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.

Associations of combined polymorphisms of the platelet membrane glycoproteins Ia and IIIa and the platelet-endothelial cell adhesion molecule-1 and P-Selectin genes with IVF implantation failures.

PubMed

Vlachadis, Nikolaos; Tsamadias, Vasileios; Vrachnis, Nikolaos; Kaparos, Georgios; Vitoratos, Nikolaos; Kouskouni, Evaggelia; Economou, Emmanuel

2017-04-01

The aim of the study was to investigate the combined impact of the genetic heterogeneity of the glycoproteins Ia (GpIa) and IIIa (GpIIIa) and the platelet-endothelial cell adhesion molecule-1 (PECAM-1) and P-Selectin genes on IVF embryo transfer implantation failures (IVF-ET failures). Sixty nulligravida women with previous IVF-ET failures and 60 fertile controls were genotyped for the GpIa-C807T, GpIIIa-PlA1/PA2, PECAM-1-C373G (Leu125Val) and P-Selectin-A37674C (Thr715Pro) polymorphisms by pyrosequencing. Compared with wild-type combined homozygotes, carriers of combinations of risk alleles in two gene loci were at significantly increased risk for IVF-ET failure, whereas carriers of the combination of GpIa-807T, GpIIIa-PlA2 and PECAM-1-373G alleles had OR = 52.50 (95%CI: 4.05-680.95, p < .001). The area under the receiver-operating characteristic curve (AUC) based on the number of polymorphisms and the number of risk alleles per subject was 75.4% (95%CI: 66.7%-82.8%, p < .001) and 72.5% (95%CI: 63.6%-80.3%, p < .001), respectively. The OR per polymorphism and risk allele increase was 4.26 (95%CI: 2.15-8.41, p < .001) and 2.85 (95%CI: 1.71-4.76, p < .001), respectively. The above associations were more robust among younger women. The combined analysis of these polymorphisms revealed strong association of combined carriers with IVF-ET failures especially for younger women and provided a genetic risk score with good diagnostic accuracy in the prediction of IVF-ET failures.

Impact of the Great East Japan Earthquake and Fukushima Nuclear Power Plant Accident on Assisted Reproductive Technology in Fukushima Prefecture: The Fukushima Health Management Survey.

PubMed

Hayashi, Masako; Fujimori, Keiya; Yasumura, Seiji; Nakai, Akihito

2017-09-01

The aim of the study was to evaluate the incidences and obstetric outcomes of women who conceived using assisted reproductive technology (ART) procedures in Fukushima Prefecture before and after the Great East Japan Earthquake and Fukushima nuclear power plant accident. Information was collected and analyzed from 12,070 women who conceived with or without ART in Fukushima Prefecture during the 9 months before and after the disaster. During the 9 months before and after the disaster, 138 (2.0%) and 102 (1.9%) women conceived with in vitro fertilization-embryo transfer (IVF-ET), respectively. The proportion of women who conceived with IVF-ET decreased during the 2 months immediately after the disaster, but returned to pre-disaster levels 3 months after the disaster. In the case of women who conceived without IVF-ET, the incidences of preterm birth and low birth weight increased after the disaster. In contrast, women who conceived with IVF-ET did not differ significantly in obstetric outcomes before and after the disaster but had a higher incidence of cesarean section and low birth weight compared to those conceived without IVF-ET, regardless of the study period. The influence of the disaster on woman who conceived using ART procedures was minimal.

Estradiol in saliva for monitoring follicular stimulation in an in vitro fertilization program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belkien, L.D.; Bordt, J.; Moeller, P.

1985-09-01

A rapid and sensitive radioimmunoassay (RIA) was developed to compare serum and saliva estradiol (E/sub 2/) levels in patients undergoing ovulation induction in an in vitro fertilization and embryo transfer (IVF-ET) program. Serum and saliva E/sub 2/ were compared in 23 patients. The sensitivity of the saliva RIA standard curve was 11 fmol/tube (equal to 3.2 pg/tube). There was a highly significant correlation between serum and saliva E/sub 2/ throughout the stimulated cycles. The ratio of serum to saliva E/sub 2/ was constant throughout the stimulated cycles. The E/sub 2/ concentration per follicle was 1548 pmol/l in serum and 23more » pmol/l in saliva. Mean E/sub 2/ levels in saliva (+/- SD) were 74 +/- 21 pmol/l at midcycle and 46 +/- 12 pmol/l at midluteal phase. The findings indicate that measurement of saliva E/sub 2/ provides a reliable, noninvasive method and may replace serum measurements for monitoring stimulated cycles in an IVF-ET program.« less

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

Intrauterine administration of recombinant human chorionic gonadotropin before embryo transfer on outcome of in vitro fertilization/ intracytoplasmic sperm injection: A randomized clinical trial

PubMed Central

Zarei, Afsoon; Parsanezhad, Mohammad Ebrahim; Younesi, Masoumeh; Alborzi, Saeed; Zolghadri, Jaleh; Samsami, Alamtaj; Amooee, Sedigheh; Aramesh, Shahintaj

2014-01-01

Background: The direct effect of hCG on the human endometrium was studied several times. Objective: The objectives of this study were to evaluate the effectiveness of intrauterine injection of recombinant human chorionic gonadotropin (rhCG) before embryo transfer (ET). Materials and Methods: In this randomized placebo-controlled clinical trial, a total number of 182 infertile patients undergoing their first in vitro fertilization/ intracytoplasmic sperm injection (IVF-ICSI) cycles were randomly assigned to receive 250μg intrauterine rhCG (n=84) or placebo (n=98) before ET. The implantation and pregnancy rates were compared between groups. Results: Patients who received intrauterine rhCG before ET had significantly higher implantation (36.9% vs. 22.4%; p=0.035), clinical pregnancy rates (34.5% vs. 20.4%; p=0.044) and ongoing pregnancy rate (32.1% vs. 18.4%; p=0.032) when compared to those who received placebo. The abortion (2.4% vs. 2.0%; p=0.929) and ectopic pregnancy rates (1.2% vs. 1.0%; p=0.976) were comparable between groups of rhCG and placebo, respectively. Conclusion: Intrauterine injection of 250μg of rhCG before ET significantly improves the implantation and pregnancy rates in IVF/ICSI cycles. Registration ID in IRCT: IRCT2012121711790N1 This article extracted from fellowship course thesis. (Masoumeh Younesi) PMID:24799855

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

High Serum FSH is Associated with Brown Oocyte Formation and a Lower Pregnacy Rate in Human IVF Parctice.

PubMed

Xu, Hongyi; Deng, Kai; Luo, Qingbing; Chen, Juan; Zhang, Xin; Wang, Xiaoyan; Diao, Honglu; Zhang, Changjun

2016-01-01

To investigate whether brown zona pellucida (ZP) of oocytes affects the outcome of fertilization, embryo quality and pregnancy rate in in vitro fertilization-embryo transfer (IVF-ET). Based on the ZP color of their oocytes, a total number of 703 patients dated from 2012 to 2014 were divided into a normal egg group (group A) and a brown oocyte group (group B), with 629 and 74 cases, respectively. Clinical characteristics, gonadotropin (Gn) days, Gn dosage, serum hormone levels on the day of human chorionic gonadotropin (HCG) injection, ZP thickness (ZPT) of the eggs, fertilization rate, rescue intracytoplasmic sperm injection (rICSI) rate, good-quality embryo rate and pregnancy rate were compared between the two groups. No significant differences were found in the duration and the causes of infertility, and their basal level of endocrine hormone before IVF-ET between normal egg group and brown egg group. The level of serum hormone including estradiol, progesterone and luteinizing hormone on the day of HCG injection were again similar. Moreover, there were no differences in number of mature oocytes, oocyte fertilization rates and rICSI rates after IVF between the two groups. However, we observed that the ZPT of brown oocytes (group B) was higher than that of normal oocytes (group A). Moreover, the Gn dosage and FSH levels on the day of HCG injection were significantly higher in group B than in group A and the good-quality embryo rate and pregnancy rate in group B were lower than those in group A. Compared with normal eggs, oocytes with a brown ZP were found to have a higher ZPT, lower embryo quality and lower pregnancy rate, which might be due to a high Gn dosage injection and high serum FSH levels during IVT-ET cycles. © 2016 The Author(s) Published by S. Karger AG, Basel.

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.

[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.

Prerequisites for successful human sperm cryobanking: sperm quality and prefreezing holding time.

PubMed

Yavetz, H; Yogev, L; Homonnai, Z; Paz, G

1991-04-01

Frozen-thawed donor semen was used in artificial inseminations and in vitro fertilization programs. Semen accepted for donation was characterized (mean +/- SE) by sperm concentration of 150 +/- 18.6 x 10(6)/mL, normal morphology of 57% +/- 1.4%, good progressive motility at 1 hour of 57% +/- 1.0%, and post-thaw motility of 45% +/- 1.0%. Delay of the freezing process for greater than 1 hour after semen delivery caused a deleterious effect to the freezability of sperm. The average monthly fecundability for the 1st 6 months after inseminations was 13.6%. This value decreased dramatically to 2.6% from the 7th month onward. In 74 IVF/embryo transfer (ET) cycles, the fertilization rate was 55.3% +/- 3.8%, pregnancy rate (PR) per ET was 39.6%, and the PR per woman was 42.8%.

Impact of the Great East Japan Earthquake and Fukushima Nuclear Power Plant Accident on Assisted Reproductive Technology in Fukushima Prefecture: The Fukushima Health Management Survey

PubMed Central

Hayashi, Masako; Fujimori, Keiya; Yasumura, Seiji; Nakai, Akihito

2017-01-01

Background The aim of the study was to evaluate the incidences and obstetric outcomes of women who conceived using assisted reproductive technology (ART) procedures in Fukushima Prefecture before and after the Great East Japan Earthquake and Fukushima nuclear power plant accident. Methods Information was collected and analyzed from 12,070 women who conceived with or without ART in Fukushima Prefecture during the 9 months before and after the disaster. Results During the 9 months before and after the disaster, 138 (2.0%) and 102 (1.9%) women conceived with in vitro fertilization-embryo transfer (IVF-ET), respectively. The proportion of women who conceived with IVF-ET decreased during the 2 months immediately after the disaster, but returned to pre-disaster levels 3 months after the disaster. In the case of women who conceived without IVF-ET, the incidences of preterm birth and low birth weight increased after the disaster. In contrast, women who conceived with IVF-ET did not differ significantly in obstetric outcomes before and after the disaster but had a higher incidence of cesarean section and low birth weight compared to those conceived without IVF-ET, regardless of the study period. Conclusion The influence of the disaster on woman who conceived using ART procedures was minimal. PMID:28811855

Shortening gametes co-incubation time improves live birth rate for couples with a history of fragmented embryos.

PubMed

Le Bras, Anne; Hesters, Laetitia; Gallot, Vanessa; Tallet, Cathie; Tachdjian, Gerard; Frydman, Nelly

2017-10-01

Short gamete co-incubation (SGCO) consists in decreasing the duration of contact between oocytes and sperm from the standard overnight insemination (SOI) toward 2 hours. However, the effectiveness of this technique to improve in vitro fertilization and embryo transfer (IVF-ET) outcomes remains controversial. Our study was designed to evaluate the efficiency of SGCO in a poor prognosis population with a history of fragmented embryos defined by the presence of at least 50% of the embryos with more than 25% of cytoplasmic fragments. From January 2010 to January 2014, 97 couples were included in a SGCO protocol. We separated women into 2 subgroups: younger and older than 35 years. Compared to SOI, after SGCO, 2-cell stage embryos were higher in all women (p<0.001) and less fragmented in women over 35 years (p<0.05). On day 2, top quality embryos obtained and transferred were higher with SCGO than with SOI, independently of the age of the women (p<0.001). Moreover, the number of embryos with less than 25% of fragmentation was higher after SGCO than SOI (p<0.001) whereas the number of multinucleated embryos was lower (p<0.001). We observed that after fresh ET, independently of the age of the women, the clinical pregnancy rate was 3 times higher after SGCO than after SOI. However, the live-birth rate was 4 times higher with SGCO than with SOI in women above 35 years but 3 times higher with SGCO than with SOI in women younger than 35 years. The present results indicate that for a particular indication, reducing the time of oocytes and sperm co-incubation may improve IVF-ET outcomes in terms of live-birth rate. AMH: anti mullerian hormone; COC: cumulus-oocytes complex; E2: estradiol; ET: embryo transfer; FET: frozen embryo transfer; FSH: follicle stimulating hormone; GnRH: gonadotrophin releasing hormone; hCG: human chorionic gonadotropin hormone; hMG: human menopausal gonadotropin hormone; IRB: institutional review board; IVF: in vitro fertilization; IVF-ET: in vitro fertilization and embryo transfer; MNB: multinucleated blastomere; mRNA: messanger ribonucleic acid; OC: oocyte retrieval; O2: oxygen; ROS: reactive oxygen species; SGCO: short gamete co-incubation; SOI: standard overnight insemination.

Human embryos secrete microRNAs into culture media--a potential biomarker for implantation.

PubMed

Rosenbluth, Evan M; Shelton, Dawne N; Wells, Lindsay M; Sparks, Amy E T; Van Voorhis, Bradley J

2014-05-01

To determine whether human blastocysts secrete microRNA (miRNAs) into culture media and whether these reflect embryonic ploidy status and can predict in vitro fertilization (IVF) outcomes. Experimental study of human embryos and IVF culture media. Academic IVF program. 91 donated, cryopreserved embryos that developed into 28 tested blastocysts, from 13 couples who had previously completed IVF cycles. None. Relative miRNA expression in IVF culture media. Blastocysts were assessed by chromosomal comparative genomic hybridization analysis, and the culture media from 55 single-embryo transfer cycles was tested for miRNA expression using an array-based quantitative real-time polymerase chain reaction analysis. The expression of the identified miRNA was correlated with pregnancy outcomes. Ten miRNA were identified in the culture media; two were specific to spent media (miR-191 and miR-372), and one was only present in media before the embryos had been cultured (miR-645). MicroRNA-191 was more highly concentrated in media from aneuploid embryos, and miR-191, miR-372, and miR-645 were more highly concentrated in media from failed IVF/non-intracytoplasmic sperm injection cycles. Additionally, miRNA were found to be more highly concentrated in ICSI and day-5 media samples when compared with regularly inseminated and day-4 samples, respectively. MicroRNA can be detected in IVF culture media. Some of these miRNA are differentially expressed according to the fertilization method, chromosomal status, and pregnancy outcome, which makes them potential biomarkers for predicting IVF success. Copyright © 2014 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

Toxic effects of ethylene oxide residues on bovine embryos in vitro.

PubMed

Holyoak, G R; Wang, S; Liu, Y; Bunch, T D

1996-04-15

The potential of ethylene oxide (EtO) residues in exposed plastic tissue culture dishes to adversely affect bovine oocyte maturation, fertilization and subsequent embryonic development was monitored. In experiment 1, the effects of aeration time and aeration combined with washing of EtO-gassed culture dishes on the extent of residual toxicity were investigated. There was no cleavage in any treatment in which oocytes were matured and fertilized in dishes exposed to EtO. EtO residues caused functional degeneration of oocytes even when culture dishes were aerated for more than 12 days post EtO-exposure and repeatedly washed. In experiment 2, the residual toxicity of EtO gas on in vitro maturation (IVM), in vitro fertilization (IVF) and in vitro culture (IVC) were evaluated. Cleavage rate significantly decreased and post-cleavage development was retarded in ova maintained in dishes treated with EtO either during IVM or IVF. EtO residues may be more detrimental to spermatozoa than to oocytes which may have been the primary cause of fertilization failure during IVF.

[From theory to clinical practice: recombinant FSH in daily practice].

PubMed

Kably Ambe, A; Barrón Vallejo, J; Góngora Rodríguez, A; Carballo Mondragón, E; Anta Jaén, E

1999-08-01

The purpose of the present study is to determine the efficacy of induction ovulation with recombinant FSH in patients treated with in vitro fertilization and embryo transfer (IVF-ET) and basic assisted reproductive techniques (ART). One hundred seven cycles were analyzed. The patients were divided in two groups: Group 1, treated with IVF (n = 12) and group 2, treated with basic ART (n = 95). Only recombinant FSH was utilized for ovulation induction; human corionic gonadotropin (hCG), 10,000 IU, were administered when one or more dominant follicles with diameter > or = 18 mm were presents; oocyte retrieval was performed 34 hour, while intrauterine insemination was practiced at 36 hours after the hCG injection. The pregnancy rate per IVF cycle was 25.0%, and 16.4% for basic ART. It is concluded that ovulation induction with recombinant FSH is a good and efficient alternative for both variations of ART.

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.

[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.

[Effects of "menstrual cycle-based acupuncture therapy" on IVF-ET in patients with decline in ovarian reserve].

PubMed

Zhou, Li; Xia, Youbing; Ma, Xiang; Tang, Limei; Lu, Jing; Tang, Qingqing; Wang, Yinping

2016-01-01

To observe the effects of "menstrual cycle-based acupuncture therapy" on ovarian function and pregnancy results of in vitro fertilization-embryo transfer (IVF-ET) in patients with decline in ovarian reserve (DOR). A total of 63 patients of DOR who received treatment of IVF/intracytoplasmic sperm injection (ICSI) were randomly divided into an observation group (30 cases) and a control group (33 cases). The patients in the observation group were treated with "menstrual cycle-based acupuncture therapy". The syndrome differentiation and treatment were given based on different phases of menstruation. Shiqizhui (EX-B 8) and Mingmen (GV 4) were selected during menstrual phase, Shenshu (BL 23), Geshu (BL 17), Sanyinjiao (SP 6) and Taixi (KI 3) were selected after menstruation, Qihai (CV 6), Guanyuan (CV 4), Zigong (EX-CA 1), Zusanli (ST 36) were selected during ovulatory period, Qihai (CV 6), Guanyuan (CV 4), Yanglingquan (GB 34), Taichong (LR 3) were selected before menstruation. The acupuncture was given twice a week until second menstrual cycle of oocyte retrieval. The total times of acupuncture was (15 ± 2). After acupuncture, patients were treated with IVF-ET. The patients in the control group were treated with IVF-ET but no acupuncture. The indices of ovarian reserve function, including basic follicle-stimulating hormone (FSH), estradiol (E2), antral follicle count (AFC), number of retrieved oocytes, number of fertilization and number of high quality embryo, were compared and analyzed before and after acupuncture in the observation group. The differences of outcomes of IVF-ET, including the cycle cancellation rate, implantation rate, the clinical pregnancy rate, were compared between the two groups. Compared before acupuncture, the E2, AFC, number of retrieved oocytes, number of high quality embrgo and number of fertilization were all increased after acupuncture in the observation group (all P< 0. 05). Compared with the control group, levels of the E2, the number of retrieved oocytes, number of fertilization and number of high quality embryo were all increased in the observation group (all P < 0.05). Also, the implantation rate, the clinical pregnancy rate were improved (both P < 0.01) and cycle cancellation rate was reduced (P< 0.01). The "menstrual cycle-based acupuncture therapy" can effectively improve the ovarian reserve function in DOR patients, leading to an improved clinical pregnancy rate of IVF-ET.

[Factors affecting the clinical pregnancy rate in an in vitro fertilization and embryo transfer program].

PubMed

Zhang, L; Wei, Z; Liu, P

1998-12-01

To analyze the various factors in an in vitro fertilization and embryo transfer (IVF-ET) program which may affect the clinical pregnacy rate. A retrospective study was done on 559 IVF-ET cycles from 1992-Nov. 1995. The indication for treatment was bilateral tubal blockage. The chi 2 analysis of single factor variants with SPSS-PC + V3.0 was used for statistics. The overall clinical pregnancy rate in 559 cycles was 21.6%. The cause of tubal blockage due to tuberculoses consisted of 28.4%, and 34.9% of secondary sterility had the history of artificial abortion. The changes of environment, the different causes of tubal blockage, the history of previous intrauterine pregnancy did not affect the clinical pregnancy rate. When the number of embryos transferred increased to 5, the clinical pregnancy rate was highest 32.5%. The cumulative embryo score or embryo quality was related significantly with clinical pregnancy rate. The number and quality of embryos transferred are important factors affecting the clinical pregnancy rate. However, measures to prevent high-order multiple pregnancy and studies on the survival potential of embryos besides their morphology should be emphasized.

Effects of triploidy incidence on clinical outcomes for IVF-ET cycles in different ovarian stimulation protocols.

PubMed

Li, Mingzhao; Xue, Xia; Zhang, Silin; Li, Wei; Zhao, Xiaoli; Ren, Wenjuan; Shi, Juanzi

2015-10-01

To discuss the relationship between triploidy incidence and clinical outcomes of embryos derived from normally fertilized oocytes from the same cohort for in vitro fertilization-embryo transfer (IVF-ET) cycles in different ovarian stimulation protocol. This study included 2070 in vitro fertilization (IVF) cycles with long-term protocol, 802 IVF cycles with ultra short-term protocol and 508 IVF-D (in vitro fertilization by donor semen) cycles with long-term protocol from January 2013 to September 2014. According to the different 3PN rate, patients were divided into three groups as follows: Group 1 included patients with 0% 3PN zygotes, Group 2 included patients with 1-25% 3PN zygotes and Group 3 included patients with >25% 3PN zygotes. female age, no. of retrieved oocytes, normal fertilization rate, day-3 grade I + II embryos rate, day-3 grade I + II + III embryos rate, implantation rate, pregnancy rate and early abortion rate. Triploidy cycle incidence rate in IVF and IVF-D cycles with long-term protocol were significantly higher than in IVF cycles with ultra short-term protocol (p < 0.001). Triploidy fertilization rate found no significant difference between the three groups (p > 0.05). In three protocols, normal fertilization rate in 3PN = 0% and 3PN = 1-25% groups were significantly higher compared to 3PN > 25% group (p < 0.001). In IVF cycles with long-term protocol, the day-3 grade I + II embryos, implantation and pregnancy rate in 3PN > 25% group were significantly lower than other two groups (p < 0.05). The day-3 grade I + II + III embryos and early abortion rate found no significant difference between the three groups (p > 0.05). In IVF cycles with ultra short-term protocol, there were no significant differences found in day-3 grade I + II embryos, day-3 grade I + II + III embryos, implantation, pregnancy and early abortion rate (p > 0.05). In IVF-D cycles with long-term protocol, the day-3 grade I + II embryos, day-3 grade I + II + III embryos and implantation rate in 3PN > 25% group were significantly lower than other two groups (p < 0.05). The pregnancy and early abortion rates found no significant difference in the three groups (p > 0.05). We observed that high proportion of triploid zygotes made a negative effect on clinical outcomes for IVF-ET cycles with long-term protocol.

Reinsemination of one-day-old oocytes by use of intracytoplasmic sperm injection.

PubMed

Lundin, K; Sjögren, A; Hamberger, L

1996-07-01

To evaluate the possible advantages of reinseminating oocytes by use of intracytoplasmic sperm injection (ICSI). Clinical study. In vitro fertilization unit with research facilities. Fifty-seven couples who were part of our regular IVF program. Nonfertilized oocytes from IVF cycles with no or very low fertilization were microinjected with spermatozoa approximately 25 hours after oocyte pick-up. Fertilization and pregnancy rates. A mean fertilization rate of 46.5% was obtained when reinseminating the oocytes on day 2 using the ICSI procedure. Of 57 cycles with completely or almost completely failed fertilization, 29 patients received ET after reinsemination by ICSI. Two of these transfers resulted in pregnancies (6.9% per ET) and two healthy babies were born. Despite this relative success, considering both the extra work involved and the potential genetic risk, it is doubtful whether ICSI on day 2 should be recommended as a routine procedure. For training and research purposes, however, this approach can be of value.

[Comparison of Alarelin and Triptorelin in the long-protocol ovulation induction in in vitro fertilization and embryo transfer].

PubMed

Duan, Jin-Liang; Jiang, Yuan-Hua; Liu, Ying; Zeng, Qiong-Fang; Huang, Ya-Dan

2010-07-01

To compare the pituitary down-regulatory effects of the two gonadotropin-releasing hormone agonists Alarelin and Triptorelin in the long protocol of ovulation induction in in vitro fertilization and embryo transfer (IVF-ET). We included in this study 122 patients aged 24-39 years treated by IVF-ET for secondary infertility, with 10-20 pre-antral follicles and obstruction of the fallopian tube. Seventy-eight of them received Alarelin, and the other 44 Triptorelin. Comparative analyses were made on the pituitary down-regulatory effects of the two gonadotropin-releasing hormone agonists and the clinical outcomes of IVF-ET. No premature LH surge and ovulation, nor severe hyperovarian stimulation syndrome was found in either group. There were no significant differences between the two groups in the mean dose and duration of gonodatropin treatment, the numbers of oocytes retrieved, mature oocytes and top-quality embryos, and the rates of 2PN, multi-sperm fertilization, cleavage, embryo transfer, embryo implantation, clinical pregnancy and early miscarriage (P > 0.05), but the rate of cancelled cycles was significantly higher in the Triptorelin than in the Alarelin group (P < 0.05). Alarelin and Triptorelin can achieve similar pituitary down-regulatory effects and clinical outcomes in IVF-ET when used in the long protocol of ovulation induction.

[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.

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.

[Association of human chorionic gonadotropin level in embryo culture media with early embryo development].

PubMed

Wang, Haiying; Zhang, Renli; Han, Dong; Liu, Caixia; Cai, Jiajie; Bi, Yanling; Wen, Anmin; Quan, Song

2014-06-01

To investigate the association of human chorionic gonadotropin (HCG) level on day 3 of embryo culture with embryo development. Spent culture media were collected from individually cultured embryos on day 3 of in vitro fertilization and embryo transfer (IVF-ET) cycles. HCG concentration in the culture media was measured using an ELISA kit and its association with embryo development was assessed. In the 163 samples of embryo culture media from 60 patients, HCG was positive in 153 sample (93.8%) with a mean level of 0.85 ± 0.43 mIU/ml. The concentration of hCG in the culture media increased gradually as the number of blastomeres increased (F=2.273, P=0.03), and decreased as the morphological grade of the embryo was lowered (F=3.900, P=0.02). ELISA is capable of detecting HCG levels in spent culture media of embryos on day 3 of in vitro culture. The concentration of HCG in spent culture media is positively correlated with the status of early embryo development and implantation rate and thus serves as a useful marker for embryo selection in IVF-ET procedure.

A Case of Unicornuate Uterus with Atypical Located Hyperstimulated Ovary after in Vitro Fertilization Pre-Embryo Transfer (IVF-ET)

PubMed Central

Angelova, Mariya Angelova; Kovachev, Emil Georgiev; Kisyov, Stefan Vasilev; Ivanova, Vilislava Robert

2015-01-01

The authors describe a case of a congenital Mullerian anomaly, uterus unicornis with missing right fallopian tube. An in Vitro Fertilization Pre-Embryo Transfer (IVF-ET) procedure was done and presently is known that the patient has left fallopian tube and left ovary, two kidneys, and right ovary is missing. No diagnostic laparoscopy and hysteroscopy were done, only hysterosalpingography (HSG) before the IVF procedure. Several days after the follicular puncture of the left ovary the patient was urgently admitted to the hospital for specialized gynaecology in Varna. Transabdominal ultrasonography showed right ovary atypically located immediately next to the liver and with emerging theca-lutein cysts. PMID:27275261

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.

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.

Abnormal chromosome behavior in human oocytes which remained unfertilized during human in vitro fertilization.

PubMed

Spielmann, H; Krüger, C; Stauber, M; Vogel, R

1985-09-01

Chromosomal abnormalities and abnormal embryonic development have previously been observed after human in vitro fertilization (IVF). Chromosomal abnormalities may arise not only after fertilization but even earlier during meiotic maturation of human oocytes in culture. Since chromosomal analysis is simple in oocytes during meiotic maturation, the chromosomal status was analyzed in oocytes which remained unfertilized in a human in vitro fertilization program. In 50 fertilization attempts the chromosomes of 62 unfertilized oocytes could be analyzed; 45 of them were in the process of meiotic maturation. In three oocytes two small polar bodies were observed 16-18 hr after insemination in the absence of fertilization. In one oocyte abnormal chromosome behavior was found during the first meiotic division, and in four oocytes during metaphase of the second meiotic division. These data suggest that chromosomal analysis of unfertilized oocytes in human IVF may improve the understanding human oocyte maturation and fertilization.

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.

Adolescents conceived by IVF: parenting and psychosocial adjustment.

PubMed

Colpin, H; Bossaert, G

2008-12-01

A follow-up study was conducted in mid-adolescence on parenting and the child's psychosocial development after in vitro fertilization (IVF). The first phase of the study had compared 31 IVF families and 31 families with a naturally conceived child when the children were 2 years old (Colpin et al., 1995). Of these, 24 IVF families and 21 control families participated again when the children were 15-16 years old. Fathers, mothers and adolescents completed questionnaires assessing parenting style and stress, and adolescent psychosocial adjustment. No significant differences were found in self- or adolescent-reported parenting style, or in parenting stress between IVF mothers and mothers in the control group, nor between IVF fathers and fathers in the control group. Neither did we find significant differences in self- or parent-reported behavioural problems between adolescents conceived by IVF and those conceived naturally. Comparison of behavioural problems between IVF adolescents informed or not informed about the IVF conception did not reveal significant differences. Parenting and 15-16-year-old adolescents' psychosocial adjustment did not differ significantly between IVF families and control families. This study is, to the best of our knowledge, the first psychosocial follow-up in mid-adolescence, and adds to the evidence that IVF children and their parents are well-adjusted. Large-scale studies in adolescence are needed to support these findings.

A randomized comparison of side effects and patient convenience between Cyclogest suppositories and Endometrin tablets used for luteal phase support in IVF treatment.

PubMed

Ng, Ernest Hung Yu; Chan, Carina Chi Wai; Tang, Oi Shan; Ho, Pak Chung

2007-04-01

This study compared side effects and patient convenience of vaginal progesterone suppositories (Cyclogest) and vaginal progesterone tablets (Endometrin) used for luteal phase support in in vitro fertilization/embryo transfer (IVF/ET) cycles using pituitary downregulation. One hundred and thirty-two infertile patients were randomized on the day of ET by a computer-generated randomization list in sealed envelopes to receive either Cyclogest 400mg or Endometrin 100mg twice daily for 14 days. On days 6 and 16 after ET, they rated side effects and patient convenience into four grades: none, mild, moderate and severe by completing a questionnaire. No significant differences in perineal irritation were found on days 6 and 16 after ET between the two groups, although there was a trend of fewer patients with perineal irritation in the Endometrin group. Significantly more patients in the Endometrin group had difficulty of administration on day 6 after ET. There were no differences in the hormonal profile on day 6 after ET and IVF outcomes between the two groups. There was no difference in perineal irritation after the use of Cyclogest suppositories or Endometrin tablets for luteal phase support although more patients found administration of Endometrin tablets difficult.

Freeze-all policy: fresh vs. frozen-thawed embryo transfer.

PubMed

Roque, Matheus; Valle, Marcello; Guimarães, Fernando; Sampaio, Marcos; Geber, Selmo

2015-05-01

To compare in vitro fertilization (IVF) outcomes between fresh embryo transfer (ET) and frozen-thawed ET (the "freeze-all" policy), with fresh ET performed only in cases without progesterone (P) elevation. Prospective, observational, cohort study. Private IVF center. A total of 530 patients submitted to controlled ovarian stimulation (COS) with a gonadotropin-releasing hormone-antagonist protocol, and cleavage-stage, day-3 ET. None. Ongoing pregnancy rates. A total of 530 cycles were included in the analysis: 351 in the fresh ET group (when P levels were ≤1.5 ng/mL on the trigger day); and 179 cycles in the freeze-all group (ET performed after endometrial priming with estradiol valerate, at 6 mg/d, taken orally). For the fresh ET group vs. the freeze-all group, respectively, the implantation rate was 19.9% and 26.5%; clinical pregnancy rate was 35.9% and 46.4%; and ongoing pregnancy rate was 31.1% and 39.7%. The IVF outcomes were significantly better in the group using the freeze-all policy, compared with the group using fresh ET. These results suggest that even in a select group of patients that underwent fresh ET (P levels ≤1.5 ng/mL), endometrial receptivity may have been impaired by COS, and outcomes may be improved by using the freeze-all policy. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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.

Quantitative morphometrical characterization of human pronuclear zygotes.

PubMed

Beuchat, A; Thévenaz, P; Unser, M; Ebner, T; Senn, A; Urner, F; Germond, M; Sorzano, C O S

2008-09-01

Identification of embryos with high implantation potential remains a challenge in in vitro fertilization (IVF). Subjective pronuclear (PN) zygote scoring systems have been developed for that purpose. The aim of this work was to provide a software tool that enables objective measuring of morphological characteristics of the human PN zygote. A computer program was created to analyse zygote images semi-automatically, providing precise morphological measurements. The accuracy of this approach was first validated by comparing zygotes from two different IVF centres with computer-assisted measurements or subjective scoring. Computer-assisted measurement and subjective scoring were then compared for their ability to classify zygotes with high and low implantation probability by using a linear discriminant analysis. Zygote images coming from the two IVF centres were analysed with the software, resulting in a series of precise measurements of 24 variables. Using subjective scoring, the cytoplasmic halo was the only feature which was significantly different between the two IVF centres. Computer-assisted measurements revealed significant differences between centres in PN centring, PN proximity, cytoplasmic halo and features related to nucleolar precursor bodies distribution. The zygote classification error achieved with the computer-assisted measurements (0.363) was slightly inferior to that of the subjective ones (0.393). A precise and objective characterization of the morphology of human PN zygotes can be achieved by the use of an advanced image analysis tool. This computer-assisted analysis allows for a better morphological characterization of human zygotes and can be used for classification.

Do lunar cycles influence in vitro fertilization results?

PubMed

Weigert, Monika; Kaali, Steven G; Kulin, Sandor; Feichtinger, Wilfried

2002-11-01

Our objective was to investigate the lunar influence on IVF-ET outcomes. Between 1992 and 1999 we have completed 7572 preprogrammed IVF-ET treatment cycles with the same stimulation protocol in two outpatient units. (Vienna, Austria and Budapest, Hungary) Multiple regression (SAS; proc Logistic) and two separate analyses were performed on pregnancy rates using a harmonic sinoidal trend based on the synodic and anomalistic lunar cycles respectively. The overall pregnancy rate was 30.9%. The amplitude of harmonic sinoidal, trend for the synodic lunar cycles was chi2 = 1.63,2d.f., p = 0.44 and chi2 = 6.27,2d.f., p = 0.044 for the anomalistic moon periods. For the anomalistic lunar months the amplitude of harmonic sinoidal trend was borderline in terms of higher pregnancy rates with the moon in Perigee. The cause of seasonal changes in IVF-ET outcomes is probably very complex. Our results indicate that lunar influence may only be one of the contributing factors. Further studies are needed to clarify unexplained fluctuations of pregnancy outcomes.

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.

[Ruling of the Inter-American Court of Human Rights, the Case of Artavia Murillo et al (in vitro fertilization) v. Costa Rica; new hopes for the reproductive freedom in Latin America].

PubMed

Brena, Ingrid

2013-01-01

Modern reproductive technology has not been completely accepted and, especially in-vitro fertilization, IVF has generated serious social, political and legal controversies in Latin America. We may distinguish two trends that show us the oppositions; on one hand, the primacy of the embryo's live and its protection during artificial reproductive process and on the other, the primacy of liberal access to assisted reproduction techniques. The debate came to the fore, after a ruling by the Costa Rica's Constitutional Chamber who banned de IVF in 2000. The damaged couples after fulfilling the process toward the Inter-American Commission on Human Rights, present a petition to the Inter-American Court of Human Rights. The Court's sentence and its arguments will be the subject of these comments as well that will allow to considered that both of them should be considered as a very important step towards the construction of a secular liberal vision over the assisted reproduction in Latin America.

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.

Blastocyst transfer does not improve cycle outcome as compared to D3 transfer in antagonist cycles with an elevated progesterone level on the day of hCG.

PubMed

Demirel, Cem; Aydoğdu, Serkan; Özdemir, Arzu İlknur; Keskin, Gülşah; Baştu, Ercan; Buyru, Faruk

2017-09-01

To evaluate the association between progesterone elevation on the day of human chorionic gonadotropin (hCG) administration and clinical pregnancy rates of gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles with the transfer of embryos at different developmental stages (day-3 versus day-5 ETs). This is a retrospective analysis of fresh IVF/ICSI; 194 cycles out of 2676 conducted in a single center. A total of 2676 cycles were analyzed, of which 386 had no progesterone measurements available. Two hundred eighteen cycles had progesterone elevation (p>1.5 ng/mL) giving an overall incidence of 9.5%. Twenty-four cycles were excluded from further analysis. Of the remaining 194 cycles, 151 had day-3 transfers and 43 had blastocyst transfers. There was no statistically significant difference in pregnancy and clinical pregnancy rates per transfer between the D3-ET and D5-ET groups (46% vs. 49%, and 39% vs. 35%, respectively). The results of this study suggest that blastocyst transfer does not improve cycle outcomes compared with D3 transfer in GnRH antagonist cycles with an elevated progesterone level on the day of hCG.

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.

Effects of the distance between small intramural uterine fibroids and the endometrium on the pregnancy outcomes of in vitro fertilization-embryo transfer.

PubMed

Lu, Na; Wang, Yang; Su, Ying-chun; Sun, Ying-pu; Guo, Yi-hong

2015-01-01

To explore the effects of the distance between small intramural uterine fibroids (≤4 cm) and the endometrium on the outcomes of in vitro fertilization-embryo transfer (IVF-ET). We prospectively analyzed pregnancy outcomes in 117 infertile women with small intramural uterine fibroids and 117 infertile women without uterine fibroids who all underwent IVF-ET. The size and number of small intramural uterine fibroids and the shortest distance between the small intramural uterine fibroids and the endometrium were measured by transvaginal three-dimensional ultrasound. The endometrial and subendometrial blood flow parameters, implantation rate, clinical pregnancy rate, abortion rate and live birth rate were compared between the women with and without small uterine fibroids and among the different shortest distances (≤1, 1-3 and >3 mm). The effects of the size and number of small intramural uterine fibroids on IVF-ET outcomes were observed. The endometrial volume on ET day, the implantation rate and the live birth rate were significantly lower, but the abortion rate was significantly higher, in the women with small intramural uterine fibroids than in those without uterine fibroids (p < 0.05). The endometrial flow index was higher in the shortest distance ≤1-mm group than in the groups with 1-3 and >3 mm, and the implantation rate was higher in ≤1-mm group than in the >3-mm group (p < 0.05). There were no significant differences in clinical outcomes between different sizes and numbers of small intramural uterine fibroids. Small intramural uterine fibroids can affect IVF-ET outcomes. Compared with other shortest distances (1-3 and >3 mm), the shortest distance of ≤1 mm has a higher implantation rate. © 2014 S. Karger AG, Basel.

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

[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.

[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.

[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.

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.

[Application of spontaneous acrosome reaction of sperm in prediction of outcome of in-vitro fertilization and embryo transfer].

PubMed

Xuan, X J; Xu, C; Zhao, Y R; Wu, K L; Chen, T; Zhang, H B; Li, X; Su, S Z; Ma, G; Tang, R; Sheng, Y; Ma, J L

2016-04-26

To investigate the clinical application of spontaneous acrosome reaction (AR) rate of sperm in predicting the outcome of in-vitro fertilization and embryo transfer (IVF-ET). The spontaneous AR rate of the sperm of patients who underwent IVF-ET treatment in our center during the period from November to December 2014 were studied. The cut-off value from 6% to 12% were set and analyzed its association between the IVF-ET outcomes (including fertility rates, normal fertilization rates and high-quality embryo rates). For those who underwent fresh embryo transplantation, the rates of chemical pregnancy and clinical pregnancy were calculated, and compared the spontaneous AR rates and quantity of acrosomal enzyme according to the pregnancy outcome. There were 202 patients in this study and the mean spontaneous AR rate was 5.99%±5.18%. For patients with the spontaneous AR rate ≥9% versus <9%, the fertility rate, normal fertilization rate and high-quality embryo rate were 81.33% vs 83.85%, 60.53% vs 60.99%, and 51.10% vs 59.67%, respectively, with statistically significant difference in the high-quality embryo rate (P=0.02). For patients who underwent fresh embryo transplantation, when comparison was made between those with spontaneous AR rate ≥8% and those <8%, the rate of chemical pregnancy and clinical pregnancy were 48.57% (17/35) vs 69.64% (78/112) and 37.14% (13/35) vs 63.39% (71/112), respectively, both with statistically significant difference (P=0.02 and P<0.01). The patients with clinical pregnancy had lower spontaneous AR rate than those without clinical pregnancy (5.41%±3.87% vs 7.40%±6.79%, P=0.04), while the quantity of acrosomal enzyme showed no significant difference [(131.79±68.50) vs (153.62±59.59) μU/10(6,) P=0.06]. Logistic regression analysis demonstrated association between spontaneous AR rates and clinical pregnancy (OR=0.93, 95%CI: 0.87-0.99, P=0.03). The spontaneous AR rate of sperm may have clinical significance in predicting the outcome of IVF-ET, as it is reversely correlated with IVF high-quality embryo rate and pregnancy rate. The quantity of acrosomal enzyme may not have significant predictive value for the outcome of IVF.

[Smoothing Gan Reinforcing Shen Method Adjuvantly Treated Poor Response of Diminished Ovari- an Reserve Patients in in vitro Fertilization and Embryo Transfer: a Clinical Study].

PubMed

Zhang, Zheng; Zhang, Xue-hong; He, Tian-you

2015-10-01

To study clinical efficacy of smoothing Gan reinforcing Shen (SGRS) method in treating poor response of diminished ovarian reserve (DOR) patients in in vitro fertilization and embryo, transfer (IVF-ET). Totally 84 DOR patients undergoing IVF-ET were assigned to the experimental group (SGRS Chinese herbs as adjuvant therapy) and the control group according to random digit table, 42 in each group. Patients in the control group received controlled ovarian hyperstimulation (COH) and IVF-ET. Those in the experimental group additionally received basic formula of SGRS method, one dose per day. The dose and use time of recombinant follicle-stimulating hormone (r-FSH) were recorded during ovarian stimulation process. On the injection day of human chorionic gonadotropin (HCG) and serum levels of estradiol (E2) on the oocyte retrieval day were determined using chemiluminescent method. E2 contents in the follicular fluid on the oocyte retrieval day were detected using ELISA. The total number of retrieved oocytes, the number of mature oocytes in metaphase II (M II), the number of normal fertilization [with two pronucleus (2PN)], the number of portable embryos, and the number of good quality embryos were recorded. The correlation between Chinese medical adjuvant therapy and the aforesaid indices were observed. The clinical pregnancy rate and the abortion rate were finally compared between the two groups. The total dose of r-FSH, the E2 level on HCG injection day, the serum E2 level on the oocyte retrieval day, the number of retrieved oocyte, the number of oocytes in M II the number of oocytes with 2PN, the number of portable embryos, and the number of good quality embryos were all positively correlated with Chinese medical adjuvant therapy (P < 0.05, P < 0.01). Compared with the control group, serum E2 levels on the HCG injection day and the oocyte retrieval day obviously increased, the number of retrieved oocytes, the number of oocytes in M II, and the number of portable embryos were increased more in the experimental group with statistical difference (P < 0.05, P < 0.01). There was no statistical significance in the clinical pregnancy rate or the abortion rate between the two groups (P > 0.05). SGRS Chinese herbs as adjuvant therapy could improve ovarian responsiveness of DOR patients undergoing IVF-ET, increase the number of retrieved oocytes, elevate the quality of oocytes and the number of embryos.

Twins conceived using IVF: a follow-up of the family environment and psychosocial adjustment in adolescence.

PubMed

Anderson, K N; Connor, J J; Koerner, A F; Rueter, M A

2016-12-01

Compared to families with IVF singletons, what are parental depressive, parent-adolescent interaction and adolescent adjustment outcomes in families with 11-17-year-old IVF twins? No differences were detected for any measured outcome between families with 11-17-year-old IVF twins and those with IVF singletons, despite high statistical power. When IVF twins are younger than 5-years-old, parents tend to have more mental health difficulties and poorer parent-child interactions relative to IVF singletons. By middle childhood, these differences may no longer exist and available studies with middle childhood-aged IVF twins challenge the expected long-term implications of the early concerns. IVF twins may even have more optimum adjustment than IVF singletons in middle childhood. Study of 280, 11-17-year-old IVF children (n = 122 twins and n = 158 singletons) from 195 families at a US reproductive endocrinology clinic. At Wave 1, clinic patients with an IVF child born between 1998 and 2004 were invited to participate in an online survey. In this follow-up study, mothers and fathers provided information on each of their 11-17-year-old IVF adolescents. There were no differences between 11- and 17-year-old IVF twins and IVF singletons in parent depressive symptoms, parent-adolescent interactions or adolescent adjustment outcomes. Although the family demographics are representative of IVF patients, participants were drawn from one US clinic. Study results provide reassurance that by adolescence IVF twins and their families function as well as IVF singletons and their families. University of Minnesota (UMN) Agriculture Experiment Station (MN-52-107), UMN Grant-in-Aid of Research, Artistry and Scholarship, UMN College of Education and Human Development Research Development Investment Grant, UMN Women's Philosophic Leadership Circle Award, UMN Eva Miller Endowed Fellowship. The authors 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 e-mail: journals.permissions@oup.com.

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

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.

Trends in ectopic pregnancy rates following assisted reproductive technologies in the UK: a 12-year nationwide analysis including 160 000 pregnancies.

PubMed

Santos-Ribeiro, Samuel; Tournaye, Herman; Polyzos, Nikolaos P

2016-02-01

Have the advancement of assisted reproductive technologies (ART) and changes in the incidence of specific causes of infertility-altered ectopic pregnancy (EP) rates following ART over time in the UK? EP rates in the UK following IVF/ICSI have progressively decreased, and this appears to be associated with a reduction in the incidence of tubal factor infertility and the increased use of both a lower number of embryos transferred and extended embryo culture. Historically, EP rates following ART are known to have increased over time. However, the impact of progress in ART procedures and changes in both policy and the incidence of specific causes of infertility on the overall EP rate in the UK has yet to be studied. A population-based retrospective analysis was carried out on all pregnancies following ART cycles carried out in the UK between 2000 and 2012 included in the anonymized database of the Human Fertilisation and Embryology Authority. Overall, 161 967 treatment cycles resulting in a pregnancy were included in the analysis. Among them, 8852 pregnancies occurred after intrauterine insemination (IUI) and 153 115 following IVF/ICSI. During this period of 12 years, ∼1.4% (n = 2244) of all pregnancies following ART were an EP. Crude EP rates were significantly higher after IVF/ICSI when compared with following IUI (1.4 versus 1.1%, P = 0.043). The incidence of EP decreased significantly over time for IVF/ICSI cycles [incidence rate ratios (IRR) 0.96 per year, 95% confidence interval (CI) 0.94-0.97], but not after IUI (IRR 0.96 per year, 95% CI 0.91-1.03).Among pregnancies resulting from IVF/ICSI, multivariable logistic regression analysis demonstrated that the major risk factor for EP was the presence of tubal infertility [adjusted odds ratio (aOR) 2.23, 95% CI 1.93-2.58), followed by the increased number of embryos transferred (aOR 1.29 for 2 versus 1 embryo transferred, 95% CI 1.11-1.49; aOR 1.69 for 3 or more versus 1 embryo transferred, 95% CI 1.35-2.11). The use of extended embryo culture to Days 3-4 or 5-7 significantly reduced the risk of EP, when compared with the transfer of early cleavage (Days 1-2) embryos (respectively, aOR 0.85, 95% CI 0.76-0.94; and aOR 0.73, 95% CI 0.63-0.84). Finally, frozen embryo transfer (ET) had no effect on the risk of EP following IVF/ICSI (aOR 0.92, 95% CI 0.76-1.11). Owing to the use of this particular registry data, well-established risk factors of EP, such as smoking habits or uterine surgery, could not be assessed. Our results provide the first evidence of a potential benefit-in terms of the reduction in EP rates-of the implementation of national programmes aiming to reduce the incidence of tubal infertility, such as the National Chlamydia Screening Programme. In addition, campaigns for the widespread introduction of single ET may not only reduce the incidence of multiple pregnancies but also the incidence of EP following IVF/ICSI. No funding was obtained for this study, and there are 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.

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.

Lapse in embryo transfer training does not negatively affect clinical pregnancy rates for reproductive endocrinology and infertility fellows.

PubMed

Kresowik, Jessica; Sparks, Amy; Duran, Eyup H; Shah, Divya K

2015-03-01

To compare rates of clinical pregnancy (CPR) and live birth (LBR) following embryo transfer (ET) performed by reproductive endocrinology and infertility (REI) fellows before and after a prolonged lapse in clinical training due to an 18-month research rotation. Retrospective cohort study. Not applicable. All women undergoing in vitro fertilization (IVF) and IVF-intracytoplasmic sperm injection (ICSI) cycles with ET performed by REI fellows from August 2003 to July 2012. Eighteen-month lapse in clinical training of REI fellows. CPR and LBR before and after the lapse in clinical training were calculated and compared per fellow and as a composite group. Alternating logistic regression models were used to calculate the odds of clinical pregnancy and live birth following transfers performed before and after the lapse in training. Unadjusted odds of clinical pregnancy and live birth were similar between the two time periods both for individual fellows and for the composite group. Alternate logistic regression analysis revealed no significant difference in CPR (odds ratio [OR] 0.94, 95% confidence interval [CI] 0.83-1.07) or LBR (OR 1.05, 95% CI 0.94-1.18) after the lapse in training compared with before. A research rotation is common in REI fellowship training programs. This prolonged departure from clinical training does not appear to negatively affect pregnancy outcome following fellow ET. Copyright © 2015 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.

Where does New Zealand stand on permitting research on human embryos?

PubMed

Jones, D Gareth

2014-08-01

In many respects New Zealand has responded to the assisted reproductive technologies (ARTs) as positively as many comparable societies, such as Australia and the UK. Consequently, in vitro fertilisation (IVF) and pre-implantation genetic diagnosis (PGD) are widely available, as is non-commercial surrogacy utilising IVF. These developments have been made possible by the Human Assisted Reproductive Technology (HART) Act 2004, overseen by its two committees, the Advisory Committee on Assisted Reproductive Technology (ACART) and the Ethics Committee (ECART). However, New Zealand stands apart from many of these other societies by the lack of permission for scientists to conduct research using human embryos. There is no doubt this reflects strongly held viewpoints on the part of some that embryos should be protected and not exploited. Legitimate as this stance is, the resulting situation is problematic when IVF is already designated as an established procedure. This is because the development of IVF involved embryo research, and continuing improvements in procedures depend upon ongoing embryo research. While prohibition of research on human embryos gives the impression of protecting embryos, it fails to do this and also fails to enhance the health and wellbeing of children born using IVF. This situation will not be rectified until research is allowed on human embryos.

[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.

A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth.

PubMed

Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

2012-01-01

a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth.

A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth

PubMed Central

Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

2012-01-01

We present a case with a severe injection error: a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth. PMID:24592042

Increased platelet factor 4 and aberrant permeability of follicular fluid in PCOS.

PubMed

Huang, Chu-Chun; Chou, Chia-Hung; Chen, Shee-Uan; Ho, Hong-Nerng; Yang, Yu-Shih; Chen, Mei-Jou

2018-05-17

Abnormal folliculogenesis is one of the cardinal presentations of polycystic ovarian syndrome (PCOS) and permeability of follicular wall has been proposed to be involved in the normal follicular growth. However, whether or not there is a change in intrafollicular permeability underlies PCOS is unknown. This was a tertiary center-based case-control study. From 2014 to 2015, thirteen patients with PCOS who underwent in vitro fertilization-embryo transfer (IVF-ET) were enrolled. Eleven normo-ovulatory patients who underwent IVF-ET due to male factor and/or tubal factor infertility were enrolled as the control group. The influence of ovarian follicular fluid (FF) on endothelial cell permeability was evaluated using a human umbilical vein endothelial cell monolayer permeability assay. The intrafollicular expression profiles of angiogenesis-related proteins were analyzed using a Human Angiogenesis Protein Array Kit. The FF from PCOS patients caused significantly poorer endothelial cell permeability comparing with the effect of FF from the control group (46% ± 12% vs. 58% ± 9%, P = 0.023). Among the 55 angiogenesis-related proteins tested, there was a significantly higher level of intrafollicular platelet factor 4 (PF4) and PF4/IL-8 complex in the PCOS group (p = 0.004). The anti-permeability effect of PF4 was related to the decrease in the intercellular gaps and antagonistic binding with IL-8. Our study provides the first evidence of the pathophysiologic contribution of the well-known angiostatic protein, PF4, on human reproductive biology. The increase of the intrafollicular PF4 and its anti-permeability effect might affect the formation of FF and folliculogenesis in PCOS. Copyright © 2018. Published by Elsevier B.V.

[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.

[Influence of the DNA integrity of optimized sperm on the embryonic development and clinical outcomes of in vitro fertilization and embryo transfer].

PubMed

Jiang, Wei-jie; Jin, Fan; Zhou, Li-ming

2016-05-01

To investigate the influence of the DNA integrity of optimized sperm on the embryonic development and clinical outcomes of in vitro fertilization and embryo transfer (IVF-ET). This study included 605 cycles of conventional IVF-ET for pure oviductal infertility performed from January 1, 2013 to December 31, 2014. On the day of retrieval, we examined the DNA integrity of the sperm using the sperm chromatin dispersion method. According to the ROC curve and Youden index, we grouped the cycles based on the sperm DNA fragmentation index (DFI) threshold value for predicting implantation failure, early miscarriage, and fertilization failure, followed by analysis of the correlation between DFI and the outcomes of IVF-ET. According to the DFI threshold values obtained, the 605 cycles fell into four groups (DFI value < 5%, 5-10%, 10-15%, and ≥ 15%). Statistically significant differences were observed among the four groups in the rates of fertilization, cleavage, high-quality embryo, implantation, clinical pregnancy, early miscarriage, and live birth (P < 0.05), but not in the rates of multiple pregnancy, premature birth, and low birth weight (P > 0.05). DFI was found to be correlated negatively with the rates of fertilization (r = -0.32, P < 0.01), cleavage (r = -0.19, P < 0.01), high-quality embryo (r = -0.40, P < 0.01), clinical pregnancy (r = -0.20, P < 0.01), and live birth (r = -0.09 P = 0.04), positively with the rate of early miscarriage (r = 0.23, P < 0.01), but not with the rates of multiple pregnancy (r = -0.01, P = 0.83), premature birth (r = 0.04, P = 0.54), and low birth weight (r = 0.03, P = 0.62). The DNA integrity of optimized sperm influences fertilization, embryonic development, early miscarriage, and live birth of IVF-ET, but its correlation with premature birth and low birth weight has to be further studied.

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.

The serum level of C-reactive protein in patients undergoing GnRH agonist protocols for in vitro fertilization cycle.

PubMed

Liu, B; Zhang, L; Guo, R W; Wang, W J; Duan, X Q; Liu, Y W

2014-01-01

The synchronization of the uterus and mature eggs at the molecular level is the key factor in embryo transfer, and the regulation of synchronization depends on a variety of cytokines. C-reactive protein (CRP), as the first acute phase reaction protein, is involved in the entire process of embryo transfer. The study is designed to investigate the correlation among CRP, sex hormone, controlled ovarian hyperstimulation (COH) cycle, and pregnancy outcome. Ninety-two patients who accepted in vitro fertilization (IVF) treatment cycles because of tubal factor were included in the study. Seventy treated cases were included to complete final analysis with the full set of results. Respectively on the second day of the menstruation (Day-2) in gonadotropin-releasing hormone agonist (GnRH-a) short program treatment, on the morning in human chorionic gonadotropin (hCG) treatment (Day-hCG) and the embryo transplant day (Day-ET), plasma CRP level was tested by enzyme-linked immunosorbent assay (ELISA). The correlativity among CRP level, sex hormone, COH, and pregnancy outcome was analyzed by statistical methods. In the short program GnRH-a of 70 cases, there was no relationship between serum CRP level and the infertility age, gonadotropin (Gn) dosage, number of oocytes retrieved, the number of normal fertilization, and sex hormone. In the short program of GnRH-a, the change of serum CRP levels in Day-2, Day-hCG, Day-ET: serum CRP in Day-2 < Day-hCG < Day-ET and the level of serum CRP gradually increased in Day-2, Day-hCG, and Day-ET in both the pregnant group and non-pregnant group. In non-pregnant group, the ratio of hCG/D2 and ET/hCG-day were significantly higher than the pregnant group. The area under receiver operating characteristic (ROC) curve was 0.806, indicating the accuracy of diagnostic tests is medium, the authors chose the point which presents the ratio of CRP in Day-ET to Day-hCG which was less than 1.752 as a predictor of treatment outcome, the sensitivity of the experiment was 77.8%, and the specificity 75%. CRP as a sensitive inflammatory marker, CRP ratio of Day-ET/Day-hCG could be a predictor of treatment outcome by ROC curve analysis in COH program.

IVF in Costa Rica

PubMed Central

Valerio, Carlos; Vargas, Karen; Raventós, Henriette

2017-01-01

For 16 years, Costa Rica was the only country in the world that banned IVF, after it had been successfully conducted from 1995 to 2000. It also has been the only country that banned IVF based on the argument that it protects the embryo. After years of conflict, the prohibition has finally been lifted and the first baby girl was born in March 2017. This paper recounts the judicial and legal struggles Costa Rica faced in order to reestablished its IVF program. PMID:28985042

Promotion of human early embryonic development and blastocyst outgrowth in vitro using autocrine/paracrine growth factors.

PubMed

Kawamura, Kazuhiro; Chen, Yuan; Shu, Yimin; Cheng, Yuan; Qiao, Jie; Behr, Barry; Pera, Renee A Reijo; Hsueh, Aaron J W

2012-01-01

Studies using animal models demonstrated the importance of autocrine/paracrine factors secreted by preimplantation embryos and reproductive tracts for embryonic development and implantation. Although in vitro fertilization-embryo transfer (IVF-ET) is an established procedure, there is no evidence that present culture conditions are optimal for human early embryonic development. In this study, key polypeptide ligands known to be important for early embryonic development in animal models were tested for their ability to improve human early embryo development and blastocyst outgrowth in vitro. We confirmed the expression of key ligand/receptor pairs in cleavage embryos derived from discarded human tri-pronuclear zygotes and in human endometrium. Combined treatment with key embryonic growth factors (brain-derived neurotrophic factor, colony-stimulating factor, epidermal growth factor, granulocyte macrophage colony-stimulating factor, insulin-like growth factor-1, glial cell-line derived neurotrophic factor, and artemin) in serum-free media promoted >2.5-fold the development of tri-pronuclear zygotes to blastocysts. For normally fertilized embryos, day 3 surplus embryos cultured individually with the key growth factors showed >3-fold increases in the development of 6-8 cell stage embryos to blastocysts and >7-fold increase in the proportion of high quality blastocysts based on Gardner's criteria. Growth factor treatment also led to a 2-fold promotion of blastocyst outgrowth in vitro when day 7 surplus hatching blastocysts were used. When failed-to-be-fertilized oocytes were used to perform somatic cell nuclear transfer (SCNT) using fibroblasts as donor karyoplasts, inclusion of growth factors increased the progression of reconstructed SCNT embryos to >4-cell stage embryos. Growth factor supplementation of serum-free cultures could promote optimal early embryonic development and implantation in IVF-ET and SCNT procedures. This approach is valuable for infertility treatment and future derivation of patient-specific embryonic stem cells.

Total number of oocytes and zygotes are predictive of live birth pregnancy in fresh donor oocyte in vitro fertilization cycles.

PubMed

Hariton, Eduardo; Kim, Keewan; Mumford, Sunni L; Palmor, Marissa; Bortoletto, Pietro; Cardozo, Eden R; Karmon, Anatte E; Sabatini, Mary E; Styer, Aaron K

2017-08-01

To evaluate the association of oocyte donor-recipient characteristics, oocyte donor response, and live birth pregnancy rate following fresh donor oocyte IVF-ET. Retrospective cohort study. Academic reproductive medicine practice. Two hundred thirty-seven consecutive fresh donor oocyte IVF-ET cycles from January 1, 2007 to December 31, 2013 at the Massachusetts General Hospital Fertility Center. None. Live birth rate per cycle initiated. The mean (±SD) age of oocyte donors and recipients was 27.0 ± 3.7 and 41.4 ± 4.6 years, respectively. Oocyte donor demographic/reproductive characteristics, ovarian reserve testing, and peak serum E 2 during ovarian stimulation were similar among cycles which did and did not result in live birth, respectively. Overall implantation, clinical pregnancy, and live birth pregnancy rates per cycle initiated were 40.5%, 60.8%, and 54.9%, respectively. The greatest probability of live birth was observed in cycles with >10 oocytes retrieved, mature oocytes, oocytes with normal fertilization (zygote-two pronuclear stage), and cleaved embryos. The number of oocytes (total and mature), zygotes, and cleaved embryos are associated with live birth following donor oocyte IVF cycles. These findings suggest that specific peri-fertilization factors may be predictive of pregnancy outcomes following donor oocyte IVF cycles. Copyright © 2017 American Society for Reproductive Medicine. All rights reserved.

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.

In vitro fertilization (IVF) in mammals: epigenetic and developmental alterations. Scientific and bioethical implications for IVF in humans.

PubMed

Ventura-Juncá, Patricio; Irarrázaval, Isabel; Rolle, Augusto J; Gutiérrez, Juan I; Moreno, Ricardo D; Santos, Manuel J

2015-12-18

The advent of in vitro fertilization (IVF) in animals and humans implies an extraordinary change in the environment where the beginning of a new organism takes place. In mammals fertilization occurs in the maternal oviduct, where there are unique conditions for guaranteeing the encounter of the gametes and the first stages of development of the embryo and thus its future. During this period a major epigenetic reprogramming takes place that is crucial for the normal fate of the embryo. This epigenetic reprogramming is very vulnerable to changes in environmental conditions such as the ones implied in IVF, including in vitro culture, nutrition, light, temperature, oxygen tension, embryo-maternal signaling, and the general absence of protection against foreign elements that could affect the stability of this process. The objective of this review is to update the impact of the various conditions inherent in the use of IVF on the epigenetic profile and outcomes of mammalian embryos, including superovulation, IVF technique, embryo culture and manipulation and absence of embryo-maternal signaling. It also covers the possible transgenerational inheritance of the epigenetic alterations associated with assisted reproductive technologies (ART), including its phenotypic consequences as is in the case of the large offspring syndrome (LOS). Finally, the important scientific and bioethical implications of the results found in animals are discussed in terms of the ART in humans.

A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF.

PubMed

Çelik, Gayem İnayet Turgay; Sütçü, Havva Kömür; Akpak, Yaşam Kemal; Akar, Münire Erman

2015-01-01

To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF). A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients' characteristics, controlled ovarian stimulation (COH) results, and laboratory results. Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%). The combination protocol does not provide additional efficacy.

A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF

PubMed Central

Turgay Çelik, Gayem İnayet; Sütçü, Havva Kömür; Akpak, Yaşam Kemal; Akar, Münire Erman

2015-01-01

Objective. To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF). Study Design. A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients' characteristics, controlled ovarian stimulation (COH) results, and laboratory results. Results. Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%). Conclusion. The combination protocol does not provide additional efficacy. PMID:26161425

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.

Reduced live-birth rates after IVF/ICSI in women with previous unilateral oophorectomy: results of a multicentre cohort study.

PubMed

Lind, Tekla; Holte, Jan; Olofsson, Jan I; Hadziosmanovic, Nermin; Gudmundsson, Johannes; Nedstrand, Elizabeth; Lood, Mikael; Berglund, Lars; Rodriguez-Wallberg, Kenny

2018-02-01

Is there a reduced live-birth rate (LBR) after IVF/ICSI treatment in women with a previous unilateral oophorectomy (UO)? A significantly reduced LBR after IVF/ICSI was found in women with previous UO when compared with women with intact ovaries in this large multicentre cohort, both crudely and after adjustment for age, BMI, fertility centre and calendar period and regardless of whether the analysis was based on transfer of embryos in the fresh cycle only or on cumulative results including transfers using frozen-thawed embryos. Similar pregnancy rates after IVF/ICSI have been previously reported in case-control studies and small cohort studies of women with previous UO versus women without ovarian surgery. In all previous studies multiple embryos were transferred. No study has previously evaluated LBR in a large cohort of women with a history of UO. This research was a multicentre cohort study, including five reproductive medicine centres in Sweden: Carl von Linné Clinic (A), Karolinska University Hospital (B), Uppsala University Hospital (C), Linköping University Hospital (D) and Örebro University Hospital (E). The women underwent IVF/ICSI between January 1999 and November 2015. Single embryo transfer (SET) was performed in approximately 70% of all treatments, without any significant difference between UO exposed women versus controls (68% versus 71%), respectively (P = 0.32), and a maximum of two embryos were transferred in the remaining cases. The dataset included all consecutive treatments and fresh and frozen-thawed cycles. The exposed cohort included 154 women with UO who underwent 301 IVF/ICSI cycles and the unexposed control cohort consisted of 22 693 women who underwent 41 545 IVF/ICSI cycles. Overall, at the five centres (A-E), the exposed cohort underwent 151, 34, 35, 41 and 40 treatments, respectively, and they were compared with controls of the same centre (18 484, 8371, 5575, 4670 and 4445, respectively). The primary outcome was LBR, which was analysed per started cycle, per ovum pick-up (OPU) and per embryo transfer (ET). Secondary outcomes included the numbers of oocytes retrieved and supernumerary embryos obtained, the Ovarian Sensitivity Index (OSI), embryo quality scores and cumulative pregnancy rates. We used a Generalized Estimating Equation (GEE) model for statistical analysis in order to account for repeated treatments. The exposed (UO) and control women's groups were comparable with regard to age and performance of IVF or ICSI. Significant differences in LBR, both crude and age-adjusted, were observed between the UO and control groups: LBR per started cycle (18.6% versus 25.4%, P = 0.007 and P = 0.014, respectively), LBR/OPU (20.3% versus 27.1%, P = 0.012 and P = 0.015, respectively) and LBR/ET (23.0% versus 29.7%, P = 0.022 and P = 0.025, respectively). The differences in LBR remained significant after inclusion of both fresh and frozen-thawed transfers (both crude and age-adjusted data): LBR/OPU (26.1% versus 34.4%, P = 0.005 and P = 0.006, respectively) and LBR/ET (28.3% versus 37.1%, P = 0.006 and P = 0.006, respectively). The crude cancellation rate was significantly higher among women with a history of UO than in controls (18.9% versus 14.5%, P = 0.034 and age-adjusted, P = 0.178). In a multivariate GEE model, the cumulative odds ratios for LBR (fresh and frozen-thawed)/OPU (OR 0.70, 95% CI 0.52-0.94, P = 0.016) and LBR (fresh and frozen-thawed)/ET (OR 0.68, 95% CI 0.51-0.92, P = 0.012) were approximately 30% lower in the group of women with UO when adjusted for age, BMI, reproductive centre, calendar period and number of embryos transferred when appropriate. The OSI was significantly lower in women with a history of UO than in controls (3.6 versus 6.0) and the difference was significant for both crude and age-adjusted data (P = <0.001 for both). Significantly fewer oocytes were retrieved in treatments of women with UO than in controls (7.2 versus 9.9, P = <0.001, respectively). Due to the nature of the topic, this is a retrospective analysis, with all its inherent limitations. Furthermore, the cause for UO was not possible to obtain in all cases. A diagnosis of endometriosis was also more common in the UO group, i.e. a selection bias in terms of poorer patient characteristics in the UO group cannot be completely ruled out. However, adjustment for all known confounders did not affect the general results. To date, this is the largest cohort investigated and the first study indicating an association of achieving reduced live birth after IVF/ICSI in women with previous UO. These findings are novel and contradict the earlier notion that IVF/ICSI treatment is not affected, or is only marginally affected by previous UO. None. Not applicable. © 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

Efficacy of testicular sperm chromatin condensation assay using aniline blue-eosin staining in the IVF-ET cycle.

PubMed

Park, Yong-Seog; Kim, Myo Kyung; Lee, Sun-Hee; Cho, Jae Won; Song, In Ok; Seo, Ju Tae

2011-09-01

This study was performed to evaluate testicular sperm chromatin condensation using aniline blue-eosin (AB-E) staining and its effects on IVF-ET. Chromatin condensation was analyzed using AB-E staining in 27 cases of testicular sperm extraction. There were 19 cases of obstructive azoospermia (OA) and 8 cases of non-obstructive azoospermia (NOA) in IVF-ET. Mature sperm heads were stained red-pink whereas immature sperm heads were stained dark blue. The percentage of sperm chromatin condensation was calculated from the ratio of the number of red-pink sperm to the total number of sperm analyzed. The overall percentages of chromatin condensation in OA and NOA were 31.1±11.2% and 26.3±14.4%, respectively. The fertilization rate was significant higher in OA than NOA (p<0.05); however, the rates of good embryos and clinical pregnancy did not show statistical differences. In OA and NOA, statistical differences were not observed in the rate of chromatin condensation, fertilization, good embryos, and clinical pregnancy between the pregnant group and non-pregnant group. Chromatin condensation is less stable than OA and showed a low fertilization rate in NOA. While there were no significant differences in chromatin condensation results between NOA and OA, we propose that a pattern of decreased chromatin condensation in NOA is one of the factors of low fertilization results requiring further study.

Freeze-all cycle in reproductive medicine: current perspectives.

PubMed

Roque, Matheus; Valle, Marcello; Kostolias, Alessandra; Sampaio, Marcos; Geber, Selmo

2017-02-01

The freeze-all strategy has emerged as an alternative to fresh embryo transfer (ET) during in vitro fertilization (IVF) cycles. Although fresh ET is the norm during assisted reproductive therapies (ART), there are many concerns about the possible adverse effects of controlled ovarian stimulation (COS) over the endometrium. The supra-physiologic hormonal levels that occur during a conventional COS are associated with modifications in the peri-implantation endometrium, which may be related to a decrease in pregnancy rates and poorer obstetric and perinatal outcomes when comparing fresh to frozen-thawed embryo transfers. The main objective of this study was to assess the available literature regarding the freeze-all strategy in IVF cycles, in regards to effectiveness and safety. Although there are many potential advantages in performing a freeze-all cycle over a fresh ET, it seems that the freeze-all strategy is not designed for all IVF patients. There is a need to develop a non-invasive clinical tool to evaluate the endometrial receptivity during a fresh cycle, which enables the selection of patients that would benefit from this strategy. Today, it is reasonable to perform elective cryopreservation of all oocytes/embryos in cases with a risk of OHSS development, and in patients with supra-physiologic hormonal levels during the follicular phase of COS. It is not clear if all normal responders and poor responders may benefit from this strategy.

Freeze-all cycle in reproductive medicine: current perspectives

PubMed Central

Roque, Matheus; Valle, Marcello; Kostolias, Alessandra; Sampaio, Marcos; Geber, Selmo

2017-01-01

The freeze-all strategy has emerged as an alternative to fresh embryo transfer (ET) during in vitro fertilization (IVF) cycles. Although fresh ET is the norm during assisted reproductive therapies (ART), there are many concerns about the possible adverse effects of controlled ovarian stimulation (COS) over the endometrium. The supra-physiologic hormonal levels that occur during a conventional COS are associated with modifications in the peri-implantation endometrium, which may be related to a decrease in pregnancy rates and poorer obstetric and perinatal outcomes when comparing fresh to frozen-thawed embryo transfers. The main objective of this study was to assess the available literature regarding the freeze-all strategy in IVF cycles, in regards to effectiveness and safety. Although there are many potential advantages in performing a freeze-all cycle over a fresh ET, it seems that the freeze-all strategy is not designed for all IVF patients. There is a need to develop a non-invasive clinical tool to evaluate the endometrial receptivity during a fresh cycle, which enables the selection of patients that would benefit from this strategy. Today, it is reasonable to perform elective cryopreservation of all oocytes/embryos in cases with a risk of OHSS development, and in patients with supra-physiologic hormonal levels during the follicular phase of COS. It is not clear if all normal responders and poor responders may benefit from this strategy. PMID:28333033

Human embryo culture media comparisons.

PubMed

Pool, Thomas B; Schoolfield, John; Han, David

2012-01-01

Every program of assisted reproduction strives to maximize pregnancy outcomes from in vitro fertilization and selecting an embryo culture medium, or medium pair, consistent with high success rates is key to this process. The common approach is to replace an existing medium with a new one of interest in the overall culture system and then perform enough cycles of IVF to see if a difference is noted both in laboratory measures of embryo quality and in pregnancy. This approach may allow a laboratory to select one medium over another but the outcomes are only relevant to that program, given that there are well over 200 other variables that may influence the results in an IVF cycle. A study design that will allow for a more global application of IVF results, ones due to culture medium composition as the single variable, is suggested. To perform a study of this design, the center must have a patient caseload appropriate to meet study entrance criteria, success rates high enough to reveal a difference if one exists and a strong program of quality assurance and control in both the laboratory and clinic. Sibling oocytes are randomized to two study arms and embryos are evaluated on day 3 for quality grades. Inter and intra-observer variability are evaluated by kappa statistics and statistical power and study size estimates are performed to bring discriminatory capability to the study. Finally, the complications associated with extending such a study to include blastocyst production on day 5 or 6 are enumerated.

Can IVF influence human evolution?

PubMed

Hanevik, Hans Ivar; Hessen, Dag O; Sunde, Arne; Breivik, Jarle

2016-07-01

IVF, a procedure in which pharmacological and technological manipulation is used to promote pregnancy, offers help to infertile couples by circumventing selection at the most fundamental level. Fertility is clearly one of the key fitness-promoting drivers in all forms of sexually reproducing life, and fertilization and pregnancy are fundamental evolutionary processes that involve a range of pre- and post-zygotic screening mechanisms. Here, we discuss the various selection and screening factors involved in fertilization and pregnancy and assess IVF practices in light of these factors. We then focus on the possible consequences of these differences in selection pressures, mainly at the individual but also at the population level, to evaluate whether changes in the reproducing genotype can affect human evolution. The aim of the article is not to argue for or against IVF, but to address aspects of assisted reproduction in an evolutionary context. © 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.

Recovery of motile sperm using the migration-sedimentation technique in an in-vitro fertilization-embryo transfer programme.

PubMed

Lucena, E; Lucena, C; Gómez, M; Ortiz, J A; Ruiz, J; Arango, A; Diaz, C; Beuerman, C

1989-02-01

Sperm washing techniques, based on the swim-up principle used before inseminating the human oocyte in in-vitro fertilization and embryo transfer programmes (IVF-ET), usually require prior centrifugation which causes damage to the sperm cell. A technique is described for separating sperm at laboratory temperature based on sperm migration--sedimentation principles, using two concentric tubes and recovering 70-90% forward-moving cells. A group of 17 patients is presented who were managed with this method. The results were 85% fertilization rate, 4% polyspermia and six clinical pregnancies.

Thirteen -weeks ovarian pregnancy following in vitro fertilization for primary infertility treatment: A case report.

PubMed

Ashrafganjoei, Tahereh; Nemati Honar, Behzad; Defaee, Sara

2014-11-01

Ovarian pregnancy constitutes 0.15-3% of all ectopic pregnancies. The incidence of ectopic pregnancy is on the rise owing to evolution in assisted reproductive techniques (ART). The incidence reported following In vitro fertilization (IVF) or embryo transfer (ET) is 0.27% per clinical pregnancy. We present a case of a 13-weeks ovarian pregnancy following IVF-ET and through a review of the literature, the specific symptomatology, diagnostic criteria, and treatment of this particular pathology will be described. Ovarian pregnancy is a rare condition and its diagnosis is difficult and relies on criteria based on intraoperative and histopathological findings. The management is, in spite of medical improvement, based on surgery. But the trend has shifted towards conservative surgeries in majority of cases.

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.

Experience of in vitro fertilization surrogacy in Finland.

PubMed

Söderström-Anttila, Viveca; Blomqvist, Tom; Foudila, Tuija; Hippeläinen, Maritta; Kurunmäki, Henri; Siegberg, Rita; Tulppala, Maija; Tuomi-Nikula, Merja; Vilska, Sirpa; Hovatta, Outi

2002-08-01

In vitro fertilization (IVF) surrogacy makes it possible for women who do not have a functional uterus to have their own genetic offspring. We describe here our experience of IVF surrogacy in Finland over a 10-year period. This retrospective study included 17 women who underwent ovarian stimulation in connection with surrogacy in 1991-2001 at four clinics. The surrogate mothers were unpaid volunteers: six sisters, three mothers, one husband's sister, one cousin, four friends and three other volunteers. Thorough counseling was given to the commissioning couples and to the surrogate mothers and their partners. The commissioning couples were prepared to adopt their biological children. Twenty-eight surrogate IVF cycles were started in 17 women. One couple received donated oocytes. Trans-vaginal oocyte retrieval was feasible in every case, including those five women with congenital absence of the vagina and uterus. An average of 1.8 embryos was transferred at a time, and 11 pregnancies were achieved [50% per fresh embryo transfer (ET) and 16% per frozen-thawed ET]. Nine healthy singletons and one set of twins were born. One pregnancy ended in miscarriage. The mean birth weight of singleton infants was 3498 g (2270-4650 g). The birth weights of the twins were 2900 and 2400 g. In all cases the genetic parents took care of the infant immediately after birth. Two surrogate mothers had postpartum depression. Altruistic IVF surrogacy works well, but careful counseling of all parties involved is essential.

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.

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

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.

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.

Clinical outcomes after IVF or ICSI using human blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum.

PubMed

Itoi, Fumiaki; Asano, Yukiko; Shimizu, Masashi; Nagai, Rika; Saitou, Kanako; Honnma, Hiroyuki; Murata, Yasutaka

2017-04-01

In this study the clinical and neo-natal outcomes after transfer of blastocysts derived from oocytes containing aggregates of smooth endoplasmic reticulum (SER) were compared between IVF and intracytoplasmic sperm injection (ICSI) cycles. Clinical and neo-natal outcomes of blastocysts in cycles with at least one SER metaphase II oocyte (SER + MII; SER + cycles) did not significantly differ between the two insemination methods. When SER + MII were cultured to day 5/6, fertilization, embryo cleavage and blastocyst rates were not significantly different between IVF and ICSI cycles. In vitrified-warmed blastocyst transfer cycles, the clinical pregnancy rates from SER + MII in IVF and ICSI did not significantly differ. In this study, 52 blastocysts (27 IVF and 25 ICSI) derived from SER + MII were transferred, yielding 15 newborns (5 IVF and 10 ICSI) and no malformations. Moreover, 300 blastocysts (175 IVF and 125 ICSI) derived from SER-MII were transferred, yielding 55 newborns (24 IVF and 31 ICSI cycles). Thus, blastocysts derived from SER + cycles exhibited an acceptable ongoing pregnancy rate after IVF (n = 125) or ICSI (n = 117) cycles. In conclusion, blastocysts from SER + MII in both IVF and ICSI cycles yield adequate ongoing pregnancy rates with neo-natal outcomes that do not differ from SER-MII. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Current trends of reproductive immunology practices in in vitro fertilization (IVF) - a first world survey using IVF-Worldwide.com.

PubMed

Kwak-Kim, Joanne; Han, Ae Ra; Gilman-Sachs, Alice; Fishel, Simon; Leong, Milton; Shoham, Zeev

2013-01-01

Reproductive immunology has evolved from basic research studies to clinical applications. In this study, we aim to investigate the actual application of reproductive immunology concepts and findings in clinical reproductive medicine such as recurrent pregnancy losses (RPL), repeated implantation failures (RIF), and failed in vitro fertilization (IVF) cycles. A web-based survey was performed on IVF-Worldwide.com. Collected data were analyzed by the computerized software. A significant proportion of physicians recommend thrombophilia workups (86%), parental genetic study (79%), and immunologic evaluations (69%) to IVF candidates who have a history of RPL or chemical pregnancy losses. IVF physicians consider an immunologic workup when patients have two (30%) or three (21%) failed IVF cycles. Assays for anticardiolipin antibody, lupus anticoagulant, thyroid peroxidase antibody, and antinuclear antibody are the four most commonly ordered immunologic tests for RPL (88, 84, 50, 47% each) and RIF (68, 63, 38, 38% each). Cellular immune evaluations, such as NK assay, human leukocyte antigen study, Th1/Th2 study or immunophenotype assay, are less commonly ordered. Reproductive immunology principles have been applied to the clinical management of RPL, RIF, and failed IVF cycles, and a significant proportion of IVF physicians acknowledge the importance of immunologic alterations with reproductive outcomes. © 2012 John Wiley & Sons A/S.

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.

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.

Embryo transfer simulation improves pregnancy rates and decreases time to proficiency in Reproductive Endocrinology and Infertility fellow embryo transfers.

PubMed

Heitmann, Ryan J; Hill, Micah J; Csokmay, John M; Pilgrim, Justin; DeCherney, Alan H; Deering, Shad

2017-05-01

To design and evaluate an ET simulator to train Reproductive Endocrinology and Infertility (REI) fellows' techniques of ET. Simulation model development and retrospective cohort analysis. Not applicable. Patients undergoing IVF. Simulation model evaluation and implementation of ET simulation training. Pregnancy rates. The REI fellow and faculty evaluation responses (n = 19/21 [90%]) of the model demonstrated realistic characteristics, with evaluators concluding the model was suitable for training in almost all evaluated areas. A total of 12 REI fellows who performed ET were analyzed: 6 before ET trainer and 6 after ET trainer. Pregnancy rates were 31% in the initial 10 ETs per fellow before simulator vs. 46% after simulator. One of six pre-ET trainer fellows (17%) had pregnancy rates ≥40% in their first 10 ETs; whereas four of six post-ET trainer fellows had pregnancy rates ≥40% in their first 10 ETs. The average number of ETs to obtain >40% pregnancy efficiency was 27 ETs before trainer vs. 15 ETs after trainer. Pregnancy rates were similar in the two groups after 20 ETs, and collective terminal pregnancy rates were >50% after 40 ETs. Embryo transfer simulation improved REI fellow pregnancy rates in their first 10 transfers and led to a more rapid ET proficiency. These data suggest potential value in adopting ET simulation, even in programs with a robust history of live ET in fellowship training. Published by Elsevier Inc.

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.

Bacterial endotoxin in the endometrium and its clinical significance in reproduction.

PubMed

Kamiyama, Shigeru; Teruya, Yoko; Nohara, Makoto; Kanazawa, Koji

2004-10-01

Bacterial endotoxin was detected in menstrual effluent from infertile women. Endometrial endotoxin appears to influence reproductive process because the pregnancy rate after IVF-ET was significantly associated with an endotoxin level.

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

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.

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.

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.

Comparison of protocols for cryopreservation of rhesus monkey spermatozoa by post-thaw motility recovery and hyperactivation.

PubMed

Nichols, S M; Bavister, B D

2006-01-01

Cryopreservation of spermatozoa is useful for gene banking and for in vitro fertilisation (IVF). This study compared several published cryopreservation techniques to find the most efficient for rhesus macaques. Effectiveness was assessed by sperm longevity (post-thaw motility % and duration) and ability to hyperactivate in response to chemical activators (caffeine, dibutyryl cyclic AMP). Each ejaculate from three males was treated with four published cryopreservation protocols (Seier et al. 1993; Sanchez-Partida et al. 2000; Si et al. 2000; Isachenko et al. 2005). Upon thawing, each sub-sample was incubated either at 37 degrees C in 5% CO2 in air with or without activators or at approximately 22 degrees C in atmospheric air without activators for 0-24 h. Samples cryopreserved using one method showed zero motility and were not included in the 2 ;2 G-test statistical analysis. The other methods all demonstrated good immediate post-thaw motility rates (68%, 73% and 62% respectively) and underwent capacitation after exposure to activators. Sperm motility in each treatment decreased over time at both temperatures but overall, incubation at 22 degrees C preserved motility better in all three methods. In summary, cryopreservation of rhesus spermatozoa using the method published by Sanchez-Partida et al. or Seier et al. appeared best, potentially supporting gene banking as well as allowing for multiple IVF uses from the same sample.

[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.

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.

Impaired Glucose Metabolism in Response to High Fat Diet in Female Mice Conceived by In Vitro Fertilization (IVF) or Ovarian Stimulation Alone

PubMed Central

Chen, Miaoxin; Wu, Linda; Wu, Fang; Wittert, Gary A.; Norman, Robert J.; Robker, Rebecca L.; Heilbronn, Leonie K.

2014-01-01

Individuals conceived by in vitro fertilization (IVF) may be at increased risk of cardio-metabolic disorders. We recently reported that IVF conceived male mice displayed impaired glucose metabolism at normal and high body weights. In this study, we examined glucose metabolism in mature female C57BL/6J mice that were conceived by natural conception (NC), by ovarian stimulation (OS) or by IVF following chow or high-fat diet (HFD) for 8 weeks. By design, litter size was comparable between groups, but interestingly the birth weight of IVF and OS females was lower than NC females (p≤0.001). Mature IVF female mice displayed increased fasting glucose as compared to NC and OS mice, irrespective of diet. Mature IVF and OS mice were also more susceptible to the metabolic consequences of high fat diet as compared with NC females, with impaired glucose tolerance (p≤0.01), whereas peripheral insulin resistance and increased hepatic expression of gluconeogenic genes Ppargc1α, Pck1 and G6pc was observed in IVF mice only (p<0.05). This study suggests that ovarian stimulation alone and IVF program distinct metabolic effects in females, but that high fat diet may be required to unmask these effects. This study adds to the growing body of literature that assisted reproduction procedures may increase the risk of developing type 2 diabetes in an obesity prone environment. PMID:25405530

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.

Cost-effectiveness analysis of preimplantation genetic screening and in vitro fertilization versus expectant management in patients with unexplained recurrent pregnancy loss.

PubMed

Murugappan, Gayathree; Ohno, Mika S; Lathi, Ruth B

2015-05-01

To determine whether in vitro fertilization with preimplantation genetic screening (IVF/PGS) is cost effective compared with expectant management in achieving live birth for patients with unexplained recurrent pregnancy loss (RPL). Decision analytic model comparing costs and clinical outcomes. Academic recurrent pregnancy loss programs. Women with unexplained RPL. IVF/PGS with 24-chromosome screening and expectant management. Cost per live birth. The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing $45,300 per live birth compared with $418 per live birth with expectant management. In this model, IVF/PGS was not a cost-effective strategy for increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be 91% to be cost effective compared with expectant management. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

History of the KC-10A Aircraft Acquisition

DTIC Science & Technology

1988-04-01

in other research reports or educational pursuits contingent upon the following stipulations: - Reproduction rights do not extend to any copyrighted...MAC, AFLC, and others) would create data for flight, maintenance, and technical data manuals, and evaluate human engineering factors. This testing...productio); ond deli.erme:; ra.. a fa:st rate and the acquisition program began to phase out.. The, total fleot gjrew to 52 aircraft, and del ivf , ics of th:ý

Altered gene expression in human placentas after IVF/ICSI.

PubMed

Nelissen, Ewka C M; Dumoulin, John C M; Busato, Florence; Ponger, Loïc; Eijssen, Lars M; Evers, Johannes L H; Tost, Jörg; van Montfoort, Aafke P A

2014-12-01

Is gene expression in placental tissue of IVF/ICSI patients altered when compared with a spontaneously conceived group, and are these alterations due to loss of imprinting (LOI) in the case of imprinted genes? An altered imprinted gene expression of H19 and Pleckstrin homology-like domain family A member 2 (PHLDA2), which was not due to LOI, was observed in human placentas after IVF/ICSI and several biological pathways were significantly overrepresented and mostly up-regulated. Genomic imprinting plays an important role in placental biology and in placental adaptive responses triggered by external stimuli. Changes in placental development and function can have dramatic effects on the fetus and its ability to cope with the intrauterine environment. An increased frequency of placenta-related problems as well as an adverse perinatal outcome is seen in IVF/ICSI derived pregnancies, but the role of placental epigenetic deregulation is not clear yet. In this prospective cohort study, a total of 115 IVF/ICSI and 138 control couples were included during pregnancy. After applying several exclusion criteria (i.e. preterm birth or stillbirth, no placental samples, pregnancy complications or birth defects), respectively, 81 and 105 placentas from IVF/ICSI and control pregnancies remained for analysis. Saliva samples were collected from both parents. We quantitatively analysed the mRNA expression of several growth-related imprinted genes [H19, insulin-like growth factor 2 (IGF2), PHLDA2, cyclin-dependent kinase inhibitor 1C (CDKN1C), mesoderm-specific transcript homolog (MEST) isoform α and β by quantitative PCR] after standardization against three housekeeping genes [Succinate dehydrogenase A (SDHA), YWHAZ and TATA-binding protein (TBP)]. A quantitative allele-specific expression analysis of the differentially expressed imprinted genes was performed to investigate LOI, independent of the mechanism of imprinting. Furthermore, a microarray analysis was carried out (n = 10 in each group) to investigate the expression of non-imprinted genes as well. Both H19 and PHLDA2 showed a significant change, respectively, a 1.3-fold (P = 0.033) and 1.5-fold (P = 0.002) increase in mRNA expression in the IVF/ICSI versus control group. However, we found no indication that there is an increased frequency of LOI in IVF/ICSI placental samples. Genome-wide mRNA expression revealed 13 significantly overrepresented biological pathways involved in metabolism, immune response, transmembrane signalling and cell cycle control, which were mostly up-regulated in the IVF/ICSI placental samples. Only a subset of samples was found to be fully informative, which unavoidably led to lower sample numbers for our LOI analysis. Our study cannot distinguish whether the reported differences in the IVF/ICSI group are exclusively attributable to the IVF/ICSI technique itself or to the underlying subfertility of the patients. Whether these placental adaptations observed in pregnancies conceived by IVF/ICSI might be connected to an adverse perinatal outcome after IVF remains unknown. However, it is possible that these differences affect fetal development and long-term patterns of gene expression, as well as maternal gestational physiology. Partly funded by an unrestricted research grant by Organon BV (now MSD BV) and GROW School for Oncology and Developmental Biology without any role in study design, data collection and analysis or preparation of the manuscript. No conflict of interests to declare. Dutch Trial Registry (NTR) number 1298. © 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.

Leptin and its potential interest in assisted reproduction cycles.

PubMed

Catteau, A; Caillon, H; Barrière, P; Denis, M G; Masson, D; Fréour, T

2016-04-01

Leptin, an adipose hormone, has been shown to control energy homeostasis and food intake, and exert many actions on female reproductive function. Consequently, this adipokine is a pivotal factor in studies conducted on animal models and humans to decipher the mechanisms behind the infertility often observed in obese women. A systematic PubMed search was conducted on all articles, published up to January 2015 and related to leptin and its actions on energy balance and reproduction, using the following key words: leptin, reproduction, infertility, IVF and controlled ovarian stimulation. The available literature was reviewed in order to provide an overview of the current knowledge on the physiological roles of leptin, its involvement in female reproductive function and its potential interest as a prognostic marker in IVF cycles. Animal and human studies show that leptin communicates nutritional status to the central nervous system and emerging evidence has demonstrated that leptin is involved in the control of reproductive functions by acting both directly on the ovaries and indirectly on the central nervous system. With respect to the clinical use of leptin as a biomarker in IVF cycles, a systematic review of the literature suggested its potential interest as a predictor of IVF outcome, as high serum and/or follicular fluid leptin concentrations have correlated negatively with cycle outcome. However, these preliminary results remain to be confirmed. Leptin regulates energy balance and female reproductive function, mainly through its action on hypothalamic-pituitary-ovarian function, whose molecular and cellular aspects are progressively being deciphered. Preliminary studies evaluating leptin as a biomarker in human IVF seem promising but need further confirmation. © 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.

[Correlation of the DNA fragmentation index and malformation rate of optimized sperm with embryonic development and early spontaneous abortion in IVF-ET].

PubMed

Jiang, Wei-Jie; Jin, Fan; Zhou, Li-Ming

2016-06-01

To investigate the effects of the DNA fragmentation index (DFI) and malformation rate (SMR) of optimized sperm on embryonic development and early spontaneous abortion in conventional in vitro fertilization and embryo transfer (IVF-ET). We selected 602 cycles of conventional IVF-ET for pure oviductal infertility that had achieved clinical pregnancies, including 505 cycles with ongoing pregnancy and 97 cycles with early spontaneous abortion. On the day of ovum retrieval, we examined the DNA integrity and morphology of the rest of the optimized sperm using the SCD and Diff-Quik methods, established the joint predictor (JP) by logistic equation, and assessed the value of DFI and SMR in predicting early spontaneous abortion using the ROC curve. The DFI, SMR, and high-quality embryo rate were (15.91±3.69)%, (82.85±10.24)%, and 46.53% (342/735) in the early spontaneous abortion group and (9.30±4.22)%, (77.32±9.19)%, and 56.43% (2263/4010) respectively in the ongoing pregnancy group, all with statistically significant differences between the two groups (P<0.05 ). Both the DFI and SMR were the risk factors of early spontaneous abortion (OR = 5.96 and 1.66; both P< 0.01). The areas under the ROC curve for DFI, SMR and JP were 0.893±0.019, 0.685±0.028, and 0.898±0.018, respectively. According to the Youden index, the optimal cut-off values of the DFI and SMR obtained for the prediction of early spontaneous abortion were approximately 15% and 80%. The DFI was correlated positively with SMR (r= 0.31, P<0.01) but the high-quality embryo rate negatively with both the DFI (r= －0.45, P<0.01) and SMR (r= －0.22, P<0.01). The DFI and SMR of optimized sperm are closely associated with embryonic development in IVF. The DFI has a certain value for predicting early spontaneous abortion with a threshold of approximately 15%, but SMR may have a lower predictive value.

Clinical efficacy and cost-effectiveness of HP-human FSH (Fostimon®) versus rFSH (Gonal-F®) in IVF-ICSI cycles: a meta-analysis.

PubMed

Gerli, Sandro; Bini, Vittorio; Favilli, Alessandro; Di Renzo, Gian Carlo

2013-06-01

Clinical efficacy of human-derived follicle-stimulating hormone (FSH) versus recombinant FSH (rFSH) in IVF-ICSI cycles has long been compared, but no clear evidence of the superiority of a preparation over the other has been found. Human gonadotropins have been often grouped together, but a different glycosylation may be present in each preparation, therefore influencing the specific bioactivity. To exclude confounding factors, a meta-analysis and a cost-effectiveness analysis were designed to compare effectiveness and cost-effectiveness of a specific highly purified human FSH (HP-hFSH) (Fostimon®) versus rFSH (Gonal-F®) in IVF/ICSI cycles. Research methodology filters were applied in MEDLINE, Current Contents and Web of Science from 1980 to February 2012. Eight randomized trials met selection criteria. The meta-analysis showed no significant differences between rFSH and HP-hFSH treatment in live-birth rate (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.63-1.11), clinical pregnancy rate (OR 0.85, 95% CI 0.68-1.07), number of oocytes retrieved, number of mature oocytes and days of stimulation. The cost-effectiveness ratio was € 7174 in the rFSH group and € 2056 in the HP-hFSH group. HP-hFSH is as effective as rFSH in ovarian stimulation for IVF-ICSI cycles, but the human preparation is more cost-effective.

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.

Effect of a mind-body therapeutic program for infertile women repeating in vitro fertilization treatment on uncertainty, anxiety, and implantation rate.

PubMed

Kim, Miok; Kim, Sue; Chang, Soon-bok; Yoo, Ji-Soo; Kim, Hee Kyung; Cho, Jung Hyun

2014-03-01

The study aimed to develop a mind-body therapeutic program and evaluate its effects on mitigating uncertainty, anxiety, and implantation rate of second-trial in vitro fertilization (IVF) women. This study employed a nonequivalent control group nonsynchronized design. The conceptual framework and program content were developed from a preliminary survey of eight infertile women and the extensive review of the literature. Program focuses on three uncertainty-induced anxieties in infertile women: cognitive, emotional, and biological responses. To evaluate the effect of the intervention, the infertile women with unknown cause preparing for a second IVF treatment were sampled at convenience (26 experimental and 24 control). The experimental group in the study showed greater decrease in uncertainty and anxiety in premeasurements and postmeasurements than the control group did. However, no statistically significant differences in the implantation rate between groups were observed. This study is meaningful as the first intervention program for alleviating uncertainty and anxiety provided during the IVF treatment process. The positive effects of the mind-body therapeutic program in alleviating both uncertainty and anxiety have direct meaning for clinical applications. Copyright © 2014. Published by Elsevier B.V.

40 years of bovine IVF in the new genomic selection context.

PubMed

Sirard, Marc-Andre

2018-04-10

The development of a complex technology such as in vitro fertilization (IVF) requires years of experimentation, sometimes comparing several species to learn how to create the right in vitro environment for oocytes, spermatozoa, and early embryos. At the same time, individual species characteristics such as gamete physiology and gamete interaction are recently evolved traits and must be analysed within the context of each species. In the last 40 years since the birth of Louise Brown, IVF techniques progressed and are now used in multiple domestic and non-domestic animal species around the world. This does not mean that the technology is completely matured or satisfactory; a number of problems remain to be solved and several procedures still need to be optimized. The development of IVF in cattle is particularly interesting since agriculture practices permitted the commercial development of the procedure and it is now used at a scale comparable to human IVF (millions of newborns). The genomic selection of young animals or even embryos combined with sexing and freezing technologies is driving a new era of IVF in the Dairy sector. The time has come for a retrospective analysis of the success and pitfalls of the last 40 years of bovine IVF and for the description of the challenges to overcome in the years to come.

Effect of semen quality on human sex ratio in in vitro fertilization and intracytoplasmic sperm injection: an analysis of 27,158 singleton infants born after fresh single-embryo transfer.

PubMed

Arikawa, Mikiko; Jwa, Seung Chik; Kuwahara, Akira; Irahara, Minoru; Saito, Hidekazu

2016-04-01

To evaluate the effect of semen quality on human sex ratio in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Retrospective cohort study. Not applicable. A total of 27,158 singleton infants born between 2007 and 2012 after fresh single-embryo transfer. None. Proportion of male infants among liveborn infants. There were 14,996 infants born after IVF, 12,164 infants born after ICSI with ejaculated sperm, and 646 infants born after ICSI with nonejaculated sperm. The sex ratio of IVF was 53.1% (95% confidence interval [CI], 52.3-53.9); the sex ratio of ICSI with ejaculated and nonejaculated sperm demonstrated as statistically significant reduction (48.2%; 95% CI, 47.3-49.1 and 47.7%; 95% CI, 43.8-51.6, respectively). In IVF, lower sperm motility, including asthenozoospermia (sperm motility <40%), was associated with a statistically significantly lower sex ratio compared with normal sperm (51.0%; 95% CI, 48.6-53.3 vs. 53.4%; 95% CI, 52.5-54.3). In ICSI with ejaculated sperm, there was no association between sperm motility and sex ratio. Sperm concentration was not associated with sex ratio in both IVF and ICSI. In IVF, lower sperm motility was associated with a statistically significant reduction in sex ratio; ICSI with either ejaculated or nonejaculated sperm was associated with a statistically significant reduction in sex ratio regardless of semen quality. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The Use of Tailored Testing with Instructional Programs.

DTIC Science & Technology

1986-03-01

AVAILABILITY OF REPORT Approved for public release: distribution un- t~X DWNCADNGSCHiEDULE li-mited. Reproduction in whole or in part is...of Education ,-’ Washington, DC 20V 0 Chicago, IL r06𔄁 Air Force Human Resources Lab Cdt. Arnold Bohrer . AFHRL/MPD Sectie Psychologisch Cnderzoek...University of Texas-Austin Univ-ir-tat Puss-ldorf Measurement and Evalu-,tion Er zi, gswi ssensch;ftl iches Cpnter Un ivf rsit ’tsst r. 1 Austin, TX 787

Combined analysis of endometrial thickness and pattern in predicting outcome of in vitro fertilization and embryo transfer: a retrospective cohort study.

PubMed

Chen, Shi-Ling; Wu, Fang-Rong; Luo, Chen; Chen, Xin; Shi, Xiao-Yun; Zheng, Hai-Yan; Ni, Yun-Ping

2010-03-24

To evaluate the combined effect of endometrial thickness and pattern on clinical outcome in patients undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Cycles of IVF/ICSI-ET conducted between January 2003 and December 2008 at a university-based reproductive center were reviewed retrospectively. Endometrial ultrasonographic characteristics were recorded on the day of hCG administration. In the combined analysis, endometrial thickness groups (group 1: equal or <7 mm; group 2: 7-14 mm; group 3: >14 mm) were subdivided into two endometrial patterns (pattern A: triple-line; pattern B: no-triple line). Clinical pregnancy rate (CPR) and early miscarriage rate in different groups were analyzed. A total of 2896 cycles were reviewed. Clinical pregnancy rate (CPR) was 24.4% in group 1-A. There were no second trimester pregnancies in group 1-B. Miscarriage rate in group 2-A was significantly lower compared to group 2-B (P < 0.01), although CPR did not show any significant differences between the groups. A no-triple line endometrial pattern with moderate endometrial thickness (7-14 mm) had a detrimental effect on pregnancy outcome, but not the occurrence of pregnancy. In group 3, there was no difference in CPR and miscarriage rates between the two patterns; adequate endometrial thickness (>14 mm) seemed to mitigate the detrimental impact (high miscarriage rate) of pattern B. Combined analysis of endometrial thickness and pattern on the day of hCG administration was a better predictor of the outcome of IVF/ICSI-ET and may be more helpful for patient counseling than the separate analyses.

A preliminary study of the relationship between the long arm of the Y chromosome (Yqh+) and reproductive outcomes in IVF/ICSI-ET.

PubMed

Xiao, Zhuoni; Zhou, Xin; Xu, Wangming; Yang, Jing

2012-11-01

To compare the reproductive outcomes of Yqh+-carrying and control couples undergoing IVF/ICSI treatments. Retrospective analysis of 72 Yqh+ carriers and 986 Yqh+ non-carriers undergoing their first cycle of ART in a single centre between August 2005 and May 2011. Yqh+ carrying couples had significantly worse reproductive outcomes compared with control couples undergoing IVF treatment. There were a significantly higher cancellation rate (20.69% vs 7.9%; P<0.05; OR, 3.03; CI, 1.18-7.79) and a significant lower fertilisation rate (50.05% vs 66.01%; P<0.05; OR, 0.61; CI, 0.49-0.57), implantation rate (8.33% vs 20.87%; P<0.05; OR, 0.35; CI, 0.14-0.87), good quality embryo ratio (44.70% vs 57.89%; P<0.05; OR, 0.59; CI, 0.43-0.80) and clinical pregnancy rate (17.39% vs 39.59%; P<0.05; OR, 0.32; CI, 0.11-0.96) in Yqh+ group compared with control group undergoing IVF treatment. Yqh+ carrying couples had similar reproductive outcomes compared with control couples undergoing ICSI treatment. The Y chromosome polymorphic variant Yqh+ most likely plays a role in infertility. Yqh+ couples with poor reproductive outcomes in IVF treatment can be advised to undergo ICSI to improve their reproductive results in the next cycle. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The Moderating Influence of International Courts on Social Movements: Evidence from the IVF Case Against Costa Rica.

PubMed

Lemaitre, Julieta; Sieder, Rachel

2017-06-01

Feminists and religious conservatives across the globe have increasingly turned to courts in their battles over abortion. Yet while a significant literature analyzes legal mobilization on abortion issues, it tends to focus predominantly on domestic scenarios. In this article, we consider the effects of this contentious engagement of pro-choice and anti-abortion movements in international human rights fora, asking what happens to social movement claims when they reach international human rights courts. We answer the question through a detailed description of a single case, Gretel Artavia Murillo et al. v. Costa Rica , decided by the Inter-American Court of Human Rights in 2012 but with ongoing repercussions for abortion rights, given its authoritative interpretation of embryonic right to life. Through our analysis of Artavia Murillo , we show how legal mobilization before international human rights courts moderates social movement claims within the legal arena, as rivals respond to one another and argue within the frame of courts' norms and language.

The use of berberine for women with polycystic ovary syndrome undergoing IVF treatment.

PubMed

An, Yuan; Sun, Zhuangzhuang; Zhang, Yajuan; Liu, Bin; Guan, Yuanyuan; Lu, Meisong

2014-03-01

Previous studies have indicated that berberine is an effective insulin sensitizer with comparable activity to metformin (Diabetes 2006, 55, 2256). Reduced insulin sensitivity is reportedly a factor adversely affecting the outcome of IVF in patients with polycystic ovary syndrome (PCOS) (Human Reproduction 2006, 21, 1416). Our objective was to evaluate the clinical, metabolic and endocrine effects of berberine vs metformin in PCOS women scheduled for IVF treatment and to explore the potential benefits to the IVF process. We performed a prospective study in 150 infertile women with PCOS undergoing IVF treatment. Patients were randomized to receive berberine, metformin or placebo tablets for 3 months before ovarian stimulation. The clinical, endocrine, metabolic parameters and the outcome of IVF. Compared with placebo, greater reductions in total testosterone, free androgen index, fasting glucose, fasting insulin and HOMA-IR, and increases in SHBG, were observed in the berberine and metformin groups. Three months of treatment with berberine or metformin before the IVF cycle increased the pregnancy rate and reduced the incidence of severe ovarian hyperstimulation syndrome. Furthermore, treatment with berberine, in comparison with metformin, was associated with decreases in BMI, lipid parameters and total FSH requirement, and an increase in live birth rate with fewer gastrointestinal adverse events. Berberine and metformin treatments prior to IVF improved the pregnancy outcome by normalizing the clinical, endocrine and metabolic parameters in PCOS women. Berberine has a more pronounced therapeutic effect and achieved more live births with fewer side effects than metformin. © 2013 John Wiley & Sons Ltd.

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.

Normal saline is associated with increased sickle red cell stiffness and prolonged transit times in a microfluidic model of the capillary system.

PubMed

Carden, Marcus A; Fay, Meredith; Sakurai, Yumiko; McFarland, Brynn; Blanche, Sydney; DiPrete, Caleb; Joiner, Clinton H; Sulchek, Todd; Lam, Wilbur A

2017-07-01

Vaso-occlusive crisis (VOC) is a complex process that occurs in patients with sickle cell disease (SCD) and is often associated with pain and urgent hospitalization. A major instigator of VOC is microvascular obstruction by pathologically stiffened sickle red blood cells (RBCs), and thus, therapy relies heavily on optimizing intravenous fluid (IVF) hydration to increase RBC deformability. However, no evidence-based guidelines regarding the choice of IVF currently exist. We therefore analyzed alterations in biomechanical properties of sickle RBCs isolated from patients with homozygous SCD (hemoglobin SS) after exposure to different osmolarities of clinical IVF formulations. Atomic force microscopy (AFM) was used to assess stiffness of RBCs after exposure to different IVFs. A microfluidic model of the human capillary system was used to assess transit time (TT) and propensity to occlusion after exposure to the different IVF formulations. Sickle RBCs exposed to normal saline (NS) had increased stiffness, TTs, and propensity to microchannel occlusion compared to other osmolarities. NS, an IVF formulation often used to treat patients with SCD during VOC, may induce localized microvascular obstruction due to alterations of sickle RBC biomechanical properties. © 2017 John Wiley & Sons Ltd.

Abnormalities in human pluripotent cells due to reprogramming mechanisms

PubMed Central

Ma, Hong; Morey, Robert; O’Neil, Ryan C.; He, Yupeng; Daughtry, Brittany; Schultz, Matthew D.; Hariharan, Manoj; Nery, Joseph R.; Castanon, Rosa; Sabatini, Karen; Thiagarajan, Rathi D.; Tachibana, Masahito; Kang, Eunju; Tippner-Hedges, Rebecca; Ahmed, Riffat; Gutierrez, Nuria Marti; Van Dyken, Crystal; Polat, Alim; Sugawara, Atsushi; Sparman, Michelle; Gokhale, Sumita; Amato, Paula; Wolf, Don P.; Ecker, Joseph R.; Laurent, Louise C.; Mitalipov, Shoukhrat

2016-01-01

Human pluripotent stem cells hold potential for regenerative medicine, but available cell types have significant limitations. Although embryonic stem cells (ES cells) from in vitro fertilized embryos (IVF ES cells) represent the ‘gold standard’, they are allogeneic to patients. Autologous induced pluripotent stem cells (iPS cells) are prone to epigenetic and transcriptional aberrations. To determine whether such abnormalities are intrinsic to somatic cell reprogramming or secondary to the reprogramming method, genetically matched sets of human IVF ES cells, iPS cells and nuclear transfer ES cells (NT ES cells) derived by somatic cell nuclear transfer (SCNT) were subjected to genome-wide analyses. Both NT ES cells and iPS cells derived from the same somatic cells contained comparable numbers of de novo copy number variations. In contrast, DNA methylation and transcriptome profiles of NT ES cells corresponded closely to those of IVF ES cells, whereas iPS cells differed and retained residual DNA methylation patterns typical of parental somatic cells. Thus, human somatic cells can be faithfully reprogrammed to pluripotency by SCNT and are therefore ideal for cell replacement therapies. PMID:25008523

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.

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.

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.

How compliant are in vitro fertilization member clinics in following embryo transfer guidelines? An analysis of 59,689 fresh first in vitro fertilization autologous cycles from 2011 to 2012.

PubMed

Keyhan, Sanaz; Acharya, Kelly S; Acharya, Chaitanya R; Yeh, Jason S; Provost, Meredith P; Goldfarb, James M; Muasher, Suheil J

2016-09-01

To determine whether IVF clinics are compliant with American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology (SART) (ASRM/SART) guidelines and assess the multiple pregnancy outcomes according to the number of embryos transferred. Retrospective cohort study. Not applicable. Data from 59,689 fresh first autologous IVF cycles from the 2011-2012 SART registry. None. Percentage of compliant cycles, multiple pregnancy rate (PR). Between 2011 and 2012, a total of 59,689 fresh first autologous cycles were analyzed. Among cleavage-stage ET cycles, the noncompliance rate ranged from 10%-27.4% depending on the age group. The multiple PR was significantly increased in noncompliant cycles involving patients <35 years (38.1% vs. 28.7%) and 35-37 years (35.4% vs. 24.5%) compared with compliant cycles. Among blastocyst-stage ET cycles, the highest rate of noncompliance was seen in patients <35 years old (71%), which resulted in a statistically higher multiple PR (48.3% vs. 2.8%) compared with compliant cycles. Far fewer cycles were noncompliant in patients 35-40 years of age. In a subanalysis of compliant cycles, transferring two blastocyst embryos in patients 35-37 years and 38-40 years resulted in a higher live birth rate compared with the transfer of one embryo (50.4% vs. 40.9% and 42.1% vs. 30.0%, respectively) but the multiple PR was also significantly higher (40.5% vs. 1.7% and 34.0% vs. 2.0%, respectively). Most first fresh autologous IVF cycles performed from 2011-2012 were compliant with ASRM/SART guidelines, except those that involved a blastocyst ET in patients <35 years. Despite compliance, cycles that involved the transfer of >1 embryo resulted in a high multiple PR, whereas noncompliant cycles resulted in an even more remarkable multiple PR for both cleavage and blastocyst-stage embryos. Clinics need to be more compliant with ET limits and ASRM/SART need to consider revising their guidelines to limit the number of blastocyst transfer to one in patients ≤40 years of age undergoing their first IVF cycle. Furthermore, decreasing the number of cleavage-stage embryos transferred in patients ≤40 years of age should also be considered. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Low-Dose Urinary Human Chorionic Gonadotropin Is Effective for Oocyte Maturation in In Vitro Fertilization/ Intracytoplasmic Sperm Injection Cycles Independent of Body Mass Index

PubMed Central

R. Hoyos, Luis; Khan, Sana; Dai, Jing; Singh, Manvinder; P. Diamond, Michael; E. Puscheck, Elizabeth; O. Awonuga, Awoniyi

2017-01-01

Background: Currently, there is no agreement on the optimal urinary derived human chorionic gonadotropin (u-hCG) dose requirement for initiating final oocyte maturation prior to oocyte collection in in vitro fertilization (IVF), but doses that range from 2500- 15000 IU have been used. We intended to determine whether low dose u-hCG was effective for oocyte maturation in IVF/intracytoplasmic sperm injection (ICSI) cycles independent of body mass index (BMI). Materials and Methods: We retrospectively evaluated a cohort of 295 women who underwent their first IVF/ICSI cycles between January 2003 and December 2010 at the Division of Reproductive Endocrinology and Infertility, Wayne State University, Detroit, MI, USA. Treatment cycles were divided into 3 groups based on BMI (kg/ m2): <25 (n=136), 25- <30 (n=84), and ≥30 (n=75) women. Patients received 5000, 10000 or 15000 IU u-hCG for final maturation prior to oocyte collection. The primary outcome was clinical pregnancy rates (CPRs) and secondary outcome was live birth rates (LBRs). Results: Only maternal age negatively impacted (P<0.001) CPR [odds ratio (OR=0.85, confidence interval (CI: 0.79-0.91)] and LBR (OR=0.84, CI: 0.78-0.90). Conclusion: Administration of lower dose u-hCG was effective for oocyte maturation in IVF and did not affect the CPRs and LBRs irrespective of BMI. Women’s BMI need not be taken into consideration in choosing the appropriate dose of u-hCG for final oocyte maturation prior to oocyte collection in IVF. Only maternal age at the time of IVF negatively influenced CPRs and LBRs in this study. PMID:28367299

Nuchal translucency measurement, free β-hCG and PAPP-A concentrations in IVF/ICSI pregnancies: systematic review and meta-analysis.

PubMed

Cavoretto, Paolo; Giorgione, Veronica; Cipriani, Sonia; Viganò, Paola; Candiani, Massimo; Inversetti, Annalisa; Ricci, Elena; Parazzini, Fabio

2017-06-01

So far, data on the effect of assisted reproductive technologies (ART) on the components of first trimester combined screening for Down syndrome are still controversial. A systematic search of the literature was performed in order to identify the effect of ART, particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with fresh embryo transfer, on the nuchal translucency, free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein-A measurements. Moreover, a meta-analysis and a descriptive graphical representation of the ratios between ART and spontaneous pregnancies (controls) values of median of the multiple of median (m 0 MoM) were performed. Free beta-human chorionic gonadotrophin test showed slightly higher values in the ICSI group than controls (RR = 1.09, 95%CI: 1.03-1.16) but not in the IVF group (RR = 1.03, 95%CI: 0.94-1.12). Pregnancy-associated plasma protein-A values for IVF/ICSI, IVF and ICSI showed lower values in comparison with controls (RR, 95%CI 0.85, 0.80-0.90; 0.82, 0.74-0.89 and 0.83, 0.79-0.86, respectively). The nuchal translucency measurement did not show any statistical differences between study groups (IVF and ICSI) and controls (RR = 1.00, 95%CI: 0.94-1.08 and RR = 1.01, 95%CI: 0.97-1.05, respectively). These results may be due to alterations in the placentation of ART pregnancies. Differentiating further subgroups of ART pregnancies may explain the differences in biomarker concentrations, in prenatal behavior and in obstetric outcomes between ART and spontaneous pregnancies. © 2017 John Wiley & Sons, Ltd. © 2017 John Wiley & Sons, Ltd.

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.

Comprehensive genetic assessment of the human embryo: can empiric application of microarray comparative genomic hybridization reduce multiple gestation rate by single fresh blastocyst transfer?

PubMed

Sills, Eric Scott; Yang, Zhihong; Walsh, David J; Salem, Shala A

2012-09-01

The unacceptable multiple gestation rate currently associated with in vitro fertilization (IVF) would be substantially alleviated if the routine practice of transferring more than one embryo were reconsidered. While transferring a single embryo is an effective method to reduce the clinical problem of multiple gestation, rigid adherence to this approach has been criticized for negatively impacting clinical pregnancy success in IVF. In general, single embryo transfer is viewed cautiously by IVF patients although greater acceptance would result from a more effective embryo selection method. Selection of one embryo for fresh transfer on the basis of chromosomal normalcy should achieve the dual objective of maintaining satisfactory clinical pregnancy rates and minimizing the multiple gestation problem, because embryo aneuploidy is a major contributing factor in implantation failure and miscarriage in IVF. The initial techniques for preimplantation genetic screening unfortunately lacked sufficient sensitivity and did not yield the expected results in IVF. However, newer molecular genetic methods could be incorporated with standard IVF to bring the goal of single embryo transfer within reach. Aiming to make multiple embryo transfers obsolete and unnecessary, and recognizing that array comparative genomic hybridization (aCGH) will typically require an additional 12 h of laboratory time to complete, we propose adopting aCGH for mainstream use in clinical IVF practice. As aCGH technology continues to develop and becomes increasingly available at lower cost, it may soon be considered unusual for IVF laboratories to select a single embryo for fresh transfer without regard to its chromosomal competency. In this report, we provide a rationale supporting aCGH as the preferred methodology to provide a comprehensive genetic assessment of the single embryo before fresh transfer in IVF. The logistics and cost of integrating aCGH with IVF to enable fresh embryo transfer are also discussed.

Does the type of culture medium used influence birthweight of children born after IVF?

PubMed

Zandstra, Heleen; Van Montfoort, Aafke P A; Dumoulin, John C M

2015-03-01

Do culture media influence birthweight of children born after IVF? Some studies have observed a significant effect of culture media on birthweight, while others have not, but since most studies compared different culture media, conventional meta-analysis was not possible. Animal studies suggest that in vitro culture of embryos can have a significant effect on the birthweight of offspring when compared with in vivo developed embryos. The type of culture medium (or certain components of the medium) used is one of the causal factors. We reviewed all available literature reporting on a relation between culture medium and birthweight in human studies and a selection of animal studies. An extensive literature search on Pubmed and Medline was performed with relevant search criteria relating to IVF, birthweight and culture medium. Eleven studies reporting on a relationship between culture medium and birthweight in human were included in this review. Five of these found significant differences in birthweight when offspring born after culture in different culture media were compared. The remaining studies did not find differences in birthweight after changing culture medium. The number of human studies is limited and different culture media with different compositions are compared which makes a comparison between the studies difficult, if not impossible. Furthermore, most study designs were retrospective with consecutive use of different culture media and limited sample sizes, which makes bias of the results likely. If it could be confirmed that the type of culture medium used does indeed influence phenotypic characteristics (such as birthweight) of children born after IVF, it would underline the importance of monitoring the health of IVF children in relation to aspects of the laboratory techniques used during embryo culture. No funding was applicable to this study. No conflict of interest is declared. © 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.

Experience with the bonanno catheter in the management of OHSS from IVF-ET Cycles.

PubMed

Okohue, J E; Oriji, V K; Ikimalo, J I

2017-07-01

To document our experience with the use of the Bonanno catheter as a closed abdominal drain for OHSS Methods: A retrospective study of all IVF embryo transfer (ET) treatment cycles carried out between May 2006 and April 2009 at a dedicated IVF centre. Case notes of patients with OHSS were retrieved and the outcome of the continuous closed abdominal drain with Bonanno catheter documented. Within the period under review, 234 patients had controlled ovarian stimulation with ultrasound guided egg retrieval. Two hundred and twenty eight (228) got to the stage of embryo transfer with 72 clinical pregnancies. The clinical pregnancy rate was 31.58%. Fourteen (6%) of those who were stimulated developed OHSS and had a closed abdominal drain of the ascitic fluid using the Bonanno catheter. The average number of days of the abdominal drainage was 7.5days and the average volume of ascitic fluid drained from a patient per day was 2454.9 + 748mls. Eight (8) patients who had OHSS achieved clinical pregnancy (six intrauterine, one ectopic and one heterotopic pregnancies), giving a clinical pregnancy rate of 57.14% in patients with OHSS. Four patients had blocked Bonanno catheters and three of them had the catheter changed while the fourth had the catheter successfully flushed. Four patients had the insertion site dressing changed due to soaking with ascitic fluid. There was no incidence of injury to intra abdominal organs or broken catheter. Bonanno Catheter is both effective and safe in draining ascitic fluid following OHSS.

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.

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.

A protocol for rat in vitro fertilization during conventional laboratory working hours.

PubMed

Aoto, Toshihiro; Takahashi, Ri-ichi; Ueda, Masatsugu

2011-12-01

In vitro fertilization (IVF) is a valuable technique for the propagation of experimental animals. IVF has typically been used in mice to rapidly expand breeding colonies and create large numbers of embryos. However, applications of IVF in rat breeding experiments have stalled due to the inconvenient laboratory work schedules imposed by current IVF protocols for this species. Here, we developed a new rat IVF protocol that consists of experimental steps performed during common laboratory working hours. Our protocol can be completed within 12 h by shortening the period of sperm capacitation from 5 to 1 h and the fertilization time from 10 to 8 h in human tubal fluid (HTF) medium. This new protocol generated an excellent birth rate and was applicable not only to closed colony rat strains, such as Wistar, Long-Evans, and Sprague-Dawley (SD), but also to the inbred Lewis strain. Moreover, Wistar and Long-Evans embryos prepared by this protocol were successfully frozen by vitrification and later successfully thawed and resuscitated. This protocol is practical and can be easily adopted by laboratory workers.

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

Making muslim babies: Ivf and gamete donation in sunni versus shi’a islam

PubMed Central

2006-01-01

Medical anthropological research on science, biotechnology, and religion has focused on the “local moral worlds” of men and women as they make difficult decisions regarding their health and the beginnings and endings of human life. This paper focuses on the local moral worlds of infertile Muslims as they attempt to make, in the religiously correct fashion, Muslim babies at in vitro fertilization (IVF) clinics in Egypt and Lebanon. As early as 1980, authoritative fatwas issued from Egypt’s famed Al-Azhar University suggested that IVF and similar technologies are permissible as long as they do not involve any form of third-party donation (of sperm, eggs, embryos, or uteruses). Since the late 1990s, however, divergences in opinion over third-party gamete donation have occurred between Sunni and Shi’ite Muslims, with Iran’s leading ayatollah permitting gamete donation under certain conditions. This Iranian fatwa has had profound implications for the country of Lebanon, where a Shi’ite majority also seeks IVF services. Based on three periods of ethnographic research in Egyptian and Lebanese IVF clinics, this paper explores official and unofficial religious discourses surrounding the practice of IVF and third-party donation in the Muslim world, as well as the gender implications of gamete donation for Muslim marriages. PMID:17051430

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.

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.

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.

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.

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.

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.

Fresh embryo donation for human embryonic stem cell (hESC) research: the experiences and values of IVF couples asked to be embryo donors

PubMed Central

Haimes, E.; Taylor, K.

2009-01-01

BACKGROUND This article reports on an investigation of the views of IVF couples asked to donate fresh embryos for research and contributes to the debates on: the acceptability of human embryonic stem cell (hESC) research, the moral status of the human embryo and embryo donation for research. METHODS A hypothesis-generating design was followed. All IVF couples in one UK clinic who were asked to donate embryos in 1 year were contacted 6 weeks after their pregnancy result. Forty four in-depth interviews were conducted. RESULTS Interviewees were preoccupied with IVF treatment and the request to donate was a secondary consideration. They used a complex and dynamic system of embryo classification. Initially, all embryos were important but then their focus shifted to those that had most potential to produce a baby. At that point, ‘other’ embryos were less important though they later realise that they did not know what happened to them. Guessing that these embryos went to research, interviewees preferred not to contemplate what that might entail. The embryos that caused interviewees most concern were good quality embryos that might have produced a baby but went to research instead. ‘The’ embryo, the morally laden, but abstract, entity, did not play a central role in their decision-making. CONCLUSIONS This study, despite missing those who refuse to donate embryos, suggests that debates on embryo donation for hESC research should include the views of embryo donors and should consider the social, as well as the moral, status of the human embryo. PMID:19502616

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.

Revised guidelines for good practice in IVF laboratories (2015).

PubMed

De los Santos, Maria José; Apter, Susanna; Coticchio, Giovanni; Debrock, Sophie; Lundin, Kersti; Plancha, Carlos E; Prados, Fernando; Rienzi, Laura; Verheyen, Greta; Woodward, Bryan; Vermeulen, Nathalie

2016-04-01

Which recommendations can be provided by the European Society of Human Reproduction and Embryology Special Interest Group (ESHRE SIG) Embryology to support laboratory specialists in the organization and management of IVF laboratories and the optimization of IVF patient care? Structured in 13 sections, the guideline development group formulated recommendations for good practice in the organization and management of IVF laboratories, and for good practice of the specific procedures performed within the IVF laboratory. NA. The guideline was produced by a group of 10 embryologists representing different European countries, settings and levels of expertise. The group evaluated the document of 2008, and based on this assessment, each group member rewrote one or more sections. Two 2-day meetings were organized during which each of the recommendations was discussed and rewritten until consensus within the guideline group was reached. After finalizing the draft, the members of the ESHRE SIG embryology were invited to review the guideline. NA. The guideline provides recommendations on the general organization of an IVF laboratory (staffing and direction, quality management, laboratory safety), and on the specific aspects of the procedures performed in IVF laboratories (Identification of patients and traceability of their reproductive cells, consumables, handling of biological material, oocyte retrieval, sperm preparation, insemination of oocytes, scoring for fertilization, embryo culture and transfer, and cryopreservation). A last section provides recommendations regarding an Emergency plan for IVF laboratories. Evidence on most of the issues described is scarce, and therefore it was decided not to perform a formal search for and assessment of scientific evidence. However, recommendations published in the EUTCD and relevant and recent documents, manuals and consensus papers were taken into account when formulating the recommendations. Despite the limitations, the guideline group is confident that this document will be helpful to directors and managers involved in the management and organization of IVF laboratories, but also to embryologists and laboratory technicians performing daily tasks. The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings. The guideline group members did not receive payment. Dr Coticchio reports speaker's fees from IBSA and Cook, outside the submitted work; Dr Lundin reports grants from Vitrolife, personal fees from Merck Serono, non-financial support from Unisense, outside the submitted work; Dr. Rienzi reports personal fees from Merck Serono, personal fees from MSD, grants from GFI, outside the submitted work; the other authors had nothing to disclose. NA. © 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.

Germline Manipulation and Our Future Worlds.

PubMed

Harris, John

2015-01-01

Two genetic technologies capable of making heritable changes to the human genome have revived interest in, and in some quarters a very familiar panic concerning, so-called germline interventions. These technologies are: most recently the use of CRISPR/Cas9 to edit genes in non-viable IVF zygotes and Mitochondrial Replacement Therapy (MRT) the use of which was approved in principle in a landmark vote earlier this year by the United Kingdom Parliament. The possibility of using either of these techniques in humans has encountered the most violent hostility and suspicion. However it is important to be aware that much of this hostility dates back to the fears associated with In Vitro Fertilization (IVF) and other reproductive technologies and by cloning; fears which were baseless at the time concerning both IVF and cloning the use of both of which have proved to be highly beneficial to humanity and which have been effectively regulated and controlled. This paper argues that CRISPR should by pursued through researh until it is safe enough for use in humans but there is no reason to suppose at this stage that such use will be unsafe or unethical (Collins 2015).

Residential proximity to major roadways and traffic in relation to outcomes of in vitro fertilization.

PubMed

Gaskins, Audrey J; Hart, Jaime E; Mínguez-Alarcón, Lidia; Chavarro, Jorge E; Laden, Francine; Coull, Brent A; Ford, Jennifer B; Souter, Irene; Hauser, Russ

2018-06-01

Emerging data from animal and human studies suggest that traffic-related air pollution adversely affects early pregnancy outcomes; however evidence is limited. We examined whether residential proximity to major roadways and traffic, as proxies for traffic-related air pollution, are associated with in vitro fertilization (IVF) outcomes. This analysis included 423 women enrolled in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study, who underwent 726 IVF cycles (2004-2017). Using geocoded residential addresses collected at study entry, we calculated the distance to nearest major roadway and the traffic density within a 100 m radius. IVF outcomes were abstracted from electronic medical records. We used multivariable generalized linear mixed models to evaluate the associations between residential proximity to major roadways and traffic density and IVF outcomes adjusting for maternal age, body mass index, race, education level, smoking status, and census tract median income. Closer residential proximity to major roadways was statistically significantly associated with lower probability of implantation and live birth following IVF. The adjusted percentage of IVF cycles resulting in live birth for women living ≥400 m from a major roadway was 46% (95% CI 36, 56%) compared to 33% (95% CI 26, 40%) for women living <50 m (p-for-comparison, 0.04). Of the intermediate outcomes, there were suggestive associations between living closer to major roadways and slightly higher estradiol trigger concentrations (p-trend = 0.16) and lower endometrial thickness (p-trend = 0.06). Near-residence traffic density was not associated with outcomes of IVF. Closer residential proximity to major roadways was related to reduced likelihood of live birth following IVF. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Association of GSTM1 and GSTT1 gene polymorphisms and in-vitro fertilisation outcome in a population in northern Iran.

PubMed

Karimlo, F K; Mashayekhi, F; Sorouri, Z Z; Bahador, M H; Salehi, Z

2015-01-01

Implantation failure is a major limiting step for in-vitro fertilisation (IVF). Embryo implantation is the result of the interaction of the embryo with the endometrium. Oxidative stress (OS) can cause defective embryo development and retardation. Genetic polymorphisms of detoxicating enzymes, such as glutathione S-transferases (GSTs), may play an important role in the outcome of embryo implantation. GSTM1 and GSTT1 are known to be highly polymorphic. The aim of this study was to examine the association of GSTM1 and GSTT1 gene polymorphisms with IVF-ET outcome in a population in northern Iran. Blood samples were collected from 120 infertile women who underwent an IVF cycle, and 108 healthy volunteers. Genomic DNA was prepared from peripheral blood leucocytes. Genotype frequencies were determined in patients and healthy controls using polymerase chain reaction (PCR). It was found that 25.8% of the infertile women and 0% of the controls had the GSTM1 null genotype (odds ratio (OR) = 76.37; 95% CI = 4.6-1,265.7; p = 0.0025). On the other hand, 5% of the cases and 0% of the controls had the GSTT1 null genotype (OR = 12.3, 95% CI = 0.68-221/3, p = 0.088). These results suggest that GSTM1 null type might be associated with IVF outcome in a population in northern Iran.

Human rights to in vitro fertilization.

PubMed

Zegers-Hochschild, Fernando; Dickens, Bernard M; Dughman-Manzur, Sandra

2013-10-01

The Inter-American Court of Human Rights (the Court) has ruled that the Supreme Court of Costa Rica's judgment in 2000 prohibiting in vitro fertilization (IVF) violated the human right to private and family life, the human right to found and raise a family, and the human right to non-discrimination on grounds of disability, financial means, or gender. The Court's conclusions of violations contrary to the American Convention on Human Rights followed from its ruling that, under the Convention, in vitro embryos are not "persons" and do not possess a right to life. Accordingly, the prohibition of IVF to protect embryos constituted a disproportionate and unjustifiable denial of infertile individuals' human rights. The Court distinguished fertilization from conception, since conception-unlike fertilization-depends on an embryo's implantation in a woman's body. Under human rights law, legal protection of an embryo "from conception" is inapplicable between its creation by fertilization and completion of its implantation in utero. © 2013.

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.

Quality of life of immigrant and non-immigrant infertile patients in a publicly funded in vitro fertilisation program: a cross-sectional study.

PubMed

Hasson, J; Tulandi, T; Shavit, T; Shaulov, T; Seccareccia, E; Takefman, J

2017-11-01

To investigate whether there are differences in fertility quality of life (FertiQoL) and socio-demographic characteristics between immigrants and non-immigrant patients attending a government-funded fertility program. Cross-sectional study. McGill University Reproductive Center in Montreal, Canada, at a time when governmental funding for in vitro fertilisation (IVF) was provided to all residents. All infertile patients, males and females, attending the center between March and July 2015. Patients were invited to complete anonymous questionnaires which included socio-demographic items and the validated FertiQoL questionnaire. Socio-demographic characteristics (age, gender, marital state, infertility type & duration, previous IVF attempts; education, employment, income, ethnicity, spoken languages) and FertiQoL scores. In all, 1020 patients completed the questionnaires; of these, 752 (77.7%) non-immigrant Canadian citizens and 215 (22.3%) resident immigrants were included in the analysis. Median duration in Canada for immigrants was 4 years. Immigrants were more likely to have university/graduate degrees (75% versus 64%), to be unemployed (37% versus 13.1%) and to have lower annual household incomes (72.8% versus 39.5%, all P < 0.05). They also reported poorer QoL and achieved significantly lower scores in the emotional, mind/body, social, treatment and total FertiQoL domains. Multivariate analysis showed male gender, lower education level and Caucasian/European ethnicity to be significantly associated with higher QoL. Despite governmental funding of IVF, immigrants experience reduced fertility QoL, implying cost is not the only barrier to IVF use. The reduced QoL may stem from cross-cultural differences in infertility perception. This population may be at greater risk for depression and anxiety and should be flagged accordingly. Immigrants' fertility QoL is lower despite publicly funded IVF implying cost is not the only barrier to IVF use. © 2017 Royal College of Obstetricians and Gynaecologists.

A comparison of biochemical pregnancy rates between women who underwent IVF and fertile controls who conceived spontaneously†.

PubMed

Zeadna, Atif; Son, Weon Young; Moon, Jeong Hee; Dahan, Michael H

2015-04-01

Does IVF affect the biochemical pregnancy rate? The likelihood of an early pregnancy loss may be lower and is certainly not higher in IVF cycles when compared with published rates of biochemical pregnancy in fertile women ≤42 years old. The use of gonadotrophins to stimulate multi-folliculogenesis alters endometrial expression of genes and proteins, compared with unstimulated cycles. Exogenous estrogen and progesterone taken for endometrial preparation in frozen embryo transfer cycles, also cause changes in endometrial gene and protein expression .These endometrial alterations may compromise the ability of embryos to develop once implanted, possibly increasing the biochemical pregnancy rate. This is a retrospective study, involving 1636 fresh and 188 frozen, single embryo transfer (SET) IVF cycles performed between August 2008 and December 2012. The biochemical pregnancy rate of the 1824 combined IVF and frozen cycles were compared with fertile controls, derived from the three prospective studies in the medical literature that evaluate this rate. Subjects ≤42-years old, who underwent a SET, as part of a fresh or thawed IVF cycle were considered for inclusion. Each subject is represented only once. The biochemical pregnancy rates were compared with those of historical standard, fertile populations with spontaneous conceptions. The pregnancy rates per transfer for fresh and frozen IVF cycles were similar at 39 and 40%, respectively. There was also no significant difference in the likelihood of pregnancy outcomes (clinical, biochemical and ectopic pregnancy) between fresh IVF and frozen cycles (85.4 versus 85.6%, 13.8 versus 14.8%, 0.5 versus 0%, P = 0.82). However, pregnancy rates decreased in older patients when compared with younger ones P < 0.0001. The biochemical pregnancy rate for fresh and frozen IVF cycles combined was 13.8% of all pregnancies. IVF and frozen cycles were combined as the IVF group treated with hormones for further comparison with the fertile control group. The biochemical pregnancy rate (14%) in the IVF group was lower than the rate based on the total fertile group (18%), P = 0.01 and differed significantly from the rate in two out of the three studies used to establish the normative rate. The age ranges of the IVF and fertile controls were 21-42 years. The mean age in the IVF population was 34.8 years, as compared with 29 years, 29, 4 years and 30.6 years (Zinaman) in the three published studies (mean: 29.4 years). This is a retrospective study and it was impossible to recruit an in-house biochemical pregnancy control population. Lower early pregnancy wastage after IVF may be due to the opportunity to select the embryo for transfer. This finding should be confirmed in further studies but supports the idea that embryo selection is an important step. 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.

Numerical Modeling of an Integrated Vehicle Fluids System Loop for Pressurizing a Cryogenic Tank

NASA Technical Reports Server (NTRS)

LeClair, A. C.; Hedayat, A.; Majumdar, A. K.

2017-01-01

This paper presents a numerical model of the pressurization loop of the Integrated Vehicle Fluids (IVF) system using the Generalized Fluid System Simulation Program (GFSSP). The IVF propulsion system, being developed by United Launch Alliance to reduce system weight and enhance reliability, uses boiloff propellants to drive thrusters for the reaction control system as well as to run internal combustion engines to develop power and drive compressors to pressurize propellant tanks. NASA Marshall Space Flight Center (MSFC) conducted tests to verify the functioning of the IVF system using a flight-like tank. GFSSP, a finite volume based flow network analysis software developed at MSFC, has been used to support the test program. This paper presents the simulation of three different test series, comparison of numerical prediction and test data and a novel method of presenting data in a dimensionless form. The paper also presents a methodology of implementing a compressor map in a system level code.

Impaired imprinted X chromosome inactivation is responsible for the skewed sex ratio following in vitro fertilization

PubMed Central

Tan, Kun; An, Lei; Miao, Kai; Ren, Likun; Hou, Zhuocheng; Tao, Li; Zhang, Zhenni; Wang, Xiaodong; Xia, Wei; Liu, Jinghao; Wang, Zhuqing; Xi, Guangyin; Gao, Shuai; Sui, Linlin; Zhu, De-Sheng; Wang, Shumin; Wu, Zhonghong; Bach, Ingolf; Chen, Dong-bao; Tian, Jianhui

2016-01-01

Dynamic epigenetic reprogramming occurs during normal embryonic development at the preimplantation stage. Erroneous epigenetic modifications due to environmental perturbations such as manipulation and culture of embryos during in vitro fertilization (IVF) are linked to various short- or long-term consequences. Among these, the skewed sex ratio, an indicator of reproductive hazards, was reported in bovine and porcine embryos and even human IVF newborns. However, since the first case of sex skewing reported in 1991, the underlying mechanisms remain unclear. We reported herein that sex ratio is skewed in mouse IVF offspring, and this was a result of female-biased peri-implantation developmental defects that were originated from impaired imprinted X chromosome inactivation (iXCI) through reduced ring finger protein 12 (Rnf12)/X-inactive specific transcript (Xist) expression. Compensation of impaired iXCI by overexpression of Rnf12 to up-regulate Xist significantly rescued female-biased developmental defects and corrected sex ratio in IVF offspring. Moreover, supplementation of an epigenetic modulator retinoic acid in embryo culture medium up-regulated Rnf12/Xist expression, improved iXCI, and successfully redeemed the skewed sex ratio to nearly 50% in mouse IVF offspring. Thus, our data show that iXCI is one of the major epigenetic barriers for the developmental competence of female embryos during preimplantation stage, and targeting erroneous epigenetic modifications may provide a potential approach for preventing IVF-associated complications. PMID:26951653

Ethical opinions and personal attitudes of young adults conceived by in vitro fertilisation.

PubMed

Siegel, S; Dittrich, R; Vollmann, J

2008-04-01

Today in vitro fertilisation (IVF) is a widespread and important technique of reproductive medicine. When the technique was first used, it was considered ethically controversial. This is the first study conducted of adult IVF-offspring in order to learn about their ethical opinions and personal attitudes towards this medical technology. We recruited the participants from the first cases of in vitro fertilisation in Germany at the Gynaecological Clinic of the University Hospital Erlangen. Our qualitative interview study consisted of in-depth, face-to-face interviews with 16 adults who had been conceived by IVF. Our data was analysed with methods of Grounded Theory. For these adults, the most important factor influencing their personal attitudes towards IVF was the knowledge that they were deeply wanted children. The artificiality of their conception seemed irrelevant for their ethical opinion. All participants mentioned that it was important for them to be informed about the circumstances of their conception by their parents. IVF seems to be a medical technique which, although it affects intimate aspects of human existence, can be integrated into the lives of the affected persons without any great difficulties. The findings suggest that parents should inform their children about their fertilisation at an early age and as part of a process over time, not only on a single occasion. Physicians should advise IVF-parents accordingly.

Embryological outcomes in cycles with human oocytes containing large tubular smooth endoplasmic reticulum clusters after conventional in vitro fertilization.

PubMed

Itoi, Fumiaki; Asano, Yukiko; Shimizu, Masashi; Honnma, Hiroyuki; Murata, Yasutaka

2016-01-01

There have been no studies analyzing the effect of large aggregates of tubular smooth endoplasmic reticulum (aSERT) after conventional in vitro fertilization (cIVF). The aim of this study was to investigate whether aSERT can be identified after cIVF and the association between the embryological outcomes of oocytes in cycles with aSERT. This is a retrospective study examining embryological data from cIVF cycles showing the presence of aSERT in oocytes 5-6 h after cIVF. To evaluate embryo quality, cIVF cycles with at least one aSERT-metaphase II (MII) oocyte observed (cycles with aSERT) were compared to cycles with normal-MII oocytes (control cycles). Among the 4098 MII oocytes observed in 579 cycles, aSERT was detected in 100 MII oocytes in 51 cycles (8.8%). The fertilization rate, the rate of embryo development on day 3 and day 5-6 did not significantly differ between cycles with aSERT and control group. However, aSERT-MII oocytes had lower rates for both blastocysts and good quality blastocysts (p < 0.05). aSERT can be detected in the cytoplasm by removing the cumulus cell 5 h after cIVF. However, aSERT-MII oocytes do not affect other normal-MII oocytes in cycles with aSERT.

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.

[Effect of kuntai capsule on the number of retrieved oocytes, high-quality oocytes and embryos in in vitro fertilization of poor ovarian response patients].

PubMed

Lian, Fang; Jiang, Xiao-Yuan

2014-08-01

To observe the effect of Kuntai Capsule (KC) on the number of retrieved oocytes, the quality of high-quality oocytes and embryos in in vitro fertilization of poor ovarian response (POR) patients. Totally 70 POR patients preparing for in vitro fertilization-embryo transfer (IVF-ET) were randomly assigned to the observation group and the control group, 35 cases in each group. KC was administered to patients in the observation group in the preparation cycle (i.e., three menstrual cycles before IVF-ET) and during the superovulation process. Those in the control group took placebo during this period. Before and after medication the improvement of Shen yin deficiency syndrome (SYDS) was observed in the two groups. The basal follicle-stimulating hormone (bFSH), luteinizing hormone (LH), estradiol (E2), anti-Mullerian hormone (AMH), the ratio of FSH to LH, and antral follicle count (AFC) were observed. Besides, the E2 level of a single ovum on the day of HCG injection, the number of retrieved oocytes, the high-quality oocyte rate, and the high-quality embryos were observed. Compared with the control group, the SYDS, decreased bFSH and LH levels, increased ACF numbers, the E2 level of a single ovum on the day of HCG injection, the number of retrieved oocytes, high-quality oocytes, and high-quality embryos were superior in the observation group (P < 0.05). There was no statistical difference in the decreased FSH/LH level (P > 0.05). E2 and AMH increased after medication of KC in the observation group, while they decreased after administration of placebos in the control group. There was statistical difference in the post-pre treatment difference of E2 and AMH between the two groups (P < 0.05). KC could increase the number of retrieved oocytes, and elevate the quality of occytes and embryos in the IVF-ET.

[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.

Ensoulment and IVF embryos.

PubMed Central

Shea, M C

1987-01-01

This paper examines the metaphysical question of 'ensoulment' in relation to the theory, put forward in an earlier paper, that human life begins when the newly formed body organs and systems of the embryo begin to function as an organised whole, at which stage there is evidence of a change of nature. Although Roman Catholic theology teaches that a human being is a union of physical body and spiritual soul, it is incorrect to interpret this in a dualistic sense. The meaning of 'soul' is considered and the conclusion reached that although both in the religious context and apart from it abortion is difficult to justify at any stage after conception, it does not follow that the use of 'spare' In Vitro Fertilisation (IVF) embryos should be rejected. If 'ensoulment' does not occur until the new organism functions as a whole then a decision not to make use of IVF embryos for medical purposes would be a heavy responsibility and not a 'safe' way out. PMID:3612702

Effect of recombinant human follicle-stimulating hormone and luteinizing hormone on in vitro maturation of porcine oocytes evaluated by the subsequent in vitro development of embryos obtained by in vitro fertilization, intracytoplasmic sperm injection, or parthenogenetic activation.

PubMed

Silvestre, M A; Alfonso, J; García-Mengual, E; Salvador, I; Duque, C C; Molina, I

2007-05-01

The aim of this work was to study the effect of recombinant human (rh) FSH and LH on in vitro maturation of pig oocytes compared with a conventional hormonal supplement based on equine (PMSG) and human chorionic gonadotropins (hCG), as evaluated by the developmental ability of 3 types of pig embryos obtained by in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), or artificial activation (ATA). In Exp. 1, one cumulus-oocyte complex group (A group) was supplemented with rh-FSH and rh-LH (0.1 IU/mL each), and the other group (B group) was supplemented with PMSG and hCG (10 IU/mL each). No differences in nuclear maturation between the A and B groups were observed (68.5 vs. 71.4%, respectively). No differences were detected between hormonal treatments in the rates of cleavage or blastocyst formation of ATA, IVF, and ICSI embryos. Total cell number of the embryos was not significantly different in any experimental group (A: 31.1, 28.5, and 19.8 vs. B: 25.2, 25.5, and 20.6 for ATA, IVF, and ICSI embryos, respectively). In Exp. 2, the effects of different concentrations of rh-FSH and rh-LH (0.5, 0.1, or 0.05 IU/mL) in maturation medium on nuclear maturation and in vitro development of embryos obtained by IVF were studied. No effect of different hormonal concentrations on blastocyst formation rates was observed (8.5, 13.0, and 5.7%, respectively). Blastocyst cell number was not different in any experimental group. In conclusion, the results obtained here permit us to substitute PMSG and hCG with rh-FSH and rh-LH and to produce pig embryos obtained by IVF, ICSI, or ATA.

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF.

PubMed

Brown, Sean G; Publicover, Stephen J; Mansell, Steven A; Lishko, Polina V; Williams, Hannah L; Ramalingam, Mythili; Wilson, Stuart M; Barratt, Christopher L R; Sutton, Keith A; Da Silva, Sarah Martins

2016-06-01

Are significant abnormalities in outward (K(+)) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K(+) channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K(+) channels in human spermatozoa or the incidence and functional consequences of K(+) channel defects. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca(2+) influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K(+) signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. Patch clamp electrophysiology was used to assess outward (K(+)) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca(2+)]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized. The majority of the data were obtained using funding from MRC project grants (#MR/K013343/1, MR/012492/1). Additional funding was provided by NHS Tayside, TENOVUS, Chief Scientist Office NRS Fellowship and University of Abertay. The authors declare that there is no conflict of interest. Not applicable. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

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.

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.

Air bubble location inside the uterus after transfer: is the embryo really there?

PubMed

Soares, Sérgio Reis; Godinho, Catarina; Nunes, Sofia; Pellicer, António

2008-08-01

To demonstrate that the location of the air bubble after embryo transfer (ET) does not necessarily indicate the final embryo location. Case report. Private clinic. A couple with primary infertility for whom a diagnosis of bicornuate uterus with a very open angle between horns was confirmed. Laparoscopy and hysteroscopy were performed before an IVF cycle in which a single embryo was replaced. Air bubble image immediately after ET and gestational sac location 3 weeks later. Immediately after a single ET, the air bubble was seen in the left uterine horn. Three weeks later, a gestational sac was seen in the right uterine horn. The location of the air bubble immediately after ET does not necessarily indicate the final embryo location.

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.

Specific loss of CatSper function is sufficient to compromise fertilizing capacity of human spermatozoa.

PubMed

Williams, Hannah L; Mansell, Steven; Alasmari, Wardah; Brown, Sean G; Wilson, Stuart M; Sutton, Keith A; Miller, Melissa R; Lishko, Polina V; Barratt, Christopher L R; Publicover, Steven J; Martins da Silva, Sarah

2015-12-01

Are significant abnormalities of CatSper function present in IVF patients with normal sperm concentration and motility and if so what is their functional significance for fertilization success? Sperm with a near absence of CatSper current failed to respond to activation of CatSper by progesterone and there was fertilization failure at IVF. In human spermatozoa, Ca(2+) influx induced by progesterone is mediated by CatSper, a sperm-specific Ca(2+) channel. A suboptimal Ca(2+) influx is significantly associated with, and more prevalent in, men with abnormal semen parameters, and is associated with reduced fertilizing capacity. However, abnormalities in CatSper current can only be assessed directly using electrophysiology. There is only one report of a CatSper-deficient man who showed no progesterone potentiated CatSper current. A CatSper 2 genetic abnormality was present but there was no information on the [Ca(2+)]i response to CatSper activation by progesterone. Additionally, the semen samples had indicating significant abnormalities (oligoasthenoteratozoospermia) multiple suboptimal functional responses in the spermatozoon. As such it cannot be concluded that impaired CatSper function alone causes infertility or that CatSper blockade is a potential safe target for contraception. Spermatozoa were obtained from donors and subfertile IVF patients attending a hospital assisted reproductive techniques clinic between January 2013 and December 2014. In total 134 IVF patients, 28 normozoospermic donors and 10 patients recalled due to a history of failed/low fertilization at IVF took part in the study. Samples were primarily screened using the Ca(2+) influx induced by progesterone and, if cell number was sufficient, samples were also assessed by hyperactivation and penetration into viscous media. A defective Ca(2+) response to progesterone was defined using the 99% confidence interval from the distribution of response amplitudes in normozoospermic donors. Samples showing a defective Ca(2+) response were further examined in order to characterize the potential CatSper abnormalities. In men where there was a consistent and robust failure of calcium signalling, a direct assessment of CatSper function was performed using electrophysiology (patch clamping), and a blood sample was obtained for genetic analysis. A total of 101/102 (99%) IVF patients and 22/23 (96%) donors exhibited a normal Ca(2+) response. The mean (± SD) normalized peak response did not differ between donors and IVF patients (2.57 ± 0.68 [n = 34 ejaculates from 23 different donors] versus 2.66 ± 0.68 [n = 102 IVF patients], P = 0.63). In recall patients, 9/10 (90%) showed a normal Ca(2+) response. Three men were initially identified with a defective Ca(2+) influx. However, only one (Patient 1) had a defective response in repeat semen samples. Electrophysiology experiments on sperm from Patient 1 showed a near absence of CatSper current and exon screening demonstrated no mutations in the coding regions of the CatSper complex. There was no increase in penetration of viscous media when the spermatozoa were stimulated with progesterone and importantly there was failed fertilization at IVF. A key limitation relates to working with a specific functional parameter (Ca(2+) influx induced by progesterone) in fresh sperm samples from donors and patients that have limited viability. Therefore, for practical, technical and logistical reasons, some men (∼ 22% of IVF patients) could not be screened. As such the incidence of significant Ca(2+) abnormalities induced by progesterone may be higher than the ∼ 1% observed here. Additionally, we used a strict definition of a defective Ca(2+) influx such that only substantial abnormalities were selected for further study. Furthermore, electrophysiology was only performed on one patient with a robust and repeatable defective calcium response. This man had negligible CatSper current but more subtle abnormalities (e.g. currents present but significantly smaller) may have been present in men with either normal or below normal Ca(2+) influx. These data add significantly to the understanding of the role of CatSper in human sperm function and its impact on male fertility. Remarkably, these findings provide the first direct evidence that CatSper is a suitable and specific target for human male contraception. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

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.

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.

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

IVF culture media: past, present and future.

PubMed

Chronopoulou, Elpiniki; Harper, Joyce C

2015-01-01

The advances in the world of IVF during the last decades have been rapid and impressive and culture media play a major role in this success. Until the 1980s fertility centers made their media in house. Nowadays, there are numerous commercially available culture media that contain various components including nutrients, vitamins and growth factors. This review goes through the past, present and future of IVF culture media and explores their composition and quality assessment. A computerized search was performed in PubMed regarding IVF culture media including results from 1929 until March 2014. Information was gathered from the websites of companies who market culture media, advertising material, instructions for use and certificates of analysis. The regulation regarding IVF media mainly in the European Union (EU) but also in non-European countries was explored. The keyword 'IVF culture media' gave 923 results in PubMed and 'embryo culture media' 12 068 results dating from 1912 until March 2014, depicting the increased scientific activity in this field. The commercialization of IVF culture media has increased the standards bringing a great variety of options into clinical practice. However, it has led to reduced transparency and comparisons of brand names that do not facilitate the scientific dialogue. Furthermore, there is some evidence suggesting that suboptimal culture conditions could cause long-term reprogramming in the embryo as the periconception period is particularly susceptible to epigenetic alterations. IVF media are now classified as class III medical devices and only CE (Conformité Européene)-marked media should be used in the EU. The CE marking of IVF culture media is a significant development in the field. However, the quality and efficiency of culture media should be monitored closely. Well-designed randomized controlled trials, large epidemiological studies and full transparency should be the next steps. Reliable, standardized models assessing multiple end-points and post-implantation development should replace the mouse embryo assay. Structured long-term follow-up of children conceived by assisted reproduction technologies and traceability are of paramount importance. © 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.

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.

Robert Edwards: the path to IVF☆

PubMed Central

Johnson, Martin H

2011-01-01

The early influences on Robert Edwards’ approach to the scientific research that led to human IVF are described. His interest as a graduate student in the genetics of early mammalian development stimulated him later to investigate whether the origins of human genetic diseases such as Down, Klinefelter and Turner syndromes might be explained by events during egg maturation. This clinical problem provided the most powerful stimulus to achieve both oocyte maturation and fertilization in vitro in humans. Indeed, preimplantation genetic diagnosis was his main goal until he met Patrick Steptoe in 1968. A re-evaluation of his meeting with Steptoe suggests that initially Steptoe’s laparoscopic skill was of interest for its potential to solve the sperm capacitation problem. Steptoe’s impact on Edwards was twofold. First, Steptoe’s long-held interest in infertility raised this application of IVF higher in Edwards’ priorities. Second, Steptoe offered a long-term partnership, in which oocyte collection without in-vitro maturation was a possibility. The professional criticism generated by their work together encouraged Edwards to pursue a deliberate programme of public education about the issues raised and to challenge and develop professional bioethical thought and discourse about reproduction. The early life and career of Robert Edwards are described and re-evaluated in the light of documentary evidence. His early interest in the genetics of development provided the major motivation behind his goal of achieving IVF in humans. Through this work, he aimed to understand and hopefully to reduce the transmission of genetic disease in humans. His meeting with Patrick Steptoe, the details of which are re-examined, increased the significance for Edwards of infertility as an outcome of IVF. It also led to a creative long-term research partnership, initiated a long-term programme of public education in the UK about reproductive science and stimulated the development of bioethical thinking. PMID:21680248

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

Influence of embryo culture medium on incidence of ectopic pregnancy in in vitro fertilization.

PubMed

Lin, Shengli; Li, Rong; Zheng, Xiaoying; Chi, Hongbin; Ren, Xiulian; Yang, Rui; Liu, Ping; Qiao, Jie

2015-12-01

To explore the effect of type of media used to culture embryos for IVF on the incidence of ectopic pregnancy (EP). Retrospective analysis. University-affiliated IVF center. The retrospective analysis involved 23,481 women who underwent IVF-ET cycles between 2011 and 2013. None. There was an association between EP and the culture medium. During 23,481 fresh transfer cycles, 364 patients were diagnosed with EP. The EP to clinical pregnancy rate was 3.01% in the G5 group, 3.89% in the G5 Plus group, and 4.04% in the Global group. The EP to clinical pregnancy rates were significantly higher in the G5 Plus and Global groups than in the G5 group. After adjusting for confounding factors, the incidence of EP was significantly associated with the G5 Plus and Global media. Our results showed that there is an association between incidence of EP and the culture medium. The rates of EP to clinical pregnancy were significantly higher in the G5 Plus and Global media than in the G5 medium. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The effect of G-CSF on infertile women undergoing IVF treatment: A meta-analysis.

PubMed

Li, Jie; Mo, Sien; Chen, Yang

2017-08-01

Evidence for the effect of granulocyte colony stimulating factor (G-CSF) on infertile women undergoing in vitro fertilization (IVF) remains inconsistent. This study aimed to evaluate the effectiveness of G-CSF on infertile women undergoing IVF. PubMed and EMBASE databases were searched before August 2016. Comparing the transvaginal perfusion of G-CSF and placebo or no treatment, the available studies were considered. The pooled risk ratio (RR) with 95% confidence intervals (CIs) was used in the analysis and six studies were included. Transvaginal perfusion of G-CSF was significantly associated with a higher clinical pregnancy rate versus the placebo (RR=1.563, 95%CI: 1.122, 2.176), especially for the Asian population. Among patients with a thin endometrium or repeated IVF failure, the implantation and biochemical pregnancy rates were also significantly increased in patients with the use of G-CSF (implantation rate: RR = 1.887, 95% CI: 1.256, 2.833; biochemical pregnancy rate: RR = 2.385, 95% CI: 1.414, 4.023). However, no statistical significance in increasing endometrial thickness was detected. Transvaginal perfusion of G-CSF for infertile women may play a critical role in assisting human reproduction, especially for patients with a thin endometrium or repeated IVF failure in the Asian population.

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.

The secretions of oviduct epithelial cells increase the equine in vitro fertilization rate: are osteopontin, atrial natriuretic peptide A and oviductin involved?

PubMed

Mugnier, Sylvie; Kervella, Morgane; Douet, Cécile; Canepa, Sylvie; Pascal, Géraldine; Deleuze, Stefan; Duchamp, Guy; Monget, Philippe; Goudet, Ghylène

2009-11-19

Oviduct epithelial cells (OEC) co-culture promotes in vitro fertilization (IVF) in human, bovine and porcine species, but no data are available from equine species. Yet, despite numerous attempts, equine IVF rates remain low. Our first aim was to verify a beneficial effect of the OEC on equine IVF. In mammals, oviductal proteins have been shown to interact with gametes and play a role in fertilization. Thus, our second aim was to identify the proteins involved in fertilization in the horse. In the first experiment, we co-incubated fresh equine spermatozoa treated with calcium ionophore and in vitro matured equine oocytes with or without porcine OEC. We showed that the presence of OEC increases the IVF rates. In the subsequent experiments, we co-incubated equine gametes with OEC and we showed that the IVF rates were not significantly different between 1) gametes co-incubated with equine vs porcine OEC, 2) intact cumulus-oocyte complexes vs denuded oocytes, 3) OEC previously stimulated with human Chorionic Gonadotropin, Luteinizing Hormone and/or oestradiol vs non stimulated OEC, 4) in vivo vs in vitro matured oocytes. In order to identify the proteins responsible for the positive effect of OEC, we first searched for the presence of the genes encoding oviductin, osteopontin and atrial natriuretic peptide A (ANP A) in the equine genome. We showed that the genes coding for osteopontin and ANP A are present. But the one for oviductin either has become a pseudogene during evolution of horse genome or has been not well annotated in horse genome sequence. We then showed that osteopontin and ANP A proteins are present in the equine oviduct using a surface plasmon resonance biosensor, and we analyzed their expression during oestrus cycle by Western blot. Finally, we co-incubated equine gametes with or without purified osteopontin or synthesized ANP A. No significant effect of osteopontin or ANP A was observed, though osteopontin slightly increased the IVF rates. Our study shows a beneficial effect of homologous and heterologous oviduct cells on equine IVF rates, though the rates remain low. Furthers studies are necessary to identify the proteins involved. We showed that the surface plasmon resonance technique is efficient and powerful to analyze molecular interactions during fertilization.

The secretions of oviduct epithelial cells increase the equine in vitro fertilization rate: are osteopontin, atrial natriuretic peptide A and oviductin involved?

PubMed Central

2009-01-01

Background Oviduct epithelial cells (OEC) co-culture promotes in vitro fertilization (IVF) in human, bovine and porcine species, but no data are available from equine species. Yet, despite numerous attempts, equine IVF rates remain low. Our first aim was to verify a beneficial effect of the OEC on equine IVF. In mammals, oviductal proteins have been shown to interact with gametes and play a role in fertilization. Thus, our second aim was to identify the proteins involved in fertilization in the horse. Methods & results In the first experiment, we co-incubated fresh equine spermatozoa treated with calcium ionophore and in vitro matured equine oocytes with or without porcine OEC. We showed that the presence of OEC increases the IVF rates. In the subsequent experiments, we co-incubated equine gametes with OEC and we showed that the IVF rates were not significantly different between 1) gametes co-incubated with equine vs porcine OEC, 2) intact cumulus-oocyte complexes vs denuded oocytes, 3) OEC previously stimulated with human Chorionic Gonadotropin, Luteinizing Hormone and/or oestradiol vs non stimulated OEC, 4) in vivo vs in vitro matured oocytes. In order to identify the proteins responsible for the positive effect of OEC, we first searched for the presence of the genes encoding oviductin, osteopontin and atrial natriuretic peptide A (ANP A) in the equine genome. We showed that the genes coding for osteopontin and ANP A are present. But the one for oviductin either has become a pseudogene during evolution of horse genome or has been not well annotated in horse genome sequence. We then showed that osteopontin and ANP A proteins are present in the equine oviduct using a surface plasmon resonance biosensor, and we analyzed their expression during oestrus cycle by Western blot. Finally, we co-incubated equine gametes with or without purified osteopontin or synthesized ANP A. No significant effect of osteopontin or ANP A was observed, though osteopontin slightly increased the IVF rates. Conclusion Our study shows a beneficial effect of homologous and heterologous oviduct cells on equine IVF rates, though the rates remain low. Furthers studies are necessary to identify the proteins involved. We showed that the surface plasmon resonance technique is efficient and powerful to analyze molecular interactions during fertilization. PMID:19925651

"Mitochondrial Replacement" Technologies and Human Germline Nuclear Modification.

PubMed

Lane, Alyssa; Nisker, Jeff

2016-08-01

In 2015 the United Kingdom became the first jurisdiction to approve "mitochondrial replacement techniques" (MRT), thereby dropping prohibitions against creating human embryos with a permanently altered genetic make-up for purposes of reproduction. MRT is a misnomer because in fact it is the nucleus of the oocyte of the woman who wants a genetically related child that is transferred to the enucleated oocyte of a woman paid to undergo IVF to provide the oocyte. MRT thus constitutes nuclear transfer, which is prohibited by criminal sanctions under sections of laws on reproductive cloning in Canada, the United States, Australia, and European countries that regulate assisted reproduction. By adopting policies permitting the use of MRT, the United Kingdom has become the first jurisdiction to counteract an international consensus prohibiting germline modification. Analyses of the legal, ethical, and societal implications of MRT in assisted human reproduction are essential. Copyright © 2016 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.

The role of management in an in vitro fertilization practice.

PubMed

Masler, Steve; Strickland, Robert R

2013-05-01

An in vitro fertilization (IVF) practice is an enterprise. Like any enterprise, it has management that plays a major role, forming the structure, framework, and components that make the practice viable. Management of an IVF practice consists of two key teams: the fertility team and the management team. Management activities of the teams fall into eight core areas: business operations, financial, human resources, information technology, organizational governance, risk management, patient care systems, and quality management. Shady Grove Fertility Centers and Huntington Reproductive Center are two examples of professionally managed large fertility practices, one managed mostly centrally and the other largely managed in a decentralized way. Management is what takes a physician's IVF practice and converts it to a professional enterprise. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Individualized decision-making in IVF: calculating the chances of pregnancy.

PubMed

van Loendersloot, L L; van Wely, M; Repping, S; Bossuyt, P M M; van der Veen, F

2013-11-01

Are we able to develop a model to calculate the chances of pregnancy prior to the start of the first IVF cycle as well as after one or more failed cycles? Our prediction model enables the accurate individualized calculation of the probability of an ongoing pregnancy with IVF. To improve counselling, patient selection and clinical decision-making in IVF, a number of prediction models have been developed. These models are of limited use as they were developed before current clinical and laboratory protocols were established. This was a cohort study. The development set included 2621 cycles in 1326 couples who had been treated with IVF or ICSI between January 2001 and July 2009. The validation set included additional data from 515 cycles in 440 couples treated between August 2009 and April 2011. The outcome of interest was an ongoing pregnancy after transfer of fresh or frozen-thawed embryos from the same stimulated IVF cycle. If a couple became pregnant after an IVF/ICSI cycle, the follow-up was at a gestational age of at least 11 weeks. Women treated with IVF or ICSI between January 2001 and April 2011 in a university hospital. IVF/ICSI cycles were excluded in the case of oocyte or embryo donation, surgically retrieved spermatozoa, patients positive for human immunodeficiency virus, modified natural IVF and cycles cancelled owing to poor ovarian stimulation, ovarian hyperstimulation syndrome or other unexpected medical or non-medical reasons. Thirteen variables were included in the final prediction model. For all cycles, these were female age, duration of subfertility, previous ongoing pregnancy, male subfertility, diminished ovarian reserve, endometriosis, basal FSH and number of failed IVF cycles. After the first cycle: fertilization, number of embryos, mean morphological score per Day 3 embryo, presence of 8-cell embryos on Day 3 and presence of morulae on Day 3 were also included. In validation, the model had moderate discriminative capacity (c-statistic 0.68, 95% confidence interval: 0.63-0.73) but calibrated well, with a range from 0.01 to 0.56 in calculated probabilities. In our study, the outcome of interest was ongoing pregnancy. Live birth may have been a more appropriate outcome, although only 1-2% of all ongoing pregnancies result in late miscarriage or stillbirth. The model was based on data from a single centre. The IVF model presented here is the first to calculate the chances of an ongoing pregnancy with IVF, both for the first cycle and after any number of failed cycles. The generalizability of the model to other clinics has to be evaluated more extensively in future studies (geographical validation). Centres with higher or lower success rates could use the model, after recalibration, by adjusting the intercept to reflect the IVF success rates in their centre. This project was funded by the NutsOhra foundation (Grant 1004-179). The NutsOhra foundation had no role in the development of our study, in the collection, analysis and interpretation of data; in writing of the manuscript, and in the decision to submit the manuscript for publication. There were no competing interests.

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.

Direct Visualization of Surfaces from Computed Tomography Data,

DTIC Science & Technology

1988-01-01

dominant method - slice-by-slice - makes comprehension of convoluted, small, or faint structures difficult. From a densitometric point of view, the human ...Di t SPeclal 4 N(xI) = Vf(lx) IVf (XI)I* There are many ways to estimate the gradient vector Vf(xi). The selection of an operator depends on the...the data is relatively noise-free or has been pre-smoothed. A graph of a(xi) as a function of f(xi) and IVf (xl)l for three tissue types A, B, and C

Singleton birth at term: an old alarm or a new debate?

PubMed

Hughes, Edward G

2015-10-01

In 2004, Human Reproduction published a debate series focusing on the rising tide of multiple pregnancy associated with IVF. The premise of the primary report in that debate was that by considering IVF outcomes differently-by focusing on healthy singleton birth at term rather than clinical pregnancy, the standard currency at that time-the necessary shift toward reduced numbers of embryos transferred might be accelerated. The choice of end-point in that debate-Birth Emphasizing a Successful Singleton at Term (BESST)-was not an effort to 'dumb down' the complex equation linking risks and benefits. That balance is a dynamic and various mix of issues that clinicians discuss with patients on a daily basis. And BESST was certainly not proposed as a new primary outcome for application to other treatment modalities in reproductive medicine, such as ovulation induction. It was simply a responsible and brave call for change in the accelerating and competitive world of IVF. © 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.

NGS Analysis of Human Embryo Culture Media Reveals miRNAs of Extra Embryonic Origin.

PubMed

Sánchez-Ribas, Immaculada; Diaz-Gimeno, Patricia; Quiñonero, Alicia; Ojeda, María; Larreategui, Zaloa; Ballesteros, Agustín; Domínguez, Francisco

2018-01-01

Our objective in this work was to isolate, identify, and compare micro-RNAs (miRNAs) found in spent culture media of euploid and aneuploid in vitro fertilization (IVF) embryos. Seventy-two embryos from 62 patients were collected, and their spent media were retained. A total of 108 spent conditioned media samples were analyzed (n = 36 day 3 euploid embryos, n = 36 day 3 aneuploid embryos, and n = 36 matched control media). Fifty hed-control media embryos were analyzed using next-generation sequencing (NGS) technology. We detected 53 known human miRNAs present in the spent conditioned media of euploid and aneuploid IVF embryos. miR-181b-5p and miR-191-5p were found the most represented. We validated our results by quantitative polymerase chain reaction (qPCR), but no significant results were obtained between the groups. In conclusion, we obtained the list of miRNAs present in the spent conditioned media from euploid and aneuploid IVF embryos, but our data suggest that these miRNAs could have a nonembryonic origin.

Do estrogen receptor alpha polymorphisms have any impact on the outcome in an ART program?

PubMed

Anagnostou, Elli; Malamas, Fotodotis; Mavrogianni, Despina; Dinopoulou, Vasiliki; Drakakis, Peter; Kallianidis, Konstantinos; Loutradis, Dimitris

2013-04-01

To investigate two of the most studied estrogen receptor alpha polymorphisms (PvuII and XbaI) in combination, in order to evaluate their impact on an ART program outcome. 203 normally ovulating women who underwent IVF or ICSI treatment were genotyped for PvuII and XbaI polymorphisms in ESR1 intron 1 using Real-Time PCR. The relationship between the presence of polymorphic alleles and the ovulation induction parameters and outcome was examined. Women were grouped according to the number of polymorphic alleles they carried in two groups (0-2 versus 3-4 polymorphic alleles). The presence of 3 or more polymorphic alleles was associated with significantly lower E2 levels on the day of hCG administration and a significantly lower rate of good quality embryos. There is an association between ESR1 polymorphisms and some ART parameters such as the level of E2 on the day of hCG administration and the quality of the embryos. These results underline the importance of ESR1 as a candidate gene for the prediction of ovarian response to IVF/ICSI protocols. Future research work concerning several more genes is necessary for a better evaluation of patients before entering an IVF/ICSI program.

Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

PubMed Central

Brown, Sean G.; Publicover, Stephen J.; Mansell, Steven A.; Lishko, Polina V.; Williams, Hannah L.; Ramalingam, Mythili; Wilson, Stuart M.; Barratt, Christopher L.R.; Sutton, Keith A.; Da Silva, Sarah Martins

2016-01-01

STUDY QUESTION Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized. STUDY FUNDING/COMPETING INTEREST(S) The majority of the data were obtained using funding from MRC project grants (#MR/K013343/1, MR/012492/1). Additional funding was provided by NHS Tayside, TENOVUS, Chief Scientist Office NRS Fellowship and University of Abertay. The authors declare that there is no conflict of interest. TRIAL REGISTRATION NUMBER Not applicable. PMID:27052499

The Effect of Reactive Oxygen Species on Embryo Quality in IVF.

PubMed

Siristatidis, Charalampos; Vogiatzi, Paraskevi; Varounis, Christos; Askoxylaki, Marily; Chrelias, Charalampos; Papantoniou, Nikolaos

2016-01-01

BACKROUND/AIM: Reactive oxygen species (ROS) are involved in critical biological processes in human reproduction. The aim of this study was to evaluate the association of embryo quality following in vitro fertilization (IVF), with ROS levels in the serum and follicular fluid (FF). Eighty-five participants underwent ovarian stimulation and IVF; ROS levels were measured in blood samples on the day of oocyte retrieval and in the FF from follicular aspirates using enzyme-linked immunosorbent assay. These values were associated with the quality of embryos generated. Univariable zero-inflated Poisson model revealed that ROS levels at both oocyte retrieval and in FF were not associated with the number of grade I, II, III and IV embryos (p>0.05). Age, body mass index, stimulation protocol and smoking status were not associated with the number of embryos of any grade (p>0.05). Neither ROS levels in serum nor in FF are associated with the quality of embryos produced following IVF. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Donation of surplus frozen pre-embryos to research in Israel: underlying motivations.

PubMed

Raz, Aviad; Amer-Alshiek, Jonia; Goren-Margalit, Mor; Jacobi, Gal; Hochberg, Alyssa; Amit, Ami; Azem, Foad; Amir, Hadar

2016-01-01

The high number of IVF procedures performed in Israel has had an unforeseen consequence: accumulation of large amounts of surplus frozen embryos. After five years that the frozen embryos are kept for free, patients need to make an embryo disposition decision. One option is donation for research. The donation rate in Israel is very low. Our aim was to understand the attitudes, values and perceptions of female IVF patients that decided to donate their surplus frozen embryos to research. The study setting was a tertiary IVF unit which during the 2000-2009 period treated 241 patients who had their frozen pre-embryos stored for more than five years. The study population consists of the 12 patients (from among the 241) who had decided to donate their excess frozen pre-embryos to research. In-depth interviews were carried out with 8 of those 12 patients. IVF patients who donated their surplus frozen pre-embryos to research viewed the frozen embryo as a valuable resource that does not have human identity yet. The majority expressed a gradualist approach to the human status of the embryo as requiring successful implantation and development in the uterus. All the respondents chose donation to research not because it was their first choice but because they did not want or were unable to use the pre-embryos in the future, in addition to not willing to thaw them. For many of the respondents, donation to research was accompanied by a sense of uncertainty. All would have preferred to donate their pre-embryos to infertile women or couples, an option which is currently prohibited in Israel. The moral reasoning behind decisions that patients make regarding excess pre-embryos is important for health care practitioners to consider when offering decision-making alternatives and counseling. For our respondents, the scarcity of donating excess frozen pre-embryos to research may reflect patients' preference for embryo donation to infertile couples. Recommended ways to increase donation to research may include public education and awareness, as well as targeted communication with IVF patients by multi-professional IVF unit teams comprised of a medical doctor and a professional trained in bioethics.

Determining the status of non-transferred embryos in Ireland: a conspectus of case law and implications for clinical IVF practice

PubMed Central

Sills, Eric Scott; Murphy, Sarah Ellen

2009-01-01

The development of in vitro fertilisation (IVF) as a treatment for human infertilty was among the most controversial medical achievements of the modern era. In Ireland, the fate and status of supranumary (non-transferred) embryos derived from IVF brings challenges both for clinical practice and public health policy because there is no judicial or legislative framework in place to address the medical, scientific, or ethical uncertainties. Complex legal issues exist regarding informed consent and ownership of embryos, particularly the use of non-transferred embryos if a couple separates or divorces. But since case law is only beginning to emerge from outside Ireland and because legislation on IVF and human embryo status is entirely absent here, this matter is poised to raise contractual, constitutional and property law issues at the highest level. Our analysis examines this medico-legal challenge in an Irish context, and summarises key decisions on this issue rendered from other jurisdictions. The contractual issues raised by the Roche case regarding informed consent and the implications the initial judgment may have for future disputes over embryos are also discussed. Our research also considers a putative Constitutional 'right to procreate' and the implications EU law may have for an Irish case concerning the fate of frozen embryos. Since current Medical Council guidelines are insufficient to ensure appropriate regulation of the advanced reproductive technologies in Ireland, the report of the Commission on Assisted Human Reproduction is most likely to influence embryo custody disputes. Public policy requires the establishment and implementation of a more comprehensive legislative framework within which assisted reproductive medical services are offered. PMID:19589140

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.

[Culture conditions for gametes and embryos: Which culture medium? Which impact on newborn?

PubMed

Koscinski, I; Merten, M; Kazdar, N; Guéant, J-L

2018-05-01

Many studies have examined the impact of cell/embryo culture media on the development of human embryo during IVF process, but few studies have followed up and compared the effects of these culture media on the developmental outcome of children conceived by IVF. As recurrent experimental evidence from animal studies suggests potential long-term effects of embryo culture media on the health outcome of IVF-conceived children, more studies are needed to clarify the role of the culture media and mechanisms underlying such effects. In human, however, the effects of culture media are difficult to pinpoint due to complications stem from both the influence of maternal nutrition during the gestational period and the parental genetic. Based on a simple review of the literature integrating animal experimentations and human clinic studies, we suggest that the composition of culture medium should be considered beyond the character of unique or sequential medium, corresponding to "let embryo choose" or "back to nature" respectively. Instead, we suggest that the main components of embryo culture media should be considered from the point of view of metabolic consequences and potential epigenetic effects. Given that energetic metabolites can regulate epigenetic machinery, we hypothesize that metabolic abnormalities linked to morphological abnormalities could reveal epigenetic defects in embryos. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Assisted reproductive technology (ART) in humans: facts and uncertainties.

PubMed

Ménézo, Y J; Veiga, A; Pouly, J L

2000-01-15

Since the first in vitro fertilization (IVF) in human, the number of patients using Assisted Reproductive Technologies (ART) has increased tremendously. ART technologies have increased in number and their spectrum has also widened. The first IVF babies are now more than 20 years old. All the retrospective analyses have demonstrated that the obstetrical and pediatrical impact has not really affected single births. The main problems observed occur with multiple pregnancies, including high costs for the couples and for society. The decrease in the number of embryos transferred has improved the situation and moreover does not impair the final results. IntraCytoplasmic Sperm Injection (ICSI) is a more debatable and questionable technique with a real negative genetic impact. The main problem is chromosome abnormalities more specifically related to the sex chromosomes. The question of a systematic genetic work-up on the patients entering ICSI programs is discussed. No negative impact of cryopreservation has been demonstrated even though some controversy arises from time to time. Pre-implantation Genetic Diagnosis (PGD) is now a interesting tool for patients carrying genetic defects. Blastocyst biopsy now has a future role in reproductive medicine. Gender selection through sperm sorting is also now a reality. As with the other developing bio-technologies related to reproduction, there are ethical questions. The decisions concerning these technologies do not belong solely to scientists but are rather a matter for society to decide.

IVF culture medium affects post-natal weight in humans during the first 2 years of life.

PubMed

Kleijkers, Sander H M; van Montfoort, Aafke P A; Smits, Luc J M; Viechtbauer, Wolfgang; Roseboom, Tessa J; Nelissen, Ewka C M; Coonen, Edith; Derhaag, Josien G; Bastings, Lobke; Schreurs, Inge E L; Evers, Johannes L H; Dumoulin, John C M

2014-04-01

Is post-natal growth during the first 2 years of life in IVF singletons affected by type of medium used for culturing human embryos during an IVF treatment? The in vitro culture of human embryos in medium from Cook resulted in singletons with a lower weight during the first 2 years of life compared with singletons born after embryo culture in medium from Vitrolife. In a previous study, we reported that type of medium used for culturing human IVF embryos during the first few days after fertilization until fresh embryo transfer significantly affects fetal growth and consequently birthweight of the resulting singletons. From July 2003 to December 2006, a total of 1432 IVF treatment cycles with fresh embryo transfer were randomly allocated to have all embryos cultured in medium from Vitrolife AB (n = 715) or from Cook (n = 717). Two years after delivery, questionnaires were sent to the parents of all children requesting data about weight, height and head circumference around 1, 2, 3, 4, 6, 7.5, 9, 11, 14, 18 and 24 months of age. These measurements were collected as part of the children's health programme at municipal infant welfare centres in the Netherlands by health professionals unaware of this study. Patients requiring donor oocytes or applying for PGD were excluded from the study. From the 294 live born singletons that fulfilled our inclusion criteria, 29 were lost to follow-up. The remaining 265 singletons (Cook group: 117, Vitrolife group: 148) were included in the analysis. Data analysis included linear regression, to compare cross-sectionally weight standard deviation score (SDS), height SDS and head circumference, and the first order Berkey-Reed model for a longitudinal analysis of the growth data. Singletons in the Vitrolife group were heavier during the first 2 years of life compared with singletons in the Cook group. Cross-sectional analyses showed that adjusted weight SDS differed between groups at 1 (0.35 ± 0.14, P = 0.010), 2 (0.39 ± 0.14, P = 0.006), 3 (0.35 ± 0.14, P = 0.011), 4 (0.30 ± 0.13, P = 0.020), 11 (0.28 ± 0.13, P = 0.036), 14 (0.32 ± 0.13, P = 0.014) and 24 (0.39 ± 0.15, P = 0.011) months of age, while adjusted height SDS was only significantly different at 1 (0.21 ± 0.11, P = 0.048) month of age. Head circumference was similar between the two groups at all ages. Longitudinal analyses showed that both post-natal weight (P = 0.005) and height (P = 0.031) differed between the groups throughout the first 2 years of life, while the growth velocity was not significantly different between the two groups. Factors that might influence post-natal growth were included in the analysis; however, it was not possible to include all such factors, for example childhood diseases or nutrition, as this information was not available. The effect of culture medium during the first few days after fertilization on prenatal growth and birthweight persists during the first 2 years of life. This suggests that the human embryo is sensitive to its very early environment, and that the culture medium used in IVF may have lasting consequences. Further monitoring of the long-term growth, development and health of IVF children is therefore warranted. W.V. was funded with an unrestricted research grant from the Stichting Fertility Foundation. The authors declare no conflict of interest. Not applicable.

Review: Toxicants in reproductive fluid and in vitro fertilization (IVF) outcome.

PubMed

Kumar, Sunil; Mishra, Vineet V

2010-09-01

Some of the physical, chemical, dietary, occupational and environmental factors are having adverse effect on human reproduction. Increasing trend in reproductive disorders in recent years at least in part might be associated with these factors. The data available suggests less success rate of in vitro fertilization (IVF) outcome of parents exposed to some of the reproductive toxic chemicals as compared to parents who were not exposed to such chemicals. However, data are very meager and require more studies as some debatable data also exists. But existing positive findings encourage in advising that sub-fertile subjects, who are planning to go for the IVF, should reduce toxic exposure well in advance by adopting positive life style and work environment. Further, clinician ought to be aware of occupational and environmental exposure history of the participating couple.

Perinatal outcomes after gestational surrogacy versus autologous IVF: analysis of national data.

PubMed

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

2017-12-01

Anonymized data were obtained from the Human Fertilization and Embryology Authority to determine whether gestational surrogacy influences perinatal outcomes compared with pregnancies after autologous IVF. A total of 103,160 singleton live births, including 244 after gestational surrogacy, 87,571 after autologous fresh IVF and intractyoplasmic sperm injection (ICSI) and 15,345 after autologous frozen embryo transfers were analysed. Perinatal outcomes of pretern birth (PTB), low birth weight (LBW) and high birth weight (HBW) were compared. No difference was found in the risk of PTB and LBW after gestational surrogacy compared with autologous fresh IVF-ICSI: PTB (adjusted OR 0.90, 95% CI 0.56 to 1.42), LBW (adjusted OR 0.90, 95% CI 0.57 to 1.43) and gestational surrogacy compared with autologous frozen embryo transfers: PTB (adjusted OR 0.96, 95% CI 0.58 to 1.60), LBW (adjusted OR 1.16, 95% CI 0.69 to 1.96). The incidence of HBW was significantly higher after gestational surrogacy compared with fresh IVF-ICSI (adjusted OR 1.94, 95% CI 1.38 to 2.75); no difference was found in HBW between gestational surrogacy and autologous frozen embryo transfers. The dataset is limited by lack of information on confounders, i.e. ethnicity, body mass index, underlying medical history, which could result in residual confounding. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Emotional adaptation following successful in vitro fertilization.

PubMed

Hjelmstedt, Anna; Widström, Ann-Marie; Wramsby, Håkan; Collins, Aila

2004-05-01

To assess the emotional impact of infertility after successful IVF and to compare parents who have undergone IVF (IVF parents) and parents who have not undergone IVF (non-IVF parents) regarding parental stress and the marital relationship during the transition to parenthood. A study with qualitative and longitudinal quantitative assessments. University IVF clinics and antenatal clinics in Stockholm. Fifty-five IVF mothers, 53 IVF fathers, 40 non-IVF mothers, and 36 non-IVF fathers. IVF parents were interviewed. All subjects completed self-rating scales in early pregnancy and at 2 and 6 months postpartum. Interviews about perception of infertility and scalar measurement of parental stress and the marital relationship. Negative feelings related to infertility were not easily overcome among the IVF parents. Their levels of stress related to parenthood were similar to those of non-IVF parents, and both groups reported decreased satisfaction with the marital relationship during the transition to parenthood. The inability to conceive naturally continues to affect the current lives of a proportion of IVF parents. The results suggest that IVF parents may benefit from counseling with regard to the potential long-term impacts of infertility, disclosure issues, and decisions regarding future children. However, levels of parental stress and patterns of partner satisfaction are similar to those of parents with children conceived "naturally."

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.

Comparing blastocyst quality and live birth rates of intravaginal culture using INVOcell™ to traditional in vitro incubation in a randomized open-label prospective controlled trial.

PubMed

Doody, Kevin J; Broome, E Jason; Doody, Kathleen M

2016-04-01

The purpose of this study is to to compare the efficacy of intravaginal culture (IVC) of embryos in INVOcell™ (INVO Bioscience, MA, USA) to traditional in vitro fertilization (IVF) incubators in a laboratory setting using a mild pre-determined stimulation regimen based solely on anti-mullerian hormone (AMH) and body weight with minimal ultrasound monitoring. The primary endpoint examined was total quality blastocysts expressed as a percentage of total oocytes placed in incubation. Secondary endpoints included percentage of quality blastocysts transferred, pregnancy, and live birth rates. In this prospective randomized open-label controlled single-center study, 40 women aged <38 years of age with a body mass index (BMI) of <36 and an AMH of 1-3 ng/mL were randomized prior to trigger to receive either IVC or IVF. Controlled ovarian stimulation was administered with human menopausal gonadotropin (hMG) in a fixed gonadotropin-releasing hormone (GnRH) agonist cycle based solely on AMH and body weight. A single ultrasound-monitoring visit was performed on the 10th day of stimulation. One or two embryos were transferred following 5 days of culture. IVF produced a greater percentage of total quality embryos as compared to IVC (50.6 vs. 30.7 %, p = 0.0007, respectively). There was no significant difference between in IVF and IVC in the percentage of quality blastocysts transferred (97.5 vs. 84.9 %, p = 0.09) or live birth rate (60 % IVF, 55 % IVC). IVF was shown to be superior to IVC in creating quality blastocysts. However, both IVF and IVC produced identical blastocysts for transfer resulting in similar live birth rates. IVC using INVOcell™ is effective and may broaden access to fertility care in selected patient populations by ameliorating the need for a traditional IVF laboratory setting. Further studies will help elucidate the potential physiological, psychological, geographic, and financial impact of IVC on the delivery of fertility care.

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.

Absence from work and emotional stress in women undergoing IVF or ICSI: an analysis of IVF-related absence from work in women and the contribution of general and emotional factors.

PubMed

Bouwmans, Clazien A M; Lintsen, Bea A M E; Al, Maiwen; Verhaak, Chris M; Eijkemans, René J C; Habbema, J Dik F; Braat, Didi D M; Hakkaart-Van Roijen, Leona

2008-01-01

To assess productivity losses due to absence from work during in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment and to describe the pattern of IVF-related absence from work. Additionally, the influence of general and psychological variables on IVF-related absence from work was analyzed. Prospective cohort study. Eight IVF hospitals participated in the study. Women undergoing their first treatment with IVF/ICSI. The Health and Labour Questionnaire (HLQ) was used to estimate the costs of IVF-related absence from work (n=384). Diaries were used to collect background information and reasons for IVF-related absence. Psychological data were derived using the Spielberger State and Trait Anxiety Inventory (STAI), the Beck Depression Inventory for Primary Care (BDI-PC) and the Inventory Social Relations and the Illness Cognition Questionnaire. Regression analyses were performed using two models, one without and one with psychological data, to assess the impact of the different variables on IVF-related absence from work. IVF-related absence from work and the costs of productivity losses due to IVF/ICSI per treatment. Overall absence from work during IVF/ICSI treatment was on average 33 hours, of which 23 hours were attributed to IVF/ICSI. Costs of productivity losses due to IVF/ICSI were euro596 per woman. Significant predictors of IVF-related absence from work were the number of hours of paid work, age and self-reported physical and/or emotional problems due to IFV treatment. Women experiencing emotional complaints and women with physical complaints due to IVF/ICSI reported significantly more IVF-related absence from work.

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

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.

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

DNA methylation changes at infertility genes in newborn twins conceived by in vitro fertilisation.

PubMed

Castillo-Fernandez, Juan E; Loke, Yuk Jing; Bass-Stringer, Sebastian; Gao, Fei; Xia, Yudong; Wu, Honglong; Lu, Hanlin; Liu, Yuan; Wang, Jun; Spector, Tim D; Saffery, Richard; Craig, Jeffrey M; Bell, Jordana T

2017-03-24

The association of in vitro fertilisation (IVF) and DNA methylation has been studied predominantly at regulatory regions of imprinted genes and at just thousands of the ~28 million CpG sites in the human genome. We investigated the links between IVF and DNA methylation patterns in whole cord blood cells (n = 98) and cord blood mononuclear cells (n = 82) from newborn twins using genome-wide methylated DNA immunoprecipitation coupled with deep sequencing. At a false discovery rate (FDR) of 5%, we identified one significant whole blood DNA methylation change linked to conception via IVF, which was located ~3 kb upstream of TNP1, a gene previously linked to male infertility. The 46 most strongly associated signals (FDR of 25%) included a second region in a gene also previously linked to infertility, C9orf3, suggesting that our findings may in part capture the effect of parental subfertility. Using twin modelling, we observed that individual-specific environmental factors appear to be the main overall contributors of methylation variability at the FDR 25% IVF-associated differentially methylated regions, although evidence for methylation heritability was also obtained at several of these regions. We replicated previous findings of differential methylation associated with IVF at the H19/IGF2 region in cord blood mononuclear cells, and we validated the signal at C9orf3 in monozygotic twins. We also explored the impact of intracytoplasmic sperm injection on the FDR 25% signals for potential effects specific to male or female infertility factors. To our knowledge, this is the most comprehensive study of DNA methylation profiles at birth and IVF conception to date, and our results show evidence for epigenetic modifications that may in part reflect parental subfertility.

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.

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.

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.

Numerical Modeling of Pressurization of Cryogenic Propellant Tank for Integrated Vehicle Fluid System

NASA Technical Reports Server (NTRS)

Majumdar, Alok K.; LeClair, Andre C.; Hedayat, Ali

2016-01-01

This paper presents a numerical model of pressurization of a cryogenic propellant tank for the Integrated Vehicle Fluid (IVF) system using the Generalized Fluid System Simulation Program (GFSSP). The IVF propulsion system, being developed by United Launch Alliance, uses boiloff propellants to drive thrusters for the reaction control system as well as to run internal combustion engines to develop power and drive compressors to pressurize propellant tanks. NASA Marshall Space Flight Center (MSFC) has been running tests to verify the functioning of the IVF system using a flight tank. GFSSP, a finite volume based flow network analysis software developed at MSFC, has been used to develop an integrated model of the tank and the pressurization system. This paper presents an iterative algorithm for converging the interface boundary conditions between different component models of a large system model. The model results have been compared with test data.

In Vitro Fertilization (IVF)

MedlinePlus

... or eggs are implanted in your uterus. One cycle of IVF takes about two weeks. IVF is ... Specific steps of an in vitro fertilization (IVF) cycle carry risks, including: Multiple births. IVF increases the ...

Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization.

PubMed

Xu, Juanjuan; Fang, Rui; Chen, Li; Chen, Daozhen; Xiao, Jian-Ping; Yang, Weimin; Wang, Honghua; Song, Xiaoqing; Ma, Ting; Bo, Shiping; Shi, Chong; Ren, Jun; Huang, Lei; Cai, Li-Yi; Yao, Bing; Xie, X Sunney; Lu, Sijia

2016-10-18

Preimplantation genetic screening (PGS) is widely used to select in vitro-fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. Here, we present and validate a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. By using multiple annealing and looping-based amplification cycles (MALBAC) for whole-genome amplification (WGA), we performed next-generation sequencing (NGS) on the spent culture medium used to culture human blastocysts (n = 42) and obtained the ploidy information of all 24 chromosomes. We validated these results by comparing each with their corresponding whole donated embryo and obtained a high correlation for identification of chromosomal abnormalities (sensitivity, 0.882, and specificity, 0.840). With this validated NICS method, we performed chromosome screening on IVF embryos from seven couples with balanced translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved successful clinical pregnancies, and five have already achieved healthy live births thus far. The NICS method avoids the need for embryo biopsy and therefore substantially increases the safety of its use. The method has the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness.

The effect of a rise or fall of serum estradiol the day before oocyte retrieval in women aged 40-42 with diminished egg reserve.

PubMed

Check, J H; Amui, J; Choe, J K; Cohen, R

2015-01-01

To determine the effect of a drop in serum estradiol the day after injection of human chorionic gonadotropin (hCG) in in vitro fertilization-embryo transfer (IVF-ET) cycles in women aged 40-42 with diminished oocyte reserve. Retrospective study with further requirement that the female partner had a day 3 serum follicle stimulating hormone (FSH) of ≥ 12 miU/mL and ≥ five antral follicles. A drop in serum estradiol the day after hCG injection is not associated with a lower chance of pregnancy compared to those women whose serum estradiol increases. However, their chances of releasing the oocyte before retrieval is significantly higher. A drop in serum estradiol in women of advanced reproductive age with diminished oocyte reserve should not signal the need to cancel the retrieval.

Pregnancy derived from human zygote pronuclear transfer in a patient who had arrested embryos after IVF.

PubMed

Zhang, John; Zhuang, Guanglun; Zeng, Yong; Grifo, Jamie; Acosta, Carlo; Shu, Yimin; Liu, Hui

2016-10-01

Nuclear transfer of an oocyte into the cytoplasm of another enucleated oocyte has shown that embryogenesis and implantation are influenced by cytoplasmic factors. We report a case of a 30-year-old nulligravida woman who had two failed IVF cycles characterized by all her embryos arresting at the two-cell stage and ultimately had pronuclear transfer using donor oocytes. After her third IVF cycle, eight out of 12 patient oocytes and 12 out of 15 donor oocytes were fertilized. The patient's pronuclei were transferred subzonally into an enucleated donor cytoplasm resulting in seven reconstructed zygotes. Five viable reconstructed embryos were transferred into the patient's uterus resulting in a triplet pregnancy with fetal heartbeats, normal karyotypes and nuclear genetic fingerprinting matching the mother's genetic fingerprinting. Fetal mitochondrial DNA profiles were identical to those from donor cytoplasm with no detection of patient's mitochondrial DNA. This report suggests that a potentially viable pregnancy with normal karyotype can be achieved through pronuclear transfer. Ongoing work to establish the efficacy and safety of pronuclear transfer will result in its use as an aid for human reproduction. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

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.

Biobanking of different body fluids within the frame of IVF-a standard operating procedure to improve reproductive biology research.

PubMed

Schenk, Michael; Huppertz, Berthold; Obermayer-Pietsch, Barbara; Kastelic, Darja; Hörmann-Kröpfl, Martina; Weiss, Gregor

2017-02-01

The aim of the present study was to develop a standard operating procedure (SOP) for the collection, transport, and storage of human cumulus cells, follicular fluid, blood serum, seminal plasma, embryo culture supernatant, and embryo culture supernatant control obtained within the IVF process under approved protocols and written informed consent from participating patients. The SOP was developed at the Kinderwunsch Institut Schenk, Dobl, Austria, together with Biobank Graz of the Medical University of Graz, Austria. The SOP provides comprehensive details of laboratory procedures and sampling of the different fluids within the IVF process. Furthermore, information on sample coding, references of involved laboratory techniques (e.g., oocyte retrieval with a Steiner-TAN needle), ethical approvals, and biobanking procedures are presented. The result of the present study is a standard operating procedure. The SOP ensures a professional way for collection and scientific use of IVF samples by the Kinderwunsch Institut Schenk, Dobl, Austria, and Biobank Graz of the Medical University of Graz, Austria. It can be used as a template for other institutions to unify specimen collection procedures in the field of reproductive health research.

Human sperm devoid of germinal angiotensin-converting enzyme is responsible for total fertilization failure and lower fertilization rates by conventional in vitro fertilization.

PubMed

Li, Le-Jun; Zhang, Feng-Bin; Liu, Shu-Yuan; Tian, Yong-Hong; Le, Fang; Wang, Li-Ya; Lou, Hang-Ying; Xu, Xiang-Rong; Huang, He-Feng; Jin, Fan

2014-06-01

In conventional in vitro fertilization (IVF), complete failure of fertilization occurs in 5% to 15% of treatments. Although the causes may be unclear, sperm defects appear to be the major contributor. However, a convincing test is not yet available that can predict the risk of fertilization failure. In this study, we found that germinal angiotensin-converting enzyme (gACE) (also called testicular ACE) was undetectable in sperm from patients who had total fertilization failure (TFF) and lower fertilization rates (LFRs) by IVF based on Western blot and indirect immunofluorescence analyses. Additionally, almost all of the patients without gACE on sperm (23 of 25) manifested a TT genotype of the rs4316 single-nucleotide polymorphism of ACE. Overall, our results indicate that the absence of gACE expression is responsible for TFF and LFRs by IVF. The rs4316 polymorphism of ACE might be associated with infertility in those patients. We conclude that sperm lacking gACE may be recognized before commencing IVF and that the patients may be directed instead to consider intracytoplasmic sperm injection. © 2014 by the Society for the Study of Reproduction, Inc.

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.

Psychological study of in vitro fertilization-embryo transfer participants' attitudes toward the destiny of their supernumerary embryos.

PubMed

Laruelle, C; Englert, Y

1995-05-01

To study the motivations underlying IVF-ET participants' choice to donate or destroy their supernumerary embryos. Couples' opinions are studied through a questionnaire and a psychological interview. Two hundred couples about to undergo IVF-ET. The fertility unit of an academic hospital. Couples' choice for supernumerary embryos' destiny; opinions on embryo status, on importance of genetic lineage in the filial bonding, on gamete donation, and on multiple pregnancy risk. Donation is the most frequent choice but destruction is tolerated by almost all the couples (92%). Couples considering the embryo as a child choose destruction as frequently as donation but refuse experimentation on the embryo. Donation is highest among couples who stress education more than genetic lineage in parental bonding. This is confirmed by the choice of the couples requiring donor gametes. Couples express differing attitudes toward risks of twins and risks of triplets: twins are much more desired than triplets, which are frequently refused. Couples' opinions on the respective importance of genetic lineage and education in defining parental bonding are more determinant in their decision to destroy or to donate their supernumerary embryos than their opinions on the in vitro embryo status, which only determines their attitude toward experimentation.

[The Evans case and the right not to be forced to reproduce].

PubMed

Alkorta Idiakez, Itziar

2006-01-01

The article analyses the ruling of the European Court of Human Rights, Evans v. United Kingdom, of March 7, 2006 (application no. 6339/05) from the perspective of the nature and the effects of a consent together with the conservation and disposal of cryopreserved embryos. Several prevailing normative models are studied in order to look at the disposal of embryos and to test its legal consistency. As a conclusion and basing it on the Evans case, there is a proposition to distinguish between the acts of disposal of spare embryos from IVF programs and the deposit of embryos as a way to prevent lack of fertility.

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.

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.

Hospital costs during the first 5 years of life for multiples compared with singletons born after IVF or ICSI.

PubMed

van Heesch, M M J; Evers, J L H; van der Hoeven, M A H B M; Dumoulin, J C M; van Beijsterveldt, C E M; Bonsel, G J; Dykgraaf, R H M; van Goudoever, J B; Koopman-Esseboom, C; Nelen, W L D M; Steiner, K; Tamminga, P; Tonch, N; Torrance, H L; Dirksen, C D

2015-06-01

Do in vitro fertilization (IVF) multiples generate higher hospital costs than IVF singletons, from birth up to age 5? Hospital costs from birth up to age 5 were significantly higher among IVF/ICSI multiple children compared with IVF/ICSI singletons; however, when excluding the costs incurred during the birth admission period, hospital costs of multiples and singletons were comparable. Concern has risen over the long-term outcome of children born after IVF. The increased incidence of multiple births in IVF as a result of double-embryo transfer predisposes children to a poorer neonatal outcome such as preterm birth and low birthweight. As a consequence, IVF multiples require more medical care. Costs and consequences of poorer neonatal outcomes in multiples may also exist later in life. All 5497 children born from IVF in 2003-2005, whose parents received IVF or ICSI treatment in one of five participating Dutch IVF centers, served as a basis for a retrospective cohort study. Based on gestational age, birthweight, Apgar and congenital malformation, children were assigned to one of three risk strata (low-, moderate- or high-risk). To enhance the efficiency of the data collection, 816 multiples and 584 singletons were selected for 5-year follow-up based on stratified (risk) sampling. Parental informed consent was received of 322 multiples and 293 singletons. Individual-level hospital resource use data (hospitalization, outpatient visits and medical procedures) were retrieved from hospital information systems and patient charts for 302 multiples and 278 singletons. The risk of hospitalization (OR 4.9, 95% CI 3.3-7.0), outpatient visits (OR 2.6, 95% CI 1.8-3.6) and medical procedures (OR 1.7, 95% CI 1.2-2.2) was higher for multiples compared with singletons. The average hospital costs amounted to €10 018 and €2093 during the birth admission period (P < 0.001), €1131 and €696 after the birth admission period to the first birthday (not significant (n.s.)) and €1084 and €938 from the second to the fifth life year (n.s.) for multiples and singletons, respectively. Hospital costs from birth up to age 5 were 3.3-fold higher for multiples compared with singletons (P < 0.001). Among multiples and singletons, respectively, 90.8 and 76.2% of the total hospital costs were caused by hospital admission days and 8.9 and 25.2% of the total hospital costs during the first 5 years of life occurred after the first year of life. Resource use and costs outside the hospital were not included in the analysis. This study confirms the increased use of healthcare resources by IVF/ICSI multiples compared with IVF/ICSI singletons. Single-embryo transfer may result in substantial savings, particularly in the birth admission period. These savings need to be compared with the extra costs of additional embryo transfers needed to achieve a successful pregnancy. Besides costs, health outcomes of children born after single-embryo transfer should be compared with those born after double-embryo transfer. This study was supported by a research grant (grant number 80-82310-98-09094) from the Netherlands Organization for Health Research and Development (ZonMw). There are no conflicts of interest in connection with this article. Not applicable. © 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.

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.

Establishing the role of pre-implantation genetic diagnosis with human leucocyte antigen typing: what place do "saviour siblings" have in paediatric transplantation?

PubMed

Samuel, G N; Strong, K A; Kerridge, I; Jordens, C F C; Ankeny, R A; Shaw, P J

2009-04-01

Not all children in need of a haematopoietic stem cell transplant have a suitable relative or unrelated donor available. Recently, in vitro fertilisation (IVF) with pre-implantation genetic diagnosis (PGD) for human leucocyte antigen (HLA) tissue typing has been used to selectively transfer an IVF embryo in order to produce a child who may provide umbilical cord blood for transplantation to an ill sibling. Such children are sometimes called "saviour siblings". To examine the published clinical and epidemiological evidence relevant to the use of this technology, with the aim of clarifying those situations where IVF and PGD for HLA typing should be discussed with parents of an ill child. A critical analysis of published literature on comparative studies of umbilical cord blood versus other sources of stem cells for transplantation; comparative studies of matched unrelated donor versus matched related donor transplantation; and the likelihood of finding an unrelated stem cell donor. IVF and PGD for HLA typing is only applicable when transplantation is non-urgent and parents are of reproductive age. Discussions regarding this technology may be appropriate where no suitable related or unrelated donor is available for a child requiring a transplant, or where no suitable related donor is available and transplantation is only likely to be entertained with a matched sibling donor. Discussion may also be considered in the management of any child lacking a matched related donor who requires a non-urgent transplant or may require a transplant in the future.

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.

A detailed cost analysis of in vitro fertilization and intracytoplasmic sperm injection treatment.

PubMed

Bouwmans, Clazien A M; Lintsen, Bea M E; Eijkemans, Marinus J C; Habbema, J Dik F; Braat, Didi D M; Hakkaart, Leona

2008-02-01

To provide detailed information about costs of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment stages and to estimate the cost per IVF and ICSI treatment cycle and ongoing pregnancy. Descriptive micro-costing study. Four Dutch IVF centers. Women undergoing their first treatment cycle with IVF or ICSI. IVF or ICSI. Costs per treatment stage, per cycle started, and for ongoing pregnancy. Average costs of IVF and ICSI hormonal stimulation were euro 1630 and euro 1585; the costs of oocyte retrieval were euro 500 and euro 725, respectively. The cost of embryo transfer was euro 185. Costs per IVF and ICSI cycle started were euro 2381 and euro 2578, respectively. Costs per ongoing pregnancy were euro 10,482 and euro 10,036, respectively. Hormonal stimulation covered the main part of the costs per cycle (on average 68% and 61% for IVF and ICSI, respectively) due to the relatively high cost of medication. The costs of medication increased with increasing age of the women, irrespective of the type of treatment (IVF or ICSI). Fertilization costs (IVF laboratory) constituted 12% and 20% of the total costs of IVF and ICSI. The total cost per ICSI cycle was 8.3% higher than IVF.

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

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.

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.

Management of the first in vitro fertilization cycle for unexplained infertility: a cost-effectiveness analysis of split in vitro fertilization-intracytoplasmic sperm injection

PubMed Central

Vitek, Wendy S.; Galárraga, Omar; Klatsky, Peter C.; Robins, Jared C.; Carson, Sandra A.; Blazar, Andrew S.

2015-01-01

Objective To determine the cost-effectiveness of split IVF-intracytoplasmic sperm injection (ICSI) for the treatment of couples with unexplained infertility. Design Adaptive decision model. Setting Academic infertility clinic. Patient(s) A total of 154 couples undergoing a split IVF-ICSI cycle and a computer-simulated cohort of women <35 years old with unexplained infertility undergoing IVF. Intervention(s) Modeling insemination method in the first IVF cycle as all IVF, split IVF-ICSI, or all ICSI, and adapting treatment based on fertilization outcomes. Main Outcome Measure(s) Live birth rate, incremental cost-effectiveness ratio (ICER). Result(s) In a single cycle, all IVF is preferred as the ICER of split IVF-ICSI or all ICSI ($58,766) does not justify the increased live birth rate (3%). If two cycles are needed, split IVF/ICSI is preferred as the increased cumulative live birth rate (3.3%) is gained at an ICER of $29,666. Conclusion(s) In a single cycle, all IVF was preferred as the increased live birth rate with split IVF-ICSI and all ICSI was not justified by the increased cost per live birth. If two IVF cycles are needed, however, split IVF/ICSI becomes the preferred approach, as a result of the higher cumulative live birth rate compared with all IVF and the lesser cost per live birth compared with all ICSI. PMID:23876534

Management of the first in vitro fertilization cycle for unexplained infertility: a cost-effectiveness analysis of split in vitro fertilization-intracytoplasmic sperm injection.

PubMed

Vitek, Wendy S; Galárraga, Omar; Klatsky, Peter C; Robins, Jared C; Carson, Sandra A; Blazar, Andrew S

2013-11-01

To determine the cost-effectiveness of split IVF-intracytoplasmic sperm injection (ICSI) for the treatment of couples with unexplained infertility. Adaptive decision model. Academic infertility clinic. A total of 154 couples undergoing a split IVF-ICSI cycle and a computer-simulated cohort of women <35 years old with unexplained infertility undergoing IVF. Modeling insemination method in the first IVF cycle as all IVF, split IVF-ICSI, or all ICSI, and adapting treatment based on fertilization outcomes. Live birth rate, incremental cost-effectiveness ratio (ICER). In a single cycle, all IVF is preferred as the ICER of split IVF-ICSI or all ICSI ($58,766) does not justify the increased live birth rate (3%). If two cycles are needed, split IVF/ICSI is preferred as the increased cumulative live birth rate (3.3%) is gained at an ICER of $29,666. In a single cycle, all IVF was preferred as the increased live birth rate with split IVF-ICSI and all ICSI was not justified by the increased cost per live birth. If two IVF cycles are needed, however, split IVF/ICSI becomes the preferred approach, as a result of the higher cumulative live birth rate compared with all IVF and the lesser cost per live birth compared with all ICSI. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Randomized comparison of next-generation sequencing and array comparative genomic hybridization for preimplantation genetic screening: a pilot study.

PubMed

Yang, Zhihong; Lin, James; Zhang, John; Fong, Wai Ieng; Li, Pei; Zhao, Rong; Liu, Xiaohong; Podevin, William; Kuang, Yanping; Liu, Jiaen

2015-06-23

Recent advances in next-generation sequencing (NGS) have provided new methods for preimplantation genetic screening (PGS) of human embryos from in vitro fertilization (IVF) cycles. However, there is still limited information about clinical applications of NGS in IVF and PGS (IVF-PGS) treatments. The present study aimed to investigate the effects of NGS screening on clinical pregnancy and implantation outcomes for PGS patients in comparison to array comparative genomic hybridization (aCGH) screening. This study was performed in two phases. Phase I study evaluated the accuracy of NGS for aneuploidy screening in comparison to aCGH. Whole-genome amplification (WGA) products (n = 164) derived from previous IVF-PGS cycles (n = 38) were retrospectively analyzed with NGS. The NGS results were then compared with those of aCGH. Phase II study further compared clinical pregnancy and implantation outcomes between NGS and aCGH for IVF-PGS patients. A total of 172 patients at mean age 35.2 ± 3.5 years were randomized into two groups: 1) NGS (Group A): patients (n = 86) had embryos screened with NGS and 2) aCGH (Group B): patients (n = 86) had embryos screened with aCGH. For both groups, blastocysts were vitrified after trophectoderm biopsy. One to two euploid blastocysts were thawed and transferred to individual patients primarily based on the PGS results. Ongoing pregnancy and implantation rates were compared between the two study groups. NGS detected all types of aneuploidies of human blastocysts accurately and provided a 100 % 24-chromosome diagnosis consistency with the highly validated aCGH method. Moreover, NGS screening identified euploid blastocysts for transfer and resulted in similarly high ongoing pregnancy rates for PGS patients compared to aCGH screening (74.7 % vs. 69.2 %, respectively, p >0.05). The observed implantation rates were also comparable between the NGS and aCGH groups (70.5 % vs. 66.2 %, respectively, p >0.05). While NGS screening has been recently introduced to assist IVF patients, this is the first randomized clinical study on the efficiency of NGS for preimplantation genetic screening in comparison to aCGH. With the observed high accuracy of 24-chromosome diagnosis and the resulting high ongoing pregnancy and implantation rates, NGS has demonstrated an efficient, robust high-throughput technology for PGS.

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.

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.

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.

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

Hormonal induction of gamete release, and in-vitro fertilisation, in the critically endangered Southern Corroboree Frog, Pseudophryne corroboree

PubMed Central

2010-01-01

Background Conservation Breeding Programs (CBP's) are playing an important role in the protection of critically endangered anuran amphibians, but for many species recruitment is not successful enough to maintain captive populations, or provide individuals for release. In response, there has been an increasing focus on the use of Assisted Reproductive Technologies (ART), including the administration of reproductive hormones to induce gamete release followed by in vitro fertilisation. The objective of this study was to test the efficacy of two exogenous hormones to induce gamete release, for the purpose of conducting in vitro fertilisation (IVF), in one of Australia's most critically endangered frog species, Pseudophryne corroboree. Methods Male frogs were administered a single dose of either human chorionic gonadotropin (hCG) or luteinizing hormone-releasing hormone (LHRHa), while female frogs received both a priming and ovulatory dose of LHRHa. Spermiation responses were evaluated at 3, 7, 12, 24, 36, 48, 60 and 72 h post hormone administration (PA), and sperm number and viability were quantified using fluorescent microscopy. Ovulation responses were evaluated by stripping females every 12 h PA for 5 days. Once gametes were obtained, IVF was attempted by combining spermic urine with oocytes in a dilute solution of simplified amphibian ringer (SAR). Results Administration of both hCG and LHRHa induced approximately 80% of males to release sperm over 72 h. Peak sperm release occurred at 12 h PA for hCG treated males and 36 h PA for LHRHa treated males. On average, LHRHa treated males released a significantly higher total number of live sperm, and a higher concentration of sperm, over a longer period. In female frogs, administration of LHRHa induced approximately 30% of individuals to release eggs. On average, eggs were released between 24 and 48 h PA, with a peak in egg release at 36 h PA. IVF resulted in a moderate percentage (54.72%) of eggs being fertilised, however all resultant embryos failed prior to gastrulation. Conclusions Hormone treatment successfully induced spermiation and ovulation in P. corroboree, but refinement of gamete induction and IVF techniques will be required before ART protocols can be used to routinely propagate this species. PMID:21114857

Rapid mapping of chromosomal breakpoints: from blood to BAC in 20 days.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Chun-Mei; Kwan, Johnson; Weier, Jingly F.

2009-02-25

Structural chromosome aberrations and associated segmental or chromosomal aneusomies are major causes of reproductive failure in humans. Despite the fact that carriers of reciprocal balanced translocation often have no other clinical symptoms or disease, impaired chromosome homologue pairing in meiosis and karyokinesis errors lead to over-representation of translocations carriers in the infertile population and in recurrent pregnancy loss patients. At present, clinicians have no means to select healthy germ cells or balanced zygotes in vivo, but in vitro fertilization (IVF) followed by preimplantation genetic diagnosis (PGD) offers translocation carriers a chance to select balanced or normal embryos for transfer. Althoughmore » a combination of telomeric and centromeric probes can differentiate embryos that are unbalanced from normal or unbalanced ones, a seemingly random position of breakpoints in these IVF-patients poses a serious obstacle to differentiating between normal and balanced embryos, which for most translocation couples, is desirable. Using a carrier with reciprocal translocation t(4;13) as an example, we describe our state-of-the-art approach to the preparation of patient-specific DNA probes that span or 'extent' the breakpoints. With the techniques and resources described here, most breakpoints can be accurately mapped in a matter of days using carrier lymphocytes, and a few extra days are allowed for PGD-probe optimization. The optimized probes will then be suitable for interphase cell analysis, a prerequisite for PGD since blastomeres are biopsied from normally growing day 3 - embryos regardless of their position in the mitotic cell cycle. Furthermore, routine application of these rapid methods should make PGD even more affordable for translocation carriers enrolled in IVF programs.« less

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.

Does freeze-all policy affect IVF outcomes in poor responders?

PubMed

Roque, Matheus; Valle, Marcello; Sampaio, Marcos; Geber, Selmo

2017-12-27

To evaluate whether the freeze-all strategy affects in vitro fertilization (IVF) outcomes in poor ovarian responders following the Bologna criteria. We performed a retrospective cohort study conducted between January 2012 and December 2016. A total of 433 poor responders (per the Bologna criteria) fulfilled the inclusion/exclusion criteria and were included in the study, with 277 patients included in the fresh group and 156 in the freeze-all group. All patients were submitted to controlled ovarian stimulation (COS) with a gonadotropin-releasing hormone antagonist protocol and cleavage-stage embryo transfer (ET). The main outcome measure was ongoing pregnancy rate. Secondary outcomes included implantation and clinical pregnancy rates. The freeze-all strategy was implemented when the progesterone serum level was >1.5 ng/mL on the trigger day, when the endometrium was <7 mm on the trigger day, or as a patient preference. Patients with previous failed fresh embryo transfer were also submitted to fresh or freeze-all strategy considering the indications mentioned above. The patients' mean age in the freeze-all group was 39.5±3.6 years, while that of patients in the fresh group was 39.7±3.8 years (P=0.54). The mean number of embryos transferred (nET) was 1.53±0.6 and 1.60±0.6 (P=0.12) in the freeze-all and fresh groups, respectively. Ongoing pregnancy rates did not significantly differ between the freeze-all and fresh groups (9.6% versus 10.1%, respectively; Relative Risk [RR]: 0.95; 95% CI: 0.52-1.73), nor did the clinical pregnancy rates (14.1% versus 13.7%, respectively; RR: 1.03; 95% CI: 0.63-1.76). Implantation rates were 9.6% and 9.8% (P=0.82) in the freeze-all and fresh groups, respectively. The logistic regression analysis (including age, antral follicle count [AFC], the number of retrieved oocytes, the number of mature oocytes, nET, and fresh versus freeze-all strategy) indicated that age (P<0.001) and the nET (P=0.039) were the only independent variables associated with ongoing pregnancy rates. In this study, the freeze-all strategy had no impact on IVF outcomes among poor responders according to the Bologna criteria. Multi-centric study including a large number of patients should be carried out to extend the results of our study to reach conclusions about the benefits offered to poor responders. This article is protected by copyright. All rights reserved.

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.

Establishment of an oocyte donor program. Donor screening and selection.

PubMed

Quigley, M M; Collins, R L; Schover, L R

1991-01-01

IVF with donated oocytes, followed by embryo placement in the uterus of a recipient who has been primed with exogenous steroids, is a successful treatment for special cases of infertility. Preliminary results indicate that the success rate in this situation is even greater than that usually seen with normal IVF (with placement of the embryos back into the uteri of the women from whom the oocytes were recovered). Although different sources for donated oocytes have been identified, the use of "excess" oocytes from IVF cycles and the attempted collection of oocytes at the time of otherwise indicated pelvic surgery have ethical and practical problems associated with their use. We have herein described the establishment of a successful program relying on anonymous volunteers who go through ovarian stimulation, monitoring, and oocyte recovery procedures solely to donate oocytes. The potential donors go through an exhaustive screening and education process before they are accepted in the program. Psychological evaluation of our potential donors indicated a great degree of turmoil in their backgrounds and a wide variety of motivations for actually participating. Despite the extensive educational and screening process, a substantial percentage of the donors did not complete a donation cycle, having either voluntarily withdrawn or been dropped because of lack of compliance. Further investigation of the psychological aspects of participating in such a program is certainly warranted. The use of donated oocytes to alleviate specific types of infertility is quite successful, but the application of this treatment is likely to be limited by the relative unavailability of suitable oocyte donors.

What a difference two days make: "personalized" embryo transfer (pET) paradigm: a case report and pilot study.

PubMed

Ruiz-Alonso, M; Galindo, N; Pellicer, A; Simón, C

2014-06-01

Embryo implantation requires that the blastocyst will attach during the receptive stage of the endometrium, known as window of implantation (WOI). Historically, it has been assumed that the WOI is always constant in all women. However, molecular analyses of endometrial receptivity demonstrates a personalized WOI (pWOI) that is displaced in one out of four patients suffering from recurrent implantation failure (RIF) of endometrial origin and illustrates the utility of a personalized endometrial diagnostic approach. Here, we report a clinical case of successful personalized embryo transfer (pET) after four IVF and three oocyte donation failed attempts in which different embryo transfer strategies were attempted. This case report is complemented by a pilot study of 17 patients undergoing oocyte donation and who suffered failed implantations with routine embryo transfer (ET) but were then treated with pET after the personalized diagnosis of their WOI.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whittaker, Peter A.

A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparingmore » immunocompatible pluripotent stem cells are indicated.« less

The new Italian IVF legislation.

PubMed

Benagiano, Giuseppe; Gianaroli, Luca

2004-08-01

Last February, the Italian Parliament gave final approval to a new Law regulating assisted reproduction technology. The new legislation fell short of the expectations of infertile couples and of all specialists in the field. There are three problems with the new Italian law; they involve social issues, human rights and the application of technology. The present paper focuses on the fact that the new rules infringe upon basic human rights and the proper application of IVF technology, because they mandate procedures that are against the best interest of the woman seeking pregnancy. The main point of controversy is the combination of a mandatory limit of three embryos for transfer, and an obligation to reimplant all produced embryos; cryopreservation of excess embryos is prohibited. Obviously, this decreases the chances of most women to achieve pregnancy, while at the same time it increases the number and complexity of procedures they need to undergo and may expose some to an unacceptable increase in the risk of multiple pregnancy. The new law is inspired by the desire to protect every newly produced embryo; this is a commendable aim, although it is in total opposition to a law passed over 25 years ago that liberalized voluntary termination of first trimester pregnancies. This means that today Italy has a law that protects every early, pre-implantation embryo, and another that allows the 'suppression' of every post-implantation one. From a technical point of view, given the low level of human fecundity, the only way to prevent the 'loss' of even one preimplantation embryo is to simply ban IVF altogether, an option that Italian legislators obviously did not have the courage to opt for. The tragedy is that Italian infertile couples are now confronted with new rules that not only severely limit the ability of physicians to correctly apply IVF technology, but are so confused that, depending on the interpretation, anyone may try to nullify the main ideological premise upon which the entire law has been structured.

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

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.

Specific loss of CatSper function is sufficient to compromise fertilizing capacity of human spermatozoa

PubMed Central

Williams, Hannah L.; Mansell, Steven; Alasmari, Wardah; Brown, Sean G.; Wilson, Stuart M.; Sutton, Keith A.; Miller, Melissa R.; Lishko, Polina V.; Barratt, Christopher L.R.; Publicover, Steven J.; Martins da Silva, Sarah

2015-01-01

STUDY QUESTION Are significant abnormalities of CatSper function present in IVF patients with normal sperm concentration and motility and if so what is their functional significance for fertilization success? SUMMARY ANSWER Sperm with a near absence of CatSper current failed to respond to activation of CatSper by progesterone and there was fertilization failure at IVF. WHAT IS KNOWN ALREADY In human spermatozoa, Ca2+ influx induced by progesterone is mediated by CatSper, a sperm-specific Ca2+ channel. A suboptimal Ca2+ influx is significantly associated with, and more prevalent in, men with abnormal semen parameters, and is associated with reduced fertilizing capacity. However, abnormalities in CatSper current can only be assessed directly using electrophysiology. There is only one report of a CatSper-deficient man who showed no progesterone potentiated CatSper current. A CatSper 2 genetic abnormality was present but there was no information on the [Ca2+]i response to CatSper activation by progesterone. Additionally, the semen samples had indicating significant abnormalities (oligoasthenoteratozoospermia) multiple suboptimal functional responses in the spermatozoon. As such it cannot be concluded that impaired CatSper function alone causes infertility or that CatSper blockade is a potential safe target for contraception. STUDY DESIGN, SIZE, DURATION Spermatozoa were obtained from donors and subfertile IVF patients attending a hospital assisted reproductive techniques clinic between January 2013 and December 2014. In total 134 IVF patients, 28 normozoospermic donors and 10 patients recalled due to a history of failed/low fertilization at IVF took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS Samples were primarily screened using the Ca2+ influx induced by progesterone and, if cell number was sufficient, samples were also assessed by hyperactivation and penetration into viscous media. A defective Ca2+ response to progesterone was defined using the 99% confidence interval from the distribution of response amplitudes in normozoospermic donors. Samples showing a defective Ca2+ response were further examined in order to characterize the potential CatSper abnormalities. In men where there was a consistent and robust failure of calcium signalling, a direct assessment of CatSper function was performed using electrophysiology (patch clamping), and a blood sample was obtained for genetic analysis. MAIN RESULTS AND THE ROLE OF CHANCE A total of 101/102 (99%) IVF patients and 22/23 (96%) donors exhibited a normal Ca2+ response. The mean (±SD) normalized peak response did not differ between donors and IVF patients (2.57 ± 0.68 [n = 34 ejaculates from 23 different donors] versus 2.66 ± 0.68 [n = 102 IVF patients], P = 0.63). In recall patients, 9/10 (90%) showed a normal Ca2+ response. Three men were initially identified with a defective Ca2+ influx. However, only one (Patient 1) had a defective response in repeat semen samples. Electrophysiology experiments on sperm from Patient 1 showed a near absence of CatSper current and exon screening demonstrated no mutations in the coding regions of the CatSper complex. There was no increase in penetration of viscous media when the spermatozoa were stimulated with progesterone and importantly there was failed fertilization at IVF. LIMITATIONS, REASONS FOR CAUTION A key limitation relates to working with a specific functional parameter (Ca2+ influx induced by progesterone) in fresh sperm samples from donors and patients that have limited viability. Therefore, for practical, technical and logistical reasons, some men (∼22% of IVF patients) could not be screened. As such the incidence of significant Ca2+ abnormalities induced by progesterone may be higher than the ∼1% observed here. Additionally, we used a strict definition of a defective Ca2+ influx such that only substantial abnormalities were selected for further study. Furthermore, electrophysiology was only performed on one patient with a robust and repeatable defective calcium response. This man had negligible CatSper current but more subtle abnormalities (e.g. currents present but significantly smaller) may have been present in men with either normal or below normal Ca2+ influx. WIDER IMPLICATIONS OF THE FINDINGS These data add significantly to the understanding of the role of CatSper in human sperm function and its impact on male fertility. Remarkably, these findings provide the first direct evidence that CatSper is a suitable and specific target for human male contraception. STUDY FUNDING/COMPETING INTEREST(S) Initial funding was from NHS Tayside, Infertility Research Trust, TENOVUS, Chief Scientist Office NRS Fellowship, the Wellcome Trust, University of Abertay. The majority of the data were obtained using funding from a MRC project grant (# 4190). The authors declare that there is no conflict of interest. TRIAL REGISTRATION NUMBER Not applicable. PMID:26453676

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

Presence of bile acids in human follicular fluid and their relation with embryo development in modified natural cycle IVF.

PubMed

Nagy, R A; van Montfoort, A P A; Dikkers, A; van Echten-Arends, J; Homminga, I; Land, J A; Hoek, A; Tietge, U J F

2015-05-01

Are bile acids (BA) and their respective subspecies present in human follicular fluid (FF) and do they relate to embryo quality in modified natural cycle IVF (MNC-IVF)? BA concentrations are 2-fold higher in follicular fluid than in serum and ursodeoxycholic acid (UDCA) derivatives were associated with development of top quality embryos on Day 3 after fertilization. Granulosa cells are capable of synthesizing BA, but a potential correlation with oocyte and embryo quality as well as information on the presence and role of BA subspecies in follicular fluid have yet to be investigated. Between January 2001 and June 2004, follicular fluid and serum samples were collected from 303 patients treated in a single academic centre that was involved in a multicentre cohort study on the effectiveness of MNC-IVF. Material from patients who underwent a first cycle of MNC-IVF was used. Serum was not stored from all patients, and the available material comprised 156 follicular fluid and 116 matching serum samples. Total BA and BA subspecies were measured in follicular fluid and in matching serum by enzymatic fluorimetric assay and liquid chromatography-mass spectrometry, respectively. The association of BA in follicular fluid with oocyte and embryo quality parameters, such as fertilization rate and cell number, presence of multinucleated blastomeres and percentage of fragmentation on Day 3, was analysed. Embryos with eight cells on Day 3 after oocyte retrieval were more likely to originate from follicles with a higher level of UDCA derivatives than those with fewer than eight cells (P < 0.05). Furthermore, follicular fluid levels of chenodeoxycholic derivatives were higher and deoxycholic derivatives were lower in the group of embryos with fragmentation compared with those without (each P < 0.05). Levels of total BA were 2-fold higher in follicular fluid compared with serum (P < 0.001), but had no predictive value for oocyte and embryo quality. Only samples originating from first cycle MNC-IVF were used, which resulted in 14 samples only from women with an ongoing pregnancy, therefore further prospective studies are required to confirm the association of UDCA with IVF pregnancy outcomes. The inter-cycle variability of BA levels in follicular fluid within individuals has yet to be investigated. We checked for macroscopic signs of contamination of follicular fluid by blood but the possibility that small traces of blood were present within the follicular fluid remains. Finally, although BA are considered stable when stored at -20°C, there was a time lag of 10 years between the collection and analysis of follicular fluid and serum samples. The favourable relation between UDCA derivatives in follicular fluid and good embryo development and quality deserves further prospective research, with live birth rates as the end-point. This work was supported by a grant from the Netherlands Organisation for Scientific Research (VIDI Grant 917-56-358 to U.J.F.T.). No competing interests are reported. © 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.

Realizing a desired family size: when should couples start?

PubMed

Habbema, J Dik F; Eijkemans, Marinus J C; Leridon, Henri; te Velde, Egbert R

2015-09-01

Until what age can couples wait to start a family without compromising their chances of realizing the desired number of children? The latest female age at which a couple should start trying to become pregnant strongly depends on the importance attached to achieving a desired family size and on whether or not IVF is an acceptable option in case no natural pregnancy occurs. It is well established that the treatment-independent and treatment-dependent chances of pregnancy decline with female age. However, research on the effect of age has focused on the chance of a first pregnancy and not on realizing more than one child. An established computer simulation model of fertility, updated with recent IVF success rates, was used to simulate a cohort of 10 000 couples in order to assess the chances of realizing a one-, two- or three-child family, for different female ages at which the couple starts trying to conceive. The model uses treatment-independent pregnancy chances and pregnancy chances after IVF/ICSI. In order to focus the discussion, we single out three levels of importance that couples could attach to realizing a desired family size: (i) Very important (equated with aiming for at least a 90% success chance). (ii) Important but not at all costs (equated with a 75% success chance) (iii) Good to have children, but a life without children is also fine (equated with a 50% success chance). In order to have a chance of at least 90% to realize a one-child family, couples should start trying to conceive when the female partner is 35 years of age or younger, in case IVF is an acceptable option. For two children, the latest starting age is 31 years, and for three children 28 years. Without IVF, couples should start no later than age 32 years for a one-child family, at 27 years for a two-child family, and at 23 years for three children. When couples accept 75% or lower chances of family completion, they can start 4-11 years later. The results appeared to be robust for plausible changes in model assumptions. Our conclusions would have been more persuasive if derived directly from large-scale prospective studies. An evidence-based simulation study (as we did) is the next best option. We recommend that the simulations should be updated every 5-10 years with new evidence because, owing to improvements in IVF technology, the assumptions on IVF success chances in particular run the risk of becoming outdated. Information on the chance of family completion at different starting ages is important for prospective parents in planning their family, for preconception counselling, for inclusion in educational courses in human biology, and for increasing public awareness on human reproductive possibilities and limitations. No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

Age of G-1 PLUS v5 embryo culture medium is inversely associated with birthweight of the newborn.

PubMed

Kleijkers, Sander H M; van Montfoort, Aafke P A; Smits, Luc J M; Coonen, Edith; Derhaag, Josien G; Evers, Johannes L H; Dumoulin, John C M

2015-06-01

Does age of G-1 PLUS v5 embryo culture medium affect IVF outcome? Birthweight of singletons born after IVF showed an inverse association with age of the embryo culture medium, while no association was found between age of culture medium and fertilization rate, embryonic development or ongoing pregnancy. It has been reported that IVF culture media can deteriorate during storage, which suggests that the capacity of culture media to support optimal embryo development decreases over time. Some animal studies showed an effect of storage time on embryo development, in contrast to other studies, while the effect of aging culture medium on IVF outcome in humans is unknown. We used data on outcome of 1832 IVF/ICSI cycles with fresh embryo transfer, performed in the period 2008-2012 to evaluate the association of fertilization rate, embryonic development, ongoing pregnancy and birthweight of singletons with age of the culture medium (Vitrolife AB G-1 PLUS v5). Age of the culture medium was calculated by subtracting the production date from the date of ovum retrieval. Data analysis included linear regression and logistic regression on continuous and categorical outcomes, respectively. Age of the culture medium was not associated with fertilization rate (P = 0.543), early cleavage rate (P = 0.155), percentage of embryos containing four or more cells on Day 2 (P = 0.401), percentage of embryos containing eight or more cells on Day 3 (P = 0.175), percentage of embryos with multinucleated blastomeres (P = 0.527), or ongoing pregnancy (P = 0.729). However, birthweight of the newborn was inversely associated with age of the medium (β = -3.6 g, SE: 1.5 g, P = 0.021), after controlling for possible confounders (day of embryo transfer, number of transferred embryos, child's gender, gestational age at birth, parity, pregnancy complications, maternal smoking, height and weight, and paternal height and weight) and the association was not biased by year of treatment, time since first opening of the bottle or batch variations. This indicates a difference of 234 g in birthweight of newborns for media with an age difference of 65 days. The results from this study may be specific for the G-1 PLUS v5 culture medium and extrapolation of the results to other media should be done with caution because of the differences in composition and shelf life. Age of G-1 PLUS v5 medium used to culture human embryos affects birthweight of the respective newborn. This could imply that the preimplantation embryo adapts to its in vitro environment with lasting in vivo consequences. Therefore, it is important that companies are transparent about the exact composition of their embryo culture media, which will allow IVF clinics to further investigate the effects of the media or media components on the health of IVF children. No funding and no competing interests declared. Not applicable. © 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.

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.

IVF outcomes in average- and poor-prognosis infertile women according to the number of embryos transferred.

PubMed

Vega, Mario G; Gleicher, Norbert; Darmon, Sarah K; Weghofer, Andrea; Wu, Yan-Guang; Wang, Qi; Zhang, Lin; Albertini, David F; Barad, David H; Kushnir, Vitaly A

2016-09-01

Outcome measures of IVF success, which account for effectiveness of IVF and perinatal outcome risks, have recently been described. The association between number of embryos transferred in average and poor-prognosis IVF patients, and the chances of having good or poor IVF and perinatal outcomes, was investigated. Good IVF and perinatal outcome was defined as the birth of a live, term, normal-weight infant (≥2500 g). Poor IVF and perinatal outcome was defined as no live birth or birth of a very low weight neonate (<1500 g) or severe prematurity (birth at <32 weeks gestation). Each neonate was analysed as a separate outcome. A total of 713 IVF cycles in 504 average and poor-prognosis patients from January 2010 to December 2013 were identified. The odds of having good IVF and perinatal outcomes increased by 28% for each additional embryo transferred. The odds of poor IVF and perinatal outcome decreased by 32% with an additional embryo transferred. The likelihood of live birth with good perinatal outcome in average- and poor-prognosis patients after IVF increases with additional embryos being transferred. These data add to recently reported evidence in favour of multiple embryo transfer in older women and those with average or poor IVF prognosis. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Home Parenteral Nutrition: Fat Emulsions and Potential Complications.

PubMed

Mundi, Manpreet S; Salonen, Bradley R; Bonnes, Sara

2016-10-01

Since the first intravenous nutrition support attempt with olive oil in the 17th century, intravenous fat emulsions (IVFEs) have evolved to become an integral component in the management of patients receiving home parenteral nutrition (HPN). IVFEs serve as a calorie source and provide essential fatty acids (linoleic acid and α-linolenic acid) in patients unable to achieve adequate intake of these fatty acids through alternative means. However, IVFE use is also associated with multiple complications, including increased infection risk, liver disease, and systemic proinflammatory states. In the United States, most IVFEs are composed of 100% soybean oil; internationally multiple alternative IVFEs (using fish oil, olive oil, and long- and medium-chain triglycerides) are available or being developed. The hope is that these IVFEs will prevent, or decrease the risk of, some of the HPN-associated complications. The goal of this article is to review how IVFEs came into use, their composition and metabolism, options for IVFE delivery in HPN, benefits and risks of IVFE use, and strategies to minimize the risks associated with IVFE use in HPN patients. © 2016 American Society for Parenteral and Enteral Nutrition.

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.

Intraovarian markers of follicular and oocyte maturation.

PubMed

Pellicer, A; Diamond, M P; DeCherney, A H; Naftolin, F

1987-08-01

The use of ovulation induction for multiple follicular growth in in vitro fertilization (IVF) has introduced the problem of follicular asynchrony. As a consequence of the asynchrony, the parameters most commonly used by IVF groups to assess follicular and oocyte quality within those follicles are not sufficiently sensitive or specific. Thus, each follicle must be considered separately, and specific markers of follicular and/or oocyte maturation must be sought from within the follicle. In this review we analyze previous reports of potential markers of follicular and oocyte maturation. In regards to the follicular fluid constituents, the level of estradiol in follicular fluid correlates with fertilization and pregnancy in stimulated cycles. Other steroids are only helpful when specific stimulation protocols are used. The level of some follicular proteins such as alpha-1-antitrypsin and fibrinogen also correlates with fertilization and pregnancy outcome. Cyclic AMP levels in follicular fluid are significantly reduced in follicles leading to conception. Regulators of oocyte maturation, such as the Oocyte Maturation Inhibitor (OMI) or the Meiosis Inducing Substance (MIS) have also been correlated with IVF outcome, but their exact structure remains still unknown. In addition, other sophisticated parameters, such as chemotactic activity of human leukocytes, or simple methods, such as the presence of intrafollicular echoes, have also been used as successful markers in predicting IVF outcome.

TP53 PIN3 and PEX4 polymorphisms and infertility associated with endometriosis or with post-in vitro fertilization implantation failure

PubMed Central

Paskulin, D D; Cunha-Filho, J S L; Souza, C A B; Bortolini, M C; Hainaut, P; Ashton-Prolla, P

2012-01-01

p53 has a crucial role in human fertility by regulating the expression of leukemia inhibitory factor (LIF), a secreted cytokine critical for blastocyst implantation. To examine whether TP53 polymorphisms may be involved with in vitro fertilization (IVF) failure and endometriosis (END), we have assessed the associations between TP53 polymorphism in intron 2 (PIN2; G/C, intron 2), PIN3 (one (N, non-duplicated) or two (D, duplicated) repeats of a 16-bp motif, intron 3) and polymorphism in exon 4 (PEX4; C/G, p.P72R, exon 4) in 98 women with END and 115 women with post-IVF failure. In addition, 134 fertile women and 300 women unselected with respect to fertility-related features were assessed. TP53 polymorphisms and haplotypes were identified by amplification refractory mutation system polymerase chain reaction. TP53 PIN3 and PEX4 were associated with both END (P=0.042 and P=0.007, respectively) and IVF (P=0.004 and P=0.009, respectively) when compared with women both selected and unselected for fertility-related features. Haplotypes D-C and N-C were related to higher risk for END (P=0.002, P=0.001, respectively) and failure of IVF (P=0.018 and P=0.002, respectively) when compared with the Fertile group. These results support that specific TP53 haplotypes are associated with an increased risk of END-associated infertility and with post-IVF failure. PMID:23013791

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.

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

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.

Just another reproductive technology? The ethics of human reproductive cloning as an experimental medical procedure

PubMed Central

Elsner, D

2006-01-01

Human reproductive cloning (HRC) has not yet resulted in any live births. There has been widespread condemnation of the practice in both the scientific world and the public sphere, and many countries explicitly outlaw the practice. Concerns about the procedure range from uncertainties about its physical safety to questions about the psychological well‐being of clones. Yet, key aspects such as the philosophical implications of harm to future entities and a comparison with established reproductive technologies such as in vitro fertilisation (IVF) are often overlooked in discussions about HRC. Furthermore, there are people who are willing to use the technology. Several scientists have been outspoken in their intent to pursue HRC. The importance of concerns about the physical safety of children created by HRC and comparisons with concerns about the safety of IVF are discussed. A model to be used to determine when it is acceptable to use HRC and other new assisted reproductive technologies, balancing reproductive freedom and safety concerns, is proposed. Justifications underpinning potential applications of HRC are discussed, and it is determined that these are highly analogous to rationalisations used to justify IVF treatment. It is concluded that people wishing to conceive using HRC should have a prima facie negative right to do so. PMID:17012502

Just another reproductive technology? The ethics of human reproductive cloning as an experimental medical procedure.

PubMed

Elsner, D

2006-10-01

Human reproductive cloning (HRC) has not yet resulted in any live births. There has been widespread condemnation of the practice in both the scientific world and the public sphere, and many countries explicitly outlaw the practice. Concerns about the procedure range from uncertainties about its physical safety to questions about the psychological well-being of clones. Yet, key aspects such as the philosophical implications of harm to future entities and a comparison with established reproductive technologies such as in vitro fertilisation (IVF) are often overlooked in discussions about HRC. Furthermore, there are people who are willing to use the technology. Several scientists have been outspoken in their intent to pursue HRC. The importance of concerns about the physical safety of children created by HRC and comparisons with concerns about the safety of IVF are discussed. A model to be used to determine when it is acceptable to use HRC and other new assisted reproductive technologies, balancing reproductive freedom and safety concerns, is proposed. Justifications underpinning potential applications of HRC are discussed, and it is determined that these are highly analogous to rationalisations used to justify IVF treatment. It is concluded that people wishing to conceive using HRC should have a prima facie negative right to do so.

Apolipoprotein B is regulated by gonadotropins and constitutes a predictive biomarker of IVF outcomes.

PubMed

Scalici, Elodie; Bechoua, Shaliha; Astruc, Karine; Duvillard, Laurence; Gautier, Thomas; Drouineaud, Véronique; Jimenez, Clément; Hamamah, Samir

2016-05-21

Follicular fluid (FF) is an important micro-environment influencing oocyte growth, its development competence, and embryo viability. The FF content analysis allows to identify new relevant biomarkers, which could be predictive of in vitro fertilization (IVF) outcomes. Inside ovarian follicle, the amount of FF components from granulosa cells (GC) secretion, could be regulated by gonadotropins, which play a major role in follicle development. This prospective study included 61 female undergoing IVF or Intra-cytoplasmic sperm injection (ICSI) procedure. Apolipoprotein B (APOB) concentrations in follicular fluid and APOB gene and protein expression in granulosa cells from reproductively aged women undergoing an in vitro fertilization program were measured. The statistical analyses were performed according to a quartile model based on the amount of APOB level found in FF. Amounts of APOB were detected in human FF samples (mean ± SD: 244.6 ± 185.9 ng/ml). The odds of obtaining an oocyte in the follicle and a fertilized oocyte increased significantly when APOB level in FF was higher than 112 ng/ml [i.e., including in Quartile Q 2, Q3 and Q4] (p = 0.001; p < 0.001, respectively). The probabilities of obtaining an embryo and a top quality embryo on day 2, were significantly higher if APOB levels were within the ranges of 112 and 330 ng/ml (i.e. in Q2 and Q3) or 112 and 230 ng/ml (i.e. in Q2), respectively (p < 0.001; p = 0.047, respectively). In addition, our experiments in vitro indicated that APOB gene and protein expression, along with APOB content into culture were significantly under-expressed in GC upon stimulation with gonadotropins (follicular stimulating hormone: FSH and/or human chorionic gonadotropin: hCG). We are reporting a positive and statistically significant associations between APOB and oocyte retrieval, oocyte fertilization, and embryo quality. Using an experimental study component, the authors report significant reduced APOB expression and content for luteinized granulosa cells cultured in the presence of gonadotropins.

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.

Forty years of embryo transfer in cattle: a review focusing on the journal Theriogenology, the growth of the industry in North America, and personal reminisces.

PubMed

Hasler, John F

2014-01-01

After the first successful transfer of mammalian embryos in 1890, it was approximately 60 years before significant progress was reported in the basic technology of embryo transfer (ET) in cattle. Starting in the early 1970s, technology had progressed sufficiently to support the founding of commercial ET programs in several countries. Today, well-established and reliable techniques involving superovulation, embryo recovery and transfer, cryopreservation, and IVF are utilized worldwide in hundreds, if not thousands, of commercial businesses located in many countries. The mean number of embryos produced via superovulation has changed little in 40 years, but there have been improvements in synchrony and hormonal protocols. Cryopreservation of in vivo-derived embryos is a reliable procedure, but improvements are needed for biopsied and in vitro-derived embryos. High pregnancy rates are achieved when good quality embryos are transferred into suitable recipients and low pregnancy rates are often owing to problems in recipient management and not technology per se. In the future, unanticipated disease outbreaks and the ever-changing economics of cattle and milk prices will continue to influence the ET industry. The issue of abnormal pregnancies involving in vitro embryos has not been satisfactorily resolved and the involvement of abnormal epigenetics associate with this technology merits continued research. Last, genomic testing of bovine embryos is likely to be available in the foreseeable future. This may markedly decrease the number of embryos that are actually transferred and stimulate the evolution of more sophisticated ET businesses. Copyright © 2014 Elsevier Inc. All rights reserved.

Metabolomic profiling of human follicular fluid from patients with repeated failure of in vitro fertilization using gas chromatography/mass spectrometry

PubMed Central

Xia, Lan; Zhao, Xiaoming; Sun, Yun; Hong, Yan; Gao, Yuping; Hu, Shuanggang

2014-01-01

Objective: To establish a gas chromatography/mass spectrometry (GC/MS)-based metabolomics method to compare the metabolites in the follicular fluid (FF) from patients with in vitro fertilization (IVF) and repeated IVF failure (RIF). Methods: A prospective study was employed in Center for Reprodutive Medcine, Renji Hospital, Shanghai, China, between January and October 2010. FF samples were collected from 13 patients with RIF and 15 patients who achieved pregnancy after the first IVF cycle. Results: Partial least squares (PLS) discriminant analysis of the PCA data revealed that the samples were scattered into two different regions. FF from the two groups differed with respect to 20 metabolites. FF from RIF group showed elevated levels of several amino acids (valine, threonine, isoleucine, cysteine, serine, proline, alanine, phenylalanine, lysine, methionine and ornithine), and reduced levels of dicarboxylic acids, cholesterol and some organic acids. Conclusions: The studies corroborated successful determination of the levels of metabolite in the FF. PMID:25400819

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.

Does delaying early intravenous fat emulsion during parenteral nutrition reduce infections during critical illness?

PubMed

Gerlach, Anthony T; Thomas, Sheela; Murphy, Claire V; Stawicki, P Stanislaw P; Whitmill, Melissa L; Pourzanjani, Lydia; Steinberg, Steven M; Cook, Charles H

2011-02-01

Because early administration of intravenous fat emulsions (IVFEs) has been linked to infectious complications in trauma patients, we began withholding IVFE for the first seven to ten days of parenteral nutrition (PN) in all surgical intensive care unit (SICU) patients. Prior to this, IVFE had been infused from the start of PN. To evaluate the influence of delaying IVFE on infectious complications in SICU patients. Retrospective review from October 2006 to June 2009 of SICU patients before and after a change in IVFE practice patterns in a 44-bed SICU at an academic medical center. Adult patients who received PN for more than six days were included. Patients receiving PN with IVFE prior to SICU admission or being given other lipid emulsion therapy were excluded. The data collected included demographics, transfusion requirements, nutritional assessments, and laboratory and microbiology results. The infectious complications studied were pneumonia, urinary tract infections (UTIs), blood stream infections (BSIs), and catheter-related blood stream infections (CRBSIs). Sixty-four patients received IVFE; 30 at initiation of PN and 34 starting after seven to ten days. The two groups had similar demographics, severity of illness, transfusion requirements, and duration of PN. Infectious complications occurred in 65.6% of patients (63.3% having immediate IVFE vs. 67.6% having delayed IVFE; p = 0.79). Seventeen patients developed BSI or CRBSI while receiving PN (26.7% immediate IVFE vs. 26.5% delayed IVFE; p > 0.99). The mortality rates were 63.3% and 55.9%, respectively (p = 0.63). Withholding IVFE therapy during the first seven to ten days of PN did not influence infectious complications or the mortality rate in SICU patients. The benefits of delaying IVFE therefore may not be generalizable to all critically ill patients.

[Application study of human sperm motility bioassay in IVF laboratory quality control].

PubMed

Cai, Xia; Pomeroy, Kimball O; Mattox, John H

2006-07-01

To investigate the sensitivity of human sperm survival bioassay to using known concentrations of potential toxin of formalin and to elevate the application value of human sperm motility assay as a quality control method in detecting the components used in IVF program. Fresh semen was obtained from healthy males at andrology laboratory by masturbation. Sperm was processed on a gradient column of isolate medium and PBS medium. In experiment 1, the medium with 0.25%, 0.75% concentration of formalin and control medium were added to the Falcon culture tubes containing HTF medium with or without 0.3% bovine albumin serum and with or without light mineral oil. In experiment 2, in 3 types of culture tubes containing HTF medium with or without 0.3% bovine albumin serum and with or without light mineral oil, the sperm was exposed to each culture tube and cultured for 24 and 48 hrs at room temperature, and the motile sperms were counted under the microscope. The average sperm motility index in the HTF medium with 0.25% formalin at 24 hrs was 0.594 +/- 0.331, significantly higher than in the HTF medium with 0.75% formalin (0.450 +/- 0.284) (P < 0.01). In the medium containing 0.25% and 0.75% formalin with 0.3% bovine albumin serum and light mineral oil, the average sperm survival indexes were 0.683 +/- 0.334 and 0.527 +/- 0.345, respectively, higher than without bovine albumin serum and light mineral oil (0.394 +/- 0.311 and 0.424 +/- 0.311). The average sperm index of 7 ml tissue culture tube made in Denmark was 0.677 +/- 0.335, higher than the other two types of culture tubes made in the USA (0.551 +/- 0.317 and 0.596 +/- 0.327) (P < 0.001). When the sperm cultured in the medium with 0.3% bovine albumin serum and light mineral oil, the average sperm survival indexes were 0.821 +/- 0.259 and 0.645 +/- 0.335, respectively, higher than without bovine albumin serum or light mineral oil (0.571 +/- 0.321 and 0.395 +/- 0.245) (P < 0.01). The sperm survival bioassay is a sensitivity quality control method to detect the components in the IVF laboratory. The 7 ml tissue culture tube made in Denmark is most suitable for culturing human embryos. Sperm can be protected when cultured in the medium with 0.3% albumin bovine serum and light mineral oil.

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.

In vitro fertilization (IVF) in Sweden: risk for congenital malformations after different IVF methods.

PubMed

Källén, Bengt; Finnström, Orvar; Nygren, Karl Gösta; Olausson, Petra Otterblad

2005-03-01

The possible excess of congenital malformations in infants born after in vitro fertilization (IVF) has been much discussed in the literature, with controversial conclusions. This population based study is aimed at analyzing the presence of congenital malformations in a large group of infants born after IVF and to compare malformation risk both with that of all infants born and according to IVF method used. Infants born after IVF during the period 1982-2001 were ascertained from all IVF clinics in Sweden. The presence of congenital malformations was identified from three national health registers: the Swedish Medical Birth Register, the Swedish Registry of Congenital Malformations, and the Swedish Hospital Discharge Register. The IVF children were compared with all children born in Sweden during the same period and recorded in the Swedish Medical Birth Register. Among 16,280 IVF children (30% conceived after intracytoplasmatic sperm injection [ICSI]) a 42% excess of any congenital malformation was found, explainable by parental characteristics and in some cases by the high rate of multiple births. Among these children, 8% had a congenital malformation, and 5% had a relatively severe condition. For neural tube defects, choanal atresia, and alimentary tract atresia, an additional risk increase was seen. There was no difference in malformation rate according to IVF method except for an excess of hypospadias after ICSI. An increased risk for congenital malformations occurs after IVF, similar for the different IVF techniques used, and mainly a consequence of parental characteristics. A few specific conditions show an extra increase in risk. Copyright 2005 Wiley-Liss, Inc.

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.

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.

Use of anti-mullerian hormone for testing ovarian reserve: a survey of 796 infertility clinics worldwide.

PubMed

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

2015-10-01

The aim of this study is to assess how anti-mullerian hormone (AMH) is used worldwide to test ovarian reserve and guide in vitro fertilization (IVF) cycle management. An internet-based survey was sent electronically to registered IVF providers within the IVF-Worldwide.com network. This survey consisted of nine questions which assessed the clinics' use of AMH. The questionnaire was completed online through the IVF-Worldwide.com website, and quality assurance tools were used to verify that only one survey was completed per clinical IVF center. Results are reported as the proportion of IVF cycles represented by a particular answer choice. Survey responses were completed from 796 globally distributed IVF clinics, representing 593,200 IVF cycles worldwide. Sixty percent of the respondent-IVF cycles reported to use AMH as a first line test, and 54 % reported it as the best test for evaluating ovarian reserve. Eighty-nine percent reported that AMH results were extremely relevant or relevant to clinical practice. However in contrast, for predicting live birth rate, 81 % reported age as the best predictor. AMH is currently considered a first line test for evaluating ovarian reserve and is considered relevant to clinical practice by the majority of IVF providers.

Arrested human embryos are more likely to have abnormal chromosomes than developing embryos from women of advanced maternal age.

PubMed

Qi, Shu-Tao; Liang, Li-Feng; Xian, Ye-Xing; Liu, Jian-Qiao; Wang, Weihua

2014-01-01

Aneuploidy is one of the major factors that result in low efficiency in human infertility treatment by in vitro fertilization (IVF). The development of DNA microarray technology allows for aneuploidy screening by analyzing all 23 pairs of chromosomes in human embryos. All chromosome screening for aneuploidy is more accurate than partial chromosome screening, as errors can occur in any chromosome. Currently, chromosome screening for aneuploidy is performed in developing embryos, mainly blastocysts. It has not been performed in arrested embryos and/or compared between developing embryos and arrested embryos from the same IVF cycle. The present study was designed to examine all chromosomes in blastocysts and arrested embryos from the same cycle in patients of advanced maternal ages. Embryos were produced by routine IVF procedures. A total of 90 embryos (45 blastocysts and 45 arrested embryos) from 17 patients were biopsied and analyzed by the Agilent DNA array platform. It was found that 50% of the embryos developed to blastocyst stage; however, only 15.6% of the embryos (both blastocyst and arrested) were euploid, and most (84.4%) of the embryos had chromosomal abnormalities. Further analysis indicated that 28.9% of blastocysts were euploid and 71.1% were aneuploid. By contrast, only one (2.2%) arrested embryo was euploid while others (97.8%) were aneuploid. The prevalence of multiple chromosomal abnormalities in the aneuploid embryos was also higher in the arrested embryos than in the blastocysts. These results indicate that high proportions of human embryos from patients of advanced maternal age are aneuploid, and the arrested embryos are more likely to have abnormal chromosomes than developing embryos.

Clinical utilisation of a rapid low-pass whole genome sequencing technique for the diagnosis of aneuploidy in human embryos prior to implantation.

PubMed

Wells, Dagan; Kaur, Kulvinder; Grifo, Jamie; Glassner, Michael; Taylor, Jenny C; Fragouli, Elpida; Munne, Santiago

2014-08-01

The majority of human embryos created using in vitro fertilisation (IVF) techniques are aneuploid. Comprehensive chromosome screening methods, applicable to single cells biopsied from preimplantation embryos, allow reliable identification and transfer of euploid embryos. Recently, randomised trials using such methods have indicated that aneuploidy screening improves IVF success rates. However, the high cost of testing has restricted the availability of this potentially beneficial strategy. This study aimed to harness next-generation sequencing (NGS) technology, with the intention of lowering the costs of preimplantation aneuploidy screening. Embryo biopsy, whole genome amplification and semiconductor sequencing. A rapid (<15 h) NGS protocol was developed, with consumable cost only two-thirds that of the most widely used method for embryo aneuploidy detection. Validation involved blinded analysis of 54 cells from cell lines or biopsies from human embryos. Sensitivity and specificity were 100%. The method was applied clinically, assisting in the selection of euploid embryos in two IVF cycles, producing healthy children in both cases. The NGS approach was also able to reveal specified mutations in the nuclear or mitochondrial genomes in parallel with chromosome assessment. Interestingly, elevated mitochondrial DNA content was associated with aneuploidy (p<0.05), a finding suggestive of a link between mitochondria and chromosomal malsegregation. This study demonstrates that NGS provides highly accurate, low-cost diagnosis of aneuploidy in cells from human preimplantation embryos and is rapid enough to allow testing without embryo cryopreservation. The method described also has the potential to shed light on other aspects of embryo genetics of relevance to health and viability. 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.

Clinical utilisation of a rapid low-pass whole genome sequencing technique for the diagnosis of aneuploidy in human embryos prior to implantation

PubMed Central

Wells, Dagan; Kaur, Kulvinder; Grifo, Jamie; Glassner, Michael; Taylor, Jenny C; Fragouli, Elpida; Munne, Santiago

2014-01-01

Background The majority of human embryos created using in vitro fertilisation (IVF) techniques are aneuploid. Comprehensive chromosome screening methods, applicable to single cells biopsied from preimplantation embryos, allow reliable identification and transfer of euploid embryos. Recently, randomised trials using such methods have indicated that aneuploidy screening improves IVF success rates. However, the high cost of testing has restricted the availability of this potentially beneficial strategy. This study aimed to harness next-generation sequencing (NGS) technology, with the intention of lowering the costs of preimplantation aneuploidy screening. Methods Embryo biopsy, whole genome amplification and semiconductor sequencing. Results A rapid (<15 h) NGS protocol was developed, with consumable cost only two-thirds that of the most widely used method for embryo aneuploidy detection. Validation involved blinded analysis of 54 cells from cell lines or biopsies from human embryos. Sensitivity and specificity were 100%. The method was applied clinically, assisting in the selection of euploid embryos in two IVF cycles, producing healthy children in both cases. The NGS approach was also able to reveal specified mutations in the nuclear or mitochondrial genomes in parallel with chromosome assessment. Interestingly, elevated mitochondrial DNA content was associated with aneuploidy (p<0.05), a finding suggestive of a link between mitochondria and chromosomal malsegregation. Conclusions This study demonstrates that NGS provides highly accurate, low-cost diagnosis of aneuploidy in cells from human preimplantation embryos and is rapid enough to allow testing without embryo cryopreservation. The method described also has the potential to shed light on other aspects of embryo genetics of relevance to health and viability. PMID:25031024

Liraglutide increases IVF pregnancy rates in obese PCOS women with poor response to first-line reproductive treatments: a pilot randomized study.

PubMed

Salamun, Vesna; Jensterle, Mojca; Janez, Andrej; Vrtacnik Bokal, Eda

2018-04-27

Glucagon-like peptide-1 (GLP-1) has been investigated in regulation of reproductive system in animal models. The potential impact of short-term preconception intervention with liraglutide on fertility potential in PCOS has not been evaluated yet. A prospective randomized open-label study was conducted in 28 infertile obese PCOS patients (age 31.07±4.75 years, BMI 36.7±3.5 kg/m2, mean±SD). They were assigned to metformin (MET) 1000 mg BID or to MET 1000 mg BID combined with low-dose liraglutide 1.2 mg QD s.c. (COMBI) for 12 weeks. Ovarian stimulation protocol was started after a 4-week medication-free period. The IVF pregnancy rate (PR) was defined as the number of clinical pregnancies confirmed by ultrasound visualization of the fetal cardiac activity, divided by the total number of cycles performed or embryo transfers (ET). The spontaneous PR was followed for 12 months. Patients in the MET group on average lost 7.0±6.0 kg (P=0.001) compared with 7.5±3.9 kg in the COMBI group (P˂0.001) with no significant between-treatment difference (P=0.246). The PR per ET was significantly higher in the COMBI (85.7%) compared with the MET (28.6%) group (P=0.03). The cumulative PR in the time frame of 12 months was 69.2% in the COMBI group compared to 35.7% in the MET group. Preconception intervention with low-dose liraglutide added to metformin is superior to metformin alone in increasing PRs per ET and cumulative PRs in infertile obese women with PCOS, despite comparable weight reduction in both groups. A potential direct crosstalk between GLP-1 and reproductive system needs further exploration.

GnRH agonist for triggering of final oocyte maturation: time for a change of practice?

PubMed

Humaidan, P; Kol, S; Papanikolaou, E G

2011-01-01

GnRH agonist (GnRHa) triggering has been shown to significantly reduce the occurrence of ovarian hyperstimulation syndrome (OHSS) compared with hCG triggering; however, initially a poor reproductive outcome was reported after GnRHa triggering, due to an apparently uncorrectable luteal phase deficiency. Therefore, the challenge has been to rescue the luteal phase. Studies now report a luteal phase rescue, with a reproductive outcome comparable to that seen after hCG triggering. This narrative review is based on expert presentations and subsequent group discussions supplemented with publications from literature searches and the authors' knowledge. Moreover, randomized controlled trials (RCTs) were identified and analysed either in fresh IVF cycles with embryo transfer (ET), oocyte donation cycles or cycles without ET; risk differences were calculated regarding pregnancy rate and OHSS rate. In fresh IVF cycles with ET (9 RCTs) no OHSS was reported after GnRHa triggering [0% incidence in the GnRHa group: risk difference 5% (with 95% CI: -0.07 to 0.02)]. Importantly, the delivery rate improved significantly after modified luteal support [6% risk difference in favour of the HCG group (95% CI: -0.14 to 0.2)] when compared with initial studies with conventional luteal support [18% risk difference (95% CI: -0.36 to 0.01)]. In oocyte donation cycles (4 RCTs) the OHSS incidence is 0% [10% risk difference (95% CI: 0.02-0.40)]. GnRHa triggering is a valid alternative to hCG triggering, resulting in an elimination of OHSS. After modified luteal support there is now a non-significant difference of 6% in delivery rate in favour of hCG triggering.

Effect of pretreatment with oral contraceptives and progestins on IVF outcomes in women with polycystic ovary syndrome.

PubMed

Wei, Daimin; Shi, Yuhua; Li, Jing; Wang, Ze; Zhang, Lin; Sun, Yun; Zhou, Hong; Xu, Yuping; Wu, Chunxiang; Liu, Ling; Wu, Qiongfang; Zhuang, Lili; Du, Yanzhi; Li, Weiping; Zhang, Heping; Legro, Richard S; Chen, Zi-Jiang

2017-02-01

Do oral contraceptives (OCs) and progestins impact live birth rate of IVF when used for cycle scheduling in women with polycystic ovary syndrome (PCOS)? OCs used for scheduling IVF cycle were associated with lowered rates of pregnancy and live birth after fresh embryo transfer, whereas progestins used for this purpose yield higher rates of pregnancy and live birth than OCs. Due to oligo-menorrhea in PCOS, OCs and progestin are extensively used to schedule the start of an IVF cycle in women with PCOS. Little is known about the effect of such pretreatments on outcomes, especially, the rate of live birth. This was a nested cohort study and secondary analysis of a multicenter randomized trial, which was designed to compare live birth rate after fresh embryo transfer vs frozen embryo transfer (FET) in women with PCOS (Frefro-PCOS). A total of 1508 women were enrolled from 14 centers between June 2013 and May 2014. At the discretion of local investigators, subjects were instructed to wait for spontaneous menses (Control group, n = 323), or were prescribed progestins (P group, n = 283) or OCs (OCs group, n = 902) to induce menstruation prior to the start of ovarian stimulation. GnRH antagonist protocol was initiated at Day 2 or 3 of induced or spontaneous menses cycle. The rates of pregnancy, pregnancy loss and live birth after either fresh embryo transfer or FET were compared among these three groups. With fresh embryo transfer, women with OC-induced menses had lower rates of clinical pregnancy (48.8% vs 63.6%, relative rate (RR): 0.77, 95% CI: 0.66-0.89) and live birth (36.1% vs 48.1%, RR: 0.75, 95% CI: 0.61-0.92) than women with spontaneous menses. With freeze-all and deferred FET, women with OC-induced menses had a similar pregnancy rate but a higher pregnancy loss rate (27.7% vs 13.0%, RR: 2.13, 95% CI: 1.28-3.52) after FET than women with spontaneous menses. The live birth rate after FET in women with OC-induced menses, progestin-induced menses and spontaneous menses was 49.4%, 50.7% and 60.2%, respectively (P = 0.06). Progestin-induced menses was associated with similar rates of pregnancy, pregnancy loss and live birth after transfer of either fresh or frozen embryos compared with spontaneous menses. Multivariate logistic regression analysis showed that OCs used for menses induction was associated with lower rate of live birth. The methods for menses induction were not assigned randomly, thus selection bias was highly likely because of the study design and significant differences that were observed in the baseline characteristics of the women in the different groups. The mean BMI in this study population was relatively normal; the applicability of this result to obese PCOS women needs to be evaluated in further study. Our results suggest that either waiting for a spontaneous menses or using progestin is a better option than using OCs to induce menses in women with PCOS prior to ovarian stimulation using GnRH antagonist protocol for IVF. Further randomized controlled studies are needed to confirm our findings. This study was funded by National Basic Research Program of China (973 Program) (2012CB944700), the State Key Program of National Natural Science Foundation of China (81430029), National Natural Science Foundation of China (81471428) and Thousand Talents Program (Drs Legro and Zhang H). Dr Legro reports receiving consulting fees from Euroscreen, Kindex, Bayer and Millendo Pharmaceuticals and research funding from Ferring. Others report no disclosures. Frefro-PCOS was registered at Clinicaltrials.gov: NCT01841528. © 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.

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.

In vitro fertilization-induced pregnancies predispose to gastroesophageal reflux disease

PubMed Central

Kitapcioglu, Gul; Tavmergen Goker, Ege; Sahin, Gulnaz; Bor, Serhat

2015-01-01

Background Women conceiving following in vitro fertilization (IVF) likely have a variety of risk factors that predispose them to gastroesophageal reflux disease (GERD) in the future. Objective We aimed to investigate whether pregnancy through IVF may predispose to subsequent GERD compared with pregnancies without IVF. We also evaluate whether twin IVF pregnancies lead to additional risk for having GERD compared with singleton IVF pregnancies. Methods A validated reflux questionnaire was administered to 156 women with singleton (n = 102) or twin (n = 54) IVF birth (IVF group) and 111 women with a naturally conceived singleton birth (control group). All women included in the study were primiparas who had given birth at least 1 year prior to data collection. The diagnosis of GERD was based on the occurrence of typical symptoms (heartburn, regurgitation, or both) at least once a week. Results The prevalence of GERD was 13.5% and 4.5% in IVF and control groups (p = 0.015); in the IVF group, this was slightly higher, but not statistically significant, in women with twin compared with singleton pregnancies (14.8% vs. 12.7%, p = 0.749). Logistic regression analysis showed that IVF was strongly associated with subsequent GERD (OR, 3.30; 95% CI 1.20–9.04; p = 0.02). Conclusion The risk of developing GERD at least 1 year after delivery increased following IVF. Long-term follow-up studies are required to determine whether therapy during pregnancy can prevent this risk. PMID:27087950

Risk factors and clinical features of ovarian pregnancy: a case–control study

PubMed Central

Zhu, Qian; Li, Cheng; Zhao, Wei-Hong; Yuan, Jiang-Jing; Yan, Ming-Xing; Qin, Guo-Juan; Zhang, Jian

2014-01-01

Objective To identify risk factors for ovarian pregnancy (OP) and compare clinical features between OP and tubal pregnancy (TP) patients. Design Case–control study. Setting University hospital. Participants A case–control study was conducted from January 2005 to May 2014. Women diagnosed with OP were recruited as the case group (n=71), 145 women with TP and 146 with intrauterine pregnancy (IUP) were matched as controls at a ratio of 1:2:2. Women who refused interviews or provided incomplete information were excluded. Results OP risk was lower than TP risk in women with serological evidence of Chlamydia trachomatis infection (adjusted OR1 0.17, 95% CI 0.06 to 0.52), previous adnexal surgery (adjusted OR1 0.25, 95% CI 0.07 to 0.95), and current levonorgestrel emergency contraceptive use (adjusted OR1 0.24, 95% CI 0.07 to 0.78). In vitro fertilisation-embryo transfer (IVF-ET) carried a higher risk of OP (adjusted OR1 12.18, 95% CI 2.23 to 66.58) than natural conception. When Controlled by IUP women, current users of intrauterine devices (IUDs) carried a higher risk of OP than non-users of any contraceptives (adjusted OR2 9.60, 95% CI 1.76 to 42.20). β-Human chorionic gonadotropin (hCG) levels on the day of surgery were higher in OP patients than in TP patients (p<0.01). Women with OP were less likely to initially present with vaginal bleeding than those with TP (p=0.02). Moreover, shock (p=0.02), rupture (p<0.01), haemoperitoneum (p<0.01) and emergency laparotomy (p<0.01) were more common in the OP group than in the TP group. Conclusions IVF-ET and IUD use may be risk factors for OP, and OP patients tend to have high β-hCG levels and a poor clinical outcome (shock, rupture, haemoperitoneum and need for emergency laparotomy). Our findings may contribute to the prevention and early diagnosis of OP. PMID:25472658

In vitro fertilization affects growth and glucose metabolism in a sex-specific manner in an outbred mouse model.

PubMed

Donjacour, Annemarie; Liu, Xiaowei; Lin, Wingka; Simbulan, Rhodel; Rinaudo, Paolo F

2014-04-01

The preimplantation period is a time of reprogramming that may be vulnerable to disruption. This question has wide clinical relevance since the number of children conceived by in vitro fertilization (IVF) is rising. To examine this question, outbred mice (CF1 × B6D2F1) conceived by IVF and cultured using Whitten medium and 20% O2 (IVFWM group, less optimal) or K simplex optimized medium with amino acids and 5% O2 (IVFKAA group, more optimal and similar to conditions used in human IVF) were studied postnatally. We found that flushed blastocysts transferred to recipient mice provided the best control group (FB group), as this accounted for the effects of superovulation, embryo transfer, and litter size. We observed that many physiological parameters were normal. Reassuringly, IVFKAA offspring did not differ significantly from FB offspring. However, male IVFWM mice (but not females) were larger during the first 19 wk of life and exhibited glucose intolerance. Male IVFWM mice also showed enlarged left heart despite normal blood pressure. Expression of candidate imprinted genes (H19, Igf2, and Slc38a4) in multiple adult tissues did not show differences among the groups; only Slc38a4 was down-regulated following IVF (in both culture conditions) in female adipose tissue. These studies demonstrate that adult metabolism is affected by the type of conditions encountered during the preimplantation stage. Further, the postnatal growth trajectory and glucose homeostasis following ex vivo manipulation may be sexual dimorphic. Future work on the long-term effects of IVF offspring should focus on glucose metabolism and the cardiovascular system.

'Emotional rights', moral reasoning, and Jewish-Arab alliances in the regulation of in-vitro-fertilization in israel: theorizing the unexpected consequences of assisted reproductive technologies.

PubMed

Gooldin, Sigal

2013-04-01

Consumption rates of assisted reproductive technologies (ARTs) in Israel is internationally unprecedented, a phenomenon that has been the subject of growing anthropological and sociological attention. Explanations for the singular extent of ARTs use in Israel tend to pre-assume and conceptually prioritize the symbolic and political power of pro-natalist discourses, Jewish religious values, and the demographic interests of the Jewish state. This article attempts to understand the exceptional usage of IVF in Israel in terms of its emergent meanings and unexpected effects in a particular local setup. The question that this article tries to answer is: How is the 'Israeli character' of IVF emerges within and through the interactive practice of moral justifications, and how might this medical technology affect the networks within which it is enmeshed? The article is based on a case-study analysis of a public dispute that took place in 2003-2004 over the extent of public funding for fertility treatments. Ethnographic analysis of parliament discussions, media coverage, and an online forum of IVF consumers recorded three frames of justification for the uniquely generous public funding scheme of IVF in Israel: 'rational-economic', 'nationalist', and 'liberal'. The latter assumes shared 'emotional vulnerability' of all 'childless' Israelis, Jews and Arabs alike and advocates a universal language of 'emotional rights' and 'human rights'. This liberal framing of IVF, which is the most persuasive justification in the dispute, blurs dichotomous rivalries between Jews and Arabs and generates a potential for alliances between traditionally rival sectors. These are some of the unexpected and non-intuitive consequences of ARTs in Israel. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Does culture medium influence offspring birth weight?

PubMed

Carrasco, Beatriz; Boada, Montserrat; Rodríguez, Ignacio; Coroleu, Buenaventura; Barri, Pedro N; Veiga, Anna

2013-11-01

To determine whether the type of medium used to culture human embryos in vitro influences neonatal birth weight after IVF/intracytoplasmic sperm injection (ICSI). A prospective study and a retrospective study. Private assisted reproduction center. The prospective study included 449 IVF/ICSI cycles from August to December 2008. The retrospective analysis was performed for 2,518 IVF/ICSI cycles from October 2006 to December 2010. In the prospective study, patients were randomized for embryo culture in Cook or Vitrolife medium. The retrospective study was performed with three different culture media (MediCult, Cook, and Vitrolife). Mean birth weight, adjusted for gestational age and gender (z score) of newborns. In the prospective study, the average z score was -0.19 ± 0.85 in Cook and 0.08 ± 1.40 in Vitrolife. In the retrospective study, the z scores obtained in each group were as follows: Cook, -0.14 ± 0.96; MediCult, 0.06 ± 1.13; and Vitrolife, 0.03 ± 1.05. No significant differences were observed regarding the birth weight of children born in the different groups in both studies. The results do not show any relationship between the medium used for in vitro culture and mean birth weight adjusted for gestational age and gender of singletons born after IVF/ICSI. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Egg donation for stem cell research: ideas of surplus and deficit in Australian IVF patients' and reproductive donors' accounts.

PubMed

Waldby, Catherine; Carroll, Katherine

2012-05-01

We report on a study undertaken with an Australian in vitro fertilisation (IVF) clinic to understand IVF patients' and reproductive donors' perceptions of oocyte (egg) donation for stem cell research. Such perspectives are particularly valuable because IVF patients form a major recruitment group for oocyte donation for research, and because patients and donors have direct experience of the medical procedures involved. Similar studies of oocyte donation have been carried out elsewhere in the world, but to date very little social science research has been published that reports on donation for research, as distinct from donation for reproduction. Our respondents expressed a distinct unwillingness to donate viable oocytes for stem cell research. In our analysis we consider a number of factors that explain this unwillingness. These include the labour of oocyte production, the inscrutability of oocytes (the lack of a test to identify degrees of fertility) and the extent to which the oocytes' fertility sets the parameters for all downstream reproductive possibilities. We draw on the science studies literature on affordances to make sense of the social intractability of oocytes, and compare them with the respondents' much greater willingness to donate frozen embryos for human embryonic stem cells research. © 2011 The Authors. Sociology of Health & Illness © 2011 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

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

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.

Selective outcome reporting and sponsorship in randomized controlled trials in IVF and ICSI.

PubMed

Braakhekke, M; Scholten, I; Mol, F; Limpens, J; Mol, B W; van der Veen, F

2017-10-01

Are randomized controlled trials (RCTs) on IVF and ICSI subject to selective outcome reporting and is this related to sponsorship? There are inconsistencies, independent from sponsorship, in the reporting of primary outcome measures in the majority of IVF and ICSI trials, indicating selective outcome reporting. RCTs are subject to bias at various levels. Of these biases, selective outcome reporting is particularly relevant to IVF and ICSI trials since there is a wide variety of outcome measures to choose from. An established cause of reporting bias is sponsorship. It is, at present, unknown whether RCTs in IVF/ICSI are subject to selective outcome reporting and whether this is related with sponsorship. We systematically searched RCTs on IVF and ICSI published between January 2009 and March 2016 in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed. We analysed 415 RCTs. Per included RCT, we extracted data on impact factor of the journal, sample size, power calculation, and trial registry and thereafter data on primary outcome measure, the direction of trial results and sponsorship. Of the 415 identified RCTs, 235 were excluded for our primary analysis, because the sponsorship was not reported. Of the 180 RCTs included in our analysis, 7 trials did not report on any primary outcome measure and 107 of the remaining 173 trials (62%) reported on surrogate primary outcome measures. Of the 114 registered trials, 21 trials (18%) provided primary outcomes in their manuscript that were different from those in the trial registry. This indicates selective outcome reporting. We found no association between selective outcome reporting and sponsorship. We ran additional analyses to include the trials that had not reported sponsorship and found no outcomes that differed from our primary analysis. Since the majority of the trials did not report on sponsorship, there is a risk on sampling bias. IVF and ICSI trials are subject, to a large extent, to selective outcome reporting. Readers should be aware of this to avoid implementation of false or misleading results in clinical practice. No funding received and there are no conflicts of interest. N/A. © 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

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.

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

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

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.

Obesity adversely impacts the number and maturity of oocytes in conventional IVF not in minimal stimulation IVF.

PubMed

Zhang, John J; Feret, Maciej; Chang, Lyndon; Yang, Mingxue; Merhi, Zaher

2015-05-01

The objective of this study was to assess the relationship between BMI and oocyte number and maturity in participants who underwent minimal stimulation (mini-) or conventional IVF. Participants who underwent their first autologous cycle of either conventional (n = 219) or mini-IVF (n = 220) were divided according to their BMI to analyze IVF outcome parameters. The main outcome measure was the number of oocytes in metaphase II (MII). Secondary outcomes included the number of total oocytes retrieved, fertilized (2PN) oocytes, cleavage and blastocyst stage embryos, clinical pregnancy (CP), and live birth (LB) rates. In conventional IVF, but not in mini-IVF, the number of total oocytes retrieved (14.5  ±  0.8 versus 8.8  ±  1.3) and MII oocytes (11.2 ± 0.7 versus 7.1 ± 1.1) were significantly lower in obese compared with normal BMI women. Multivariable linear regression adjusting for age, day 3 FSH, days of stimulation, and total gonadotropin dose demonstrated that BMI was an independent predictor of the number of MII oocytes in conventional IVF (p = 0.0004). Additionally, only in conventional IVF, BMI was negatively correlated with the total number of 2PN oocytes, as well as the number of cleavage stage embryos. Female adiposity might impair oocyte number and maturity in conventional IVF but not in mini-IVF. These data suggest that mild ovarian stimulation might yield healthier oocytes in obese women.

Derivation and characterization of human embryonic stem cell lines from poor quality embryos.

PubMed

Liu, Weiqiang; Yin, Yifei; Long, Xiaolin; Luo, Yumei; Jiang, Yonghua; Zhang, Wenhong; Du, Hongzi; Li, Shaoying; Zheng, Yuhong; Li, Qing; Chen, Xinjie; Liao, Baoping; Xiao, Guohong; Wang, Weihua; Sun, Xiaofang

2009-04-01

Poor quality embryos discarded from in vitro fertilization (IVF) laboratories are good sources for deriving human embryonic stem cell (hESC) lines. In this study, 166 poor quality embryos donated from IVF centers on day 3 were cultured in a blastocyst medium for 2 days, and 32 early blastocysts were further cultured in a blastocyst optimum culture medium for additional 2 days so that the inner cell masses (ICMs) could be identified and isolated easily. The ICMs of 17 blastocysts were isolated by a mechanical method, while those of the other 15 blastocysts were isolated by immunosurgery. All isolated ICMs were inoculated onto a feeder layer for subcultivation. The rates of ICM attachment, primary ICM colony formation and the efficiency of hESC derivation were similar between the ICMs isolated by the two methods (P>0.05). As a result, four new hESC lines were established. Three cell lines had normal karyotypes and one had an unbalanced Robertsonian translocation. All cell lines showed normal hESC characteristics and had the differentiation ability. In conclusion, we established a stable and effective method for hESC isolation and culture, and it was confirmed that the mechanical isolation was an effective method to isolate ICMs from poor embryos. These results further indicate that hESC lines can be derived from poor quality embryos discarded by IVF laboratories.

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.

Impact of air pollution on fertility: a systematic review.

PubMed

Frutos, Víctor; González-Comadrán, Mireia; Solà, Ivan; Jacquemin, Benedicte; Carreras, Ramón; Checa Vizcaíno, Miguel A

2015-01-01

Air pollution has gained considerable interest because of the multiple adverse effects reported on human health, although its impact on fertility remains unclear. A systematic search was performed to evaluate the impact of air pollutants on fertility. Controlled trials and observational studies assessing animal model and epidemiological model were included. Occupational exposure and semen quality studies were not considered. Outcomes of interest included live birth, miscarriage, clinical pregnancy, implantation, and embryo quality. Ten studies were included and divided into two groups: animal studies and human epidemiological studies including the general population as well as women undergoing in vitro fertilization and embryo transfer (IVF/ET). Results from this systematic review suggest a significant impact of air pollution on miscarriage and clinical pregnancy rates in the general population, whereas among subfertile patients certain air pollutants seem to exert a greater impact on fertility outcomes, including miscarriage and live birth rates. Besides, studies in mammals observed a clear detrimental effect on fertility outcomes associated to air pollutants at high concentration. The lack of prospective studies evaluating the effect of air pollution exposure in terms of live birth constitutes an important limitation in this review. Thus, further studies are needed to confirm these findings.

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)

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.

Life and death in the Philippines.

PubMed

Dupont, P

2013-01-01

In a country in which contraception is controversial, abortion illegal and in which reproductive rights are limited, IVF is an unaffordable dream for most couples. But things are slowly changing in the only Christian democracy in Asia: the Philippines. In December 2012 the Senate passed the Reproductive Health bill and president Benigno Aquino III signed the measure into a law which is still not implemented due to the opposition of the ultra-orthodox Roman Catholic Church. However, the more liberal perspective of pope Francis on sexuality and human reproduction may have an positive impact on this issue. While government funding for contraceptives is still being opposed, the IVF market is estimated to grow considerable. This creates promising opportunities.

Life and death in the Philippines

PubMed Central

Dupont, P.

2013-01-01

In a country in which contraception is controversial, abortion illegal and in which reproductive rights are limited, IVF is an unaffordable dream for most couples. But things are slowly changing in the only Christian democracy in Asia: the Philippines. In December 2012 the Senate passed the Reproductive Health bill and president Benigno Aquino III signed the measure into a law which is still not implemented due to the opposition of the ultra-orthodox Roman Catholic Church. However, the more liberal perspective of pope Francis on sexuality and human reproduction may have an positive impact on this issue. While government funding for contraceptives is still being opposed, the IVF market is estimated to grow considerable. This creates promising opportunities. PMID:24753955

DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids

PubMed Central

Canovas, Sebastian; Ivanova, Elena; Romar, Raquel; García-Martínez, Soledad; Soriano-Úbeda, Cristina; García-Vázquez, Francisco A; Saadeh, Heba; Andrews, Simon; Kelsey, Gavin; Coy, Pilar

2017-01-01

The number of children born since the origin of Assisted Reproductive Technologies (ART) exceeds 5 million. The majority seem healthy, but a higher frequency of defects has been reported among ART-conceived infants, suggesting an epigenetic cost. We report the first whole-genome DNA methylation datasets from single pig blastocysts showing differences between in vivo and in vitro produced embryos. Blastocysts were produced in vitro either without (C-IVF) or in the presence of natural reproductive fluids (Natur-IVF). Natur-IVF embryos were of higher quality than C-IVF in terms of cell number and hatching ability. RNA-Seq and DNA methylation analyses showed that Natur-IVF embryos have expression and methylation patterns closer to in vivo blastocysts. Genes involved in reprogramming, imprinting and development were affected by culture, with fewer aberrations in Natur-IVF embryos. Methylation analysis detected methylated changes in C-IVF, but not in Natur-IVF, at genes whose methylation could be critical, such as IGF2R and NNAT. DOI: http://dx.doi.org/10.7554/eLife.23670.001 PMID:28134613

Parenthood motives in IVF-mothers.

PubMed

Colpin, H; De Munter, A; Vandemeulebroecke, L

1998-03-01

This is an exploratory study to answer two questions: (1) does in-vitro fertilization (IVF)-mothers' motivation for parenthood differ from the naturally conceiving mothers' motivation for parenthood? and (2) are IVF-mothers' parenthood motives correlated with their adjustment to parenthood (in the same way as they are for naturally conceiving mothers)? The study sample consisted of 31 mothers with a 24-30 month old, single-born child conceived by homologous IVF and a comparison group of 31 mothers with a naturally conceived child. Self-rating questionnaires were used. Overall, the parenthood motivation pattern was quite similar for IVF-mothers and mothers by natural conception. However, 'identity', 'motherhood' and 'social control' were significantly more important motives for IVF-mothers than for the naturally conceiving mothers. The two former motives remained more important for IVF-mothers when findings were adjusted for the influence of the mothers' age and educational level. Possible explanations for these findings refer to the infertility history. Overall, few correlations between parenthood motives and the adjustment to parenthood were significant, both for the IVF-mothers and for the mothers by natural conception. Further (hypothesis-testing) research is needed to support these findings.

Assisted reproduction professionals' awareness and attitudes towards their own IVF cycles.

PubMed

Bonetti, T C S; Melamed, R M M; Braga, D P A F; Madaschi, C; Iaconelli, A; Pasqualotto, F F; Borges, E

2008-12-01

Professionals involved in assisted reproductive technologies (ART) have in-depth awareness and knowledge of the risks of multiple pregnancies at the conclusion of in vitro fertilization (IVF) treatment. The aim of the study was to investigate ART professionals' attitudes towards the awareness of the risk of infertility, as well as the decision-making process in IVF issues. Seventy ART professionals answered a questionnaire covering demographic data, infertility awareness and attitudes towards IVF. Approximately half (50.8%) of the participants thought that they were not at risk of infertility. However, if they received a diagnosis of infertility, none would accept childlessness and almost all would undergo IVF. In an IVF cycle, the number of high-quality embryos transferred would be around three, but if treatment was extended to a third cycle, a higher percentage of participants would elect to transfer four or more embryos. All participants would prefer to undergo IVF and accept the risk of multiple pregnancy than remaining childless. It was found that less than a third of ART professionals considered triplets to be an unacceptable complication of IVF. Diagnosis of infertility affects all participants psychosocially, supporting the idea that the emotional aspects of wanting a biological child, and decision making about whether to undertake ART, outweigh the medical position regarding the risks and benefits of IVF.

Patterns of emotional responses to pregnancy, experience of pregnancy and attitudes to parenthood among IVF couples: a longitudinal study.

PubMed

Hjelmstedt, A; Widström, A; Wramsby, H M; Collins, A

2003-09-01

The aim of this longitudinal study was to compare couples who had conceived by in-vitro fertilization (IVF) with couples who had conceived naturally, regarding patterns of emotional response to different stages of pregnancy and to compare their expectations of and attitudes to pregnancy, parenthood and children. Fifty-seven IVF women and 55 of their male partners, and a control group of 43 pregnant women and 39 of their male partners participated. They completed scales measuring emotional responses to pregnancy, attitudes to pregnancy, parenthood and children. The IVF couples were interviewed about their experience of pregnancy. The overall anxiety about losing the pregnancy was higher among the IVF couples from early to late pregnancy. The IVF women experienced the pregnancy in a more positive way and they were less concerned about the child's gender and loss of freedom in their future lives as parents compared to controls. The IVF men were more anxious about the baby being injured during birth. The interviews with the IVF couples confirmed the self-ratings. In conclusion, the results suggest that it is important for healthcare providers to pay attention to an elevated anxiety among IVF couples and to give them extra time to discuss emotions during pregnancy and their future life as parents.

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.

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.

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.

Prior colorectal surgery for endometriosis-associated infertility improves ICSI-IVF outcomes: results from two expert centres.

PubMed

Ballester, Marcos; Roman, Horace; Mathieu, Emmanuelle; Touleimat, Salma; Belghiti, Jeremy; Daraï, Emile

2017-02-01

To assess fertility outcomes after ICSI-IVF in infertile women having undergone prior complete surgical removal of colorectal endometriosis. Prospective longitudinal cohort study in two referral French centres including 60 infertile women who underwent ICSI-IVF after complete surgical removal of colorectal endometriosis, from January 2005 to May 2014. Women underwent either conservative colorectal surgery (i.e., rectal shaving or full thickness disc excision, n=18) or segmental colorectal resection (n=42). Clinical pregnancies were defined by the presence of a gestational sac on vaginal ultrasound examination from the fifth week. The overall pregnancy rate was calculated. The Kaplan-Meier method was used to estimate the cumulative pregnancy rate (CPR). Comparisons of CPR were made using the log-rank test to detect determinant factors. The median number of ICSI-IVF cycles per patient was one (range: 1-4). Of the 60 women, 36 became pregnant (i.e., overall pregnancy rate=60%). The CPR was 41.7% after one ICSI-IVF cycle, 65% after two ICSI-IVF cycles and 78.1% after three ICSI-IVF cycles. A decreased CPR was observed for women who required segmental colorectal resection compared to those who underwent rectal shaving or full thickness disc excision (p=0.04). A trend for a decreased CPR was observed for women who received a first ICSI-IVF cycle more than 18 months following surgery (p=0.07). Among the nine women with prior ICSI-IVF failure, five (55.5%) became pregnant after surgery. Colorectal surgery for endometriosis completed by ICSI-IVF is a good option for women with proven infertility, even if prior ICSI-IVF had failed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Tachycardia-Induced J-Wave Changes in Patients With and Without Idiopathic Ventricular Fibrillation.

PubMed

Aizawa, Yoshiyasu; Takatsuki, Seiji; Nishiyama, Takahiko; Kimura, Takehiro; Kohsaka, Shun; Kaneko, Yoshiaki; Inden, Yasuya; Takahashi, Naohiko; Nagase, Satoshi; Aizawa, Yoshifusa; Fukuda, Keichi

2017-07-01

To know the underlying mechanisms of J waves, the response to atrial pacing was studied in patients with idiopathic ventricular fibrillation (IVF) and patients with non-IVF. In 8 patients with IVF, the J-wave amplitude was measured before, during, and after atrial pacing. All patients had episodes of ventricular fibrillation without structural heart disease. The responses of J waves were compared with those of the 17 non-IVF control subjects who revealed J waves but no history of cardiac arrest and underwent electrophysiological study. The IVF patients were younger than the non-IVF patients (28±10 versus 52±14 years, respectively; P =0.002) and had larger J waves with more extensive distribution. J waves decreased from 0.35±0.26 to 0.22±0.23 mV ( P =0.025) when the RR intervals were shortened from 782±88 to 573±162 ms ( P =0.001). A decrease (≥0.05 mV) in the J-wave amplitude was observed in 6 of the 8 patients. In addition, 1 patient showed a distinct reduction of J waves in the unipolar epicardial leads. In contrast, J waves were augmented in the 17 non-IVF subjects from 0.27±0.09 to 0.38±0.10 mV ( P <0.001): augmented in 9 and unchanged in the 8 subjects. The different response patterns of J waves to rapid pacing suggest different mechanisms: early repolarization in IVF patients and conduction delay in non-IVF patients. The response to atrial pacing was different between the IVF and non-IVF patients, which suggests the presence of different mechanisms for the genesis of J waves. © 2017 American Heart Association, Inc.

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

Growth during infancy and early childhood in relation to blood pressure and body fat measures at age 8-18 years of IVF children and spontaneously conceived controls born to subfertile parents.

PubMed

Ceelen, Manon; van Weissenbruch, Mirjam M; Prein, Janneke; Smit, Judith J; Vermeiden, Jan P W; Spreeuwenberg, Marieke; van Leeuwen, Flora E; Delemarre-van de Waal, Henriette A

2009-11-01

Little is known about post-natal growth in IVF offspring and the effects of rates of early post-natal growth on blood pressure and body fat composition during childhood and adolescence. The follow-up study comprised 233 IVF children aged 8-18 years and 233 spontaneously conceived controls born to subfertile parents. Growth data from birth to 4 years of age, available for 392 children (n = 193 IVF, n = 199 control), were used to study early post-natal growth. Furthermore, early post-natal growth velocity (weight gain) was related to blood pressure and skinfold measurements at follow-up. We found significantly lower weight, height and BMI standard deviation scores (SDSs) at 3 months, and weight SDS at 6 months of age in IVF children compared with controls. Likewise, IVF children demonstrated a greater gain in weight SDS (P < 0.001), height SDS (P = 0.013) and BMI SDS (P = 0.029) during late infancy (3 months to 1 year) versus controls. Weight gain during early childhood (1-3 years) was related to blood pressure in IVF children (P = 0.014 systolic, 0.04 diastolic) but not in controls. Growth during late infancy was not related to skinfold thickness in IVF children, unlike controls (P = 0.002 peripheral sum, 0.003 total sum). Growth during early childhood was related to skinfold thickness in both IVF and controls (P = 0.005 and 0.01 peripheral sum and P = 0.003 and 0.005 total sum, respectively). Late infancy growth velocity of IVF children was significantly higher compared with controls. Nevertheless, early childhood growth instead of infancy growth seemed to predict cardiovascular risk factors in IVF children. Further research is needed to confirm these findings and to follow-up growth and development of IVF children into adulthood.

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

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.

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.

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.

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 right to try.

PubMed

Pearce, Lynne

2015-01-20

Many clinical commissioning groups have ignored 2013 national guidelines requiring them to make IVF available. NICE has recently issued a quality standard to tackle this postcode lottery. Nurses can help by alerting local decision makers to the human and fi nancial cost of infertility.

Follow up of infertile patients after failed ART cycles: a preliminary report from Iran and Turkey.

PubMed

Khalili, Mohammad Ali; Kahraman, Semra; Ugur, Mete Gurol; Agha-Rahimi, Azam; Tabibnejad, Nasim

2012-03-01

Assisted reproductive technology (ART) has become an established and increasingly successful form of treatment for infertility. However, significant numbers of cycles fail after embryo transfer (ET) and it becomes necessary to follow up the infertile couples after failed ART treatments. The main goal was to follow up the infertile patients after failed IVF/ICSI+ET treatments in Iran and Turkey. 198 infertile couples from Iran and 355 infertile couples from Turkey were followed up after IVF/ICSI failures. The patients' demographic data, the couples' decisions about continuation of treatment and the spontaneous pregnancy rates were compared in the two countries. The drop-out rate was higher in Iran (28.3%) than in Turkey (23.4%). The reasons for treatment discontinuation in Iran and Turkey were: financial problem (33.9% vs. 41%), hopeless (10.7% vs. 22.9%), fear of drug side-effects (7.1% vs. 12%), achieving pregnancy (37.5% vs. 19.6%), child adoption (5.4% vs. 2.4%), lack of spouse cooperation (5.4% vs. 2.4%), and divorce (0% vs. 2.4%). Spontaneous pregnancy was significantly higher in Iran (10.1%) than in Turkey (3.9%). There was correlation between duration of infertility and female factor infertility with spontaneous pregnancy. Since the majority of couples that discontinued treatment had financial problems, it is essential for health professionals to support infertile couples during their childlessness crisis. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Human oocyte cryopreservation and the fate of cortical granules.

PubMed

Ghetler, Yehudith; Skutelsky, Ehud; Ben Nun, Isaac; Ben Dor, Liah; Amihai, Dina; Shalgi, Ruth

2006-07-01

To examine the effect of the commonly used oocyte cryopreservation protocol on the cortical granules (CGs) of human immature germinal vesicle (GV) and mature metaphase II (MII) oocytes. Laboratory study. IVF unit. Unfertilized, intracytoplasmic sperm injected (ICSI) oocytes, and immature oocytes were cryopreserved using a slow freezing-rapid thawing program with 1,2-propanediol (PROH) as a cryoprotectant. Cortical granule exocytosis (CGE) was assessed by either confocal microscopy or transmission electron microscopy (TEM). The survival rates of frozen-thawed oocytes (mature and immature) were significantly lower compared with zygotes. Both mature and immature oocytes exhibited increased fluorescence after cryopreservation, indicating the occurrence of CGE. Mere exposure of oocytes to cryoprotectants induced CGE of 70% the value of control zygotes. The TEM revealed a drastic reduction in the amount of CGs at the cortex of frozen-thawed GV and MII oocytes, as well as appearance of vesicles in the ooplasm. The commonly used PROH freezing protocol for human oocytes resulted in extensive CGE. This finding explains why ICSI is needed to achieve fertilization of frozen-thawed human oocytes.

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.

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.

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.

Creatine enhances the duration of sperm capacitation: a novel factor for improving in vitro fertilization with small numbers of sperm.

PubMed

Umehara, Takashi; Kawai, Tomoko; Goto, Masaaki; Richards, JoAnne S; Shimada, Masayuki

2018-06-01

Why are many sperm required for successful fertilization of oocytes in vitro, even though fertilization occurs in vivo when only a few sperm reach the oocyte? Creatine produced in the ovary promotes efficient fertilization in vivo; however, in vitro, creatine is not contained in the in vitro fertilization (IVF) medium. The IVF medium enables capacitation of sperm. However, the IVF medium does not fully mimic the in vivo environment during fertilization. Consequently, fertilization in vitro is more inefficient than in the oviduct. Follicular and oviductal fluids were collected and then analyzed for creatine and glucose levels. To determine the physiological functions of creatine, the creatine antagonist 3-guanidinopropionic acid (GPA) was injected into hormonally primed mice. Using conventional IVF protocols, sperm were pre-incubated in IVF medium with creatine and then co-cultured with 10 ovulated cumulus-oocyte complexes (1-1000 per oocyte) in 50 μl medium droplets. Glucose and creatine levels were measured using commercial enzymatic assay kits. The effect of creatine in vivo was assessed by mating experiments using mice treated with or without GPA just before ovulation. To assess the functions of sperm incubated in IVF medium containing creatine, we analyzed (1) the motility of sperm using computer-assisted sperm assay, (2) the capacitation level of sperm by western blot analyses, and (3) the condition of sperm acrosomes by peanut agglutinin lectin-FITC staining. Oviductal creatine levels were significantly increased following ovulation. Injecting mice with GPA just before ovulation significantly reduced the number of fertilized oocytes. The addition of creatine to IVF medium enhanced sperm capacitation by increasing ATP levels. Successful fertilization was achieved with as few as five sperm/oocyte in the creatine group, and the number of fertilized oocytes was significantly higher than in the control without creatine (P < 0.01). In the present study, a pharmacological approach, creatine antagonist (GPA) treatment, but not a knockout mouse model, was used to understand the role of creatine in vivo. The role of creatine in fertilization processes can only be shown in a mouse model. A modified IVF technique using creatine-containing medium was developed and shown to markedly improve fertilization with small numbers of sperm. This approach has the potential to be highly beneficial for human assisted reproductive technologies, especially for patients with a limited number of good quality sperm. This work was supported in part by JSPS KAKENHI Grant numbers JP24688028, JP16H05017 (to M.S.), and JP15J05331 (to T.U.), the Japan Agency for Medical Research and Development (AMED) (16gk0110015h0001 to M.S.), and National Institutes of Health (NIH-HD-076980 to J.S.R). The authors have nothing to disclose.

In vitro fertilization (IVF)

MedlinePlus

IVF; Assisted reproductive technology; ART; Test-tube baby procedure; Infertility - in vitro ... conception. IVF is a form of assisted reproductive technology (ART). This means special medical techniques are used ...

Outdoor air pollution and human infertility: a systematic review.

PubMed

Checa Vizcaíno, Miguel A; González-Comadran, Mireia; Jacquemin, Benedicte

2016-09-15

Air pollution is a current research priority because of its adverse effects on human health, including on fertility. However, the mechanisms through which air pollution impairs fertility remain unclear. In this article, we perform a systematic review to evaluate currently available evidence on the impact of air pollution on fertility in humans. Several studies have assessed the impact of air pollutants on the general population, and have found reduced fertility rates and increased risk of miscarriage. In subfertile patients, women exposed to higher concentrations of air pollutants while undergoing IVF showed lower live birth rates and higher rates of miscarriage. After exposure to similar levels of air pollutants, comparable results have been found regardless of the mode of conception (IVF versus spontaneous conception), suggesting that infertile women are not more susceptible to the effects of pollutants than the general population. In addition, previous studies have not observed impaired embryo quality after exposure to air pollution, although evidence for this question is sparse. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Laser effects in the manipulation of human eggs and embryos for in vitro fertilization.

PubMed

Tadir, Yona; Douglas-Hamilton, Diarmaid H

2007-01-01

Gamete manipulations using laser micro beams were introduced in 1991 and testing its application for assisted hatching occurred shortly thereafter. This procedure has now become an accepted modality of penetrating or reducing the thickness of the zona pellucida in human in vitro fertilization (IVF). Lasers used in earlier work are summarized. Although the earliest lasers used pulses as long as 15 ms, the simplest and safest laser presently used in this application is the high-power 1480-nm In GaAsP diode, used in pulses with duration typically < 1 ms. Since prevention of damage to the blastomeres is essential, we specifically discuss this system with particular attention to safety considerations. The laser operates by its thermal effect on the zona pellucida, and the implications for embryo safety are discussed in detail. A thermal model is derived using numerical analysis and the effect on the embryo of laser beam power and pulse duration is indicated. Typical recommended protocols and operating values for various applications in the human IVF laboratory are given.

Day 4 good morula embryo transfer provided compatible live birth rate with day 5 blastocyst embryo in fresh IVF/ET cycles.

PubMed

Li, Ryh-Sheng; Hwu, Yuh-Ming; Lee, Robert Kuo-Kuang; Li, Sheng-Hsiang; Lin, Ming-Huei

2018-02-01

Embryo transfers during cleavage stage (day 2 or day 3) and blastocyst stages (day 5 or day 6) are common in current daily practice in fresh IVF/ET cycles. Data regarding transferring day 4 embryos, morula/compact stage, is still restricted and the grading system is also inconsistent, as between IVF clinics. This study provided a new detailed classification system for morula/compact stage embryos and compared successes rates between day 4 and day 5 ET. This was a retrospective study. A review of medical records from January 1st, 2013, to December 31st 2015, performed for all conventional insemination and ICSI cycles with a GnRH-antagonist protocol at the Infertility Division of MacKay Memorial Hospital in Taipei City, Taiwan. There were 427 cycles included in our study, 107 in study group (day 4 MET) and 320 in control group (day 5 BET). Pregnancy rates and live birth rate were compatible, as between morula embryo transfer (MET) and blastocyst embryo transfer (BET). The implantation rate (36.3% vs. 39.6%, respectively, p = 0.500), clinical pregnancy rate (49.5% vs. 51.9%, respectively, p = 0.737), and live birth rate (42.1% vs. 45.6%, respectively, p = 0.574) were statistically insignificant between groups. The term birth rate was statistically higher in the MET group than in the BET group (95.7% vs. 79.5%, respectively, p = 0.006). When the clinical outcomes between day 4 good MET and day 5 good BET were compared, the results were compatible. The implantation rate (48.8% vs. 41.1%, respectively, p = 0.335), clinical pregnancy rate (55.0% vs. 53.2%, respectively, p = 0.867), and live birth rate (47.5% vs. 47.1%, respectively, p = 1.000) showed no significant difference. The term birth rate was also higher in day 4 good MET group than in day 5 good BET group (100% vs. 78.3%, respectively, p = 0.025). In this study, we performed day 4 MET avoid BET on Sunday. The grading system we provided was more detailed for embryo selection and it was easier to remember. Our data showed that morula embryo transfer might be a flexible, easier and applicable method for embryo transfer in daily routine. Copyright © 2018. Published by Elsevier B.V.

Live birth following IVF/ICSI using oocytes from donor who was conceived via IVF: a case report.

PubMed

Kavoussi, Shahryar K; Odenwald, Kate C; Summers-Colquitt, Roxanne B; Kavoussi, Parviz K; Kavoussi, K M; Shelinbarger, Caitlin L; Pool, Thomas B

2015-11-01

The purpose of the study was to report a case of live birth following donor oocyte in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in which the oocyte donor herself was conceived via IVF. To our knowledge, such a case has not been previously reported. Retrospective chart review; this case is reported after chart review of a successful outcome. A 42 year-old woman, with diminished ovarian reserve, and her husband desired to conceive. She underwent a fresh IVF/ICSI cycle with her own oocytes, which unfortunately was not fruitful in terms of pregnancy or cryopreserved embryos. The couple was counseled regarding the option of donor oocytes, and they elected to proceed with a fresh cycle of donor oocyte IVF/ICSI. The couple selected an anonymous oocyte donor from a donor agency who was a first-time oocyte donor and, interestingly, was conceived via IVF herself. The fresh donor oocyte/IVF/ICSI cycle did not result in pregnancy; however, two supernumerary blastocysts were cryopreserved for future cycles. The recipient's subsequent frozen-thawed embryo transfer (FET) resulted in a singleton gestation and live birth. An oocyte donor who was conceived via IVF had good ovarian response to stimulation, a good number of oocytes retrieved, and the formation and cryopreservation of blastocysts which, in a subsequent FET cycle, resulted in pregnancy and live birth for a recipient couple. To our knowledge, this is the first case reported of live birth with the use of donor oocytes from an oocyte donor who herself was conceived via IVF.

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.

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.

Urinary bisphenol A concentrations and association with in vitro fertilization outcomes among women from a fertility clinic.

PubMed

Mínguez-Alarcón, Lidia; Gaskins, Audrey J; Chiu, Yu-Han; Williams, Paige L; Ehrlich, Shelley; Chavarro, Jorge E; Petrozza, John C; Ford, Jennifer B; Calafat, Antonia M; Hauser, Russ

2015-09-01

Are urinary BPA concentrations associated with in vitro fertilization (IVF) outcomes among women attending an academic fertility center? Urinary BPA concentrations were not associated with adverse reproductive and pregnancy outcomes among women from a fertility clinic. Bisphenol A (BPA), an endocrine disruptor, is detected in the urine of most Americans. Although animal studies have demonstrated that BPA reduces female fertility through effects on the ovarian follicle and uterus, data from human populations are scarce and equivocal. This prospective cohort study between 2004 and 2012 at the Massachusetts General Hospital Fertility Center included 256 women (n = 375 IVF cycles) who provided up to two urine samples prior to oocyte retrieval (total N = 673). Study participants were women enrolled in the Environment and Reproductive Health (EARTH) Study. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. We used generalized linear mixed models with random intercepts to evaluate the association between urinary BPA concentrations and IVF outcomes adjusted by age, race, body mass index, smoking status and infertility diagnosis. The specific gravity-adjusted geometric mean of BPA was 1.87 µg/l, which is comparable to that for female participants in the National Health and Nutrition Examination Survey, 2011-2012. Urinary BPA concentrations were not associated with endometrial wall thickness, peak estradiol levels, proportion of high quality embryos or fertilization rates. Furthermore, there were no associations between urinary BPA concentrations and implantation, clinical pregnancy or live birth rates per initiated cycle or per embryo transfer. Although we did not find any associations between urinary BPA concentrations and IVF outcomes, the relation between BPA and endometrial wall thickness was modified by age. Younger women (<37 years old) had thicker endometrial thickness across increasing quartiles of urinary BPA concentrations, while older women (≥37 years old) had thinner endometrial thickness across increasing quartiles of urinary BPA concentrations. Limitations to this study include a possible misclassification of BPA exposure and difficulties in extrapolating the findings to the general population. Data on the relation between urinary BPA concentrations and reproductive outcomes remain scarce and additional research is needed to clarify its role in human reproduction. This work was supported by NIH grants R01ES022955, R01ES009718 and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32DK00770316 from the National Institute of Child Health and Human Development (NICHD). None of the authors has any conflicts of interest to declare. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. © 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.

Analysis of in vitro fertilization data with multiple outcomes using discrete time-to-event analysis

PubMed Central

Maity, Arnab; Williams, Paige; Ryan, Louise; Missmer, Stacey; Coull, Brent; Hauser, Russ

2014-01-01

In vitro fertilization (IVF) is an increasingly common method of assisted reproductive technology. Because of the careful observation and followup required as part of the procedure, IVF studies provide an ideal opportunity to identify and assess clinical and demographic factors along with environmental exposures that may impact successful reproduction. A major challenge in analyzing data from IVF studies is handling the complexity and multiplicity of outcome, resulting from both multiple opportunities for pregnancy loss within a single IVF cycle in addition to multiple IVF cycles. To date, most evaluations of IVF studies do not make use of full data due to its complex structure. In this paper, we develop statistical methodology for analysis of IVF data with multiple cycles and possibly multiple failure types observed for each individual. We develop a general analysis framework based on a generalized linear modeling formulation that allows implementation of various types of models including shared frailty models, failure specific frailty models, and transitional models, using standard software. We apply our methodology to data from an IVF study conducted at the Brigham and Women’s Hospital, Massachusetts. We also summarize the performance of our proposed methods based on a simulation study. PMID:24317880

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.

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.

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.

No effect of embryo culture media on birthweight and length of newborns.

PubMed

Lin, Shengli; Li, Ming; Lian, Ying; Chen, Lixue; Liu, Ping

2013-07-01

Does the type of media used to culture embryos for IVF influence the birthweight and length of neonates? No significant differences were observed in birthweight and length among the three embryo culture media used for in vitro embryo culture. Since the establishment of IVF as an assisted reproductive technology (ART), many different culture systems have been used for the development of human embryos. Some studies have shown that the types of culture media influence the newborn birthweight; however, other studies have shown no effect. To further explore this contradictory issue, we compared the birthweight and length of neonates born after the transfer of embryos cultured in one of three commercially available media. This retrospective analysis of birthweight and length of newborns included 1201 women who delivered singletons and 445 women who delivered twins. The following three commercially available culture media were used: G5™, Global and Quinn's advantage media. Women who underwent IVF-ET cycles between 2008 and 2010 were analyzed. Patients younger than 40 years of age with a body mass index (BMI) <30 kg/m(2) were analyzed. Only data from singletons and twins born alive after the 20th week of gestation were included in the data analysis. Patients who received preimplantation genetic diagnosis (PGD) and donor oocytes were excluded. The analysis of 1201 singletons and 445 sets of twins showed no significant association between mean birthweight or mean birth length and the type of embryo culture medium. Inter-twin mean birthweight and length disparities were analyzed, but were not shown to be significantly different. Multiple linear regression analysis showed that maternal weight, maternal height, gestational age and infant gender were significantly related to birthweight, and paternal height, gestational age and newborn complications were significantly associated with birth length. The current study showed that birthweight and length of newborns were not associated with the embryo culture medium. More research needs to be performed to analyze the effects of other culture medium formulations and to evaluate the long-term effects of embryo culture medium on the health of children conceived through ART. WIDER IMPLICATIONS OF THESE FINDINGS: Our retrospective study suggests that embryo culture medium does not influence neonatal birthweight and length; however, the effects of culture medium on epigenetic variation of embryos need to be studied further.

Should fertile people have access to in vitro fertilisation?

PubMed

Dawson, K; Singer, P

1990-01-20

Some existing laws and some proposed legislation regulating the practice of in vitro fertilization (IVF) limit its availability to infertile couples. Dawson and Singer question whether it is reasonable to so restrict access to IVF, and examine some of the medical and social circumstances in which IVF and the related procedures of embryo freezing, embryo biopsy, and embryo transfer might be used by the fertile. They argue that while society may object to some uses of IVF by the fertile, the principle of governmental non-interference with personal liberties except to prevent harm mitigate against legally restricting IVF to the infertile.

Preterm delivery risk factors in singletons born after in vitro fertilization procedures.

PubMed

Ban Frangez, Helena; Korosec, Sara; Verdenik, Ivan; Kotar, Vanja; Kladnik, Urska; Vrtacnik Bokal, Eda

2014-05-01

Women delivering singletons after in vitro fertilization (IVF) procedures have a greater risk of preterm delivery (PD). The aim of our study was to analyze PD risk factors and to identify those that could possibly be prevented. In our matched controlled study we analyzed 1127 singleton deliveries after IVF and transfer of fresh embryos performed at the University Medical Center Ljubljana between 1 January 2002 and 31 December 2010. For every delivery included in the study group we chose three consecutive controls matched by maternal age, parity and maternity hospital. The main outcome measure was PD (<37 weeks). Investigated variables were: previous PD (PPD), conization, pregestational diabetes mellitus, uterine anomaly, operation on the uterus, chronic renal disease, maternal age and parity, and body mass index (BMI). Variables investigated within the IVF group were: stimulation protocol, laboratory procedure, number of retrieved oocytes and number and quality of transferred embryos. The PD rate after IVF was 1.5 times higher than after natural conception (11.5% in the IVF group and 7.7% in the control group, p<0.001). Conization and chronic renal disease were shown to be significant risk factors for PD in both the IVF group and the naturally conceiving controls. BMI>30 was an important risk factor only in the IVF group (OR 1.86 (1.06-3.27) vs. 1.10 (0.67-1.80)) and PPD only in the controls (OR 1.83 (0.78-4.28) vs. 3.22 (1.55-6.67)). Among the investigated PD risk factors, an IVF procedure was shown to be the fifth most important one. On analyzing parameters of the ovarian stimulation and IVF procedure, no PD risk factor was identified. IVF was shown to be a significant risk factor for PD. In the IVF population, BMI plays a far more important role in PD than in the fertile population. In our research PD reoccurrence in IVF group was less than expected, which could perhaps be explained by the surgical correction of gynecological pathology and, where necessary, its being combined with cerclage. The investigation of parameters related to the IVF procedure did not identify any risk factors for PD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Live birth of twins after IVF of oocytes that were cryopreserved almost 12 years before.

PubMed

Quintans, Carlos J; Donaldson, Monica J; Urquiza, M Fernanda; Carretero, Inés; Pasqualini, R Agustín; Horton, Marcos; Pasqualini, R Sergio

2012-12-01

A 45-year-old woman received embryos from IVF by intracytoplasmic sperm injection (ICSI) with her own oocytes that were cryopreserved (slow freezing in a low-sodium medium) 11 years and 7 and a half months before, when she was 33 years old. From seven metaphase-II oocytes thawed, five survived, four were fertilized after ICSI and two cleaving embryos were transferred on day 3. A diamniotic dichorionic term pregnancy was achieved, ending with the delivery of two healthy girls. As far as is known, this case represents, to date, the longest storage period of cryopreserved human oocytes resulting in a live birth. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. 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.

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.

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.

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.

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.

Freeze-all cycle for all normal responders?

PubMed

Roque, Matheus; Valle, Marcello; Guimarães, Fernando; Sampaio, Marcos; Geber, Selmo

2017-02-01

The purpose of this study is to evaluate the freeze-all strategy in subgroups of normal responders, to assess whether this strategy is beneficial regardless of ovarian response, and to evaluate the possibility of implementing an individualized embryo transfer (iET) based on ovarian response. This was an observational, cohort study performed in a private IVF center. A total of 938 IVF cycles were included in this study. The patients were submitted to controlled ovarian stimulation (COS) with a gonadotropin-releasing hormone (GnRH) antagonist protocol and a cleavage-stage day 3 embryo transfer. We performed a comparison of outcomes between the fresh embryo transfer (n = 523) and the freeze-all cycles (n = 415). The analysis was performed in two subgroups of patients based on the number of retrieved oocytes: Group 1 (4-9 oocytes) and Group 2 (10-15 oocytes). In Group 1 (4-9 retrieved oocytes), the implantation rates (IR) were 17.9 and 20.5% (P = 0.259) in the fresh and freeze-all group, respectively; the ongoing pregnancy rates (OPR) were 31 and 33% (P = 0.577) in the fresh and freeze-all group, respectively. In Group 2 (10-15 oocytes), the IR were 22.1 and 30.1% (P = 0.028) and the OPR were 34 and 47% (P = 0.021) in the fresh and freeze-all groups, respectively. Although the freeze-all policy may be related to better in vitro fertilization (IVF) outcomes in normal responders, these potential advantages decrease with worsening ovarian response. Patients with poorer ovarian response do not benefit from the freeze-all strategy.

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.

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.

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.

Occurrence of maternal and paternal spindles in unfertilized human oocytes: possible relationship to nucleation defects after silent fertilization.

PubMed

Van Blerkom, Jonathan; Davis, Patrick; Alexander, Samuel

2004-04-01

Experience with conventional clinical IVF indicates that a first cleavage can occur in the absence of detectable pronuclear formation (so-called silent fertilization). In these instances, the first division is often asymmetrical and delayed when compared with normally fertilized siblings. In this study, DNA configurations and spindle organization were examined by fluorescence microscopy in metaphase II human oocytes that remained unfertilized after conventional IVF and were considered likely candidates for silent fertilization. The results show comparatively high frequencies of penetration in the absence of detectable pronuclear evolution, and that both a maternal meiotic and a sperm-derived mitotic-like spindle can coexist in the same oocyte. Patterns of cell division and blastomere nucleation in silent fertilizations suggest the possibility that this division may involve uniparental chromosomal segregation in which maternal and paternal DNA is differentially partitioned into daughter blastomeres. This pattern of inheritance may generate certain types of ploidy and nucleation defects detected at the 2- to 4-cell stage.

The incidence of histological chorioamnionitis in IVF/GIFT preterm births.

PubMed

Williams, H; Jeffery, H

1994-08-01

A retrospective case control study was designed to investigate the role of subclinical infection as a risk factor for the high rate of preterm deliveries in IVF/GIFT pregnancies. The cases and the controls were identified from the records of consecutive livebirths of < 35 weeks' gestational age (GA), at King George V Hospital from 1987-1993. Fifty one singleton and 58 twin IVF/GIFT preterm births were matched for GA, year of birth, plurality, maternal age, parity, preclampsia and antepartum haemorrhage. As a marker of subclinical infection, the incidence of histological chorioamnionitis (HCA) in the 2 groups (as defined by the standardized, semiquantitative method of Benirschke) was compared. The matched variables did not differ significantly between the IVF/GIFT group and the control group. No significant difference in the incidence of HCA was detected between IVF/GIFT and control groups for singletons or twins. Overall 24% of IVF/GIFT and 30% of controls showed evidence of HCA, odds ratio (95% confidence intervals), 0.72 (0.40-1.31). This study showed no evidence that the incidence of HCA, is significantly increased in IVF/GIFT preterm births compared with other matched, preterm births. Therefore, we conclude that subclinical infection/inflammation cannot explain the 4-fold increase in preterm births in the IVF/GIFT population.

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.

Parental adjustment and attitudes to parenting after in vitro fertilization.

PubMed

Gibson, F L; Ungerer, J A; Tennant, C C; Saunders, D M

2000-03-01

To examine the psychosocial and parenthood-specific adjustment and attitudes to parenting at 1 year postpartum of IVF parents. Prospective, controlled study. Volunteers in a teaching hospital environment. Sixty-five primiparous women with singleton IVF pregnancies and their partners, and a control group of 61 similarly aged primiparous women with no history of infertility and their partners. Completion of questionnaires and interviews. Parent reports of general and parenthood-specific adjustment and attitudes to parenting. The IVF mothers tended to report lower self-esteem and less parenting competence than control mothers. Although there were no group differences on protectiveness, IVF mothers saw their children as significantly more vulnerable and "special" compared with controls. The IVF fathers reported significantly lower self-esteem and marital satisfaction, although not less competence in parenting. Both IVF mothers and fathers did not differ from control parents on other measures of general adjustment (mood) or those more specific to parenthood (e.g., attachment to the child and attitudes to child rearing). The IVF parents' adjustment to parenthood is similar to naturally conceiving comparison families. Nonetheless, there are minor IVF differences that reflect heightened child-focused concern and less confidence in parenting for mothers, less satisfaction with the marriage for the fathers, and vulnerable self-esteem for both parents.

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.

77 FR 47693 - Pilot Program on NAFTA Trucking Provisions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-09

..., including confirming the validity of each driver's Licencia Federal de Conductor and English language..., Section IV(f)). Factor 1 includes the General Requirements outlined in parts 387 (Minimum Levels of... of Drivers and Longer Combination Vehicle (LCV) Driver Instructors). O. Passed Phase 1, Factor 3: A...

78 FR 20373 - Pilot Program on NAFTA Trucking Provisions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-04

..., including confirming the validity of each driver's Licencia Federal de Conductor and English language..., Section IV(f)). Factor 1 includes the General Requirements outlined in parts 387 (Minimum Levels of... of Drivers and Longer Combination Vehicle (LCV) Driver Instructors). O. Passed Phase 1, Factor 3: A...

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

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.

Pregnancy rate and birth rate of calves from a large-scale IVF program using reverse-sorted semen in Bos indicus, Bos indicus-taurus, and Bos taurus cattle.

PubMed

Morotti, F; Sanches, B V; Pontes, J H F; Basso, A C; Siqueira, E R; Lisboa, L A; Seneda, M M

2014-03-15

Obtaining sexed sperm from previously frozen doses (reverse-sorted semen [RSS]) provides an important advantage because of the possibility of using the semen of bulls with desired genetic attributes that have died or have become infertile but from whom frozen semen is available. We report the efficiency of RSS on the pregnancy rate and birth rate of calves in a large-scale program using ovum pick-up and in vitro embryo production (IVEP) from Bos indicus, Bos indicus-taurus, and Bos taurus cattle. From 645 ovum pick-up procedures (Holstein, Gir, and Nelore), 9438 viable oocytes were recovered. A dose of frozen semen (Holstein, Nelore, Brahman, Gir, and Braford) was thawed, and the sperm were sex-sorted and cooled for use in IVF. Additionally, IVF with sperm from three Holstein bulls with freeze-thawed, sex-sorted (RSS) or sex-sorted, freeze-thawed (control) was tested. A total of 2729 embryos were produced, exhibiting a mean blastocyst rate of 29%. Heifers and cows selected for adequate body condition, estrus, and health received 2404 embryos, and 60 days later, a 41% average pregnancy rate was observed. A total of 966 calves were born, and 910 were of a predetermined sex, with an average of 94% accuracy in determining the sex. Despite the lower blastocyst rate with freeze-thawed, sex-sorted semen compared with sex-sorted semen, (P < 0.05), the pregnancy rate (bull I, 45% vs. 40%; II, 35% vs. 50%; and III, 47% vs. 48% for RSS and control, respectively; P > 0.05) and sex-sorted efficiency (bull I, 93% vs. 98%; II, 96% vs. 94%; and III, 96% vs. 97% for RSS and control, respectively; P > 0.05) were similar for each of the three bulls regardless of the sperm type used in the IVF. The sexing of previously frozen semen, associated with IVEP, produces viable embryos with a pregnancy rate of up to 40%, and calves of the desired sex are born even if the paternal bull has acquired some infertility, died, or is located a long distance from the sexing laboratory. Furthermore, these data show the feasibility of the process even when used in a large-scale IVEP program. Copyright © 2014 Elsevier Inc. All rights reserved.

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.

The clinical significance of calcium-signalling pathways mediating human sperm hyperactivation

PubMed Central

Alasmari, Wardah; Barratt, Christopher L.R.; Publicover, Stephen J.; Whalley, Katherine M.; Foster, Erica; Kay, Vanessa; Martins da Silva, Sarah; Oxenham, Senga K.

2013-01-01

STUDY QUESTION What is the prevalence of defects in the Ca2+-signalling pathways mediating hyperactivation (calcium influx and store mobilization) among donors and sub-fertile patients and are they functionally significant, i.e. related to fertilization success at IVF? SUMMARY ANSWER This study identifies, for the first time, the prevalence of Ca2+ store defects in sperm from research donors, IVF and ICSI patients. It highlights the biological role and importance of Ca2+ signalling (Ca2+ store mobilization) for fertilization at IVF. WHAT IS KNOWN ALREADY Sperm motility and hyperactivation (HA) are important for fertility, mice with sperm incapable of HA are sterile. Recently, there has been significant progress in our knowledge of the factors controlling these events, in particular the generation and regulation of calcium signals. Both pH-regulated membrane Ca2+ channels (CatSper) and Ca2+ stores (potentially activating store-operated Ca2+ channels) have been implicated in controlling HA. STUDY DESIGN, SIZE, AND DURATION This was a prospective study examining a panel of 68 donors and 181 sub-fertile patients attending the Assisted Conception Unit, Ninewells Hospital Dundee for IVF and ICSI. Twenty-five of the donors gave a second sample (∼4 weeks later) to confirm consistency/reliability of the recorded responses. Ca2+ signalling was manipulated using three agonists, NH4Cl (activates CatSper via pH), progesterone (direct activation of CatSper channels, potentially enhancing mobilization of stored Ca2+ by CICR) and 4-aminopyridine (4-AP) (effect on pH equivalent to NH4Cl and mobilizes stored Ca2+). The broad-spectrum phosphodiesterase inhibitor 3-isobutyl-1-methyxanthine (IBMX), a potent activator of HA was also used for comparison. For patient samples, an aliquot surplus to requirements for IVF/ICSI treatment was examined, allowing direct comparison of Ca2+ signalling and motility data with functional competence of the sperm. MATERIALS, SETTING, METHODS The donors and sub-fertile patients were screened for HA (using CASA) and changes in intracellular Ca2+ were assessed by loading with Fura-2 and measuring fluorescence using a plate reader (FluoStar). MAIN RESULTS AND THE ROLE OF CHANCE The relative efficacy of the stimuli in inducing HA was 4-AP >> IBMX > progesterone. NH4Cl increased [Ca2+]i similarly to 4-AP and progesterone but did not induce a significant increase in HA. Failure of samples to generate HA (no significant increase in response to stimulation with 4-AP) was seen in just 2% of research donors but occurred in 10% of IVF patients (P = 0.025). All donor samples generated a significant [Ca2+]i increase when stimulated with 4-AP but 3.3% of IVF and 28.6% of ICSI patients failed to respond. Amplitudes of HA and [Ca2+]i responses to 4-AP were correlated with fertilization rate at IVF (P= 0.029; P = 0.031, respectively). Progesterone reliably induced [Ca2+]i responses (97% of donors, 100% of IVF patients) but was significantly less effective than 4-AP in inducing HA. Twenty seven per cent of ICSI patients failed to generate a [Ca2+]i response to progesterone (P= 0.035). Progesterone-induced [Ca2+]i responses were correlated with fertilization rate at IVF (P= 0.037) but induction of HA was not. In donor samples examined on more than one occasion consistent responses for 4-AP-induced [Ca2+]i (R2 = 0.97) and HA (R2 = 0.579) were obtained. In summary, the data indicate that defects in Ca2+ signalling leading to poor HA do occur and that ability to undergo Ca2+ -induced HA affects IVF fertilizing capacity. The data also confirm that release of stored Ca2+ is the crucial component of Ca2+ signals leading to HA and that Ca2+ store defects may therefore underlie HA failure. LIMITATIONS, REASONS FOR CAUTION This is an in vitro study of sperm function. While the repeatability of the [Ca2+]i and HA responses in samples from the same donor were confirmed, data for patients were from 1 assessment and thus the robustness of the failed responses in patients’ needs to be established. The focus of this study was on using 4AP, which mobilizes stored Ca2+ and is a potent inducer of HA. The n values for other agonists, especially calcium assessments, are smaller. WIDER IMPLICATIONS OF THE FINDINGS Previous studies have shown a significant relationship between basal levels of HA, calcium responses to progesterone and IVF fertilization rates. Here, we have systematically investigated the ability/failure of human sperm to generate Ca2+ signals and HA in response to targeted pharmacological challenge and, related defects in these responses to IVF success. [Ca2+]i signalling is fundamental for sperm motility and data from this study will lead to assessment of the nature of these defects using techniques such as single-cell imaging and patch clamping. STUDY FUNDING/COMPETING INTEREST(S) Resources from a Wellcome Trust Project Grant (#086470, Publicover and Barratt PI) primarily funded the study. The authors have no competing interests. PMID:23406974

Selection of Suitable Internal Control Genes for Accurate Normalization of Real-Time Quantitative PCR Data of Buffalo (Bubalus bubalis) Blastocysts Produced by SCNT and IVF.

PubMed

Sood, Tanushri Jerath; Lagah, Swati Viviyan; Sharma, Ankita; Singla, Suresh Kumar; Mukesh, Manishi; Chauhan, Manmohan Singh; Manik, Radheysham; Palta, Prabhat

2017-10-01

We evaluated the suitability of 10 candidate internal control genes (ICGs), belonging to different functional classes, namely ACTB, EEF1A1, GAPDH, HPRT1, HMBS, RPS15, RPS18, RPS23, SDHA, and UBC for normalizing the real-time quantitative polymerase chain reaction (qPCR) data of blastocyst-stage buffalo embryos produced by hand-made cloning and in vitro fertilization (IVF). Total RNA was isolated from three pools, each of cloned and IVF blastocysts (n = 50/pool) for cDNA synthesis. Two different statistical algorithms geNorm and NormFinder were used for evaluating the stability of these genes. Based on gene stability measure (M value) and pairwise variation (V value), calculated by geNorm analysis, the most stable ICGs were RPS15, HPRT1, and ACTB for cloned blastocysts, HMBS, UBC, and HPRT1 for IVF blastocysts and RPS15, GAPDH, and HPRT1 for both the embryo types analyzed together. RPS18 was the least stable gene for both cloned and IVF blastocysts. Following NormFinder analysis, the order of stability was RPS15 = HPRT1>GAPDH for cloned blastocysts, HMBS = UBC>RPS23 for IVF blastocysts, and HPRT1>GAPDH>RPS15 for cloned and IVF blastocysts together. These results suggest that despite overlapping of the three most stable ICGs between cloned and IVF blastocysts, the panel of ICGs selected for normalization of qPCR data of cloned and IVF blastocyst-stage embryos should be different.

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

Effect of in-utero diethylstilboestrol exposure on human oocyte quality and fertilization in a programme of in-vitro fertilization.

PubMed

Kerjean, A; Poirot, C; Epelboin, S; Jouannet, P

1999-06-01

Genital tract abnormalities and adverse pregnancy outcome are well known in women exposed in utero to diethylstilboestrol (DES). Data about adverse reproductive performance in women exposed to DES have been published, including controversial reports of menstrual dysfunction, poor responses after ovarian stimulation, oocyte maturation and fertilization abnormalities. We compared oocyte quality, in-vitro fertilization results and embryo quality for women exposed in utero to DES with a control group. Between 1989 and 1996, 56 DES-exposed women who had 125 in-vitro fertilization (IVF) attempts were retrospectively compared to a control group of 45 women with tubal disease, who underwent 73 IVF attempts. Couples suffering from male infertility were excluded. The parameters compared were oocyte quality (maturation abnormalities, immature oocyte, mature oocyte), fertilization and cleavage rate (per treated and metaphase II oocytes), and embryo quality (number and grade). We found no significant difference in oocyte maturational status, fertilization rates, cleavage rates, embryo quality and development between DES-exposed subjects and control subjects. These results suggest that in-utero exposure to DES has no significant influence on oocyte quality and fertilization ability as judged during IVF attempts.

Absence of luteal phase defect and spontaneous pregnancy in IVF patients despite GnRH-agonist trigger and "freeze all policy" without luteal phase support: a report of four cases.

PubMed

Gurbuz, Ali Sami; Deveer, Ruya; Ozcimen, Necati; Ozcimen, Emel Ebru; Lawrenz, Barbara; Banker, Manish; Garcia-Velasco, Juan Antonio; Fatemi, Human Mousavi

2016-01-01

Human chorionic gonadotropin (hCG) is commonly used for final oocyte maturation in "in vitro fertilization" (IVF)-treatment cycles, however, the main important risk is development of severe ovarian hyperstimulation syndrome (OHSS). OHSS can almost be avoided by using gonadotrophin-releasing-hormone agonist for final oocyte maturation in an antagonist protocol. However, primarily this approach lead to a very poor reproductive outcome, despite the use of a standard luteal phase support. The reason seems to be severe luteolysis. Obviously, luteolysis post-gonadotropin-releasing-hormone-agonist (post-GnRH-a) trigger is individual specific, and not all patients will develop a complete luteolysis, as expected previously. Luteolysis can been reverted by the administration of hCG. Unprotected intercourse around the time of ovulation induction and oocyte retrieval can lead to a spontaneous conception in IVF treatment and, endogenous hCG, produced by the trophoblast, will rescue the corpora lutea. Therefore, one should not rely on complete luteolysis after GnRH-a triggering and, especially patients for egg donation and pre-implantation-genetic diagnosis for single gene disorder, have to be counselled to avoid unprotected intercourse.

Candidate selection and psychosocial considerations of in-vitro fertilization procedures.

PubMed

Greenfeld, D; Haseltine, F

1986-03-01

The psychological impact of the new reproductive technology should not be understated. The history of infertility treatment and failure to achieve pregnancy that most couples bring to the program, along with their hopes and expectations for success, makes them extremely vulnerable to anxiety, unrealistic expectations, and grief reactions. When a cycle of IVF fails, the intensity of the experience and the disappointment may be overwhelming for a while, but most couples are willing to try it again. One patient wrote about her feelings after IVF treatment after having read comments in a popular magazine which implied that medical science was taking control of reproduction. Those of us who go through in-vitro fertilization think long and hard about what we are doing. Most of us weigh the pros and cons very thoroughly. We weigh the risks to our potential children just as people who have genetically linked diseases do before they conceive. (Our fetuses are not "bombarded" by ultrasound procedures any more than many other pregnant women's fetuses are these days.) Most of us are thankful that the technology is now available to us, if we choose to participate. Physicians who work with IVF patients do realize that the procedure is stressful. Often the stress is viewed as primarily the patients', and we are asked to study the level of stress. To a large extent that is the subject matter of this chapter. Nevertheless, the stress is perceived because the physicians and staff are also under stress. The failure of an IVF cycle is immediately known to the health care givers.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Hysteroscopic Findings in Patients with A History of Two Implantation Failures Following In Vitro Fertilization

PubMed Central

Moini, Ashraf; Kiani, Kiandokht; Ghaffari, Firouzeh; Hosseini, Fatemeh

2012-01-01

Background This study was designed to evaluate the incidence of uterine pathologies in infertile women with a history of two implantation failures after in vitro fertilization (IVF) and estimate the effect of hysteroscopic correction on achieving a pregnancy in these patients. Materials and Methods The retrospective study population included 238 infertile women attended the outpatient infertility clinic between November 2007 and December 2008. Patients with at least two previous IVF failures were eligible for this study. All patients had normal findings on hysterosalpingography performed prior their first attempt for IVF. Standard transvaginal ultrasonography and diagnostic hysteroscopy were performed in patients before the subsequent IVF attempt. Results Out of 238 patients with previous IVF failure who underwent hysteroscopic evaluation, 158 patients (66.4%) showed normal uterine cavity. Abnormal cavity was found in 80 patients (33.6%). We found polyp as the most common abnormality (19.7%) in the patients with previous history of IVF failure. The pregnancy rate was similar between IVF failure patients who treated by hysteroscopy for a detected uterine abnormality (24.6%) and similar patients with normal uterine cavity (21.2%) in hysteroscopic examinations. Conclusion The intrauterine lesions diagnosed by hysteroscopy in patients with previous IVF failure ranges from 0.8%-19.7%. Correction of abnormalities such as myoma and polyp showed good outcome, similar to that achieved in patients with a normal hysteroscopy. PMID:25505508

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

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.

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.

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.

Eliminating Preventable Death on the Battlefield

DTIC Science & Technology

2011-08-15

Phases of Tactical Combat Casualty Care Between October 1, 2001, and March 31, 2010 Intervention IVF Dose, mL Casualties, No. Saline lock only NA 35...Saline lock and IVF NA 55 Normal saline 250 1 500 25a 1000 6 1500 1 Hextendb 250 2 500 12a,c 1000 1 Normal salineHextendb 500500 3 1000250 1 500100...1a Lactated ringers 500 2a Abbreviations: IVF , intravenous fluid; NA, not applicable. aFour casualties received 2 saline locks and IVF . bHextend is

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.

Electronic witness system in IVF-patients perspective.

PubMed

Forte, Marina; Faustini, Federica; Maggiulli, Roberta; Scarica, Catello; Romano, Stefania; Ottolini, Christian; Farcomeni, Alessio; Palagiano, Antonio; Capalbo, Antonio; Ubaldi, Filippo Maria; Rienzi, Laura

2016-09-01

The objective of this study is to evaluate patient concerns about in vitro fertilization (IVF) errors and electronic witness systems (EWS) satisfaction. The design of this study is a prospective single-center cohort study. The setting of this study was located in the private IVF center. Four hundred eight infertile patients attending an IVF cycle at a GENERA center in Italy were equipped with an EWS. Although generally recognized as a very rare event in IVF, biological sample mix-up has been reported in the literature. For this reason, some IVF laboratories have introduced EWS with the aim to further reduce the risk of error during biological samples handling. Participating patients received a questionnaire developed through a Likert scale ranging from 1 to 6. Patient concerns about sample mix-up without and with an EWS were assessed. 90.4 % of patients expressed significant concerns relating to sample mix-up. The EWS reduced these concerns in 92.1 % of patients, 97.1 % of which were particularly satisfied with the electronic traceability of their gametes and embryos in the IVF laboratory. 97.1 % of patients felt highly comfortable with an IVF center equipped with an EWS. Female patients had a significantly higher appreciation of the EWS when compared to their male partners (p = 0.029). A significant mix-up event occurred in an Italian hospital during the study and patient's satisfaction increased significantly towards the use of the EWS after the event (p = 0.032). EWS, by sensibly reducing the risk for sample mix-up in IVF cycles, has been proved to be a trusted strategy from patient's perspective.

The Association of Glaucomatous Visual Field Loss and Balance

PubMed Central

de Luna, Regina A.; Mihailovic, Aleksandra; Nguyen, Angeline M.; Friedman, David S.; Gitlin, Laura N.; Ramulu, Pradeep Y.

2017-01-01

Purpose To relate balance measures to visual field (VF) damage from glaucoma. Methods The OPAL kinematic system measured balance, as root mean square (RMS) sway, on 236 patients with suspect/diagnosed glaucoma. Balance was measured with feet shoulder width apart while standing on a firm/foam surface with eyes opened/closed (Instrumental Clinical Test of Sensory Integration and Balance [ICTSIB] conditions), and eyes open on a firm surface under feet together, semi-tandem, or tandem positions (standing balance conditions). Integrated VF (IVF) sensitivities were calculated by merging right and left eye 24-2 VF data. Results Mean age was 71 years (range, 57–93) and mean IVF sensitivity was 27.1 dB (normal = 31 dB). Lower IVF sensitivity was associated with greater RMS sway during eyes-open foam-surface testing (β = 0.23 z-score units/5 dB IVF sensitivity decrement, P = 0.001), but not during other ICTSIB conditions. Lower IVF sensitivity also was associated with greater RMS sway during feet together standing balance testing (0.10 z-score units/5 dB IVF sensitivity decrement, P = 0.049), but not during other standing balance conditions. Visual dependence of balance was lower in patients with worse IVF sensitivity (β = −21%/5 dB IVF sensitivity decrement, P < 0.001). Neither superior nor inferior IVF sensitivity consistently predicted balance measures better than measures of overall VF sensitivity. Conclusions Balance was worse in glaucoma patients with greater VF damage under foam surface testing (designed to inhibit proprioceptive contributions to balance) as well as feet-together firm-surface conditions when somatosensory inputs were available. Translational Relevance Good balance is essential to avoid unnecessary falls and patients with VF loss from glaucoma may be at higher risk of falls because of poor balance. PMID:28553562

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.

Phytonadione Content in Branded Intravenous Fat Emulsions.

PubMed

Forchielli, Maria Luisa; Conti, Matteo; Motta, Roberto; Puggioli, Cristina; Bersani, Germana

2017-03-01

Intravenous fat emulsions (IVFE) with different fatty acid compositions contain vitamin E as a by-product of vegetable and animal oil during the refining processes. Likewise, other lipid-soluble vitamins may be present in IVFE. No data, however, exist about phytonadione (vitamin K1) concentration in IVFE information leaflets. Therefore, our aim was to evaluate the phytonadione content in different IVFE. Analyses were carried out in triplicate on 6 branded IVFE as follows: 30% soybean oil (100%), 20% olive-soybean oil (80%-20%), 20% soybean-medium-chain triglycerides (MCT) coconut oil (50%-50%), 20% soybean-olive-MCT-fish oil (30%-25%-30%-15%), 20% soybean-MCT-fish oil (40%-50%-10%), and 10% pure fish oil (100%). Phytonadione was analyzed and quantified by a quali-quantitative liquid chromatography-mass spectrometry (LC-MS) method after its extraction from the IVFE by an isopropyl alcohol-hexane mixture, reverse phase-liquid chromatography, and specific multiple-reaction monitoring for phytonadione and vitamin d3 (as internal standard). This method was validated through specificity, linearity, and accuracy. Average vitamin K1 content was 500, 100, 90, 100, 95, and 70 µg/L in soybean oil, olive-soybean oil, soybean-MCT coconut oil, soybean-olive-MCT-fish oil, soybean-MCT-fish oil, and pure fish oil intravenous lipid emulsions (ILEs), respectively. The analytical LC-MS method was extremely effective in terms of specificity, linearity ( r = 0.99), and accuracy (coefficient of variation <5%). Phytonadione is present in IVFE, and its intake varies according to IVFE type and the volume administered. It can contribute to daily requirements and become clinically relevant when simultaneously infused with multivitamins during long-term parenteral nutrition. LC-MS seems adequate in assessing vitamin K1 intake in IVFE.

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.

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.

High gonadotropin dosage does not affect euploidy and pregnancy rates in IVF PGS cycles with single embryo transfer.

PubMed

Barash, Oleksii O; Hinckley, Mary D; Rosenbluth, Evan M; Ivani, Kristen A; Weckstein, Louis N

2017-11-01

Does high gonadotropin dosage affect euploidy and pregnancy rates in PGS cycles with single embryo transfer? High gonadotropin dosage does NOT affect euploidy and pregnancy rates in PGS cycles with single embryo transfer. PGS has been proven to be the most effective and reliable method for embryo selection in IVF cycles. Euploidy and blastulation rates decrease significantly with advancing maternal age. In order to recruit an adequate number of follicles, the average dosage of gonadotropins administered during controlled ovarian stimulation in IVF cycles often increases significantly with advancing maternal age. A retrospective study of SNP (Single Nucleotide Polymorphism) PGS outcome data from blastocysts biopsied on day 5 or day 6 was conducted to identify differences in euploidy and clinical pregnancy rates. Seven hundred and ninety four cycles of IVF treatment with PGS between January 2013 and January 2017 followed by 651 frozen embryo transfers were included in the study (506 patients, maternal age (y.o.) - 37.2 ± 4.31). A total of 4034 embryos were analyzed (5.1 ± 3.76 per case) for euploidy status. All embryos were vitrified after biopsy, and selected embryos were subsequently thawed for a hormone replacement frozen embryo transfer cycle. All cycles were analyzed by total gonadotropin dosage (<3000 IU, 3000-5000 IU and >5000 IU), by number of eggs retrieved (1-5, 5-10, 10-15 and >15 eggs) and patient's age (<35, 35-37, 38-40 and ≥41 y.o.). Clinical pregnancy rate was defined by the presence of a fetal heartbeat at 6-7 weeks of gestation. Euploidy rates within the same age group were not statistically different regardless of the total dosage of gonadotropins used or the number of eggs retrieved. In the youngest group of patients (<35 y.o. - 187 IVF cycles) euploidy rates ranged from 62.3% (<3000 IU were used in the IVF cycle) to 67.5% (>5000 IU were used in the IVF cycle) (OR = 0.862, 95% CI 0.687-1.082, P = 0.2) and from 69.5% (1-5 eggs retrieved) to 60.0% (>15 eggs retrieved) (OR = 0.658, 95% CI 0.405-1.071, P = 0.09). Similar data were obtained in the oldest group of patients (≥41 y.o. - 189 IVF cycles): euploidy rates ranged from 30.7 to 26.4% (OR = 0.811, 95% CI 0.452-1.454, P = 0.481) when analyzed by total dosage of gonadotropins used in the IVF cycle and from 40.0 to 30.7% (OR = 0.531, 95% CI 0.204-1.384, P = 0.19), when assessed by the total number of eggs retrieved. Ongoing pregnancy rates were similar, not only within particular age groups, but also between different age groups regardless of the total dosage of gonadotropins used: ranging from to 63.6% (<3000 IU, < 35 y.o.) to 54.8% (>5000 IU, ≥41 y.o) (OR = 0.696, 95% CI 0.310-1.565, P = 0.38). Retrospective study and heterogeneity of patients included. These data are reassuring for the common practice of increasing gonadotropin dosages in PGS cycles, particularly in older woman. No formal funding has been received for this study. N/A. © 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

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.

Assisted reproductive technology in the United States: 2001 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology registry.

PubMed

2007-06-01

To summarize the procedures and outcomes of assisted reproductive technologies (ART) that were initiated in the United States in 2001. Data were collected electronically using the Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System software and submitted to the American Society for Reproductive Medicine/SART Registry. Three hundred eighty-five clinics submitted data on procedures performed in 2001. Data were collated after November 2002 [corrected] so that the outcomes of all pregnancies would be known. Incidence of clinical pregnancy, ectopic pregnancy, abortion, stillbirth, and delivery. Programs reported initiating 108,130 cycles of ART treatment. Of these, 79,042 cycles involved IVF (with and without micromanipulation), with a delivery rate per retrieval of 31.6%; 340 were cycles of gamete intrafallopian transfer, with a delivery rate per retrieval of 21.9%; 661 were cycles of zygote intrafallopian transfer, with a delivery rate per retrieval of 31.0%. The following additional ART procedures were also initiated: 8,147 fresh donor oocyte cycles, with a delivery rate per transfer of 47.3%; 14,509 frozen ET procedures, with a delivery rate per transfer of 23.5%; 3,187 frozen ETs employing donated oocytes or embryos, with a delivery rate per transfer of 27.4%; and 1,366 cycles using a host uterus, with a delivery rate per transfer of 38.7%. In addition, 112 cycles were reported as combinations of more than one treatment type, 8 cycles as research, and 85 as embryo banking. As a result of all procedures, 29,585 deliveries were reported, resulting in 41,168 neonates. In 2001, there were more programs reporting ART treatment and a significant increase in reported cycles compared with 2000.

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

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/.

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.

The search for biomarkers of human embryo developmental potential in IVF: a comprehensive proteomic approach.

PubMed

Nyalwidhe, Julius; Burch, Tanya; Bocca, Silvina; Cazares, Lisa; Green-Mitchell, Shamina; Cooke, Marissa; Birdsall, Paige; Basu, Gaurav; Semmes, O John; Oehninger, Sergio

2013-04-01

The objective of these studies was to identify differentially expressed peptides/proteins in the culture media of embryos grown during in vitro fertilization (IVF) treatment to establish their value as biomarkers predictive of implantation potential and live birth. Micro-droplets of embryo culture media from IVF patients (conditioned) and control media maintained under identical culture conditions were collected and frozen at -80°C on Days 2-3 of in vitro development prior to analysis. The embryos were transferred on Day 3. The peptides were affinity purified based on their physico-chemical properties and profiled by mass spectrometry for differential expression. The identified proteins were further characterized by western blot and ELISA, and absolute quantification was achieved by multiple reaction monitoring (MRM). We identified up to 14 differentially regulated peptides after capture using paramagnetic beads with different affinities. These differentially expressed peptides were used to generate genetic algorithms (GAs) with a recognition capability of 71-84% for embryo transfer cycles resulting in pregnancy and 75-89% for those with failed implantation. Several peptides were further identified as fragments of Apolipoprotein A-1, which showed consistent and significantly reduced expression in the embryo media samples from embryo transfer cycles resulting in viable pregnancies. Western blot and ELISA, as well as quantitative MRM results, were confirmatory. These results demonstrated that peptide/protein profiles from the culture medium during early human in vitro development can discriminate embryos with highest and lowest implantation competence following uterine transfer. Further prospective studies are needed to establish validated thresholds for clinical application.

Identification of the Inorganic Pyrophosphate Metabolizing, ATP Substituting Pathway in Mammalian Spermatozoa

PubMed Central

Yi, Young-Joo; Sutovsky, Miriam; Kennedy, Chelsey; Sutovsky, Peter

2012-01-01

Inorganic pyrophosphate (PPi) is generated by ATP hydrolysis in the cells and also present in extracellular matrix, cartilage and bodily fluids. Fueling an alternative pathway for energy production in cells, PPi is hydrolyzed by inorganic pyrophosphatase (PPA1) in a highly exergonic reaction that can under certain conditions substitute for ATP-derived energy. Recombinant PPA1 is used for energy-regeneration in the cell-free systems used to study the zymology of ATP-dependent ubiquitin-proteasome system, including the role of sperm-borne proteasomes in mammalian fertilization. Inspired by an observation of reduced in vitro fertilization (IVF) rates in the presence of external, recombinant PPA1, this study reveals, for the first time, the presence of PPi, PPA1 and PPi transporter, progressive ankylosis protein ANKH in mammalian spermatozoa. Addition of PPi during porcine IVF increased fertilization rates significantly and in a dose-dependent manner. Fluorometric assay detected high levels of PPi in porcine seminal plasma, oviductal fluid and spermatozoa. Immunofluorescence detected PPA1 in the postacrosomal sheath (PAS) and connecting piece of boar spermatozoa; ANKH was present in the sperm head PAS and equatorial segment. Both ANKH and PPA1 were also detected in human and mouse spermatozoa, and in porcine spermatids. Higher proteasomal-proteolytic activity, indispensable for fertilization, was measured in spermatozoa preserved with PPi. The identification of an alternative, PPi dependent pathway for ATP production in spermatozoa elevates our understanding of sperm physiology and sets the stage for the improvement of semen extenders, storage media and IVF media for animal biotechnology and human assisted reproductive therapies. PMID:22485177

Identification of the inorganic pyrophosphate metabolizing, ATP substituting pathway in mammalian spermatozoa.

PubMed

Yi, Young-Joo; Sutovsky, Miriam; Kennedy, Chelsey; Sutovsky, Peter

2012-01-01

Inorganic pyrophosphate (PPi) is generated by ATP hydrolysis in the cells and also present in extracellular matrix, cartilage and bodily fluids. Fueling an alternative pathway for energy production in cells, PPi is hydrolyzed by inorganic pyrophosphatase (PPA1) in a highly exergonic reaction that can under certain conditions substitute for ATP-derived energy. Recombinant PPA1 is used for energy-regeneration in the cell-free systems used to study the zymology of ATP-dependent ubiquitin-proteasome system, including the role of sperm-borne proteasomes in mammalian fertilization. Inspired by an observation of reduced in vitro fertilization (IVF) rates in the presence of external, recombinant PPA1, this study reveals, for the first time, the presence of PPi, PPA1 and PPi transporter, progressive ankylosis protein ANKH in mammalian spermatozoa. Addition of PPi during porcine IVF increased fertilization rates significantly and in a dose-dependent manner. Fluorometric assay detected high levels of PPi in porcine seminal plasma, oviductal fluid and spermatozoa. Immunofluorescence detected PPA1 in the postacrosomal sheath (PAS) and connecting piece of boar spermatozoa; ANKH was present in the sperm head PAS and equatorial segment. Both ANKH and PPA1 were also detected in human and mouse spermatozoa, and in porcine spermatids. Higher proteasomal-proteolytic activity, indispensable for fertilization, was measured in spermatozoa preserved with PPi. The identification of an alternative, PPi dependent pathway for ATP production in spermatozoa elevates our understanding of sperm physiology and sets the stage for the improvement of semen extenders, storage media and IVF media for animal biotechnology and human assisted reproductive therapies.

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.

Safety, efficacy and efficiency of laser-assisted IVF in subfertile mutant mouse strains

PubMed Central

Li, Ming-Wen; Kinchen, Kristy L; Vallelunga, Jadine M; Young, Diana L; Wright, Kaleb D K; Gorano, Lisa N; Wasson, Katherine; Lloyd, K C Kent

2013-01-01

In the present report we studied the safety, efficacy and efficiency of using an infrared laser to facilitate IVF by assessing fertilization, development and birth rates after laser-zona drilling (LZD) in 30 subfertile genetically modified (GM) mouse lines. We determined that LZD increased the fertilization rate four to ten times that of regular IVF, thus facilitating the derivation of 26 of 30 (86.7%) GM mouse lines. Cryopreserved two-cell stage embryos derived by LZD-assisted IVF were recovered and developed to blastocysts in vitro at the same rate as frozen–thawed embryos derived by regular IVF. Surprisingly after surgical transfer to pseudopregnant recipients the birth rate of embryos derived by LZD-assisted IVF was significantly lower than that of embryos derived by regular IVF. However this result could be completely mitigated by the addition of 0.25 M sucrose to the culture medium during LZD which caused the oocyte to shrink in volume relative to the perivitelline space. By increasing the distance from the laser target site on the zona pellucida, we hypothesize that the hyperosmotic effect of sucrose reduced the potential for laser-induced cytotoxic thermal damage to the underlying oocytes. With appropriate preparation and cautious application, our results indicate that LZD-assisted IVF is a safe, efficacious and efficient assisted reproductive technology for deriving mutant mouse lines with male factor infertility and subfertility caused by sperm–zona penetration defects. PMID:23315689

Hair Trace Element and Electrolyte Content in Women with Natural and In Vitro Fertilization-Induced Pregnancy.

PubMed

Skalny, Anatoly V; Tinkov, Alexey A; Voronina, Irina; Terekhina, Olga; Skalnaya, Margarita G; Kovas, Yulia

2018-01-01

The objective of the present study was to perform comparative analysis of hair trace element content in women with natural and in vitro fertilization (IVF)-induced pregnancy. Hair trace element content in 33 women with IVF-induced pregnancy and 99 age- and body mass index-matched control pregnant women (natural pregnancy) was assessed using inductively coupled plasma mass spectrometry. The results demonstrated that IVF-pregnant women are characterized by significantly lower hair levels of Cu, Fe, Si, Zn, Ca, Mg, and Ba at p < 0.05 or lower. Comparison of the individual levels with the national reference values demonstrated higher incidence of Fe and Cu deficiency in IVF-pregnant women in comparison to that of the controls. IVF pregnancy was also associated with higher hair As levels (p < 0.05). Multiple regression analysis revealed a significant interrelation between IVF pregnancy and hair Cu, Fe, Si, and As content. Hair Cu levels were also influenced by vitamin/mineral supplementation and the number of pregnancies, whereas hair Zn content was dependent on prepregnancy anthropometric parameters. In turn, planning of pregnancy had a significant impact on Mg levels in scalp hair. Generally, the obtained data demonstrate an elevated risk of copper, iron, zinc, calcium, and magnesium deficiency and arsenic overload in women with IVF-induced pregnancy. The obtained data indicate the necessity of regular monitoring of micronutrient status in IVF-pregnant women in order to prevent potential deleterious effects of altered mineral homeostasis.

Increase of CD69, CD161 and CD94 on NK cells in women with recurrent spontaneous abortion and in vitro fertilization failure.

PubMed

Ghafourian, Mehri; Karami, Najmeh; Khodadadi, Ali; Nikbakht, Roshan

2014-06-01

Recurrent spontaneous abortion (RSA) and in vitro fertilization (IVF) failure with unknown causes are the controversial issues that are probably related to the immune system. To compare circulating NK cells expressing activation and inhibition surface markers between patients with RSA and IVF failure with those of healthy multiparous and successful IVF control women, respectively. In this case-control study peripheral blood samples were collected from 43 patients who included 23 women with RSA and 20 with IVF failure, plus 43 healthy control women comprising of 36 normal multiparous women and seven women with successful IVF. The expression of CD69, CD94 and CD161 surface markers on CD56+NK cells were assessed using specific monoclonal antibodies by flowcytometry. The percentage of NK cells increased significantly in patients with RSA and in women with IVF failure in comparison to healthy multiparous and successful IVF control groups (p<0.001). The overall expression of CD69, CD94, CD161 were also increased significantly on NK cells in both patient groups compared to control groups (p<0.001). Elevated expression of CD69 and CD161 on NK cells can be considered as immunological risk markers in RSA and IVF failure. However, it is not clear if high expression of CD94 on peripheral blood NK cells is related to abnormal activity of endometrial NK cells.

Comparison of in vitro fertilization/intracytoplasmic sperm injection outcomes in male factor infertility patients with and without spinal cord injuries.

PubMed

Kathiresan, Anupama S Q; Ibrahim, Emad; Aballa, Teodoro C; Attia, George R; Ory, Steven J; Hoffman, David I; Maxson, Wayne S; Barrionuevo, Marcelo J; Lynne, Charles M; Brackett, Nancy L

2011-09-01

To determine if outcomes after in vitro fertilization with intracytoplasmic sperm injection (IVF/ICSI) using sperm from men with spinal cord injury (SCI group) differ from those of other etiologies of male factor infertility (non-SCI group). In men with SCI, to determine if IVF/ICSI outcomes differ with sperm obtained by penile vibratory stimulation (PVS group) versus electroejaculation (EEJ group). Retrospective analysis. University medical center and major infertility center. Couples with male factor infertility due to SCI versus other etiologies. PVS, EEJ, surgical sperm retrieval, and IVF/ICSI. Rates of fertilization, pregnancy, and live birth. A total of 31 couples in the SCI group underwent 48 cycles of IVF/ICSI, and a total of 297 couples in the non-SCI group underwent 443 cycles of IVF/ICSI. The SCI group had lower fertilization rates but similar pregnancy and live birth rates compared with the non-SCI group. These rates, however, did not differ significantly when the PVS group was compared with the EEJ group. IVF/ICSI of sperm from men with SCI yield lower fertilization rates but similar pregnancy and live birth outcomes as IVF/ICSI of sperm from men with other etiologies of male factor infertility. Sperm collected by PVS versus EEJ in men with SCI appear to result in similar IVF/ICSI success rates. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Cardiovascular and metabolic profiles of offspring conceived by assisted reproductive technologies: a systematic review and meta-analysis.

PubMed

Guo, Xiao-Yan; Liu, Xin-Mei; Jin, Li; Wang, Ting-Ting; Ullah, Kamran; Sheng, Jian-Zhong; Huang, He-Feng

2017-03-01

To evaluate cardiovascular and metabolic features of offspring conceived by in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI). Literature review and meta-analysis. Not applicable. Offspring from IVF-ICSI versus natural conception. None. Systolic and diastolic blood pressure (SBP and DBP), cardiovascular function, body mass index (BMI), and lipid and glucose profiles. We included 19 studies that had recruited 2,112 IVF-ICSI and 4,096 naturally conceived offspring, ranging from childhood to early adulthood. The blood pressure levels of IVF-ICSI offspring were statistically significantly higher than those of naturally conceived offspring (weighted mean differences and confidence intervals: 1.88 mm Hg [95% CI, 0.27, 3.49] for SBP and 1.51 mm Hg [95% CI, 0.33, 2.70] for DBP). In addition, cardiac diastolic function was suboptimal and vessel thickness was higher among IVF-ICSI offspring. Compared with the metabolism of naturally conceived offspring, IVF-ICSI offspring displayed comparable BMI, lower low-density lipoprotein cholesterol levels, and higher fasting insulin levels. Children conceived by IVF-ICSI manifested a minor yet statistically significant increase in blood pressure without the clustering of increased BMI or impaired lipid metabolism by early adulthood. Our findings indicate a risk of cardiovascular disease among IVF-ICSI offspring, which calls for longer-term follow-ups and further investigation. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Progesterone administration for luteal phase deficiency in human reproduction: an old or new issue?

PubMed

Palomba, Stefano; Santagni, Susanna; La Sala, Giovanni Battista

2015-11-19

Luteal phase deficiency (LPD) is described as a condition of insufficient progesterone exposure to maintain a regular secretory endometrium and allow for normal embryo implantation and growth. Recently, scientific focus is turning to understand the physiology of implantation, in particular the several molecular markers of endometrial competence, through the recent transcriptomic approaches and microarray technology. In spite of the wide availability of clinical and instrumental methods for assessing endometrial competence, reproducible and reliable diagnostic tests for LPD are currently lacking, so no type-IA evidence has been proposed by the main scientific societies for assessing endometrial competence in infertile couples. Nevertheless, LPD is a very common condition that may occur during a series of clinical conditions, and during controlled ovarian stimulation (COS) and hyperstimulation (COH) programs. In many cases, the correct approach to treat LPD is the identification and correction of any underlying condition while, in case of no underlying dysfunction, the treatment becomes empiric. To date, no direct data is available regarding the efficacy of luteal phase support for improving fertility in spontaneous cycles or in non-gonadotropin induced ovulatory cycles. On the contrary, in gonadotropin in vitro fertilization (IVF) and non-IVF cycles, LPD is always present and progesterone exerts a significant positive effect on reproductive outcomes. The scientific debate still remains open regarding progesterone administration protocols, specially on routes of administration, dose and timing and the potential association with other drugs, and further research is still needed.

Sperm DNA damage has a negative association with live-birth rates after IVF.

PubMed

Simon, L; Proutski, I; Stevenson, M; Jennings, D; McManus, J; Lutton, D; Lewis, S E M

2013-01-01

Sperm DNA damage has a negative impact on pregnancy rates following assisted reproduction treatment (ART). The aim of the present study was to examine the relationship between sperm DNA fragmentation and live-birth rates after IVF and intracytoplasmic sperm injection (ICSI). The alkaline Comet assay was employed to measure sperm DNA fragmentation in native semen and in spermatozoa following density-gradient centrifugation in semen samples from 203 couples undergoing IVF and 136 couples undergoing ICSI. Men were divided into groups according to sperm DNA damage. Following IVF, couples with <25% sperm DNA fragmentation had a live-birth rate of 33%; in contrast, couples with >50% sperm DNA fragmentation had a much lower live-birth rate of 13%. Following ICSI, no significant differences in sperm DNA damage were found between any groups of patients. Sperm DNA damage was also associated with low live-birth rates following IVF in both men and couples with idiopathic infertility: 39% of couples and 41% of men with idiopathic infertility have high sperm DNA damage. Sperm DNA damage assessed by the Comet assay has a close inverse relationship with live-birth rates after IVF. Sperm DNA damage has a negative impact on assisted reproduction treatment outcome, in particular, on pregnancy rates. The aim of the present study was to examine the relationship between sperm DNA fragmentation and live-birth rates after IVF and intracytoplasmic sperm injection (ICSI). The alkaline Comet assay was employed to measure sperm DNA fragmentation in native semen and in spermatozoa following density-gradient centrifugation in semen samples from 203 couples undergoing IVF and 136 couples undergoing ICSI. Men were divided into groups according to sperm DNA damage and treatment outcome. Following IVF, couples with <25% sperm DNA fragmentation had a live birth rate of 33%. In contrast, couples with >50% sperm DNA fragmentation had a much lower live-birth rate of 13% following IVF. Following ICSI, there were no significant differences in levels of sperm DNA damage between any groups of patients. Sperm DNA damage was also associated with the very low live-birth rates following IVF in both men and couples with idiopathic infertility: 39% of couples and 41% of men have high level of sperm DNA damage. Sperm DNA damage assessed by the Comet assay has a close inverse relationship with live-birth rates after IVF. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Effect of Animated Graphic Annotations and Immediate Visual Feedback in Aiding Japanese Pronunciation Learning: A Comparative Study

ERIC Educational Resources Information Center

Hew, Soon-Hin; Ohki, Mitsuru

2004-01-01

This study examines the effectiveness of imagery and electronic visual feedback in facilitating students' acquisition of Japanese pronunciation skills. The independent variables, animated graphic annotation (AGA) and immediate visual feedback (IVF) were integrated into a Japanese computer-assisted language learning (JCALL) program focused on the…

Prospective Changes in Infertile Patients using Nonlinear Analysis

NASA Astrophysics Data System (ADS)

Takahashi, Yuko; Tomiyama, Tatsuhiro; Matsubayashi, Hidehiko; Tsukamoto, Asami; Oyama-Higa, Mayumi

2011-06-01

We measured pulse waves in 22 infertile women from the beginning of in vitro fertilization-embryo transfer (IVF-ET) through to pregnancy testing. The largest Lyapunov exponent (LLE) and autonomic nerve balance in the pregnancy group were significantly lower than that in the non-pregnancy group. In this study, we measured plethysmograms of four women who became pregnant and 18 who did not, ten times from each. We calculated LLE and a value for the autonomic nerve balance; from this analysis, we conclude that a mental state that allows for the possibility of becoming pregnant is necessary for a successful pregnancy.

Cost-effectiveness of hysteroscopy screening for infertile women.

PubMed

Kasius, Jenneke C; Eijkemans, René J C; Mol, Ben W J; Fauser, Bart C J M; Fatemi, Human M; Broekmans, Frank J M

2013-06-01

This study assessed the cost-effectiveness of office hysteroscopy screening prior to IVF. Therefore, the cost-effectiveness of two distinct strategies - hysteroscopy after two failed IVF cycles (Failedhyst) and routine hysteroscopy prior to IVF (Routinehyst) - was compared with the reference strategy of no hysteroscopy (Nohyst). When present, intrauterine pathology was treated during hysteroscopy. Two models were constructed and evaluated in a decision analysis. In model I, all patients had an increase in pregnancy rate after screening hysteroscopy prior to IVF; in model II, only patients with intrauterine pathology would benefit. For each strategy, the total costs and live birth rates after a total of three IVF cycles were assessed. For model I (all patients benefit from hysteroscopy), Routinehyst was always cost-effective compared with Nohyst or Failedhyst. For the Routinehyst strategy, a monetary profit would be obtained in the case where hysteroscopy would increase the live birth rate after IVF by ≥ 2.8%. In model II (only patients with pathology benefit from hysteroscopy), Routinehyst also dominated Failedhyst. However, hysteroscopy performance resulted in considerable costs. In conclusion, the application of a routine hysteroscopy prior to IVF could be cost-effective. However, randomized trials confirming the effectiveness of hysteroscopy are needed. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

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

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

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.

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.

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.

Longitudinal Study of Reproductive Performance of Female Cattle Produced by Somatic Cell Nuclear Transfer

PubMed Central

Polejaeva, Irina A.; Broek, Diane M.; Walker, Shawn C.; Zhou, Wenli; Walton, Mark; Benninghoff, Abby D.; Faber, David C.

2013-01-01

The objective of this study was to determine whether or not reproductive performance in cattle produced by somatic cell nuclear transfer (SCNT) is significantly different from that of their genetic donors. To address this question, we directed two longitudinal studies using different embryo production procedures: (1) superovulation followed by artificial insemination (AI) and embryo collection and (2) ultrasound-guided ovum pick-up followed by in vitro fertilization (OPU-IVF). Collectively, these two studies represent the largest data set available for any species on the reproductive performance of female clones and their genetic donors as measured by their embryo production outcomes in commercial embryo production program. The large-scale study described herein was conducted over a six-year period of time and provides a unique comparison of 96 clones to the 40 corresponding genetic donors. To our knowledge, this is the first longitudinal study on the reproductive performance of cattle clones using OPU-IVF. With nearly 2,000 reproductive procedures performed and more than 9,200 transferable embryos produced, our observations show that the reproductive performance of cattle produced by SCNT is not different compared to their genetic donors for the production of transferable embryos after either AI followed by embryo collection (P = 0.77) or OPU-IVF (P = 0.97). These data are in agreement with previous reports showing that the reproductive capabilities of cloned cattle are equal to that of conventionally produced cattle. In conclusion, results of this longitudinal study once again demonstrate that cloning technology, in combination with superovulation, AI and embryo collection or OPU-IVF, provides a valuable tool for faster dissemination of superior maternal genetics. PMID:24391930

Does endometrial integrin expression in endometriosis patients predict enhanced in vitro fertilization cycle outcomes after prolonged GnRH agonist therapy?

PubMed

Surrey, Eric S; Lietz, Annette K; Gustofson, Robert L; Minjarez, Debra A; Schoolcraft, William B

2010-02-01

To determine whether endometrial expression of the integrin alpha(v)beta(3) vitronectin can predict which endometriosis patient subgroup will benefit from pre-IVF cycle prolonged GnRH agonist (GnRHa) therapy. Prospective randomized institutional review board approved pilot trial. Private assisted reproductive technology program. IVF candidates with regular menses, surgically confirmed endometriosis, and normal ovarian reserve. All patients underwent endometrial biopsy 9 to 11 days post-LH surge to evaluate alpha(v)beta(3) integrin expression. Patients were randomized either to receive depot leuprolide acetate 3.75 mg every 28 days for three doses before controlled ovarian hyperstimulation (COH) or to proceed directly to COH and IVF. Group 1: integrin-positive controls (N = 12); group 2: integrin-positive administered prolonged GnRHa (N = 8). Group A: integrin-negative controls (N = 7); group B: integrin-negative administered prolonged GnRHa (N = 9). COH responses, ongoing pregnancy and implantation rates. There were no significant effects of GnRH agonist treatment in either of the integrin expression strata regarding ongoing pregnancy or implantation rates, although these outcomes were more frequent in group 2 vs. 1 (62.5% vs. 41.6% and 35% vs. 20.6%, respectively). This effect may have because of limited sample size. The value of a negative integrin biopsy in predicting an ongoing pregnancy after prolonged GnRH agonist therapy was only 44.4%. Endometrial alpha(v)beta(3) integrin expression did not predict which endometriosis patients would benefit from prolonged GnRHa therapy before IVF. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Longitudinal study of reproductive performance of female cattle produced by somatic cell nuclear transfer.

PubMed

Polejaeva, Irina A; Broek, Diane M; Walker, Shawn C; Zhou, Wenli; Walton, Mark; Benninghoff, Abby D; Faber, David C

2013-01-01

The objective of this study was to determine whether or not reproductive performance in cattle produced by somatic cell nuclear transfer (SCNT) is significantly different from that of their genetic donors. To address this question, we directed two longitudinal studies using different embryo production procedures: (1) superovulation followed by artificial insemination (AI) and embryo collection and (2) ultrasound-guided ovum pick-up followed by in vitro fertilization (OPU-IVF). Collectively, these two studies represent the largest data set available for any species on the reproductive performance of female clones and their genetic donors as measured by their embryo production outcomes in commercial embryo production program. The large-scale study described herein was conducted over a six-year period of time and provides a unique comparison of 96 clones to the 40 corresponding genetic donors. To our knowledge, this is the first longitudinal study on the reproductive performance of cattle clones using OPU-IVF. With nearly 2,000 reproductive procedures performed and more than 9,200 transferable embryos produced, our observations show that the reproductive performance of cattle produced by SCNT is not different compared to their genetic donors for the production of transferable embryos after either AI followed by embryo collection (P = 0.77) or OPU-IVF (P = 0.97). These data are in agreement with previous reports showing that the reproductive capabilities of cloned cattle are equal to that of conventionally produced cattle. In conclusion, results of this longitudinal study once again demonstrate that cloning technology, in combination with superovulation, AI and embryo collection or OPU-IVF, provides a valuable tool for faster dissemination of superior maternal genetics.

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.

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.

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.

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

Milder is better? advantages and disadvantages of "mild" ovarian stimulation for human in vitro fertilization

PubMed Central

2011-01-01

In the last decades, several steps have been made aiming at rendering human IVF more successful on one side, more tolerable on the other side. The "mild" ovarian stimulation approach, in which a lower-than-average dose of exogenous gonadotropins is given and gonadotropin treatment is started from day 2 to 7 of the cycle, represents a significant step toward a more patient's friendly IVF. However, a clear view of its virtues and defects is still lacking, because only a few prospective randomized trials comparing "mild" vs. conventional stimulation exist, and they do not consider some important aspects, such as, e.g., thawing cycles. This review gives a complete panorama of the "mild" stimulation philosophy, showing its advantages vs. conventional ovarian stimulation, but also discussing its disadvantages. Both patients with a normal ovarian responsiveness to exogenous gonadotropins and women with a poor ovarian reserve are considered. Overall, we conclude that the level of evidence supporting the use of "mild" stimulation protocols is still rather poor, and further, properly powered prospective studies about "mild" treatment regimens are required. PMID:21324155

[Surgery for deep infiltrating endometriosis before in vitro fertilization: no benefit for fertility?].

PubMed

Capelle, A; Lepage, J; Langlois, C; Lefebvre, C; Dewailly, D; Collinet, P; Rubod, C

2015-02-01

Does surgery for deep infiltrating endometriosis (DIE) before in vitro fertilization (IVF) improve pregnancy and birth rate? Cohort study of 177 consecutive patients with DIE related infertility and receiving IVF. Patients were divided into 3 groups according to surgical management decided during multidisciplinary team meeting. Group no surgery (NS) (n=65), group complete surgery (CS) with complete resection of all lesions (n=49) and group incomplete surgery (IS) with gestures improving ovaries accessibility for IVF and/or facilitating embryonic implantation (n=63). Pre-surgery clinical, MRI lesion locations, and history of IVF characteristics were analyzed with logistic regression. There was no significant difference in general and IVF characteristics and in the severity of endometriosis among the three groups (P=0.43). Overall pregnancy and birth rates after IVF were 45.8% and 33.3%, respectively and were not different among the 3 groups (P=0.59 and P=0.49). Four major complications during oocytes retrievals were observed in NS group, one in IS group and none in CS group. Presence of an inter-utero-rectal lesion at MRI decreased the rate of pregnancy (OR=0.49 [0.25, 0.97]). Surgery for deep infiltrating endometriosis does not improve pregnancy and birth rates before IVF. This inter-utero-rectal extensive lesion might explain IVF failures by ovarian difficult access and difficulties in embryonic transfers. Further studies should explore the impact of surgical excision of inter-utero-rectal lesion on oocyte retrieval and embryonic transfer. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Problems faced with legislating for IVF technology in a Roman Catholic country.

PubMed

Mallia, Pierre

2010-02-01

Malta traditionally enjoys a Roman Catholic Society, with the official religion of the country being cited in the second article of the constitution. Recently the government proposed to legislate to regulate human reproductive technology, in particular In Vitro Fertilization, which has been practiced for over two decades without controlling legislation. A Parliamentary Committee for social affairs was set up to study the situation inviting most stakeholders. The arguments gravitated mostly on issues of the status of the embryo and the media played a considerable role. At the end of the discussion the Archbishop made a statement which pointed out that IVF involves destruction of embryos and the process stopped. This article examines what caused the deterioration of the process and points favourably towards a way forward within the context of a Catholic Country.

In Vitro Fertilization and the Family: Quality of Parenting, Family Functioning, and Child Psychosocial Adjustment.

ERIC Educational Resources Information Center

Hahn, Chun-Shin; DiPietro, Janet A.

2001-01-01

Examined associations between in vitro fertilization (IVF) and parenting quality, family functioning, and emotional/behavioral adjustment of 3- to 7-year-olds. Found that IVF mothers reported greater protectiveness than mothers of naturally conceived children. Teachers rated IVF mothers as displaying greater warmth but not overprotective or…

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

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

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

Development master arm of 2-DOF planar parallel manipulator for In-Vitro Fertilization

NASA Astrophysics Data System (ADS)

Thamrongaphichartkul, Kitti; Vongbunyong, Supachai; Nuntakarn, Lalana

2018-01-01

Micromanipulator is a mechanical device used for manipulating miniature objects in the order of micron. It is widely used in In-Vitro Fertilization (IVF) in which sperms will be held in a micro-needle and penetrate to an oocyte for fertilization. IVF needs to be performed by high skill embryologists to control the movement of the needle accurately due to the lack of tactile perception of the user. Haptic device is a device that can transmit and simulate position, velocity and force in order to enhance interaction between the user and system. However, commercially available haptic devices have unnecessary degrees of freedom and limited workspace which are inappropriate for IVF process. This paper focuses on development of a haptic device for using in IVF process. It will be used as a master arm for the master-slave system for IVF process in order to enhance the ability of users to control the micromanipulator. As a result, the embryologist is able to carry out the IVF process more effectively with having tactile perception.

Prevalence of dental attrition in in vitro fertilization children of West Bengal.

PubMed

Kar, Sudipta; Sarkar, Subrata; Mukherjee, Ananya

2014-01-01

Dental attrition is one of the problems affecting the tooth structure. It may affect both in vitro fertilization (IVF) and spontaneously conceived children. This study was aimed to evaluate and to compare the prevalence of dental attrition in deciduous dentition of IVF and spontaneously conceived children. In a cross-sectional case control study dental attrition status of 3-5 years old children were assessed. The case group consisted of term, singleton babies who were the outcome of IVF in the studied area in 2009. The control group consisted of term, first child, singleton and spontaneously conceived 3-5 years old children who were also resident of the studied area. A sample of 153 IVF and 153 spontaneously conceived children was examined according to Hansson and Nilner classification. Statistical analysis was carried out using Chi-square tests (χ(2) ) or Z test. No statistically significant difference found in studied (IVF children) and control group (spontaneously conceived children). IVF children are considered same as spontaneously conceived children when studied in relation to dental attrition status.

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

Quality Assurance in Stem Cell Banking: Emphasis on Embryonic and Induced Pluripotent Stem Cell Banking.

PubMed

Kallur, Therése; Blomberg, Pontus; Stenfelt, Sonya; Tryggvason, Kristian; Hovatta, Outi

2017-01-01

For quality assurance (QA) in stem cell banking, a planned system is needed to ensure that the banked products, stem cells, meet the standards required for research, clinical use, and commercial biotechnological applications. QA is process oriented, avoids, or minimizes unacceptable product defects, and particularly encompasses the management and operational systems of the bank, as well as the ethical and legal frameworks. Quality control (QC ) is product oriented and therefore ensures the stem cells of a bank are what they are expected to be. Testing is for controlling, not assuring, product quality, and is therefore a part of QC , not QA. Like QA, QC is essential for banking cells for quality research and translational application (Schwartz et al., Lancet 379:713-720, 2012). Human embryonic stem cells (hESCs), as cells derived from donated supernumerary embryos from in vitro fertilization (IVF) therapy, are different from other stem cell types in resulting from an embryo that has had two donors . This imposes important ethical and legal constraints on the utility of the cells, which, together with quite specific culture conditions, require special attention in the QA system. Importantly, although the origin and derivation of induced pluripotent stem cells (iPSCs ) differ from that of hESCs, many of the principles of QA for hESC banking are applicable to iPSC banking (Stacey et al., Cell Stem Cell 13:385-388, 2013). Furthermore, despite differences between the legal and regulatory frameworks for hESC and iPSC banking between different countries, the requirements for QA are being harmonized (Stacey et al., Cell Stem Cell 13:385-388, 2013; International Stem Cell Banking Initiative, Stem Cell Rev 5:301-314, 2009).

Dual trigger of triptorelin and HCG optimizes clinical outcome for high ovarian responder in GnRH-antagonist protocols.

PubMed

Li, Saijiao; Zhou, Danni; Yin, Tailang; Xu, Wangming; Xie, Qingzhen; Cheng, Dan; Yang, Jing

2018-01-12

In this paper, a retrospective cohort study was conducted to the high ovarian responders in GnRH-antagonist protocols of IVF/ICSI cycles. The purpose of the study is to investigate whether dual triggering of final oocyte maturation with a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (HCG) can improve the clinical outcome compared with traditional dose (10000IU) HCG trigger and low-dose (8000IU) HCG trigger for high ovarian responders in GnRH-antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles. Our study included 226 couples with high ovarian responders in GnRH-antagonist protocols of IVF/ICSI cycles. Standard dosage of HCG trigger (10000 IU of recombinant HCG) versus dual trigger (0.2 mg of triptorelin and 2000 IU of recombinant HCG) and low-dose HCG trigger (8000IU of recombinant HCG) were used for final oocyte maturation. Our main outcome measures were high quality embryo rate, the number of usable embryos, the risk of OHSS, duration of hospitalization and incidence rate of complications. Our evidence demonstrated that dual trigger is capable of preventing severe OHSS while still maintaining excellent high quality embryo rate in in high ovarian responders of GnRH-antagonist protocols.

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

Parenting style of women who conceived using in vitro fertilization: a meta-analysis.

PubMed

Wang, Yu-Ming; Shu, Bih-Ching; Fetzer, Susan; Chang, Ying-Ju

2014-06-01

Research has shown that the mental health of women contributes to their parenting style. However, it remains unclear whether the experience of in vitro fertilization (IVF) affects parenting style. This study was designed to assess whether there is a difference in parenting styles between women who conceived using IVF and those who conceived naturally. This meta-analysis searched three electronic databases (MEDLINE, PsychInfo, and CINAHL) for relevant articles published between 1978 and 2011. Key words used included parenting, mothering, parent-child relations, childrearing, infertility, assisted reproductive technique, IVF, and intracytoplasmic sperm injection. Study inclusion criteria were as follows: published in an English-language peer-reviewed journal, with the definition of parenting style categorized as one of two dimensions: warmth and control; quantification of the parenting behaviors; use of a case-controlled study design to compare IVF and natural conceptions; and reported data sufficient to calculate the effect sizes. Studies that included women who conceived using a donor egg or sperm for IVF and those that included women who were either surrogates or in homosexual relationships were excluded. Three hundred ninety studies were identified. Fourteen studies met the inclusion criteria. The Newcastle-Ottawa Scale was used to appraise the quality of the data. The IVF participants used significantly greater controlling parenting behaviors than their natural conception participant peers (d = 0.148, p < .01). There was no difference between the two groups in terms of parenting behaviors related to warmth, rejection, or respect for autonomy. The homogeneity test for the effect size of warmth and controlling parenting behavior achieved significance. Women who conceive using IVF have slightly but still significantly greater controlling parenting behaviors than women who conceive naturally. The results of this study may help professionals to better understand the parenting style of IVF women and develop appropriate interventions to reduce parenting anxiety and promote the mental health of IVF women.

Low-cost in vitro fertilization: current insights

PubMed Central

Teoh, Pek Joo; Maheshwari, Abha

2014-01-01

Despite the development of in vitro fertilization (IVF) more than 30 years ago, the cost of treatment remains high. Furthermore, over the years, more sophisticated technologies and expensive medications have been introduced, making IVF increasingly inaccessible despite the increasing need. Globally, the option to undergo IVF is only available to a privileged few. In recent years, there has been growing interest in exploring strategies to reduce the cost of IVF treatment, which would allow the service to be provided in low-resource settings. In this review, we explore the various ways in which the cost of this treatment can be reduced. PMID:25187741

In vitro fertilization (IVF): a review of 3 decades of clinical innovation and technological advancement.

PubMed

Wang, Jeff; Sauer, Mark V

2006-12-01

In vitro fertilization, popularly referred to as IVF, has captured the attention of the public since its sensational introduction in 1978. Today assisted reproductive technology is available throughout most of the civilized world, and the practice is largely different from that used during the early days. Refinements in laboratory technology and clinical practice have allowed IVF to evolve into a medical procedure that is efficient, safe, readily accessible, and relatively affordable. More than 2 million IVF children have been born to date, and it is likely that continued enhancements will widen its appeal and applicability.

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.

Prognosis and cost-effectiveness of IVF in poor responders according to the Bologna Criteria.

PubMed

Busnelli, Andrea; Somigliana, Edgardo

2018-02-01

Poor ovarian response (POR) to controlled ovarian hyperstimulation for in vitro fertilization (IVF) is one of the most challenging issue in the field of reproductive medicine. However, even if improving IVF outcome in poor responders (PORs) represents a main priority, the lack of a unique definition of POR has hampered research in this area. In order to overcome this impediment, an ESHRE Campus Workshop was organized in Bologna in 2010 and reached a consensus on the criteria for the diagnosis of POR ("Bologna Criteria"). In this review we aimed to estimate the prognostic potential of the ESHRE definition, to elucidate its possible weaknesses and to analyze the economic aspects of IVF in a population of poor responders (PORs). Available evidence confirmed that the Bologna criteria are able to select a population with a poor IVF prognosis thus supporting their validity. Nonetheless, different aspects of the definition have been criticized. The main points of debate concern the homogeneity of the population identified, the cut-off values chosen for the ovarian reserve tests and the risks factors other than age associated with POR. Data concerning the economic profile of IVF in PORs are scanty. The only published study on the argument showed that IVF in these cases is not cost-effective. However, considering the potential substantial impact of cost-effectiveness analyses on public health policies, there is the need for further and independent validations.

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.

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.

Ammonium accumulation in commercially available embryo culture media and protein supplements during storage at 2-8°C and during incubation at 37°C.

PubMed

Kleijkers, Sander H M; van Montfoort, Aafke P A; Bekers, Otto; Coonen, Edith; Derhaag, Josien G; Evers, Johannes L H; Dumoulin, John C M

2016-06-01

Does ammonium accumulate in commercially available culture media and protein supplements used for in vitro development of human pre-implantation embryos during storage and incubation? Ammonium accumulates in ready-to-use in vitro fertilization (IVF) culture media during storage at 2-8°C and in ready-to-use IVF culture media and protein supplements during incubation at 37°C. Both animal and human studies have shown that the presence of ammonium in culture medium has detrimental effects on embryonic development and pregnancy rate. It is, therefore, important to assess the amount of ammonium accumulation in ready-to-use IVF culture media under conditions that are common in daily practice. Ammonium accumulation was investigated in 15 ready-to-use media, 11 protein-free media and 8 protein supplements. Ammonium was measured by the use of an enzymatic method with glutamate dehydrogenase. To simulate the storage and incubation conditions during IVF treatments, ammonium concentrations were measured at different time-points during storage at 2-8°C for 6 weeks and during incubation at 37°C for 4 days. All ready-to-use, i.e. protein supplemented, culture media showed ammonium accumulation during storage for 6 weeks (ranging from 9.2 to 99.8 µM) and during incubation for 4 days (ranging from 8.4 to 138.6 µM), resulting in levels that might affect embryo development. The protein supplements also showed ammonium accumulation, while the culture media without protein supplementation did not. The main sources of ammonium buildup in ready-to-use culture media were unstable glutamine and the protein supplements. No additional ammonium buildup was found during incubation when using an oil overlay or with the presence of an embryo in the culture droplet. In addition to the unstable glutamine and the protein supplements, other free amino acids might contribute to the ammonium buildup. We did not investigate the deterioration of other components in the media. Break-down of components into ammonium is more pronounced during incubation at 37°C, however, it is not negligible during storage at 2-8°C. This results in increasing ammonium levels in culture media over time that may affect embryo development. Therefore, it is important that the use of free l-glutamine in human embryo culture media is stopped and that the use of protein supplements is thoroughly evaluated. No funding or no competing interests declared. 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.

Effect of Quyu Jiedu granule on microenvironment of ova in patients with endometriosis.

PubMed

Lian, Fang; Li, Xin-Ling; Sun, Zhen-Gao; Zhang, Jian-Wei; Liu, Yan-He; Ma, Feng-Mei

2009-02-01

To observe the effect of Quyu Jiedu Granules (, QJG) on the micro- microenvironment of ova in patients with endometriosis (EM). environment Twenty EM patients who received in vitro fertilization and embryo transfer (IVF-ET) were randomized equally into a treated group and a control group. Further, 20 patients who received IVF-ET due to oviduct factors were enrolled into a non-endometriosis group. The dosage of gonadotrophic hormone used, the number of ova attained, fertilization rate and clinical pregnancy rate were all observed, and the levels of tumor necrosis factor alpha (TNF-right harpoon over left harpoon) and interleukin 6 (IL-6) in follicular fluid as well as their mRNA expressions in ovarian granular cells were detected by RT-PCR on the very day of ovum attainment. The ova attainment (13.80+/-6.87) and fertilization rate (0.69+/-0.31) in the treated group were all higher than the corresponding values in the control group (9.80+/-5.32 and 0.47+/-0.22); the follicular fluid contents of TNF-alpha and IL-6 in the treated group were 1.38+/-0.21 ng/mL and 130.56+/-12.81 pg/mL, respectively, which were lower than those in the control group (1.98+/-0.34 ng/mL and 146.83+/-17.65 pg/mL, respectively). Further, the treated group showed much lower mRNA expressions of TNF-alpha and IL-6 in ovarian granular cells. The elevation of TNF-alpha and IL-6 contents in follicular fluid and their mRNA expressions in ovarian granular cells are possibly related to the low quality of ova in EM; QJG might raise the ova quality by reducing TNF-alpha and IL-6 levels to improve the living micro-environment for the ova.

Embryo transfer techniques: an American Society for Reproductive Medicine survey of current Society for Assisted Reproductive Technology practices.

PubMed

Toth, Thomas L; Lee, Malinda S; Bendikson, Kristin A; Reindollar, Richard H

2017-04-01

To better understand practice patterns and opportunities for standardization of ET. Cross-sectional survey. Not applicable. Not applicable. An anonymous 82-question survey was emailed to the medical directors of 286 Society for Assisted Reproductive Technology member IVF practices. A follow-up survey composed of three questions specific to ET technique was emailed to the same medical directors. Descriptive statistics of the results were compiled. The survey assessed policies, protocols, restrictions, and specifics pertinent to the technique of ET. There were 117 (41%) responses; 32% practice in academic settings and 68% in private practice. Responders were experienced clinicians, half of whom had performed <10 procedures during training. Ninety-eight percent of practices allowed all practitioners to perform ET; half did not follow a standardized ET technique. Multiple steps in the ET process were identified as "highly conserved;" others demonstrated discordance. ET technique is divided among [1] trial transfer followed immediately with ET (40%); [2] afterload transfer (30%); and [3] direct transfer without prior trial or afterload (27%). Embryos are discharged in the upper (66%) and middle thirds (29%) of the endometrial cavity and not closer than 1-1.5 cm from fundus (87%). Details of each step were reported and allowed the development of a "common" practice ET procedure. ET training and practices vary widely. Improved training and standardization based on outcomes data and best practices are warranted. A common practice procedure is suggested for validation by a systematic literature review. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Rapid reaccumulation of hydrometra after drainage at embryo transfer in patients with hydrosalpinx.

PubMed

Hinckley, Mary D; Milki, Amin A

2003-11-01

To report the occurrence and management of hydrometra at the time of scheduled embryo transfer in two patients who underwent drainage of hydrosalpinges at oocyte retrieval. Case report. University IVF clinic. Two patients with hydrosalpinges visible on ultrasonography who deferred tubal surgery. Although no fluid was seen at the time of oocyte retrieval, hydrometra was noticed and drained before planned embryo transfer (ET). Reoccurrence of hydrometra after drainage. Rapid reaccumulation of hydrometra despite drainage was seen in both patients, one of whom had reoccurrence in 1 hour. Embryo transfer was deferred until after tubal surgery, and all embryos were cryopreserved. In patients with hydrosalpinges, ultrasonography before ET is useful to detect newly developed hydrometra. Aspiration of the uterine fluid is unlikely to help because of rapid reaccumulation of hydrometra. Cryopreservation of the embryos for future transfer after the hydrosalpinx is removed or ligated is recommended.

The timing of pronuclear formation, DNA synthesis and cleavage in the human 1-cell embryo.

PubMed

Capmany, G; Taylor, A; Braude, P R; Bolton, V N

1996-05-01

The timing of pronuclear formation and breakdown, DNA synthesis and cleavage during the first cell cycle of human embryogenesis are described. Pronuclei formed between 3 and 10 h post-insemination (hpi; median 8 hpi). S-phase commenced between 8 and 14 hpi, and was completed between 10 and 18 hpi. M-phase was observed between 22 and 31 hpi (median duration 3 h), and cleavage to the 2-cell stage took place between 25 and 33 hpi. The timing of the same events was determined in 1-cell embryos derived from re-inseminated human oocytes that had failed to fertilize during therapeutic in-vitro fertilization (IVF). In these embryos, pronuclei formed between 3 and 8 h post-re-insemination (hpr-i), coinciding with the beginning of S-phase. While S-phase was completed as early as 10 hpr-i in some embryos, it extended until at least 16 hpr-i in others. Pronuclear breakdown and cleavage occurred from 23 and 26 hpr-i respectively; however, they did not occur in some embryos until after 46 hpr-i. The results demonstrate a markedly greater degree of variation in the timing of these events in embryos derived from re-inseminated oocytes compared with embryos derived from conventional IVF, and thus throw into question the validity of using the former as models for studies of the first cell cycle of human embryogenesis.

Effects of Individualized Video Feedback Combined with Group Parent Training on Inappropriate Maternal Behavior

ERIC Educational Resources Information Center

Phaneuf, Leah; McIntyre, Laura Lee

2007-01-01

The effects of adding individualized video feedback (IVF) to Webster-Stratton's (2000, 2001) group-based parent training program (GT) were evaluated using a multiple baseline design across four mother-child dyads. During all phases of the study, inappropriate maternal behavior was recorded from videotapes of playtime with their preschoolers with…

Costs and benefits of individuals conceived after IVF: a net tax evaluation in The Netherlands.

PubMed

Moolenaar, L M; Connolly, M; Huisman, B; Postma, M J; Hompes, P G A; van der Veen, F; Mol, B W J

2014-02-01

This study evaluated the lifetime future net tax revenues from individuals conceived after IVF relative to those naturally conceived. A model based on the method of generational accounting was developed to evaluate investments in IVF. Calculations were based on average investments paid and received from the government by an individual. All costs were discounted to their net present values and adjusted for survival. The lifetime net present value of IVF-conceived individuals was -€81,374 (the minus sign reflecting negative net present value). The lifetime net present value of IVF-conceived men and women were -€47,091 and -€123,177, respectively. The lifetime net present value of naturally conceived individuals was -€70,392; respective amounts for men and women were -€36,109 and -€112,195. The model was most sensitive to changes in the growth of healthcare costs, economic growth and the discount rate. Therefore, it is concluded that, similarly to naturally conceived individuals in the Netherlands, IVF-conceived individuals have negative discounted net tax revenue at the end of life. The analytic framework described here undervalues the incremental value of an additional birth because it only considers the fiscal consequences of life and does not take into consideration broader macroeconomic benefits. This study evaluated the lifetime future net tax revenues from individuals conceived after IVF relative those naturally conceived. A model based on the method of generational accounting to evaluate investments in IVF was used. Calculations were based on average investments paid and received from the government by an individual. The lifetime net present value of IVF-conceived individuals was -€81,374 (the minus sign reflecting negative net present value). The lifetime net present value of IVF-conceived men and women were -€47,091 and -€123,177, respectively. The lifetime net present value of naturally conceived individuals was -€70,392; respective amounts for men and women were -€36,109 and -€112,195. The model was most sensitive for changes in the growth in healthcare costs, economic growth and the discount rate. Just as naturally conceived individuals in the Netherlands, IVF-conceived individuals have negative discounted net tax revenue at the end of life. The analytic framework described here undervalues the incremental value of an additional birth because it only considers the fiscal consequences of life and does not take into consideration broader macroeconomic benefits. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Tubal anastomosis after previous sterilization: a systematic review.

PubMed

van Seeters, Jacoba A H; Chua, Su Jen; Mol, Ben W J; Koks, Carolien A M

2017-05-01

Female sterilization is one of the most common contraceptive methods. A small number of women, however, opt for reversal of sterilization procedures after they experience regret. Procedures can be performed by laparotomy or laparoscopy, with or without robotic assistance. Another commonly utilized alternative is IVF. The choice between surgery and IVF is often influenced by reimbursement politics for that particular geographic location. We evaluated the fertility outcomes of different surgical methods available for the reversal of female sterilization, compared these to IVF and assessed the prognostic factors for success. Two search strategies were employed. Firstly, we searched for randomized and non-randomized clinical studies presenting fertility outcomes of sterilization reversal up to July 2016. Data on the following outcomes were collected: pregnancy rate, ectopic pregnancy rate, cost of the procedure and operative time. Eligible study designs included prospective or retrospective studies, randomized controlled trials, cohort studies, case-control studies and case series. No age restriction was applied. Exclusion criteria were patients suffering from tubal infertility from any other reason (e.g. infection, endometriosis and adhesions from previous surgery) and studies including <10 participants. The following factors likely to influence the success of sterilization reversal procedures were then evaluated: female age, BMI and duration and method of sterilization. Secondly, we searched for randomized and non-randomized clinical studies that compared reversal of sterilization to IVF and evaluated them for pregnancy outcomes and cost effectiveness. We included 37 studies that investigated a total of 10 689 women. No randomized controlled trials were found. Most studies were retrospective cohort studies of a moderate quality. The pooled pregnancy rate after sterilization reversal was 42-69%, with heterogeneity seen from the different methods utilized. The reported ectopic pregnancy rate was 4-8%. The only prognostic factor affecting the chance of conception was female age. The surgical approach (i.e. laparotomy [microscopic], laparoscopy or robotic) had no impact on the outcome, with the exception of the macroscopic laparotomic technique, which had inferior results and is not currently utilized. For older women, IVF could be a more cost-effective alternative for the reversal of sterilization. However, direct comparative data are lacking and a cut-off age cannot be stated. In sterilized women who suffer regret, surgical tubal re-anastomosis is an effective treatment, especially in younger women. However, there is a need for randomized controlled trials comparing the success rates and costs of surgical reversal with IVF. © 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

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.

The use of coenzyme Q10 and DHEA during IUI and IVF cycles in patients with decreased ovarian reserve.

PubMed

Gat, Itai; Blanco Mejia, Sonia; Balakier, Hanna; Librach, Clifford L; Claessens, Anne; Ryan, Edward A J

2016-07-01

The objective of this study is to compare the combination of dehydroepiandrosterone (DHEA) and coenzyme Q10 (CoQ10) (D + C) with DHEA alone (D) in intrauterine insemination (IUI) and in vitro fertilization (IVF) cycles among patients with decreased ovarian reserve. We retrospectively extracted data from patients charts treated by DHEA with/without CoQ10 during IUI or IVF between February 2006 and June 2014. Prestimulation parameters included age, BMI, day 3 FSH and antral follicular count (AFC). Ovarian response parameters included total gonadotropins dosage, peak serum estradiol, number of follicles > 16 mm and fertilization rate. Clinical outcomes included clinical and ongoing pregnancy rates. Three hundred and thirty IUI cycles involved D + C compared with 467 cycles of D; 78 IVF cycles involved D + C and 175 D. In both IUI and IVF, AFC was higher with D + C compared with D (7.4 ± 5.7 versus 5.9 ± 4.7, 8.2 ± 6.3 versus 5.2 ± 5, respectively, p < 0.05). D + C resulted in a more follicles > 16 mm during IUI cycles (3.3 ± 2.3 versus 2.9 ± 2.2, respectively, p = 0.01), while lower mean total gonadotropin dosage was administered after D + C supplementation compared with D (3414 ± 1141 IUs versus 3877 ± 1143 IUs respectively, p = 0.032) in IVF cycles. Pregnancy and delivery rates were similar for both IUI and IVF. D + C significantly increases AFC and improves ovarian responsiveness during IUI and IVF without a difference in clinical outcome.

The Groningen ART cohort study: the effects of ovarian hyperstimulation and the IVF laboratory procedures on neurological condition at 2 years.

PubMed

Schendelaar, P; Middelburg, K J; Bos, A F; Heineman, M J; Jongbloed-Pereboom, M; Hadders-Algra, M

2011-03-01

Up to 4% of children are born following assisted reproduction techniques (ART) yet relatively little is known on neurodevelopmental outcome of these children after 18 months of age. Only a limited number of long-term follow-up studies with adequate methodological quality have been reported. Our aim was to evaluate the effects of ovarian hyperstimulation, IVF laboratory procedures and a history of subfertility on neurological condition at 2 years. Singletons born after controlled ovarian hyperstimulation IVF (COH-IVF, n = 66), modified natural cycle IVF (MNC-IVF, n = 56), natural conception in subfertile couples (Sub-NC, n = 87) and in fertile couples (reference group, n = 101) were assessed (using Hempel approach) by neurological examination at 2 years of age. This resulted in a neurological optimality score (NOS), a fluency score and the prevalence of minor neurological dysfunction (MND). Primary outcome was the fluency score, as fluency of movements is easily affected by subtle dysfunction of the nervous system. Fluency score, NOS and prevalence of MND were similar in COH-IVF, MNC-IVF and Sub-NC children. However, the fluency score (P < 0.01) and NOS (P < 0.001) of the three subfertile groups were higher, and the prevalence of MND was lower (P = 0.045), than those in the reference group. Neurological condition of 2 year olds born after ART is similar to that of children of subfertile couples conceived naturally. Moreover, subfertility does not seem to be associated with a worse neurological outcome. These findings are reassuring, but we have to keep in mind that subtle neurodevelopmental disorders may emerge as children grow older.

In Vitro Fertilization in Women With Inflammatory Bowel Disease Is as Successful as in Women From the General Infertility Population

PubMed Central

Oza, Sveta Shah; Pabby, Vikas; Dodge, Laura E.; Moragianni, Vasiliki A.; Hacker, Michele R.; Fox, Janis H.; Correia, Katharine; Missmer, Stacey A.; Ibrahim, Yetunde; Penzias, Alan S.; Burakoff, Robert; Friedman, Sonia; Cheifetz, Adam S.

2015-01-01

BACKGROUND & AIMS Inflammatory bowel disease (IBD) affects women of reproductive age, so there are concerns about its effects on fertility. We investigated the success of in vitro fertilization (IVF) in patients with IBD compared with the general (non-IBD) IVF population. METHODS We conducted a matched retrospective cohort study of female patients with IBD who under-went IVF from 1998 through 2011 at 2 tertiary care centers. Patients were matched 4:1 to those without IBD (controls). The primary outcome was the cumulative rate of live births after up to 6 cycles of IVF. Secondary outcomes included the proportion of patients who became pregnant and the rate of live births for each cycle. RESULTS Forty-nine patients with Crohn’s disease (CD), 71 patients with ulcerative colitis (UC), 1 patient with IBD-unclassified, and 470 controls underwent IVF during the study period. The cumulative rate of live births was 53% for controls, 69% for patients with UC (P = .08 compared with controls), and 57% for patients with CD (P = .87 compared with controls). The incidence of pregnancy after the first cycle of IVF was similar among controls (40.9%), patients with UC (49.3%; P = .18), and patients with CD (42.9%; P = .79). Similarly, the incidence of live births after the first cycle of IVF was similar among controls (30.2%), patients with UC (33.8%; P = .54), and patients with CD (30.6%; P = .95). CONCLUSIONS Based on a matched cohort study, infertile women with IBD achieve rates of live births after IVF that are comparable with those of infertile women without IBD. PMID:25818081

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.

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

[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.

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.

Method of euthanasia influences the oocyte fertilization rate with fresh mouse sperm.

PubMed

Hazzard, Karen C; Watkins-Chow, Dawn E; Garrett, Lisa J

2014-11-01

In vitro fertilization (IVF) is used to produce mouse embryos for a variety of reasons. We evaluated the effect of the method of euthanasia on the fertilization rate in 2 different IVF protocols. Oocytes collected from C57BL/6J female mice euthanized by CO2 inhalation or cervical dislocation were used in IVF with fresh sperm from either wild-type or genetically engineered C57BL/6J. Compared with CO2 inhalation, cervical dislocation improved the resulting rate of fertilization by 18% in an IVF method using Cook media and by 13% in an IVF method using methyl-B cyclodextrin and reduced glutathione. The lower fertilization rate due to euthanasia by CO2 inhalation was accompanied by changes in blood pH and body temperature despite efforts to minimize temperature drops. In our hands, euthanasia by cervical dislocation improved fertilization rates and consequently reduced the number of egg-donor mice required.

Lifestyle and IVF Outcomes.

PubMed

Hornstein, Mark D

2016-12-01

Whereas much has been written about the prognostic factors associated with outcomes of in vitro fertilization (IVF) such as female age, diagnosis, and ovarian reserve, relatively little attention has been devoted to patient-oriented lifestyles that may influence IVF outcomes. Patients are particularly interested in this topic because many patients wish to partner with their physicians and want to know specific behaviors to improve their chances of IVF success. This brief review is not intended as an exhaustive literature search of all possible lifestyles that may influence assisted reproductive outcome nor is it intended to be a comprehensive review of individual topics. It does give, however, a brief overview of a number of areas in which patient-specific behaviors may influence outcomes in assisted reproduction. Specifically, this review will look at the effects of smoking, alcohol consumption, caffeine, diet, exercise, and exposure to the reproductive toxin bisphenol A on IVF outcomes. © The Author(s) 2016.

Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review.

PubMed

Irani, Mohamad; Merhi, Zaher

2014-08-01

To report an update on the role of vitamin D (VD) in ovarian physiology with a focus on genes involved in steroidogenesis, follicular development, and ovarian reserve, as well as ovulatory dysfunction associated with polycystic ovary syndrome (PCOS), and ovarian response to assisted reproductive technology (ART). Systematic review. Not applicable. Human, animal, and cell culture models. Pubmed literature search. Granulosa cell function, serum antimüllerian hormone (AMH), AMH and its receptor gene expression, soluble receptor for advanced glycation end-products (sRAGE), PCOS parameters, and ART outcome. In human granulosa cells, VD alters AMH signaling, FSH sensitivity, and progesterone production and release, indicating a possible physiologic role for VD in ovarian follicular development and luteinization. In the serum, 25-hydroxyvitamin D (25OH-D) is positively correlated with AMH, and appropriate VD supplementation in VD-depleted women can suppress the seasonal changes that occur in serum AMH. In VD-deficient women with PCOS, VD supplementation lowers the abnormally elevated serum AMH levels, possibly indicating a mechanism by which VD improves folliculogenesis. The antiinflammatory sRAGE serum levels significantly increase in women with PCOS after VD replacement. Although follicular fluid 25OH-D correlates with IVF outcomes, there is a lack of data pertaining to the impact of VD supplementation on pregnancy rates following IVF. This review underscores the need for understanding the mechanistic actions of VD in ovarian physiology and the critical need for randomized trials to elucidate the impact of VD supplementation on controlled ovarian hyperstimulation/IVF outcome and ovulatory dysfunction associated with PCOS. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Characterization and quantification of proteins secreted by single human embryos prior to implantation.

PubMed

Poli, Maurizio; Ori, Alessandro; Child, Tim; Jaroudi, Souraya; Spath, Katharina; Beck, Martin; Wells, Dagan

2015-11-01

The use of in vitro fertilization (IVF) has revolutionized the treatment of infertility and is now responsible for 1-5% of all births in industrialized countries. During IVF, it is typical for patients to generate multiple embryos. However, only a small proportion of them possess the genetic and metabolic requirements needed in order to produce a healthy pregnancy. The identification of the embryo with the greatest developmental capacity represents a major challenge for fertility clinics. Current methods for the assessment of embryo competence are proven inefficient, and the inadvertent transfer of non-viable embryos is the principal reason why most IVF treatments (approximately two-thirds) end in failure. In this study, we investigate how the application of proteomic measurements could improve success rates in clinical embryology. We describe a procedure that allows the identification and quantification of proteins of embryonic origin, present in attomole concentrations in the blastocoel, the enclosed fluid-filled cavity that forms within 5-day-old human embryos. By using targeted proteomics, we demonstrate the feasibility of quantifying multiple proteins in samples derived from single blastocoels and that such measurements correlate with aspects of embryo viability, such as chromosomal (ploidy) status. This study illustrates the potential of high-sensitivity proteomics to measure clinically relevant biomarkers in minute samples and, more specifically, suggests that key aspects of embryo competence could be measured using a proteomic-based strategy, with negligible risk of harm to the living embryo. Our work paves the way for the development of "next-generation" embryo competence assessment strategies, based on functional proteomics. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

Comparison of Ovulation Induction Protocols After Endometrioma Resection

PubMed Central

Yasa, Cenk; Dural, Ozlem; Mutlu, Mehmet Firat; Celik, Cem; Ugurlucan, Funda Gungor; Buyru, Faruk

2014-01-01

Background and Objectives: The aim of this study was to compare the in vitro fertilization (IVF) outcomes of long gonadotropin-releasing hormone agonist (GnRH-a) and GnRH-antagonist (GnRH-ant) protocols in endometriosis patients who have undergone laparoscopic endometrioma resection surgery. To our knowledge, there is no study in the current literature that compares the effectiveness of long GnRH-a and GnRH-ant protocols in management of IVF cycles in endometriosis patients who underwent laparoscopic endometrioma resection surgery. Methods: Eighty-six patients with stage III to IV endometriosis who had undergone laparoscopic resection surgery for endometrioma were divided into 2 groups: those who had ovarian stimulation with a long GnRH-a protocol (n = 44), and those who had ovarian stimulation with a GnRH-ant protocol (n = 42). Results: The number of follicles on human chorionic gonadotropin injection day, duration of hyperstimulation, number of retrieved metaphase II oocytes, and total number of grade 1 embryos were statically significantly higher in the long GnRH-a protocol. There were no significant differences in positive β-human chorionic gonadotropin pregnancy rates (25% vs 21.4%; P = .269) and ongoing pregnancy rates per patient (20.5% vs 19.1%; P = .302) between the 2 protocols. Conclusions: Long GnRH-a and GnRH-ant protocols both present similar IVF outcomes in patients with endometriosis who have undergone laparoscopic endometrioma resection surgery. A long GnRH-a protocol may lead to a higher number of embryos that can be cryopreserved, providing the possibility of additional embryo transfers without having to go through the process of ovarian stimulation again. PMID:25392665

Effectiveness of semen washing to prevent human immunodeficiency virus (HIV) transmission and assist pregnancy in HIV-discordant couples: a systematic review and meta-analysis.

PubMed

Zafer, Maryam; Horvath, Hacsi; Mmeje, Okeoma; van der Poel, Sheryl; Semprini, Augusto E; Rutherford, George; Brown, Joelle

2016-03-01

To evaluate the effectiveness of semen washing in human immunodeficiency virus (HIV)-discordant couples in which the male partner is infected. Systematic review and meta-analysis. Not applicable. Forty single-arm open-label studies among HIV-discordant couples that underwent intrauterine insemination (IUI) or in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI) using washed semen. Semen washing followed by IUI, IVF, or IVF/ICSI. HIV transmission to HIV-uninfected women; secondary outcomes: HIV transmission to newborns and proportion of couples achieving a clinical pregnancy. No HIV transmission occurred in 11,585 cycles of assisted reproduction with the use of washed semen among 3,994 women. Among the subset of HIV-infected men without plasma viral suppression at the time of semen washing, no HIV seroconversions occurred among 1,023 women after 2,863 cycles of assisted reproduction with the use of washed semen. Studies that measured HIV transmission to infants reported no cases of vertical transmission. Overall, 56.3% of couples (2,357/4,184) achieved a clinical pregnancy with the use of washed semen. Semen washing appears to significantly reduce the risk of transmission in HIV-discordant couples desiring children, regardless of viral suppression in the male partner. There are no randomized controlled studies or studies from low-income countries, especially those with a large burden of HIV. Continued development of lower-cost semen washing and assisted reproduction technologies is needed. Integration of semen washing into HIV prevention interventions could help to further reduce the spread of HIV. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Fundamentals of human embryonic growth in vitro and the selection of high-quality embryos for transfer.

PubMed

Boiso, Irene; Veiga, Anna; Edwards, Robert G

2002-01-01

Knowledge of the nature of embryo growth, and the handling and scoring of quality in human embryos are significant aspects for embryologists in IVF clinics. This review describes the formation, growth and maturation of human oocytes, many aspects of fertilization in vitro, embryonic transcription during preimplantation stages, and the formation of polarities, timing controls, role of mitochondria and functions of endocrine and paracrine systems. Modern concepts are fully discussed, together with their significance in the practice of IVF. This knowledge is essential for the correct clinical care of human embryos growing in vitro, especially in view of their uncharacteristic tendency to vary widely in implantation potential. Underlying causes of such variation have not been identified. Stringent tests must be enforced to ensure human embryos develop under optimal conditions, and are scored for quality using the most advanced techniques. Optimal methods of culture are described, including methods such as co-culture introduced to improve embryo quality but less important today. Detailed attention is given to quality as assessed from embryonic characteristics determined by timers, polarities, disturbed embryo growth and anomalous cell cycles. Methods for classification are described. Approaches to single embryo transfers are described, including the use of sequential media to produce high-quality blastocysts. These approaches, and others involved in surgical methods to remove fragments, transfer ooplasm or utilize newer approaches such as preimplantation diagnosis of chromosomal complements in embryos are covered. New outlooks in this field are summarized.

Soldier Capability - Army Combat Effectiveness (SCACE). Volume 2. Selected Bibliography

DTIC Science & Technology

1981-02-01

Human Resources Research Office, June 1963. 388. McLachlan, Joseph C., et al. Navy-Wide Standardized Proficiency Testing Program for Fleet JEZEBEL...Directorate of Evaluation, August 1979. 428. Olmstead, Joseph A., et al. Research on Training for Brigade Com- mand Groups: Factors Contributing to Unit...orormance Human Rsurces Research Organization, August 1972. 686. Vitola, B. M., Guinn, N., and Wilbourn , J. N. acm o Various Enlistment Standards on

SMART Application: One stop services bridging the gap between doctor and patients

NASA Astrophysics Data System (ADS)

Wiweko, Budi; Agung, P. G.; Narasati, Shabrina

2017-02-01

In this study, we describe the SMART IVF services that has been developed into android-based application as "SMART Application". In this application, we can find one stop services in IVF. This application is expected to help patients to plan effectively for IVF procedure, full access to their IVF information helps them ease off a lot of stress and anxiety in this very delicate and stressful phase in their lives and help the doctor to plan for the best intervention of patients who face infertility problems using Assisted Reproductive Technology (ART). SMART application will be compatible with all major mobile operating systems.

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.

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.

Prevalence of dental attrition in in vitro fertilization children of West Bengal

PubMed Central

Kar, Sudipta; Sarkar, Subrata; Mukherjee, Ananya

2014-01-01

CONTEXT: Dental attrition is one of the problems affecting the tooth structure. It may affect both in vitro fertilization (IVF) and spontaneously conceived children. AIMS: This study was aimed to evaluate and to compare the prevalence of dental attrition in deciduous dentition of IVF and spontaneously conceived children. SETTINGS AND DESIGN: In a cross-sectional case control study dental attrition status of 3-5 years old children were assessed. The case group consisted of term, singleton babies who were the outcome of IVF in the studied area in 2009. SUBJECTS AND METHODS: The control group consisted of term, first child, singleton and spontaneously conceived 3-5 years old children who were also resident of the studied area. A sample of 153 IVF and 153 spontaneously conceived children was examined according to Hansson and Nilner classification. STATISTICAL ANALYSIS USED: Statistical analysis was carried out using Chi-square tests (χ2 ) or Z test. RESULTS: No statistically significant difference found in studied (IVF children) and control group (spontaneously conceived children). CONCLUSIONS: IVF children are considered same as spontaneously conceived children when studied in relation to dental attrition status. PMID:24829529