryo production is important for research in animal reproduction, embryo transfer, transgenics, and cloning. Yet, in vitro-fertilized (IVF) embryos are generally developmentally delayed and are inferior to in vivo-derived (IVV) embryos; this discrepancy is likely a result of aberrant gene expression. Transcription of three genes implicated to be important in normal preimplantation embryo development, TRIM28, SETDB1, and TP53, was determined by quanitative PCR in IVF, somatic-cell nuclear transfer (SCNT), parthenogenetic, and IVV porcine oocytes and embryos. There was no difference in TRIM28 or SETDB1 abundance between oocytes matured in vitro versus in vivo (P > 0.05), whereas TP53 levels were higher in in vitro-matured oocytes. TRIM28 increased from metaphase-II oocytes to the 4-cell and blastocyst stages in IVF embryos, whereas IVV embryos showed a reduction in TRIM28 abundance from maturation throughout development. The relative abundance of TP53 increased by the blastocyst stage in all treatment groups, but was higher in IVF embryos compared to IVV and SCNT embryos. In contrast, SETDB1 transcript levels decreased from the 2-cell to blastocyst stage in all treatments. For each gene analyzed, SCNT embryos of both hard-to-clone and easy-to-clone cell lines were more comparable to IVV than IVF embryos. Knockdown of TRIM28 also had no effect on blastocyst development or expression of SETDB1 or TP53. Thus, TRIM28, SETDB1, and TP53 are dynamically expressed in porcine oocytes and embryos. Furthermore, TRIM28 and TP53 abundances in IVV and SCNT embryos are similar, but different from quantities in IVF embryos. Mol. Reprod. Dev. 81: 552–556, 2014. © 2014 The Authors. Published by Wiley Periodicals, Inc. PMID:24659575

Modeling of live-birth rates and cost-effectiveness of oocyte cryopreservation for cancer patients prior to high- and low-risk gonadotoxic chemotherapy.

PubMed

Lyttle Schumacher, B; Grover, N; Mesen, T; Steiner, A; Mersereau, J

2017-10-01

What is the live-birth rate (LBR) and cost-effectiveness of fertility preservation with oocyte cryopreservation (FP-OC) compared to expectant management in cancer patients age 25-40 based on estimated gonadotoxicity of treatments 5 years after cancer diagnosis? Oocyte cryopreservation prior to cancer treatment is more costly, yet more effective (producing more live births), than not undergoing oocyte cryopreservation but it is most beneficial for patients undergoing high-risk chemotherapy (HRC). The decision to undergo FP prior to treatment is multifactorial and can be costly and delay treatment. Not all treatments carry the same gonadotoxicity and patients may choose to undergo FP-OC based on the probability of premature ovarian insufficiency, predicted outcomes and cost. A comprehensive model that incorporates age at diagnosis and toxicity of treatment to help guide patients in the decision to undergo FP-OC does not yet exist. This study used a Decision Analysis Model to estimate effectiveness and cost of FP for cancer patients. Age-based estimates of LBR and cost per live birth were calculated for ages 25-40 years based on gonadotoxicity of treatment. A decision analysis model was constructed using Treeage Pro 2015 with case base probabilities derived from national registries, practice guidelines and medical records from a national network of infertility practices (IntegraMed). Compared to no FP-OC, FP-OC improved LBRs for women of all ages undergoing either low-risk chemotherapy (LRC) or HRC; however, it was most cost effective for women undergoing LRC at older ages or HRC at younger ages. Although FP-OC results in higher LBRs, it was always more costly. Using donor oocyte IVF can be a successful alternative to autologous FP-OC. Decision tree results reflect probabilities of certain events and are compiled from multiple reputable sources but are not directly derived from a recruited cohort of patients. Outcomes are based on United States estimates and should be interpreted in the broader context of individual patient diagnoses, treatment care plans and country of origin. The development of this analytic model will help guide practitioners in their counseling of women from age 25 to 40 years, who are considering FP-OC at the time of cancer diagnosis. It provides a realistic pathway from diagnosis to LB and accounts for the majority of costs and outcome possibilities. This study was partially funded by a grant from National Institute of Health (NIH)/National Institute of Child Health and Human Development (NICHD) (R01 HD67683) to A.Z.S. There are no conflicts of interest to declare. N/A. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Gestational surrogacy and the role of routine embryo screening: Current challenges and future directions for preimplantation genetic testing.

PubMed

Sills, E Scott; Anderson, Robert E; McCaffrey, Mary; Li, Xiang; Arrach, Nabil; Wood, Samuel H

2016-03-01

Preimplantation genetic screening (PGS) is a component of IVF entailing selection of an embryo for transfer on the basis of chromosomal normalcy. If PGS were integrated with single embryo transfer (SET) in a surrogacy setting, this approach could improve pregnancy rates, minimize miscarriage risk, and limit multiple gestations. Even without PGS, pregnancy rates for IVF surrogacy cases are generally satisfactory, especially when treatment utilizes embryos derived from young oocytes and transferred to a healthy surrogate. However, there could be a more general role for PGS in surrogacy, since background aneuploidy in embryos remains a major factor driving implantation failure and miscarriage for all infertility patients. At present, the proportion of IVF cases involving GS is limited, while the number of IVF patients requesting PGS appears to be increasing. In this report, the relevance of PGS for surrogacy in the rapidly changing field of assisted fertility medicine is discussed. © 2015 Wiley Periodicals, Inc.

Treatment strategies and cumulative live birth rates in WHO-II ovulation disorders.

PubMed

Braam, Sanne C; de Bruin, Jan Peter; Buisman, Erato T I A; Brandes, Monique; Nelen, Willianne L D M; Smeenk, Jesper M J; van der Steeg, Jan Willem; Mol, Ben Willem J; Hamilton, Carl J C M

2018-04-10

To assess the live birth rate in women with WHO II anovulation and the proportion of women that need second or third line treatments if the initial therapy fails. In this multicenter cohort study we included couples with unfulfilled child wish who were referred to three fertility clinics in the Netherlands and selected women with a WHO II ovulation disorder as the only final infertility diagnosis (n = 468). The cumulative live birth rate of the total group was 82% (383/468). The majority started with clomiphene-citrate as first-line treatment (n = 378) resulting in 180 (48%) live births. There were 153 couples (40%) who underwent a second-line treatment (recombinant-FSH or laparoscopic electrocoagulation of the ovaries, LEO) and 52 couples (14%) a third-line treatment (IVF/ICSI), resulting in 44% and 63% treatment dependent live births rates, respectively. Of all couples, 92 (20%) conceived naturally, 186 (40%) after clomiphene-citrate, 60 (13%) after recombinant-FSH, nine (2%) after LEO and 36 (8%) after IVF. Subfertile women with a WHO II ovulation disorder have a good prognosis on live birth, and most did so after ovulation induction with clomiphene-citrate. If first-line ovulation induction has failed ovulation induction with gonadotrophins or IVF still result in a live birth in about half of the cases. Copyright © 2018 Elsevier B.V. All rights reserved.

Juggling on a rollercoaster? Gains, loss and uncertainties in IVF patients' accounts of volunteering for a U.K. ‘egg sharing for research’ scheme

PubMed Central

Haimes, Erica

2013-01-01

The past decade has seen a growth in demand for human eggs for stem cell related research and, more recently, for mitochondrial research. That demand has been accompanied by global debates over whether women should be encouraged, by offers of payments, in cash or kind, to provide eggs. Few of these debates have been informed by empirical evidence, let alone by the views of women themselves. This article addresses that gap in knowledge by presenting findings from a UK investigation, conducted 2008–2011, which is the first systematic study of women volunteering to provide eggs under such circumstances. This article focuses on the views and experiences of 25 IVF patients who volunteered for the Newcastle ‘egg sharing for research’ scheme (NESR), in exchange for reduced IVF fees. This was an interview based study, designed to gain understandings of volunteers' perspectives and reasoning. The interviews show that volunteers approached the scheme as a way of accessing more treatment in pursuit of their goal of having a baby, against a landscape of inadequate state provision of treatment and expensive private treatment. The process of deciding to volunteer raised a wide range of uncertainties about the consequent gains and losses, for women already in the uncertain world of the ‘IVF rollercoaster’. However, interviewees preferred to have the option of the NESR, than not, and they juggled the numerous uncertainties with skill and resilience. The article is as revealing of the ongoing challenges of the UK IVF bio-economy as it is of egg provision. This article adds to the growing body of knowledge of the contributions of tissue providers to the global bio-economy. It also contributes to several areas of wider sociological interest, including debates on the social management of ‘uncertainty’ and discussions at the interface of sociology and ethics. PMID:23608093

Cryopreservation of human ovarian tissue.

PubMed

Fabbri, Raffaella; Pasquinelli, Gianandrea; Bracone, Graziella; Orrico, Catia; Di Tommaso, Barbara; Venturoli, Stefano

2006-01-01

New and often aggressive treatment schemes allow the successful healing of many young patients with cancer, but the price the young women have to pay is high: many of them lose ovarian function and fertility. Due to the improved long-term survival of adolescents and young women with malignancies undergoing gonadotoxic chemotherapy, preservation of future fertility has been the focus of recent ubiquitarian interest. A feasible solution is the cryopreservation of ovarian tissue. Ovarian tissue, after thawing, can be used in three different ways: 1. grafted into its normal site (orthotopic); 2. grafted into a site other than its normal position (heterotopic), necessitating recourse to in vitro fertilization (IVF); 3. grown and in vitro matured in order to obtain metaphase II oocytes for an IVF program. It is believed that protein supplementation, in cryopreservation solution, is essential for improving ovarian tissue cryopreservation. The aim of this study was to evaluate the ultrastructural appearance of human ovarian tissue cryopreserved in 1.5 M 1,2 propanediol (PROH), 0.2 M sucrose using different protein sources: fetal calf serum (FCS), plasmanate or syntetic serum substitute (SSS). Fresh and frozen/thawed ovarian tissues were compared by transmission electron microscope (TEM), to evaluate the appearance of stromal and follicle cells as affected by different protein sources. Our data indicate that FCS is a better protein support for ovarian tissue cryopreservation when compared to SSS or Plasmanate. In addition the follicles are more resistant to the cryopreservation with respect to stroma.

Psychological adjustment of infertile women entering IVF treatment: differentiating aspects and influencing factors.

PubMed

Bringhenti, F; Martinelli, F; Ardenti, R; La Sala, G B

1997-05-01

To evaluate the psychological adjustment of infertile women compared with a control group of mothers and to determine which personal or marital factors influence the amount of emotional disorders in the infertile group. Cross-sectional questionnaire study with a group of infertile women and a group of mothers attending a routine gynecological examination. Infertile women and mothers received the questionnaires after a psychological or medical examination respectively, at a Sterility Center in a Department of Obstetrics and Gynaecology. One hundred and twenty-two infertile women, entering an IVF program, and 57 mothers attending a routine care visit. Stressful events, self-esteem, job and marital satisfaction, care and control measures of intimate bond, state-trait anxiety, depression, psychophysiological symptoms and global emotional factor scores. The organic infertile group was higher than mothers on satisfaction with their relationship with their husbands, perception of care and state-anxiety. The emotional factor scores of infertile women, controlled for stressful events, were influenced by a) number of IVF-cycles and availability for adoption, b) job position, job satisfaction and self-esteem, c) personality dimensions. State and trait anxiety scores were influenced by the level of global marital satisfaction. Infertile women, entering an IVF treatment program, do not necessarily show signs of psychological maladjustment. Their level of state-anxiety can be considered a situational response to the treatment stress. The infertility condition and its treatment can be effectively dealt with by women having a good personality disposition, a high level of self-esteem, who are satisfied with their job and relationship with their husband, and who are willing to adopt a child as a last solution for their maternal need.

Choosing between possible lives: legal and ethical issues in preimplantation genetic diagnosis.

PubMed

Scott, Rosamund

2006-01-01

This article critically appraises the current legal scope of the principal applications of preimplantation genetic diagnosis (PGD). This relatively new technique, which is available to some parents undergoing in vitro fertilization (IVF) treatment, aims to ensure that a child is not born with a seemingly undesirable genetic condition. The question addressed here is whether there should be serious reasons to test for genetic conditions in embryos in order to be able to select between them. The Human Fertilisation and Embryology Authority and the Human Genetics Commission have decided that there should be such reasons by broadly aligning the criteria for PGD with those for selective abortion. This stance is critically explored, as are its implications for the possible use of PGD to select either against or for marginal features or for significant traits. The government is currently reviewing the legal scope and regulation of PGD.

Noninvasive imaging systems for gametes and embryo selection in IVF programs: a review.

PubMed

Omidi, Marjan; Faramarzi, Azita; Agharahimi, Azam; Khalili, Mohammad Ali

2017-09-01

Optimizing the efficiency of the in vitro fertilization procedure by improving pregnancy rates and reducing the risks of multiple pregnancies simultaneously are the primary goals of the current assisted reproductive technology program. With the move to single embryo transfers, the need for more cost-effective and noninvasive methods for embryo selection prior to transfer is paramount. These aims require advancement in a more acquire gametes/embryo testing and selection procedures using high-tech devices. Therefore, the aim of the present review is to evaluate the efficacy of noninvasive imaging systems in the current literatures, focusing on the potential clinical application in infertile patients undergoing assisted reproductive technology treatments. In this regards, three advanced imaging systems of motile sperm organelle morphology examination, polarization microscopy and time-lapse monitoring for the best selection of the gametes and preimplantation embryos are introduced in full. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

In vitro fertilization alters growth and expression of Igf2/H19 and their epigenetic mechanisms in the liver and skeletal muscle of newborn and elder mice.

PubMed

Le, Fang; Wang, Li Ya; Wang, Ning; Li, Lei; Li, Le Jun; Zheng, Ying Ming; Lou, Hang Ying; Liu, Xiao Zhen; Xu, Xiang Rong; Sheng, Jian Zhong; Huang, He Feng; Jin, Fan

2013-03-01

Epidemiological studies have reported a higher incidence of growth disorders among newborns conceived by in vitro fertilization (IVF), suggesting that IVF may be disruptive to the process of embryonic and fetal growth. However, the long-term effects of IVF on the growth and molecular mechanisms remain unclear. Therefore, we evaluated the body weight of IVF mice from birth to the age of 1.5 yr. In addition, we analyzed gene expression of insulin-like growth factor 2 (Igf2), H19, Igf2 receptor (Igf2r), and miR-483 and their DNA methylation status using real-time quantitative PCR, Western blot, and pyrosequencing. The results showed that when compared with the in vivo group, the body weight of IVF mice was significantly higher at birth, but lower at 3 wk; in addition, gene expression of Igf2 was significantly up-regulated, with down-regulated expression of H19 and miR-483 in both liver and skeletal muscle. At the same time, there were significant differences in the DNA methylation rates of Igf2/H19 differentially methylated regions (DMRs) and the IGF2 protein expression between the two groups. In the IVF treatment group, the differences in growth and expression disappeared at 10 wk. However, at 1.5 yr of age, aberrant expressions of Igf2/H19, Igf2r, and miR-483 and changes in DNA methylation rates in the liver or skeletal muscle were again observed in IVF mice. Our results indicate that IVF causes alterations in mouse growth during the postnatal periods that may be associated with alterations in Igf2/H19 expression and likely involve the regulation of miR-483 and the methylation status of Igf2/H19 DMRs.

Dietary supplementation of antioxidants improves semen quality of IVF patients in terms of motility, sperm count, and nuclear vacuolization.

PubMed

Wirleitner, Barbara; Vanderzwalmen, Pierre; Stecher, Astrid; Spitzer, Dietmar; Schuff, Maximilian; Schwerda, Delf; Bach, Magnus; Schechinger, Birgit; Herbert Zech, Nicolas

2012-12-01

This study aimed to investigate the influence of an oral antioxidative supplementation on sperm quality of in vitro fertilization (IVF) patients, as analyzed by sperm motility according to the WHO criteria and motile sperm organelle morphology examination (MSOME). Semen samples were collected from 147 patients before undergoing an IVF/intracytoplasmic morphologically-selected sperm injection (IMSI) cycle and 2 - 12 months after an antioxidative supplementation. Semen analysis was evaluated according to WHO and MSOME criteria. Spermatozoa were grouped according to the size of nuclear vacuoles within the sperm's heads. Patients were divided into oligoasthenoteratozoospermic (OAT) and non-OAT men. Between first and second semen analysis, patients were supplemented orally with an antioxidative preparation. After the antioxidative therapy we observed a significant reduction in the percentage of immotile sperm cells in the patients. Additionally, the percentage of class I spermatozoa according to MSOME criteria was significantly higher after antioxidative supplementation. In OAT patients the percentage of class I sperm was found to be increased, although not significantly. However, we observed a drastic improvement in sperm motility as well as in total sperm count in this group. The results demonstrated a considerable improvement in semen quality, notably in OAT patients. Considering the putative relationship between semen quality on the one hand and reactive oxygen species on the other, the observed changes in the sperm parameters indicate that a decline in semen quality, and even subtle morphological changes, might be associated with oxidative stress. Our findings suggest that an antioxidative and micronutrient supplementation has a remarkable benefit for IVF patients having restricted sperm parameters, in particular.

Follicular aspiration versus coasting for ovarian hyper-stimulation syndrome prevention

PubMed Central

Bushaqer, Nayla J.; Dayoub, Nawal M.; AlHattali, Khalsa K.; Ayyoub, Hisham A.; AlFaraj, Samaher S.; Hassan, Samar N.

2018-01-01

Objectives: To compare follicular reduction prior to human chorionic gonadotropin (HCG) trigger and coasting in terms of ovarian hyper-stimulation syndrome (OHSS) reduction, pregnancy, and cancellation rates in in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods: This study was designed as a prospective study. The setting was the IVF unit at King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. A total of 39 patients undergoing IVF/ICSI cycles, who were at risk of OHSS, 20 were put into a coasting group and 19 had follicular reduction instead. This occurred between October 2010 and January 2011. Our main outcome was OHSS reduction. Results: Six (30%) women developed OHSS in the coasting group and 2 (10.5%) women developed OHSS in the follicular group (p-value=0.235). The pregnancy rates in the cycles were similar for both groups: 4/20 (20%) in the coasting group and 3/19 (15.8%) in the follicular group (p-value=1.000). The cancellation rate of the cycles was similar for both groups, 6/20 (30%) in the coasting group and 1/19 (5.3%) in the follicular group (p-value=0.09). The median number of punctured follicles was significantly lower in the follicular group (16 follicles, interquartile range (IQR)=21-12) compared to the coasting group (29 follicles, IQR=37.8-19.8, p-value=0.001). The retrieved, fertilized, and cleaved oocytes, as well as the number of embryos transferred, were similar amongst both groups. Conclusion: There was no difference between follicular reduction prior to HCG and coasting, in terms of OHSS reduction, pregnancy, and cancellation rates in both the IVF and ICSI cycles. PMID:29543308

Preimplantation genetic screening in older women: a cost-effectiveness analysis.

PubMed

Mersereau, Jennifer E; Plunkett, Beth A; Cedars, Marcelle I

2008-09-01

To compare the strategy of traditional IVF with prenatal diagnosis versus IVF with preimplantation genetic screening (IVF/PGS) to prevent aneuploid births in women with advanced maternal age. A decision tree analytic model was created to compare IVF alone versus IVF/PGS to evaluate which strategy is the least costly per healthy (euploid) infant. Outpatient IVF practices. Infertile women, 38-40 and >40 years old. IVF or IVF/PGS. Cost per healthy infant. Using base-case estimates of costs and probabilities in women aged 38-40 years, after a maximum of two fresh IVF cycles and two frozen cycles, the chance of having a healthy infant was 37.8% with IVF alone versus 21.7% with IVF/PGS. The average cost for each strategy is $25,700, but the cost per healthy infant is substantially higher when IVF/PGS is applied as opposed to IVF alone ($118,713 vs. $68,026). To assess the robustness of the model, all probabilities were varied simultaneously in a Monte Carlo simulation, and in 96.2% of trials, IVF alone proved to be the most cost-effective option. Conversely, our data demonstrate that in women aged >40, IVF and IVF/PGS are essentially equal in terms of cost-effectiveness ($122,000 vs. $118,713). IVF alone is less costly per healthy infant than IVF/PGS in women ages 38-40.

Micropuncture retrieval of epididymal sperm with in vitro fertilization: importance of in vitro micromanipulation techniques.

PubMed

Schlegel, P N; Palermo, G D; Alikani, M; Adler, A; Reing, A M; Cohen, J; Rosenwaks, Z

1995-08-01

To evaluate the importance of in vitro micromanipulation techniques, specifically intracytoplasmic sperm injection (ICSI), for the fertility treatment of men with congenital absence of the vas deferens (CAV) or other unreconstructable male reproductive tract obstruction. Results using ICSI during in vitro fertilization (IVF) were compared to previously published results of IVF alone and IVF with other micromanipulation techniques at the same infertility center. Main outcome parameters evaluated were: fertilization rate per oocyte, clinical pregnancy rate, and ongoing pregnancies and deliveries. IVF with ICSI yielded a fertilization rate per oocyte of 140 of 312 (45%) and a clinical pregnancy rate of 14 of 27 (52%) per cycle of sperm and egg retrieval. Ongoing pregnancies or deliveries have occurred for 13 of 27 (48%) cycles with ICSI. These results were better than our previously published results of IVF alone or in conjunction with the micromanipulation techniques of subzonal insertion (SuZI) or partial zona dissection (PZD) that yielded a 119 of 631 (19%; P < 0.0001) fertilization rate, clinical pregnancy rate of 14 of 51 (27%; P < 0.001) and ongoing pregnancy or delivery for 12 of 51 cycles (24%; P < 0.001). Epididymal sperm retrieval should be performed only when micromanipulation is available in conjunction with IVF to maximize chances of fertilization and subsequent pregnancies. The use of ICSI for epididymal sperm appears to maximize chances of pregnancy for couples with surgically unreconstructable obstructive male infertility.

Short-term effects of a hypocaloric diet with low glycemic index and low glycemic load on body adiposity, metabolic variables, ghrelin, leptin, and pregnancy rate in overweight and obese infertile women: a randomized controlled trial.

PubMed

Becker, Geórgia F; Passos, Eduardo P; Moulin, Cileide C

2015-12-01

Obesity is related to hormonal disorders that affect the reproductive system. Low-glycemic index (LGI) diets seem to exert a positive effect on weight loss and on metabolic changes that result from obesity. We investigated the effects of a hypocaloric diet with an LGI and low glycemic load on anthropometric and metabolic variables, ghrelin and leptin concentrations, and the pregnancy rate in overweight and obese infertile women who were undergoing in vitro fertilization (IVF). The study was a randomized block-design controlled trial in which we analyzed 26 overweight or obese infertile women. Patients were assigned to a hypocaloric LGI-diet group or a control group and followed the protocol for 12 wk. Body weight, body mass index (BMI), percentage of body fat, glucose, insulin, homeostasis model assessment of insulin resistance, serum lipids, reproductive hormones, leptin, acylated ghrelin, number of oocytes retrieved in the IVF cycle, and pregnancy rate were determined. There were greater reductions in body mass, BMI, percentage of body fat, waist:hip ratio, and leptin in the LGI-diet group than in the control group (P < 0.05). Despite a change of 18% in mean values, there was no significant increase in acylated ghrelin concentrations in the LGI group compared with the control group (P = 0.215). The LGI-diet group had 85.4% more oocytes retrieved than did the control group (7.75 ± 1.44 and 4.18 ± 0.87, respectively; P = 0.039) in the IVF cycle. Three patients (21.4%) in the LGI group experienced a spontaneous pregnancy during the follow-up, which generated 3 live births. The hypocaloric LGI diet promoted a decrease in BMI, percentage of body fat, and leptin concentrations, which improved oocyte development and pregnancy rate. These results support the clinical recommendation to advise overweight and obese women to lose weight through a balanced diet before being submitted for treatment with assisted reproduction technologies. A hypocaloric diet combined with LGI foods seems to be beneficial for these patients, but additional studies are required before this treatment is recommended. This trial was registered at clinicaltrials.gov as NCT02416960. © 2015 American Society for Nutrition.