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

PubMed

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

2018-05-01

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

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.

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

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.

[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.

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 ...

Fifteen years experience with an in-vitro fertilization surrogate gestational pregnancy programme.

PubMed

Goldfarb, J M; Austin, C; Peskin, B; Lisbona, H; Desai, N; de Mola, J R

2000-05-01

The purpose of our study was to review and evaluate retrospectively the experience of an in-vitro fertilization (IVF) surrogate gestational programme in a tertiary care and academic centre. In a 15 year period from 1984 to 1999, a total of 180 cycles of IVF surrogate gestational pregnancy was started in 112 couples. On average, the women were 34.4 +/- 4.4 years of age, had 11.1 +/- 0.72 oocytes obtained per retrieval, 7.1 +/- 0.5 oocytes fertilized and 5. 8 +/- 0.4 embryos subsequently cleaved. Sixteen cycles (8.9%) were cancelled due to poor stimulation. Except for six cycles (3.3%) where there were no embryos available, an average of 3.2 +/- 0.1 embryos was transferred to each individual recipient. The overall pregnancy rate per cycle after IVF surrogacy was 24% (38 of 158), with a clinical pregnancy rate of 19% (30 of 158), and a live birth rate of 15.8% (25 of 158). When compared to patients who underwent a hysterectomy, individuals with congenital absence of the uterus had significantly more oocytes retrieved (P < 0.006), fertilized, cleaved and more embryos available for transfer despite being of comparable age. IVF surrogate gestation is an established, yet still controversial, approach to the care of infertile couples. Take-home baby rates are comparable to conventional IVF over the same 15 year span in our programme. Patients with congenital absence of the uterus responded to ovulation induction better than patients who underwent a hysterectomy, perhaps due in part to ovarian compromise from previous surgical procedures.

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.

Endometrial thickness as a predictor of the reproductive outcomes in fresh and frozen embryo transfer cycles: A retrospective cohort study of 1512 IVF cycles with morphologically good-quality blastocyst.

PubMed

Zhang, Tao; Li, Zhou; Ren, Xinling; Huang, Bo; Zhu, Guijin; Yang, Wei; Jin, Lei

2018-01-01

To evaluate the relationship between endometrial thickness during fresh in vitro fertilization (IVF) cycles and the clinical outcomes of subsequent frozen embryo transfer (FET) cycles.FET cycles using at least one morphological good-quality blastocyst conducted between 2012 and 2013 at a university-based reproductive center were reviewed retrospectively. Endometrial ultrasonographic characteristics were recorded both on the oocyte retrieval day and on the day of progesterone supplementation in FET cycles. Clinical pregnancy rate, spontaneous abortion rate, and live birth rate were analyzed.One thousand five hundred twelve FET cycles was included. The results showed that significant difference in endometrial thickness on day of oocyte retrieval (P = .03) was observed between the live birth group (n = 844) and no live birth group (n = 668), while no significant difference in FET endometrial thickness was found (P = .261) between the live birth group and no live birth group. For endometrial thickness on oocyte retrieval day, clinical pregnancy rate ranged from 50.0% among patients with an endometrial thickness of ≤6 mm to 84.2% among patients with an endometrial thickness of >16 mm, with live birth rate from 33.3% to 63.2%. Multiple logistic regression analysis of factors related to live birth indicated endometrial thickness on oocyte retrieval day was associated with improved live birth rate (OR was 1.069, 95% CI: 1.011-1.130, P = .019), while FET endometrial thickness did not contribute significantly to pregnancy outcomes following FET cycles. The ROC curves revealed the cut-off points of endometrial thickness on oocyte retrieval day was 8.75 mm for live birth.Endometrial thickness during fresh IVF cycles was a better predictor of endometrial receptivity in subsequent FET cycles than FET cycle endometrial thickness. For those females with thin endometrium in fresh cycles, additional estradiol stimulation might be helpful for adequate endometrial development.

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.

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.

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.

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

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.

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.

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

PubMed

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

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

Role of rescue IVF-ET treatment in the management of high response in stimulated IUI cycles.

PubMed

Olufowobi, O; Sharif, K; Papaioannou, S; Mohamed, H; Neelakantan, D; Afnan, M

2005-02-01

Rescue in-vitro fertilisation and embryo transfer (IVF-ET) has been used in high response gonadotrophin intrauterine insemination (IUI) cycles to minimise the risks of ovarian hyperstimulation and multiple gestation. Such unplanned IVF treatment increases the cost of treatment. But can this added cost and the risks associated with IVF be justified? We present our experience with this treatment using clinical pregnancy and live birth rates as the primary outcomes. Between 1998 to 2001, 40 women undergoing IUI cycles who over responded (>3 follicles measuring >15 mm in diameter on the planned day of hCG administration) to gonadotrophin were offered the choice of conversion to IVF-ET or cancel the cycle. 17/40 declined rescue IVF/ET and had their cycles cancelled. 23/40 converted to IVF/ET and underwent transvaginal oocyte retrieval. 21/23 had embryo transferred. The clinical pregnancy and live birth rates were 52% and 48%, respectively. Rescue IVF-ET offers excellent clinical pregnancy and live birth rates in high responders. However, affordability can be an obstacle in the utilization of this treatment option.

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

PubMed

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

2013-08-30

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

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

PubMed

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

2016-07-01

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

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.

Fresh embryo transfer versus frozen embryo transfer in in vitro fertilization cycles: a systematic review and meta-analysis.

PubMed

Roque, Matheus; Lattes, Karinna; Serra, Sandra; Solà, Ivan; Geber, Selmo; Carreras, Ramón; Checa, Miguel Angel

2013-01-01

To examine the available evidence to assess if cryopreservation of all embryos and subsequent frozen embryo transfer (FET) results in better outcomes compared with fresh transfer. Systematic review and meta-analysis. Centers for reproductive care. Infertility patient(s). An exhaustive electronic literature search in MEDLINE, EMBASE, and the Cochrane Library was performed through December 2011. We included randomized clinical trials comparing outcomes of IVF cycles between fresh and frozen embryo transfers. The outcomes of interest were ongoing pregnancy rate, clinical pregnancy rate, and miscarriage. We included three trials accounting for 633 cycles in women aged 27-33 years. Data analysis showed that FET resulted in significantly higher ongoing pregnancy rates and clinical pregnancy rates. Our results suggest that there is evidence that IVF outcomes may be improved by performing FET compared with fresh embryo transfer. This could be explained by a better embryo-endometrium synchrony achieved with endometrium preparation cycles. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

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.

Does the use of gonadotropin-releasing hormone antagonists in natural IVF cycles for poor responder patients cause more harm than benefit?

PubMed

Aksoy, Senai; Yakin, Kayhan; Seyhan, Ayse; Oktem, Ozgur; Alatas, Cengiz; Ata, Baris; Urman, Bulent

2016-06-01

Poor ovarian response to controlled ovarian stimulation (COS) is one of the most critical factors that substantially limits the success of assisted reproduction techniques (ARTs). Natural and modified natural cycle IVF are two options that could be considered as a last resort. Blocking gonadotropin-releasing hormone (GnRH) actions in the endometrium via GnRH receptor antagonism may have a negative impact on endometrial receptivity. We analysed IVF outcomes in 142 natural (n = 30) or modified natural (n = 112) IVF cycles performed in 82 women retrospectively. A significantly lower proportion of natural cycles reached follicular aspiration compared to modified natural cycles (56.7% vs. 85.7%, p < 0.001). However, the difference between the numbers of IVF cycles ending in embryo transfer (26.7% vs. 44.6%) was not statistically significant between natural cycle and modified natural IVF cycles. Clinical pregnancy (6.7% vs. 7.1%) and live birth rates per initiated cycle (6.7% vs. 5.4%) were similar between the two groups. Notably, the implantation rate was slightly lower in modified natural cycles (16% vs. 25%, p > 0.05). There was a trend towards higher clinical pregnancy (25% vs. 16%) and live birth (25% vs. 12%) rates per embryo transfer in natural cycles compared to modified natural cycles, but the differences did not reach statistical significance.

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.

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.

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)

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.

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.

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.

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

PubMed

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

2009-07-01

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

In vitro fertilization surrogate pregnancy in a patient who underwent radical hysterectomy followed by ovarian transposition, lower abdominal wall radiotherapy, and chemotherapy.

PubMed

Steigrad, Stephen; Hacker, Neville F; Kolb, Bradford

2005-05-01

To describe an IVF surrogate pregnancy from a patient who had a radical hysterectomy followed by excision of a laparoscopic port site implantation with ovarian transposition followed by abdominal wall irradiation and chemotherapy, which resulted in premature ovarian failure from which there was partial recovery. Case report. Tertiary referral university women's hospital in Sydney, Australia and private reproductive medicine clinic in California. A 34-year-old woman who underwent laparoscopy for pelvic pain, shortly afterward followed by radical hysterectomy and pelvic lymph node dissection, who subsequently developed a laparoscopic port site recurrence, which was excised in association with ovarian transposition before abdominal wall irradiation and chemotherapy. Modified IVF treatment, transabdominal oocyte retrieval, embryo cryopreservation in Australia, and transfer to a surrogate mother in the United States. Pregnancy. Miscarriage in the second cycle and a twin pregnancy in the fourth cycle. This is the first case report of ovarian stimulation and oocyte retrieval performed on transposed ovaries after a patient developed premature ovarian failure after radiotherapy and chemotherapy with subsequent partial ovarian recovery.

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.

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

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.

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.

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

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

PubMed

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

2007-12-21

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

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

PubMed Central

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

2007-01-01

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

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.

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.

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.

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.

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.

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.

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

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.

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.

Increasing synthetic serum substitute (SSS) concentrations in P1 glucose/phosphate-free medium improves implantation rate: a comparative study.

PubMed

Ben-Yosef, D; Yovel, I; Schwartz, T; Azem, F; Lessing, J B; Amit, A

2001-11-01

To assess the comparative efficacy of IVF medium (MediCult, with 5.2 mM glucose) and a glucose/phosphate-free medium, P1 (Irvine Scientific), and to investigate the influence of increasing the serum supplementation (synthetic serum substitute; SSS; Irvine Scientific) to P1 on embryo development and implantation. Patients were randomly assigned to IVF medium (Group 1, cycles n = 172) or P1 supplemented with 10% SSS (Group 2, cycles n = 229) according to the medium scheduled for use on the day of oocyte retrieval. Another 555 IVF consequent cycles (Group 3) were performed using increased SSS concentrations (20%) in P1 medium. In this large series of IVF cycles, we herein demonstrate that significantly higher pregnancy and implantation rates were found when embryos were cultured in glucose/phosphate-free medium P1 supplemented with 20% SSS compared to supplementation with the lower SSS concentration and with IVF medium.

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.

IVF endocrinology: the Edwards era.

PubMed

Hillier, Stephen G

2013-12-01

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

Impact of presence of antiphospholipid antibodies on in vitro fertilization outcome

PubMed Central

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

2018-01-01

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

The duration of gonadotropin stimulation does not alter the clinical pregnancy rate in IVF or ICSI cycles.

PubMed

Purandare, N; Emerson, G; Kirkham, C; Harrity, C; Walsh, D; Mocanu, E

2017-08-01

Ovarian stimulation is an essential part of assisted reproduction treatments. Research on whether the duration of stimulation alters the success in assisted reproduction has not been conclusive. The purpose of the study was to establish whether the duration of ovarian stimulation alters the success in assisted reproduction treatments. All fresh (non-donor) stimulation cycles performed in an academic tertiary referral ART centre over a period of 18 years, between 1st January 1997 and 31st December 2014, were identified. Data were prospectively and electronically collected. IVF and ICSI cycles were analysed independently. Each category was then subdivided into assisted reproduction cycles where the antagonist, long (down regulation) and flare protocol were used. Clinical pregnancy was the main outcome measured. A total of 10,478 stimulation cycles (6011 fresh IVF and 4467 fresh ICSI) reaching egg collection were included. We showed no significant difference in CP rates in IVF cycles for the long (p = 0.082), antagonist (p = 0.217) or flare (p = 0.741) protocol cycles or in ICSI cycles with the long (p = 0.223), antagonist (p = 0.766) or the flare (p = 0.690) protocol with regards the duration of stimulation. The duration of stimulation does not alter the CP rate in ICSI or IVF cycles using the long, antagonist or flare stimulation protocol.

Endometrial thickness as a predictor of the reproductive outcomes in fresh and frozen embryo transfer cycles

PubMed Central

Zhang, Tao; Li, Zhou; Ren, Xinling; Huang, Bo; Zhu, Guijin; Yang, Wei; Jin, Lei

2018-01-01

Abstract To evaluate the relationship between endometrial thickness during fresh in vitro fertilization (IVF) cycles and the clinical outcomes of subsequent frozen embryo transfer (FET) cycles. FET cycles using at least one morphological good-quality blastocyst conducted between 2012 and 2013 at a university-based reproductive center were reviewed retrospectively. Endometrial ultrasonographic characteristics were recorded both on the oocyte retrieval day and on the day of progesterone supplementation in FET cycles. Clinical pregnancy rate, spontaneous abortion rate, and live birth rate were analyzed. One thousand five hundred twelve FET cycles was included. The results showed that significant difference in endometrial thickness on day of oocyte retrieval (P = .03) was observed between the live birth group (n = 844) and no live birth group (n = 668), while no significant difference in FET endometrial thickness was found (P = .261) between the live birth group and no live birth group. For endometrial thickness on oocyte retrieval day, clinical pregnancy rate ranged from 50.0% among patients with an endometrial thickness of ≤6 mm to 84.2% among patients with an endometrial thickness of >16 mm, with live birth rate from 33.3% to 63.2%. Multiple logistic regression analysis of factors related to live birth indicated endometrial thickness on oocyte retrieval day was associated with improved live birth rate (OR was 1.069, 95% CI: 1.011–1.130, P = .019), while FET endometrial thickness did not contribute significantly to pregnancy outcomes following FET cycles. The ROC curves revealed the cut-off points of endometrial thickness on oocyte retrieval day was 8.75 mm for live birth. Endometrial thickness during fresh IVF cycles was a better predictor of endometrial receptivity in subsequent FET cycles than FET cycle endometrial thickness. For those females with thin endometrium in fresh cycles, additional estradiol stimulation might be helpful for adequate endometrial development. PMID:29369190

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.

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

PubMed

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

2017-07-21

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

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.

[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.

Differences in cumulus cells gene expression between modified natural and stimulated in vitro fertilization cycles.

PubMed

Papler, Tanja Burnik; Bokal, Eda Vrtačnik; Tacer, Klementina Fon; Juvan, Peter; Virant Klun, Irma; Devjak, Rok

2014-01-01

The aim of our study was to determine whether there are any differences in the cumulus cell gene expression profile of mature oocytes derived from modified natural IVF and controlled ovarian hyperstimulation cycles and if these changes could help us understand why modified natural IVF has lower success rates. Cumulus cells surrounding mature oocytes that developed to morulae or blastocysts on day 5 after oocyte retrieval were submitted to microarray analysis. The obtained data were then validated using quantitative real-time PCR. There were 66 differentially expressed genes between cumulus cells of modified natural IVF and controlled ovarian hyperstimulation cycles. Gene ontology analysis revealed the oxidation-reduction process, glutathione metabolic process, xenobiotic metabolic process and gene expression were significantly enriched biological processes in MNIVF cycles. Among differentially expressed genes we observed a large group of small nucleolar RNA's whose role in folliculogenesis has not yet been established. The increased expression of genes involved in the oxidation-reduction process probably points to hypoxic conditions in modified natural IVF cycles. This finding opens up new perspectives for the establishment of the potential role that oxidation-reduction processes have in determining success rates of modified natural IVF.

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

PubMed

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

2009-12-18

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

Laparoscopic ovarian cystectomy of endometriomas does not affect the ovarian response to gonadotropin stimulation.

PubMed

Marconi, Guillermo; Vilela, Martín; Quintana, Ramiro; Sueldo, Carlos

2002-10-01

To evaluate the ovarian response cycles of IVF-ET in patients who previously underwent laparoscopic cystectomy for endometriomas. Retrospective study with prospective selection of participants and controls. Instituto de Ginecología y Fertilidad Buenos Aires, Argentina. Thirty-nine patients underwent an operation for ovarian endometriomas by atraumatic removal of the pseudocapsule with minimal bipolar cauterization of small bleeders and an IVF-ET cycle (group A) and 39 control patients of similar age underwent an IVF-ET cycle for tubal factor infertility (group B). Laparoscopic endometrioma cystectomy, IVF-ET cycle. E(2) levels, number of gonadotropin ampoules, follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate. There were no differences in all the parameters studied (E(2) levels, number of follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate) except for the number of gonadotropin ampoules needed for ovarian hyperstimulation, which was significantly higher in group A than in group B. Our results indicate that laparoscopic cystectomy for endometriomas is an appropriate treatment since it did not negatively affect the ovarian response for IVF-ET.

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.

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

PubMed

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

2017-08-01

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

In vitro fertilization in women under 35: counseling should differ by age.

PubMed

Humm, K C; Dodge, L E; Wu, L H; Penzias, A S; Malizia, B A; Sakkas, D; Hacker, M R

2015-10-01

The aim of this study is to evaluate the outcomes of in vitro fertilization (IVF), including cumulative live birth rate, among women <25 years, 25 to <30 years, and 30 to <35 years. A retrospective cohort study of all women 18 to <35 years of age at their first fresh-embryo, non-donor IVF cycle from January 1995 through December 2012 at a single center was conducted. A competing-risk regression model was used to estimate the cumulative probability and 95 % confidence interval (CI) of the first live birth in up to 6 cycles during the study period with IVF cycle number as the time metric. Among 7243 women who underwent 16,792 cycles, there were 163 (2.3 %) women <25 years, 1691 (23.3 %) women 25 to <30 years, and 5389 (74.4 %) women 30 to <35 years. Women <25 years had the lowest cumulative live birth rate after each cycle, followed by women 30 to <35 years. In both groups, the cumulative live birth rate after 6 cycles was significantly lower than that of women 25 to <30 years; these rates were 58 % (95 % CI 0.51-0.66) among women <25 years, 69 % (95 % CI 0.67-0.71) among women 25 to <30 years, and 64 % (95 % CI 0.63-0.65) among women 30 to <35 years. Our findings are consistent with other reports of less favorable IVF treatment outcomes in women <25 years of age following their first IVF cycle. This indicates that there are underlying factors in couples with a female <25 years of age that should lead to different treatment counseling when they attempt IVF.

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

PubMed

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

2018-07-01

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

Does autoimmunity play a role in the risk of implantation failures?

PubMed

Motak-Pochrzest, Hanna; Malinowski, Andrzej

2018-02-01

158 non-pregnant women with recurrent implantation failures after IVF/ET procedures were tested for peripheral blood autoimmune profile. The control group consisted of 76 patients after first successful IVF procedure and pregnancy outcome. The objective of this study was to investigate different autoantibodies peripheral blood profile after excluding anatomical, endocrinological, endometrial and genetic disorders and to estimate the risk of implantation failures. The study's including criteria were 1.indications for IVF/ET determined by male factor and unexplained infertility 2. absence of implantation after two consecutive cycles of IVF, ICSI or frozen embryo replacement cycles. The presence of ANA in the sera increased the risk of RIF after ET/IVF procedures, especially in older patients. Patients with RIF have a higher frequency of the presence of autoantibodies ACA IgG, IgM and anti-β2GP I IgG in the sera than in patients with successful pregnancies after IVF/ET procedures.

Reproductive outcome after IVF following hysteroscopic division of incomplete uterine septum/arcuate uterine anomaly in women with primary infertility

PubMed Central

Abuzeid, M.; Ghourab, G.; Abuzeid, O.; Mitwally, M.; Ashraf, M.; Diamond, M.

2014-01-01

Objective: To determine reproductive outcome after in-vitro fertilization/embryo transfer (IVF-ET) in women with primary infertility following hysteroscopic septoplasty of incomplete uterine septum or arcuate uterine anomaly. Methods: This is a historical cohort study. The study group consisted of 156 consecutive patients who underwent a total of 221 cycles of IVF/ET following hysteroscopic septoplasty of an incomplete uterine septum or arcuate anomaly (Group 1). The control group included 196 consecutive patients with normal endometrial cavity on hysteroscopy who underwent a total of 369 cycles of IVF/ET (Group 2). The reproductive outcome after the first cycle of IVF-ET and the best reproductive outcome of all the cycles the patient underwent were calculated. In addition, we compared the reproductive outcome in the study group based on the type of the anomalies (septum versus arcuate). Results: In the first fresh cycle, following septoplasty, there were significantly higher clinical pregnancy and delivery rates in Group 1 (60.3% and 51.3% respectively) compared to Group 2 (38.8% and 33.2% respectively). However, there was no significant difference between the two groups in the clinical pregnancy (74.4% vs. 67.3%) or in the delivery (65.4% vs. 60.2%) rates per patient, respectively. There was no significant difference in the reproductive outcome after IVF-ET between patients who previously had arcuate uterine anomaly versus incomplete uterine septum. Conclusion: Reproductive outcome of IVF-ET after hysteroscopic correction of incomplete uterine septum/arcuate uterine anomaly in women with primary infertility is no different from women with normal uterine cavity. PMID:25593694

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

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.

Comparison of IVF cycles reported in a voluntary ART registry with a mandatory registry in Spain.

PubMed

Luceño, F; Castilla, J A; Gómez-Palomares, J L; Cabello, Y; Hernández, J; Marqueta, J; Herrero, J; Vidal, E; Fernández-Shaw, S; Coroleu, B

2010-12-01

Monitoring assisted reproductive technology (ART) is essential to evaluate the performance of fertility treatment and its impact on birth rates. In Europe, there are two kinds of ART registers: voluntary and mandatory. The validity of register data is very important with respect to the quality of register-based observational studies. The aim of this paper is to determine the degree of agreement between voluntary and mandatory ART registers. The two sources for the data compared in this study (referring to 2005 and 2006) were FIVCAT.NET (an official compulsory Assisted Reproduction Registry within the Health Ministry of the Regional Government of Catalonia, to which all authorized clinics, both public and private, performing assisted reproduction in the region are obliged to report) and the register of the Spanish Fertility Society (SEF), to which data are provided on a voluntary basis. The SEF register data were divided into two groups: (i) data from clinics in Catalonia (SEF-CAT); (ii) data from the rest of Spain, excluding Catalonia (SEF-wCAT). The techniques compared were IVF cycle using patients' own eggs (IVF cycle) versus donor egg cycles. For IVF cycles, the voluntary ART register reflected 77.2% of those on the official one, but the corresponding figure was only 34.4% with respect to donated eggs. The variables analysed in the IVF cycle (insemination technique used, patients' age, number of embryos transferred, pregnancy rates, multiple pregnancies and deliveries) were similar in the three groups studied. However, we observed significant differences in donor egg cycles with regard to the insemination technique used, pregnancy rates and multiple pregnancies between the voluntary and the official register. Data from the voluntary ART register for IVF cycles are valid, but those for donor egg cycles are not. Further study is necessary to determine the reasons for this difference.

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

PubMed

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

2018-05-20

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

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

PubMed

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

2006-01-01

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

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

PubMed

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

2015-12-01

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

Efficiency of metaphase II oocytes following minimal/mild ovarian stimulation in vitro fertilization.

PubMed

Zhang, John J; Yang, Mingxue; Merhi, Zaher

2016-01-01

An inverse relationship between oocyte efficiency and ovarian response was reported in conventional IVF. The purpose of this study was to report metaphase II (MII) oocyte efficiency according to oocyte yield in minimal/mild stimulation IVF (mIVF) and to assess whether oocyte yield affects live birth rate (LBR). Infertile women ( n  = 264) aged < 39 years old with normal ovarian reserve who had mIVF were recruited. All participants received the same protocol for ovarian stimulation. All the embryos were cultured to the blastocyst stage and vitrified using a freeze-all approach. This was followed by a single blastocyst transferred to each participant in subsequent cycles over a 6-month period. Ovarian response was categorized according to the number of MII oocyte yield (low: 1-2, intermediate: 3-6 and high ≥ 7 MII oocytes). MII oocyte utilization rate was calculated as the number of live births divided by the number of MII oocytes produced after only one oocyte retrieval and subsequent transfers of vitrified/warmed blastocysts. The main outcome measure was cumulative LBR over a 6-month period. Among all the participants, 1173 total retrieved oocytes (4.4 ± 0.2 per patient) resulted in 1019 (3.9 ± 0.2 per patient) total MII oocytes, a clinical pregnancy rate of 48.1 % and a LBR of 41.2 %. Oocyte utilization rate was inversely related to ovarian response where it was 30.3 % in the "low" vs. 9.3 % in the "intermediate" vs. 4.3 % in the "high" oocyte yield groups ( p  < 0.05). Implantation rate significantly dropped as the number of MII oocytes increased and was highest in the "low" oocyte yield group ( p  < 0.0001). Cumulative LBR was similar in "low," "intermediate," and "high" oocyte yield groups ( p  > 0.05). The number of MII oocytes had poor sensitivity and specificity for predicting a live birth. These data extend the hypothesis of oocyte efficiency reported in conventional IVF protocols to mIVF protocols. Registration clinicaltrials.gov: NCT00799929.

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.

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

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.

Outcomes of first IVF/ICSI in young women with diminished ovarian reserve.

PubMed

Cohen, Jonathan; Mounsambote, Leonisse; Prier, Perrine; Mathieu d'ARGENT, Emmanuelle; Selleret, Lise; Chabbert-Buffet, Nathalie; Delarouziere, Vanina; Levy, Rachel; Darai, Emile; Antoine, Jean-Marie

2017-08-01

There is no consensual definition of diminished ovarian reserve and the best therapeutic strategy has not yet been demonstrated. We performed a retrospective study to evaluate outcomes following a first in-vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycle in young women with diminished ovarian reserve. Women with tubal factor, endometriosis or previous stimulation cycle were excluded. We defined diminished ovarian reserve as women ≤38 years with an AMH ≤1.1 ng/mL or antral follicular count ≤7. Among 59 IVF/ICSI cycles (40% IVF/60% ICSI), the pregnancy rate was 17% (10/59) and live birth rate 8.5% (5/59). Miscarriage rate was 50%. Baseline characteristics and IVF outcomes of the pregnant and not pregnant women were compared. No differences in age, antral follicular count, AMH, protocol used or number of harvested oocytes were found between the groups. A higher gonadotropin starting dose in the pregnancy group (397.5±87 IU vs. 314.8±103 IU; P=0.02) and a trend to a higher total dose received (4720±1349 IU vs. 3871±1367 IU; P=0.07) were noted. The present study confirms that women with diminished ovarian reserve have low live birth rates after a first IVF-ICSI cycle and that a higher gonadotropin starting dose might be associated with better outcomes.

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

PubMed

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

2016-11-01

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

[Ten years of results of in-vitro fertilisation in the Netherlands 1996-2005].

PubMed

Kremer, J A M; Bots, R S G M; Cohlen, B; Crooij, M; van Dop, P A; Jansen, C A M; Land, J A; Laven, J S E; Kastrop, P M M; Naaktgeboren, N; Schats, R; Simons, A H M; van der Veen, F

2008-01-19

To present the numbers and results of Dutch IVF treatment from 1996-2005 and to describe trends and differences between centres. Retrospective data-collection, description and analysis. The annual statistics from all Dutch IVF centres covering the years 1996-2005 were collected, described and analysed. During this period 138,217 IVF or intracytoplasmic sperm injection (ICSI) cycles were started and 14,881 transfers of frozen-thawed embryos (cryo transfers) were performed. The number of ICSI treatments, in particular, increased to more than 6000 cycles during this period. These treatments resulted in 30,488 ongoing pregnancies (22.1% per cycle started; 19.1% for IVF and 23.4% for ICSI). The ongoing pregnancy rate per cycle increased from 17.6% in 1996 to 24.4% in 2005. The increase after cryo transfers was remarkable (from 9.4% to 17.6%). It is estimated that during this period, about 1 in 52 newborns in the Netherlands was an IVF or ICSI child (1996: 1 in 77, 2005: 1 in 43). There were differences between the individual centres regarding the ongoing pregnancy rate per cycle (range: 15.0-26.4%), the percentage of ICSI (range 20-58%), the percentage of cryo transfers per cycle (range: 4-22%) and the multiple pregnancy rate (range 5-27% in 2005). In the Netherlands the pregnancy rate has increased over the last 10 years as has the number of IVF treatments. Cryo transfers have become increasingly important and the multiple pregnancy rate has decreased. Although thanks to the collaboration of all centres, the current registry produces important data and works well, there are a number of limitations e.g. the retrospective nature with no validation, which must be tackled over the coming years.

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.

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.

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.

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.

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

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

Stress and marital satisfaction among women before and after their first cycle of in vitro fertilization and intracytoplasmic sperm injection.

PubMed

Verhaak, C M; Smeenk, J M; Eugster, A; van Minnen, A; Kremer, J A; Kraaimaat, F W

2001-09-01

To determine differences in emotional status (anxiety and depression) and marital satisfaction in pregnant and nonpregnant women before and after their first cycle of IVF and intracytoplasmic sperm injection (ICSI). Repeated measurement. Fertility department at a university and a regional hospital. Women entering their first treatment cycle of IVF or ICSI. Questionnaires on psychological factors were administered 3 to 12 days before the start of their first treatment cycle and repeated 3 weeks after the pregnancy test. State anxiety, depression, mood, and marital satisfaction. At pretreatment, the women who became pregnant showed lower levels of depression than those who did not. Higher levels of depression in the pregnant women after the first cycle were due to higher scores on vital aspects of depression, related to signs of early pregnancy. Higher levels of depression in the nonpregnant women were due to a higher score on cognitive aspects of depression. Differences in emotional status between pregnant and nonpregnant women were present before treatment and became more apparent after the first IVF and ICSI cycle. There were no differences in emotional status between the women who underwent IVF and those who underwent ICSI.

Basal serum progesterone and history of elevated progesterone on the day of hCG administration are significant predictors of late follicular progesterone elevation in GnRH antagonist IVF cycles.

PubMed

Venetis, Christos A; Kolibianakis, Efstratios M; Bosdou, Julia K; Lainas, George T; Sfontouris, Ioannis A; Tarlatzis, Basil C; Lainas, Tryfon G

2016-08-01

Are there any baseline predictors of progesterone elevation (PE) on the day of human chorionic gonadotrophin (hCG) which are not associated with the intensity of ovarian stimulation in women undergoing in vitro fertilization (IVF) using follicle stimulating hormone (FSH) and gonadotrophin-releasing hormone (GnRH) antagonists? Basal (Day 2 of the menstrual cycle) serum progesterone concentration and history of PE are baseline variables that can predict the occurrence of PE on the day of hCG independently of the intensity of ovarian stimulation. PE on the day of hCG is associated with the magnitude of the ovarian response to stimulation. For this reason, it has been hypothesized that milder ovarian stimulation might reduce the probability of PE. However, given the fact that the number of oocytes retrieved is associated with the probability of live birth, such a strategy should be considered only in patients that are at high risk of PE on the day of hCG. This is a retrospective analysis of a cohort of fresh IVF/ICSI cycles (n = 1702) performed in a single IVF centre during the period 2001-2015. Patients in whom ovarian stimulation was performed with FSH and GnRH antagonists and with basal FSH <14.0 mIU/ml, progesterone (P) ≤1.6 ng/ml and estradiol (E2) ≤80 pg/ml on the same day (prior to the initiation of stimulation) were considered eligible. PE was defined as serum progesterone concentration >1.5 ng/ml. Pre-stimulation characteristics of patients and basal hormonal profile were assessed for their ability to predict the occurrence of PE after ovarian stimulation through generalized estimating equation univariable and multivariable regression analyses, controlling for the effect of ovarian stimulation. Furthermore, a secondary analysis in a subset of patients with multiple IVF cycles explored whether the occurrence of PE in one of the previous cycles included in this study is associated with a significantly higher occurrence of PE elevation in subsequent cycles. Univariable regression analyses showed that female age (OR: 0.97; 95% CI: 0.94-0.99), basal FSH (OR: 0.85; 95% CI: 0.79-0.92) and basal P (OR: 4.20; 95% CI: 2.47-7.12) were baseline variables that could significantly predict PE on the day of hCG. When these variables were entered in the same model as covariates, only basal FSH (OR: 0.86; 95% CI: 0.80-0.94) and basal P (OR: 3.83; 95% CI: 2.24-6.56) could still predict the occurrence of PE. Basal P (OR: 6.30; 95% CI: 3.35-11.82) was the only variable that could significantly predict the occurrence of PE on the day of hCG after adjusting for the intensity of ovarian stimulation. The secondary analysis revealed that history of PE on the day of hCG in a previous cycle was also strongly associated with an increased risk of PE in a subsequent cycle. This is a retrospective analysis and although the effect of the most important confounders was controlled for in the multivariable analysis, the presence of residual bias cannot be excluded. The findings of this study might help clinicians identify patients at high risk for late follicular PE and alter the management of their cycle. 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.

Costs and outcomes associated with IVF using recombinant FSH.

PubMed

Ledger, W; Wiebinga, C; Anderson, P; Irwin, D; Holman, A; Lloyd, A

2009-09-01

Cost and outcome estimates based on clinical trial data may not reflect usual clinical practice, yet they are often used to inform service provision and budget decisions. To expand understanding of assisted reproduction treatment in clinical practice, an economic evaluation of IVF/intracytoplasmic sperm injection (ICSI) data from a single assisted conception unit (ACU) in England was performed. A total of 1418 IVF/ICSI cycles undertaken there between October 2001 and January 2006 in 1001 women were analysed. The overall live birth rate was 22% (95% CI: 19.7-24.2), with the 30- to 34-year age group achieving the highest rate (28%). The average recombinant FSH (rFSH) dose/cycle prescribed was 1855 IU. Average cost of rFSH/cycle was 646 pound(SD: 219 pound), and average total cost/cycle was 2932 pound (SD: 422 pound). Economic data based on clinical trials informing current UK guidance assumes higher doses of rFSH dose/cycle (1750-2625 IU), higher average cost of drugs/cycle (1179 pound), and higher average total cost/cycle (3266 pound). While the outcomes in this study matched UK averages, total cost/cycle was lower than those cited in UK guidelines. Utilizing the protocols and (lower) rFSH dosages reported in this study may enable other ACU to provide a greater number of IVF/ICSI cycles to patients within given budgets.

Starting and resulting testosterone levels after androgen supplementation determine at all ages in vitro fertilization (IVF) pregnancy rates in women with diminished ovarian reserve (DOR).

PubMed

Gleicher, Norbert; Kim, Ann; Weghofer, Andrea; Shohat-Tal, Aya; Lazzaroni, Emanuela; Lee, Ho-Joon; Barad, David H

2013-01-01

To investigate whether androgen conversion rates after supplementation with dehydroepiandrosterone (DHEA) differ, and whether differences between patients with diminished ovarian reserve (DOR) are predictive of pregnancy chances in association with in vitro fertilization (IVF). In a prospective cohort study we investigated 213 women with DOR, stratified for age (≤ 38 or >38 years) and ovarian FMR1 genotypes/sub-genotypes. All women were for at least 6 weeks supplemented with 75 mg of DHEA daily prior to IVF, between initial presentation and start of 1st IVF cycles. Levels of DHEA, DHEA-sulfate (DHEAS), total T (TT) and free T (FT) at baseline ((BL)) and IVF cycle start ((CS)) were then compared between conception and non-conception cycles. Mean age for the study population was 41.5 ± 4.4 years. Forty-seven IVF cycles (22.1 %) resulted in clinical pregnancy. Benefits of DHEA on pregnancy rates were statistically associated with efficiency of androgen conversion from DHEA to T and amplitude of T gain. Younger women converted significantly more efficiently than older females, and selected FMR1 genotypes/sub-genotypes converted better than others. FSH/androgen and AMH/androgen ratios represent promising new predictors of IVF pregnancy chances in women with DOR. DOR at all ages appears to represent an androgen-deficient state, benefitting from androgen supplementation. Efficacy of androgen supplementation with DHEA, however, varies depending on female age and FMR1 genotype/sub-genotype. Further clarification of FMR1 effects should lead to better individualization of androgen supplementation, whether via DHEA or other androgenic compounds.

Ovarian endometriomas and IVF: a retrospective case-control study

PubMed Central

2011-01-01

We performed this retrospective case-control study analyzing 428 first-attempt in vitro fertilization (IVF) cycles, among which 254 involved women with a previous or present diagnosis of ovarian endometriosis. First, the results of these 254 cycles were compared with 174 cycles involving patients with proven non-endometriotic tubal infertility having similar age and body mass index. Women with ovarian endometriosis had a significantly higher cancellation rate, but similar pregnancy, implantation and delivery rates as patients with tubal infertility. Second, among the women with ovarian endometriosis, the women with a history of laparoscopic surgery for ovarian endometriomas prior to IVF and no visual endometriosis at ovum pick-up (n = 112) were compared with the non-operated women and visual endometriomas at ovum pick-up (n = 142). Patients who underwent ovarian surgery before IVF had significantly shorter period, lower antral follicle count and required higher gonadotropin doses than patients with non-operated endometriomas. The two groups of women with a previous or present ovarian endometriosis did, however, have similar pregnancy, implantation and live birth rates. In conclusion, ovarian endometriosis does not reduce IVF outcome compared with tubal factor. Furthermore, laparoscopic removal of endometriomas does not improve IVF results, but may cause a decrease of ovarian responsiveness to gonadotropins. PMID:21679474

Influence of Paternal Age on Assisted Reproduction Outcome

ClinicalTrials.gov

2017-04-27

We Will Retrospectively Assess Our Databases in Our Clinic; Instituto Valenciano de Infertilidad in Valencia (Spain); Searching for Assisted Reproduction Procedures; IUI Standard IVF/ICSI Cycles and Ovum Donation IVF/ICSI Cycles; Who Were Referred to Our Unit to Cryopreserve Sperm During the Period; From January 2000 to December 2006

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

PubMed Central

Bhattacharya, Siladitya; Maheshwari, Abha; Mollison, Jill

2013-01-01

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

Impact of 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.

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

PubMed

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

2014-12-01

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

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.

Cost Implications for Subsequent Perinatal Outcomes After IVF Stratified by Number of Embryos Transferred: A Five Year Analysis of Vermont Data.

PubMed

Carpinello, Olivia J; Casson, Peter R; Kuo, Chia-Ling; Raj, Renju S; Sills, E Scott; Jones, Christopher A

2016-06-01

In states in the USA without in vitro fertilzation coverage (IVF) insurance coverage, more embryos are transferred per cycle leading to higher risks of multi-fetal pregnancies and adverse pregnancy outcomes. To determine frequency and cost of selected adverse perinatal complications based on number of embryos transferred during IVF, and calculate incremental cost per IVF live birth. Medical records of patients who conceived with IVF (n = 116) and delivered at >20 weeks gestational age between 2007 and 2011 were evaluated. Gestational age at delivery, low birth weight (LBW) term births, and delivery mode were tabulated. Healthcare costs per cohort, extrapolated costs assuming 100 patients per cohort, and incremental costs per infant delivered were calculated. The highest prematurity and cesarean section rates were recorded after double embryo transfers (DET), while the lowest rates were found in single embryo transfers (SET). Premature singleton deliveries increased directly with number of transferred embryos [6.3 % (SET), 9.1 % (DET) and 10.0 % for ≥3 embryos transferred]. This trend was also noted for rate of cesarean delivery [26.7 % (SET), 36.6 % (DET), and 47.1 % for ≥3 embryos transferred]. The proportion of LBW infants among deliveries after DET and for ≥3 embryos transferred was 3.9 and 9.1 %, respectively. Extrapolated costs per cohort were US$718,616, US$1,713,470 and US$1,227,396 for SET, DET, and ≥3 embryos transferred, respectively. Attempting to improve IVF pregnancy rates by permitting multiple embryo transfers results in sharply increased rates of multiple gestation and preterm delivery. This practice yields a greater frequency of adverse perinatal outcomes and substantially increased healthcare spending. Better efforts to encourage SET are necessary to normalize healthcare expenditures considering the frequency of very high cost sequela associated with IVF where multiple embryo transfers occur.

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.

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.

Embryonic development in human oocytes fertilized by split insemination

PubMed Central

Kim, Myo Sun; Kim, Jayeon; Youm, Hye Won; Park, Jung Yeon; Choi, Hwa Young

2015-01-01

Objective To compare the laboratory outcomes of intracytoplasmic sperm injection (ICSI) and conventional insemination using sibling oocytes in poor prognosis IVF cycles where ICSI is not indicated. Methods Couples undergoing IVF with following conditions were enrolled: history of more than 3 years of unexplained infertility, history of ≥3 failed intrauterine insemination, leukocytospermia or wide variation in semen analysis, poor oocyte quality, or ≥50% of embryos had poor quality in previous IVF cycle(s). Couples with severe male factor requiring ICSI were excluded. Oocytes were randomly assigned to the conventional insemination (conventional group) or ICSI (ICSI group). Fertilization rate (FR), total fertilization failure, and embryonic development at day 3 and day 5 were assessed. Results A total of 309 mature oocytes from 37 IVF cycles (32 couples) were obtained: 161 were assigned to conventional group and 148 to ICSI group. FR was significantly higher in the ICSI group compared to the conventional group (90.5% vs. 72.7%, P<0.001). Total fertilization failure occurred in only one cycle in conventional group. On day 3, the percentage of cleavage stage embryos was higher in ICSI group however the difference was marginally significant (P=0.055). In 11 cycles in which day 5 culture was attempted, the percentage of blastocyst (per cleaved embryo) was significantly higher in the ICSI group than the conventional group (55.9% vs. 25.9%, P=0.029). Conclusion Higher FR and more blastocyst could be achieved by ICSI in specific circumstances. Fertilization method can be tailored accordingly to improve IVF outcomes. PMID:26023671

[Effect of luteal-phase gonadotropin-releasing hormone agonist administration on pregnancy outcome in IVF/ICSI cycles: a systematic review and Meta-analysis].

PubMed

Yu, L P; Liu, N; Liu, Y

2016-11-25

Objective: To evaluate the potential efficacy and safety of gonadotropin-releasing hormone agonist(GnRH-a) administration in the luteal-phase on in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles in assisted reproductive technology (ART). Methods: The relevant papers published before November 2015 were electronically searched in PubMed, EMBASE, Cochrane Library, WHO ICTRP, ClinicalTrials.gov, CNKI, CBM and WanFang database to collect randomized controlled trial (RCT) involving GnRH-a administration in the luteal-phase on IVF/ICSI cycles in ART. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality according to the Cochrane Handbook. Then, Meta-analysis was performed using Stata 13.0. Results: A total of 3 406 patients, 3 280 IVF/ICSI cycles from 11 RCT were subjected to Meta-analysis. All cycles presented statistically significantly higher rates of live birth/ongoing pregnancy ( RR= 1.29, 95% CI: 1.11-1.51), clinical pregnancy ( RR= 1.24, 95% CI: 1.08-1.43) and multiple pregnancy ( RR= 1.95, 95% CI: 1.21-3.14) in patients who received luteal-phase GnRH-a administration compared with those who did not. Conclusions: These findings demonstrate that the luteal-phase GnRH-a administration could increase birth/ongoing pregnancy rate, clinical pregnancy rate and multiple pregnancy rate in all cycles, so it may be an ideal choice for luteal phase support in patients undergoing IVF/ICSI therapy.

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

PubMed

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

2016-08-01

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

[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.

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.

Clinical significance of intercellular contact at the four-cell stage of human embryos, and the use of abnormal cleavage patterns to identify embryos with low implantation potential: a time-lapse study.

PubMed

Liu, Yanhe; Chapple, Vincent; Feenan, Katie; Roberts, Peter; Matson, Phillip

2015-06-01

To investigate the clinical significance of intercellular contact point (ICCP) in four-cell stage human embryos and the effectiveness of morphology and abnormal cleavage patterns in identifying embryos with low implantation potential. Retrospective cohort study. Private IVF center. A total of 223 consecutive IVF and intracytoplasmic sperm injection treatment cycles, with all resulting embryos cultured in the Embryoscope, and a subset of 207 cycles analyzed for ICCP number where good-quality four-cell embryos were available on day 2 (n = 373 IVF and n = 392 intracytoplasmic sperm injection embryos). None. Morphologic score on day 3, embryo morphokinetic parameters, incidence of abnormal biological events, and known implantation results. Of 765 good-quality four-cell embryos, 89 (11.6%) failed to achieve six ICCPs; 166 of 765 (21.7%) initially had fewer than six ICCPs but were able to establish six ICCPs before subsequent division. Embryos with fewer than six ICCPs at the end of four-cell stage had a lower implantation rate (5.0% vs. 38.5%), with lower embryology performance in both conventional and morphokinetic assessments, compared with embryos achieving six ICCPs by the end of four-cell stage. Deselecting embryos with poor morphology, direct cleavage, reverse cleavage, and fewer than six ICCPs at the four-cell stage led to a significantly improved implantation rate (33.6% vs. 22.4%). Embryos with fewer than six ICCPs at the end of the four-cell stage show compromised subsequent development and reduced implantation potential. Deselection of embryos with poor morphology and abnormal cleavage revealed via time-lapse imaging could provide the basis of a qualitative algorithm for embryo selection. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

In Vitro Fertilization in 37 Women with Systemic Lupus Erythematosus or Antiphospholipid Syndrome: A Series of 97 Procedures.

PubMed

Orquevaux, Pauline; Masseau, Agathe; Le Guern, Véronique; Gayet, Vanessa; Vauthier, Danièle; Guettrot-Imbert, Gaelle; Huong, Du Le Thi; Wechsler, Bertrand; Morel, Nathalie; Cacoub, Patrice; Pennaforte, Jean-Loup; Piette, Jean-Charles; Costedoat-Chalumeau, Nathalie

2017-05-01

To compile and assess data about complication and success rates for in vitro fertilization (IVF) of women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). To date, such data are sparse. This retrospective study described women with SLE and/or APS who have had at least 1 IVF cycle. Thirty-seven women with SLE (n = 23, including 8 with antiphospholipid antibodies), SLE with APS (n = 4), or primary APS (n = 10) underwent 97 IVF procedures. For 43% of cases, the infertility was female in origin, for 19% male, 14% mixed, and 24% unexplained. No women had premature ovarian insufficiency because of cyclophosphamide. Median age at IVF was 34 years (range 26-46). The median number of IVF cycles was 2.6 (1-8). Patients were treated with hydroxychloroquine (72%), steroids (70%), azathioprine (3%), aspirin (92%), and/or low molecular weight heparin (62%). There were 27 (28%) pregnancies, 23 live births among 26 neonates (3 twin pregnancies), 2 miscarriages, and 2 terminations for trisomy 13 and 21. Six spontaneous pregnancies occurred during the followup. Finally, 26 women (70%) delivered at least 1 healthy child. Complications occurred in or after 8 IVF cycles (8%): SLE flares in 4 (polyarthritis in 3 and lupus enteritis in 1) and thromboembolic events in 4 others. One SLE flare was the first sign of previously undiagnosed SLE. Poor treatment adherence was obvious in 2 other flares and 2 thromboses. No ovarian hyperstimulation syndrome was reported. These preliminary results confirm that IVF can be safely and successfully performed in women with SLE and/or APS.

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

PubMed

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

2015-10-01

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

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 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.

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

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

PubMed

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

2011-01-01

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

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

PubMed

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

2009-01-01

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

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

PubMed

Chen, Xiao; Geng, Ling; Li, Hong

2014-04-01

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

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

PubMed

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

2012-08-08

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

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

PubMed Central

2012-01-01

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

Serum estradiol:oocyte ratio as a predictor of reproductive outcome: an analysis of data from >9000 IVF cycles in the Republic of Ireland.

PubMed

Vaughan, Denis A; Harrity, Conor; Sills, E Scott; Mocanu, Edgar V

2016-04-01

The purpose of this study was to evaluate the serum estradiol (E2) per oocyte ratio (EOR) as a function of selected embryology events and reproductive outcomes with IVF. This retrospective analysis included all IVF cycles where oocyte collection and fresh transfer occurred between January 2001 and November 2012 at a single institution. Patients were divided by three age groups (<35, 35-39, and ≥40 years) and further stratified into nine groups based on EOR (measured in pmol/L/oocyte). Terminal serum E2 (pmol/mL) was recorded on day of hCG trigger administration, and fertilization rate, cleavage rate, number of good quality embryos, and reproductive outcomes were recorded for each IVF cycle. During the study interval, 9109 oocyte retrievals were performed for 5499 IVF patients (mean = 1.7 cycles/patient). A total of 63.4 % of transfers were performed on day 3 (n = 4926), while 36.6 % were carried out on day 5 (n = 2843). Clinical pregnancy rates were highest in patients with EOR of 250-750 and declined as this ratio increased, independent of patient age. While the odds ratio (OR) for clinical pregnancy where EOR = 250-750 vs. EOR > 1500 was 3.4 (p < 0.001; 95 % CI 2.67-4.34), no statistically significant correlation was seen in fertilization, cleavage rates or number of good quality embryos as a function of EOR. Predicting reproductive outcomes with IVF has great utility both for patients and providers. The former have the opportunity to build realistic expectations, and the latter are better able to counsel according to measured clinical parameters. A better understanding of follicular dynamics and ovarian response to gonadotropin stimulation could optimize IVF treatments going forward.

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

Cost effectiveness of ovarian reserve testing in in vitro fertilization: a Markov decision-analytic model.

PubMed

Moolenaar, Lobke M; Broekmans, Frank J M; van Disseldorp, Jeroen; Fauser, Bart C J M; Eijkemans, Marinus J C; Hompes, Peter G A; van der Veen, Fulco; Mol, Ben Willem J

2011-10-01

To compare the cost effectiveness of ovarian reserve testing in in vitro fertilization (IVF). A Markov decision model based on data from the literature and original patient data. Decision analytic framework. Computer-simulated cohort of subfertile women aged 20 to 45 years who are eligible for IVF. [1] No treatment, [2] up to three cycles of IVF limited to women under 41 years and no ovarian reserve testing, [3] up to three cycles of IVF with dose individualization of gonadotropins according to ovarian reserve, and [4] up to three cycles of IVF with ovarian reserve testing and exclusion of expected poor responders after the first cycle, with no treatment scenario as the reference scenario. Cumulative live birth over 1 year, total costs, and incremental cost-effectiveness ratios. The cumulative live birth was 9.0% in the no treatment scenario, 54.8% for scenario 2, 70.6% for scenario 3 and 51.9% for scenario 4. Absolute costs per woman for these scenarios were €0, €6,917, €6,678, and €5,892 for scenarios 1, 2, 3, and 4, respectively. Incremental cost-effectiveness ratios (ICER) for scenarios 2, 3, and 4 were €15,166, €10,837, and €13,743 per additional live birth. Sensitivity analysis showed the model to be robust over a wide range of values. Individualization of the follicle-stimulating hormone dose according to ovarian reserve is likely to be cost effective in women who are eligible for IVF, but this effectiveness needs to be confirmed in randomized clinical trials. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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.

Effect of metformin and oral contraceptives on polycystic ovary syndrome and IVF cycles.

PubMed

Kalem, M N; Kalem, Z; Gurgan, T

2017-07-01

The aim of this study is to investigate the effect of metformin and/or OC added to the treatment of PCOS patients at our clinic on IVF outcome. This study is a retrospective study that assesses the data of PCOS patients who received IVF between 2005 and 2015 at a private IVF center. The study included 496 PCOS cases aged between 24 and 40. Participants diagnosed with PCOS were divided into 4 groups according to the use of metformin and OC prior to the IVF cycle: 11.1% were in the metformin group, 31.3% in the OC group, 14.9% in the Metformin + OC group, and 42.7% in the control group. No difference was found in the total gonadotropin dose and duration of stimulation between the groups. Clinical pregnancy rates and implantation rates were similar in all groups, although the numbers of oocytes, mature oocytes, fertilized oocytes, and transferred embryos were lower in the treatment groups received metformin compared to the OC group and control group. There was no significant difference in the presence of OHSS and the singleton and multiple pregnancies between the four groups. The present study established no positive role of metformin and OC use in increasing the treatment success in IVF/ICSI cycles in PCOS patients. It would be appropriate to limit the use of these agents with special indications such as decreasing insulin resistance or synchronizing follicular cohort.

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

PubMed

Stevenson, Eleanor Lowndes; Sloane, Richard

2017-01-01

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

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.

Surrogate pregnancy in a patient who underwent radical hysterectomy and bilateral transposition of ovaries.

PubMed

Azem, Foad; Yovel, Israel; Wagman, Israel; Kapostiansky, Rita; Lessing, Joseph B; Amit, Ami

2003-05-01

To evaluate IVF-surrogate pregnancy in a patient with ovarian transposition after radical hysterectomy for carcinoma of the cervix. Case report. A maternity hospital in Tel Aviv that is a major tertiary care and referral center. A 29-year-old woman who underwent Wertheim's hysterectomy for carcinoma of the uterine cervix and ovarian transposition before total pelvic irradiation. Standard IVF treatment, transabdominal oocyte retrieval, and transfer to surrogate mother. Outcome of IVF cycle. A twin pregnancy in the first cycle. This is the second reported case of controlled ovarian stimulation and oocyte retrieval performed on a transposed ovary.

Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008-2010 Society for Assisted Reproductive Technology registry.

PubMed

Provost, Meredith P; Acharya, Kelly S; Acharya, Chaitanya R; Yeh, Jason S; Steward, Ryan G; Eaton, Jennifer L; Goldfarb, James M; Muasher, Suheil J

2016-03-01

To examine the effect of body mass index (BMI) on IVF outcomes in fresh autologous cycles. Retrospective cohort study. Not applicable. A total of 239,127 fresh IVF cycles from the 2008-2010 Society for Assisted Reproductive Technology registry were stratified into cohorts based on World Health Organization BMI guidelines. Cycles reporting normal BMI (18.5-24.9 kg/m(2)) were used as the reference group (REF). Subanalyses were performed on cycles reporting purely polycystic ovary syndrome (PCOS)-related infertility and those with purely male-factor infertility (34,137 and 89,354 cycles, respectively). None. Implantation rate, clinical pregnancy rate, pregnancy loss rate, and live birth rate. Success rates and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for all pregnancy outcomes were most favorable in cohorts with low and normal BMIs and progressively worsened as BMI increased. Obesity also had a negative impact on IVF outcomes in cycles performed for PCOS and male-factor infertility, although it did not always reach statistical significance. Success rates in fresh autologous cycles, including those done for specifically PCOS or male-factor infertility, are highest in those with low and normal BMIs. Furthermore, there is a progressive and statistically significant worsening of outcomes in groups with higher BMIs. More research is needed to determine the causes and extent of the influence of BMI on IVF success rates in other patient populations. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The use of serum anti-Mullerian hormone (AMH) levels and antral follicle count (AFC) to predict the number of oocytes collected and availability of embryos for cryopreservation in IVF.

PubMed

Kotanidis, L; Nikolettos, K; Petousis, S; Asimakopoulos, B; Chatzimitrou, E; Kolios, G; Nikolettos, N

2016-12-01

To investigate the predictive value of anti-Mullerian hormone (AMH) and antral follicle count (AFC) on the final number of oocytes retrieved and the availability of embryos for cryopreservation in in vitro fertilization (IVF) cycles. In this prospective study, one hundred and twenty women in their first IVF treatment were enrolled. The short stimulation agonist protocol was used for controlled ovarian hyperstimulation in all cases. Serum AMH levels were measured during the menstrual cycle preceding treatment. AFC was measured in cycle day 2, just before starting ovarian stimulation. A strong, positive correlation between AMH, AFC and the number of collected oocytes was found. The patients with available and suitable supplementary embryos for cryopreservation had higher levels of AMH and larger numbers of AFC. AMH and AFC appear to be valuable markers mainly for ovarian reserve and response to IVF treatment. Serum AMH levels and AFC are significantly associated with the number of retrieved oocytes. Also, a positive correlation with the availability of supernumerary embryos suitable for cryopreservation was observed.

Single embryo transfer: the role of natural cycle/minimal stimulation IVF in the future.

PubMed

Nygren, Karl-Gösta

2007-05-01

There are several good reasons to assume that single embryo transfer (SET) eventually will become the norm internationally in IVF treatments. A tendency is clearly visible, as demonstrated in the latest IVF World Report. The Nordic countries and Belgium have been leading the way. Sweden at present has 70% SET, with 5% twins and a pregnancy rate per transfer remaining constant at about 30%. As a consequence, recent data show a drastic reduction of the risk of prematurity and therefore of child morbidity and perinatal mortality. It is now time to discuss alternatives to the current clinical policy of quite an aggressive ovarian stimulation in settings where SET is the norm. When and at what proportion could natural cycle/soft stimulation be used? What group of patients would benefit? What will the consequences be in terms of efficacy, safety, cost, time and quality of life? Selection of the most beneficial, rather than the most aggressive, ovarian stimulation protocol by clinicians and by the couples themselves in the future may well include a much wider use of natural cycle/soft stimulation in IVF.

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.

National trends and outcomes of autologous in vitro fertilization cycles among women ages 40 years and older.

PubMed

Hipp, Heather; Crawford, Sara; Kawwass, Jennifer F; Boulet, Sheree L; Grainger, David A; Kissin, Dmitry M; Jamieson, Denise

2017-07-01

The purpose of the study was to describe trends in and investigate variables associated with clinical pregnancy and live birth in autologous in vitro fertilization (IVF) cycles among women ≥40 years. We used autologous IVF cycle data from the National ART Surveillance System (NASS) for women ≥40 years at cycle start. We assessed trends in fresh and frozen cycles (n = 371,536) from 1996 to 2013. We reported perinatal outcomes and determined variables associated with clinical pregnancy and live birth in fresh cycles between 2007 and 2013. From 1996 to 2013, the total number of cycles in women ≥40 years increased from 8672 to 28,883 (p < 0.0001), with frozen cycles almost tripling in the last 8 years. Cycles in women ≥40 years accounted for 16.0% of all cycles in 1996 and 21.0% in 2013 (p < 0.0001). For fresh cycles from 2007 to 2013 (n = 157,890), the cancelation rate was 17.1%. Among cycles resulting in transfer (n = 112,414), the live birth rate was 16.1%. The following were associated with higher live birth rates: multiparity, fewer prior ART cycles, use of standard agonist or antagonist stimulation, lower gonadotropin dose, ovarian hyperstimulation syndrome, more oocytes retrieved, use of pre-implantation genetic screening/diagnosis, transferring more and/or blastocyst stage embryos, and cryopreserving more supernumerary embryos. Of the singleton infants born (n = 14,992), 86.9% were full term and 88.3% normal birth weight. The NASS allows for a comprehensive description of IVF cycles in women ≥40 years in the USA. Although live birth rate is less than 20%, identifying factors associated with IVF success can facilitate treatment option counseling.

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.

Outcome of in vitro fertilization in women with subclinical hypothyroidism.

PubMed

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

2017-05-25

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

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.

Cell-free DNA and telomere length among women undergoing in vitro fertilization treatment.

PubMed

Czamanski-Cohen, J; Sarid, O; Cwikel, J; Douvdevani, A; Levitas, E; Lunenfeld, E; Har-Vardi, I

2015-11-01

The current research is aimed at finding potential non-invasive bio-markers that will help us learn more about the mechanisms at play in failed assisted reproduction treatment. This exploratory pilot study examined the relationship between cell-free DNA (CFD) in plasma and telomere length in lymphocytes among women undergoing in vitro fertilization (IVF) and compared telomere length and CFD levels to a healthy control group. Blood of 20 women undergoing IVF was collected at three time points during the IVF cycle. We assessed the relationship between CFD and telomere length as well as controlling for morning cortisol levels. We also collected blood of 10 healthy controls at two time points (luteal and follicular phases of the menstrual cycle) and compared mean telomere length, CFD, and cortisol levels between the IVF patients and healthy controls. The results revealed an inverse relationship between CFD levels and telomere lengths at several time points that remained significant even after controlling for cortisol levels. Women undergoing IVF had statistically significant higher levels of CFD and shorter telomeres compared to healthy controls. The relationship between telomere length and CFD should be further explored in larger studies in order to uncover potential mechanisms that cause both shortened telomere length and elevated CFD in women undergoing IVF.

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

PubMed

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

2018-05-18

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

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.

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.

Initial experience with a donor egg bank.

PubMed

Akin, James W; Bell, Katrina A; Thomas, Diana; Boldt, Jeffrey

2007-08-01

To report on the establishment of a commercial donor egg bank (CryoEggs International, LP) and to present our initial experience from the first four patients to receive eggs. Case report. Private fertility clinic. The four recipient women were aged 43, 43, 40, and 33 years. All had cycle day FSH levels greater than 25 mIU/mL. All were given the option of fresh donor egg IVF but opted to use frozen donor oocytes. Purchased and quarantined frozen donor eggs were thawed and inseminated using intracytoplasmic sperm injection (ICSI). Subsequent embryos were transferred on day 3. Clinical pregnancy as defined by presence of cardiac activity. There was a thawed egg survival rate of 76%, a fertilization rate of 74%, a pregnancy rate (PR) of 50%, with an average of 2.75 embryos per transfer and an implantation rate of 27%. Although very preliminary, these results indicate that more widespread use of frozen donor eggs obtained from a commercial egg bank may be feasible in the future, changing the landscape of donor egg IVF.

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

PubMed

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

2016-06-01

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

[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.

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.

Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI: a multicentre trial and cost-effectiveness analysis.

PubMed

van Tilborg, Theodora C; Oudshoorn, Simone C; Eijkemans, Marinus J C; Mochtar, Monique H; van Golde, Ron J T; Hoek, Annemieke; Kuchenbecker, Walter K H; Fleischer, Kathrin; de Bruin, Jan Peter; Groen, Henk; van Wely, Madelon; Lambalk, Cornelis B; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M; Torrance, Helen L

2017-12-01

Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment? In women initiating IVF/ICSI, AFC-based individualized FSH dosing does not improve live birth rates or reduce costs as compared to a standard FSH dose. In IVF or ICSI, ovarian reserve testing is often used to adjust the FSH dose in order to normalize ovarian response and optimize live birth rates. However, no robust evidence for the (cost-)effectiveness of this practice exists. Between May 2011 and May 2014 we performed a multicentre prospective cohort study with two embedded RCTs in women scheduled for IVF/ICSI. Based on the AFC, women entered into one of the two RCTs (RCT1: AFC < 11; RCT2: AFC > 15) or the cohort (AFC 11-15). The primary outcome was ongoing pregnancy achieved within 18 months after randomization resulting in a live birth (delivery of at least one live foetus after 24 weeks of gestation). Data from the cohort with weight 0.5 were combined with both RCTs in order to conduct a strategy analysis. Potential half-integer numbers were rounded up. Differences in costs and effects between the two treatment strategies were compared by bootstrapping. In both RCTs women were randomized to an individualized (RCT1:450/225 IU, RCT2:100 IU) or standard FSH dose (150 IU). Women in the cohort all received the standard dose (150 IU). Anti-Müllerian hormone (AMH) was measured to assess AMH post-hoc as a biomarker to individualize treatment. For RCT1 dose adjustment was allowed in subsequent cycles based on pre-specified criteria in the standard group only. For RCT2 dose adjustment was allowed in subsequent cycles in both groups. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. We included 1515 women, of whom 483 (31.9%) entered the cohort, 511 (33.7%) RCT1 and 521 (34.4%) RCT2. Live births occurred in 420/747 (56.3%) women in the individualized strategy and 447/769 (58.2%) women in the standard strategy (risk difference -0.019 (95% CI, -0.06 to 0.02), P = 0.39; a total of 1516 women due to rounding up the half integer numbers). The individualized strategy was more expensive (delta costs/woman = €275 (95% CI, 40 to 499)). Individualized dosing reduced the occurrence of mild and moderate ovarian hyperstimulation syndrome (OHSS) and subsequently the costs for management of these OHSS categories (costs saved/woman were €35). The analysis based on AMH as a tool for dose individualization suggested comparable results. Despite a training programme, the AFC might have suffered from inter-observer variation. In addition, although strict cancel criteria were provided, selective cancelling in the individualized dose group (for poor response in particular) cannot be excluded as observers were not blinded for the FSH dose and small dose adjustments were allowed in subsequent cycles. However, as both first cycle live birth rates and cumulative live birth rates show no difference between strategies, the open design probably did not mask a potential benefit for the individualized group. Despite increasing consensus on using GnRH antagonist co-treatment in women predicted for a hyper response in particular, GnRH agonists were used in almost 80% of the women in this study. Hence, in those women, the AFC and bloodsampling for the post-hoc AMH analysis were performed during pituitary suppression. As the correlation between AFC and ovarian response is not compromised during GnRH agonist use, this will probably not have influenced classification of response. Individualized FSH dosing for the IVF/ICSI population as a whole should not be pursued as it does not improve live birth rates and it increases costs. Women scheduled for IVF/ICSI with a regular menstrual cycle are therefore recommended a standard FSH starting dose of 150 IU per day. Still, safety management by individualized dosing in predicted hyper responders is open for further research. This study was funded by The Netherlands Organisation for Health Research and Development (ZonMW number 171102020). AMH measurements were performed free of charge by Roche Diagnostics. TCT, HLT and SCO received an unrestricted personal grant from Merck BV. AH declares that the department of Obstetrics and Gynecology, University Medical Centre Groningen receives an unrestricted research grant from Ferring pharmaceutics BV, The Netherlands. CBL receives grants from Merck, Ferring and Guerbet. BWJM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. FJMB receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV (the Netherlands) and Merck Serono (the Netherlands) for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development (Switzerland) and for a research cooperation with Ansh Labs (USA). All other autors have nothing to declare. Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number: NTR2657. © 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

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.

Effect of progesterone elevation in follicular phase of IVF-cycles on the endometrial receptivity.

PubMed

Lawrenz, B; Fatemi, H M

2017-04-01

The premature rise of progesterone during the late follicular phase in stimulated IVF cycles is a frequent event, and emerging evidence shows that premature progesterone rise does negatively affect the outcome of assisted reproductive techniques. The effect of elevated peripheral progesterone levels in the late follicular phase seems to be on the endometrium and the window of implantation, which may lead to asynchrony between the endometrium and the developing embryo. In stimulated cycles, endometrial maturation is advanced on the day of oocyte retrieval, and patients with a progesterone level above 1.5 ng/ml on the day of final oocyte maturation have different endometrial gene expression profiles. This progesterone level seems to represent the critical threshold, at which a negative effect on the ongoing pregnancy rate in fresh IVF cycles can be observed. Moreover, no association exists between progesterone elevation in the fresh cycle, and the probability of pregnancy after transfer of frozen-thawed embryos, originating from that cycle. The causes of premature progesterone elevation during ovarian stimulation are still unclear; however, recent studies point towards enhanced FSH-stimulation as a cause for progesterone elevation. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

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.

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.

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

PubMed

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

2017-05-01

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

The impact of introducing patient co-payments in Germany on the use of IVF and ICSI: a price-elasticity of demand assessment.

PubMed

Connolly, M P; Griesinger, G; Ledger, W; Postma, M J

2009-11-01

Authorities concerned by rising healthcare costs have a tendency to target reproductive treatments because of the perception that infertility is a low priority. In 2004 German health authorities introduced a 50% co-payment for patients, in an effort to save cost. We explored the impact of this pricing policy on the utilization of reproductive treatments in Germany. Using aggregated annual in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycle data in Germany, we evaluated the relationship between changes in the number of cycles in relation to changes in costs faced by consumers following the introduction of a patient co-payment from 'no fees' to 1500-2000 euros by estimating the short-run price-elasticity of demand. The impact of introducing patient co-payments for IVF/ICSI on the likelihood of switching to other low-cost fertility treatments was evaluated using the cross-price elasticity methodology. RESULTS The reduction in demand for IVF and ICSI cycles in the year following the introduction of patient co-payments resulted in elasticities of -0.41 and -0.34, respectively. The price-elasticity for the combined reduction of IVF/ICSI in relation to the co-payment was estimated to be -0.36. The cross-price elasticity for clomifene was close to zero (-0.01) suggesting that demand for these interventions are independent of each other and no substitution occurred. We report price elasticities for IVF and ICSI of -0.41 and -0.34 after introducing a 500-2000 euros co-payment. These findings likely represent short-run elasticities that are likely to vary over time as factors that influence the supply and demand for fertility treatments change.

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.

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

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.

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.

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.

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.

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.

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.

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

Risk factors for strong regret and subsequent IVF request after having tubal ligation.

PubMed

Kariminia, Azar; Saunders, Douglas M; Chamberlain, Marie

2002-11-01

To identify and describe pre-sterilisation characteristics most consistently associated with intensive post-sterilisation regret and subsequent request for IVF. Case control study. Fertility clinic in a tertiary referral urban hospital, Sydney, Australia. SAMPLE CASES: Ninety-seven sterilised women who underwent evaluation for IVF during the period 1986-1996; 101 sterilised women who remained satisfied with their tubal ligation. Variables known at the time of sterilisation including age, number of living children, history of abortion, underlying medical diseases, marital status, race, education, and timing of sterilisation. In the multivariate analysis of data, age at the time of sterilisation had the most pronounced effect on strong regret. Women younger than 30 years old at the time of sterilisation were more likely to request IVF treatment than women 30 to 34 years old. A concurrent caesarean section was associated with a threefold risk (95% CI, 1.05-10.03) relative to an interval procedure. A strong protective effect (OR = 0.07; 95% CI, 0.01-0.65) was found for women with more than two children compared to childless women. The overwhelming reason stated by women requesting IVF was change in marital status, and the desire to have a child with the new partner. Women with such characteristics who are considering tubal ligation need further caution and counselling.

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.

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

PubMed

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

2013-09-01

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

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

PubMed

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

2012-12-01

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

[CHALLENGING THE OPTIMAL NUMBER OF RETRIEVED OOCYTES AND ITS IMPACT ON PREGNANCY AND LIVE BIRTH RATES IN IVF/ICSI CYCLES].

PubMed

Blais, Idit; Lahav-Baratz, Shirly; Koifman, Mara; Wiener-Megnazi, Zofnat; Auslender, Ron; Dirnfeld, Martha

2015-06-01

Large numbers of retrieved oocytes are associated with higher chances of having cryopreservation of embryos. However, the process entailed exposes women to increased risk for ovarian hyperstimulation syndrome. Furthermore, mild ovary stimulation protocols are more patient-friendly and with less adverse effects. Only limited reports exist on the significance of the number of retrieved oocytes achieved in a single stimulation cycle. To investigate the optimal number of retrieved oocytes to achieve pregnancy and live birth. This retrospective analysis included 1590 IVF cycles. Oocytes maturation, fertilization, cleavage, as well as pregnancy and live birth rates were analyzed according to the number of retrieved oocytes. Oocyte maturation, fertilization and cleavage rates were lower in cycles with more than 10 retrieved oocytes compared with other groups. Live birth rates were highest when the number of retrieved oocytes was 11-15. Retrieval of more than 15 oocytes was not associated with a significant increase in chances of conception and birth. The better oocyte quality with 10 or less oocytes retrieved could be the result of a possible interference with the natural selection, or the minimized exposure of growing follicles to the potentially negative effects of ovarian stimulation. Although the average number of available embryos was higher when more than 10 oocytes were retrieved, achievement of more than 15 oocytes did not improve IVF outcome in terms of pregnancy and delivery rates. Analysis of 1590 IVF cycles including the frozen-thawed transfers shows that the best outcomes were achieved with an optimal number of 11-15 oocytes.

The Impact of Progesterone Level on Day Of hCG Injection in IVF Cycles on Clinical Pregnancy Rate.

PubMed

Ashmita, Jawa; Vikas, Swarankar; Swati, Garg

2017-01-01

Premature progesterone rise (PPR) has long been implicated as contributing to implantation failure. Despite the use of gonadotropin-releasing hormone (GnRH) analogues, subtle increases in serum progesterone ( P 4 ) levels beyond a threshold progesterone concentration were observed on the day of trigger in controlled ovarian hyperstimulation cycles. The purpose of the study was to evaluate the incidence of PPR on the day of trigger in conventional IVF/ICSI cycles and its impact on clinical pregnancy rate. A total of 235 patients undergoing conventional IVF/IVF-ICSI by fresh embryo transfer cycles from January 2016 to December 2016 at the infertility unit of a tertiary care hospital were prospectively analyzed. Patients included in the study were subjected to GnRH agonist long/antagonist protocol. Ovulation induction was given with rFSH and/or HMG in both the protocols. The cutoff for defining PPR was P 4 ≥ 1.5 ng/ml, and an analysis of the role of P 4 on clinical pregnancy rate was performed. Statistical analysis was performed with the Statistical Package for the Social Sciences trial version 23.0 software for Windows and Primer software. The overall clinical pregnancy rate per embryo transfer was 30.6%. The clinical pregnancy rate in the patients with P 4 <1.5 ng/ml was significantly higher than those with elevated levels, P 4 ≥ 1.5 ng/ml (33.3% vs. 12.9%; P = 0.037). Premature progesterone elevation in ART cycles is possibly associated with lower clinical pregnancy rates.

Injection of embryo culture supernatant to the endometrial cavity does not affect outcomes in IVF/ICSI or oocyte donation cycles: a randomized clinical trial.

PubMed

Prapas, Yannis; Petousis, Stamatios; Panagiotidis, Yannis; Gullo, Giuseppe; Kasapi, Lia; Papadeothodorou, Achilleas; Prapas, Nikos

2012-06-01

To evaluate whether intrauterine injection of embryo culture supernatant before embryo transfer has any impact on pregnancy and implantation rates. A total of 400 cycles, of which 200 IVF/ICSI and 200 oocyte donor (OD), were randomly assigned to have their uterine cavity injected (group I) or not (group II). Primary endpoints to be studied were pregnancy and implantation rates. Clinical pregnancy rate per transfer (47.87%, 90/188 versus 48.45%, 94/194) based on transvaginal scan findings at 7 weeks of gestation and implantation rate (25.6% versus 26.5%) were similar in the two groups. The day of embryo transfer, day 3 or day 5, did not affect the final outcome. Injection of embryo culture supernatant into the uterine cavity, 30 min before the embryo transfer on either day 3 or 5, neither improves nor adversely affects the pregnancy rate in IVF/ICSI or oocyte donation cycles. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

PubMed

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

2001-08-01

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

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

PubMed

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

2010-02-01

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

Effects of female increased body mass index on in vitro fertilization cycles outcome.

PubMed

Caillon, Hélène; Fréour, Thomas; Bach-Ngohou, Kalyane; Colombel, Agnès; Denis, Marc G; Barrière, Paul; Masson, Damien

2015-01-01

As being overweight can impair female spontaneous fertility or after assisted reproductive technology (ART) cycles, the aim of this study was to compare in vitro fertilization (IVF) outcome according to women's body mass index (BMI). Retrospective study conducted from 2006 to 2009 in the IVF unit of Nantes University Hospital, France. 582 patients undergoing standard infertility workup and controlled ovarian stimulation were categorized according to BMI into two groups: group 1: normal weight (20-24.9 kg/m(2); n=409) and group 2: overweight and obese (≥25 kg/m(2); n=149). Basal hormonal status, smoking habitus, infertility duration, IVF cycle parameters and outcome were recorded. Basal LH, FSH and estradiol levels were higher in group 1 than group 2, but ovarian reserve markers were comparable across the two BMI groups. Higher doses of gonadotropins were required in group 2 to obtain equivalent ovarian response than in group 1. No difference was observed on ovarian response and embryonic parameters. Cycle outcome were not significantly different between both groups, but we found a strong trend towards increasing transfer cancellation and miscarriage rates in group 2. Although overweight and obesity do not compromise ovarian stimulation results whenever adaptation of recombinant FSH doses is made, our data suggest an increased risk of cancellation transfer and miscarriage rate, leading to poorer IVF outcome. Copyright © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-03-01

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

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.

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

PubMed

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

2012-12-01

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

Defining poor and optimum performance in an IVF programme.

PubMed

Castilla, Jose A; Hernandez, Juana; Cabello, Yolanda; Lafuente, Alejandro; Pajuelo, Nuria; Marqueta, Javier; Coroleu, Buenaventura

2008-01-01

At present there is considerable interest in healthcare administration, among professionals and among the general public concerning the quality of programmes of assisted reproduction. There exist various methods for comparing and analysing the results of clinical activity, with graphical methods being the most commonly used for this purpose. As yet, there is no general consensus as to how the poor performance (PP) or optimum performance (OP) of assisted reproductive technologies should be defined. Data from the IVF/ICSI register of the Spanish Fertility Society were used to compare and analyse different definitions of PP or OP. The primary variable best reflecting the quality of an IVF/ICSI programme was taken to be the percentage of singleton births per IVF/ICSI cycle initiated. Of the 75 infertility clinics that took part in the SEF-2003 survey, data on births were provided by 58. A total of 25 462 cycles were analysed. The following graphical classification methods were used: ranking of the proportion of singleton births per cycles started in each centre (league table), Shewhart control charts, funnel plots, best and worst-case scenarios and state of the art methods. The clinics classified as producing PP or OP varied considerably depending on the classification method used. Only three were rated as providing 'PP' or 'OP' by all methods, unanimously. Another four clinics were classified as 'poor' or 'optimum' by all the methods except one. On interpreting the results derived from IVF/ICSI centres, it is essential to take into account the characteristics of the method used for this purpose.

Omics in Reproductive Medicine: Application of Novel Technologies to Improve the IVF Success Rate.

PubMed

Nerenz, R D

Treatment for many infertile couples often consists of in vitro fertilization (IVF) but an estimated 70% of IVF cycles fail to produce a live birth. In an attempt to improve the live birth rate, the vast majority of IVF cycles performed in the United States involve the transfer of multiple embryos, a practice that increases the risk of multiple gestation pregnancy. This is a concern because multiple gestation pregnancies are associated with an increased incidence of maternal and fetal complications and significant cost associated with the care of preterm infants. As the ideal outcome of each IVF cycle is the birth of a single healthy baby, significant effort has focused on identifying embryos with the greatest developmental potential. To date, selection of euploid embryos using comprehensive chromosome screening (CCS) is the most promising approach while metabolomic and proteomic assessment of spent culture medium have the potential to noninvasively assess embryo viability. Endometrial gene expression profiling may help determine the optimal time to perform embryo transfer. While CCS has been implemented in some clinics, further development and optimization will be required before analysis of spent culture medium and endometrial gene expression profiling make the transition to clinical use. This review will describe efforts to identify embryos with the greatest potential to result in a healthy, live birth, with a particular emphasis on detection of embryo aneuploidy and metabolic profiling of spent embryo culture medium. Assessment of endometrial receptivity to identify the optimal time to perform embryo transfer will also be discussed. © 2016 Elsevier Inc. All rights reserved.

Low body mass index compromises live birth rate in fresh transfer in vitro fertilization cycles: a retrospective study in a Chinese population.

PubMed

Cai, Jiali; Liu, Lanlan; Zhang, Junwen; Qiu, Huiling; Jiang, Xiaoming; Li, Ping; Sha, Aiguo; Ren, Jianzhi

2017-02-01

To evaluate the effects of low body mass index (BMI) on in vitro fertilization (IVF) outcomes in fresh transfer cycles. Retrospective cohort study. University-affiliated hospital. A total of 4,798 cycles with conventional stimulation and fresh transfer in a single IVF center during the period 2013-2014. Low BMI (<18.5 kg/m 2 ) was defined according to World Health Organization guidelines, and cycles within a normal weight range (18.5-24.9 kg/m 2 ) were used as reference. None. Live birth rate per fresh embryo transfer. Low BMI was associated with reduced live birth rates and increased miscarriage rates compared with normal weight, controlling for important covariates known to influence IVF outcomes. Patient age was the most potent confounder, causing a 10.5% reduction in the odds ratio (OR) for live birth between the groups compared. When an interaction term (age × BMI) was introduced, the OR for live birth was reduced in cycles of those aged ≥35 years compared with cycles of those aged 28-34 years, whereas the change in OR between cycles in those aged <28 and cycles in those aged 28-34 years was insignificant. Low BMI is associated with negative outcomes in fresh transfer cycles, especially for women of advanced age. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2008-04-16

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

Improvements in IVF in women of advanced age.

PubMed

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

2016-07-01

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

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.

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

Lights and Shadows about the Effectiveness of IVF in HIV Infected Women: A Systematic Review

PubMed Central

Marques, Catarina; Guerreiro, Cristina; Soares, Sérgio Reis

2015-01-01

Background. HIV infected women have higher rates of infertility. Objective. The purpose of this literature review is to evaluate the effectiveness of fresh IVF/ICSI cycles in HIV infected women. Materials and Methods. A search of the PubMed database was performed to identify studies assessing fresh nondonor oocyte IVF/ICSI cycle outcomes of serodiscordant couples with an HIV infected female partner. Results and Discussion. Ten studies met the inclusion criteria. Whenever a comparison with a control group was available, with the exception of one case, ovarian stimulation cancelation rate was higher and pregnancy rate (PR) was lower in HIV infected women. However, statistically significant differences in both rates were only seen in one and two studies, respectively. A number of noncontrolled sources of bias for IVF outcome were identified. This fact, added to the small size of samples studied and heterogeneity in study design and methodology, still hampers the performance of a meta-analysis on the issue. Conclusion. Prospective matched case-control studies are necessary for the understanding of the specific effects of HIV infection on ovarian response and ART outcome. PMID:26778910

Lights and Shadows about the Effectiveness of IVF in HIV Infected Women: A Systematic Review.

PubMed

Marques, Catarina; Guerreiro, Cristina; Soares, Sérgio Reis

2015-01-01

HIV infected women have higher rates of infertility. Objective. The purpose of this literature review is to evaluate the effectiveness of fresh IVF/ICSI cycles in HIV infected women. A search of the PubMed database was performed to identify studies assessing fresh nondonor oocyte IVF/ICSI cycle outcomes of serodiscordant couples with an HIV infected female partner. Ten studies met the inclusion criteria. Whenever a comparison with a control group was available, with the exception of one case, ovarian stimulation cancelation rate was higher and pregnancy rate (PR) was lower in HIV infected women. However, statistically significant differences in both rates were only seen in one and two studies, respectively. A number of noncontrolled sources of bias for IVF outcome were identified. This fact, added to the small size of samples studied and heterogeneity in study design and methodology, still hampers the performance of a meta-analysis on the issue. Conclusion. Prospective matched case-control studies are necessary for the understanding of the specific effects of HIV infection on ovarian response and ART outcome.

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

PubMed

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

2013-09-01

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

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.

Factors associated with a poor prognosis for the IVF-ICSI live birth rate in women with rAFS stage III and IV endometriosis.

PubMed

Roux, Pauline; Perrin, Jeanne; Mancini, Julien; Agostini, Aubert; Boubli, Léon; Courbiere, Blandine

2017-07-01

To assess the factors associated with a poor prognosis for a cumulative IVF live birth rate (LBR) in women with stage III and IV endometriosis according to the revised classification of the American Fertility Society (rAFS). A retrospective cohort study was conducted between January 1, 2010, and December 31, 2014, in our Reproductive Medicine Center. We analyzed different factors associated with a poor prognosis for a cumulative IVF LBR in women with rAFS stage III and IV endometriosis. A total of 101 patients were included, representing 232 IVF-ICSI cycles and 212 embryo transfers. The primary endpoint was the cumulative LBR per cycle and per patient. The cumulative LBR per cycle was 14.7% (n = 34) and that per patient was 31.7% (n = 32). The cumulative LBR was significantly decreased by active smoking [ adj OR = 3.4, 95% CI (1.12-10.60), p = 0.031], poor ovarian response (POR) according to the Bologna criteria [ adj OR = 11.5, 95% CI (1.37-96.83), p = 0.024], and rAFS stage IV [ adj OR = 3.2, 95% CI (1.13-8.95), p = 0.024]. The cumulative LBR per women was 59.4% without factors associated with a poor prognosis and 25.6% in the case of one factor, and it decreased to 7.7% in the case of two or three factors (p < 0.001). Active smoking, POR according to the Bologna criteria, and rAFS stage IV endometriosis had a negative impact on the IVF-ICSI cumulative LBR for women with rAFS stage III and IV endometriosis. Because smoking dramatically decreases the LBR with endometriosis, stopping smoking before IVF-ICSI should be strongly advised.

Outcomes from a university-based low-cost in vitro fertilization program providing access to care for a low-resource socioculturally diverse urban community.

PubMed

Herndon, Christopher N; Anaya, Yanett; Noel, Martha; Cakmak, Hakan; Cedars, Marcelle I

2017-10-01

To report on outcomes from a university-based low-cost and low-complexity IVF program using mild stimulation approaches and simplified protocols to provide basic access to ART to a socioculturally diverse low-income urban population. Retrospective cohort study. Academic infertility center. Sixty-five infertile couples were enrolled from a county hospital serving a low-resource largely immigrant population. Patients were nonrandomly allocated to one of four mild stimulation protocols: clomiphene/letrozole alone, two clomiphene/letrozole-based protocols involving sequential or flare addition of low-dose gonadotropins, and low-dose gonadotropins alone. Clinical fellows managed all aspects of cycle preparation, monitoring, oocyte retrieval, and embryo transfer under an attending preceptor. Retrieval was undertaken without administration of deep anesthesia, and laboratory interventions were minimized. All embryo transfers were performed at the cleavage stage. Sociomedical demographics, treatment response, and pregnancy outcomes were recorded. From August 2010 to June 2016, 65 patients initiated 161 stimulation IVF cycles, which resulted in 107 retrievals, 91 fresh embryo transfers, and 40 frozen embryo transfer cycles. The mean age of patients was 33.3 years, and mean reported duration of infertility was 5.3 years; 33.5% (54/161) of cycles were cancelled before oocyte retrieval, with 13% due to premature ovulation. Overall, cumulative live birth rates per retrieval including subsequent use of frozen embryos was 29.0%; 44.6% (29/65) of patients enrolled in the program achieved pregnancy. Use of mild stimulation protocols, simplified monitoring, and minimized laboratory handling procedures enabled access to care in a low-resource socioculturally diverse infertile population. Copyright © 2017. Published by Elsevier Inc.

Estimating the net effect of progesterone elevation on the day of hCG on live birth rates after IVF: a cohort analysis of 3296 IVF cycles.

PubMed

Venetis, Christos A; Kolibianakis, Efstratios M; Bosdou, Julia K; Lainas, George T; Sfontouris, Ioannis A; Tarlatzis, Basil C; Lainas, Tryfon G

2015-03-01

What is the proper way of assessing the effect of progesterone elevation (PE) on the day of hCG on live birth in women undergoing fresh embryo transfer after in vitro fertilization (IVF) using GnRH analogues and gonadotrophins? This study indicates that a multivariable approach, where the effect of the most important confounders is controlled for, can lead to markedly different results regarding the association between PE on the day of hCG and live birth rates after IVF when compared with the bivariate analysis that has been typically used in the relevant literature up to date. PE on the day of hCG is associated with decreased pregnancy rates in fresh IVF cycles. Evidence for this comes from observational studies that mostly failed to control for potential confounders. This is a retrospective analysis of a cohort of fresh IVF/intracytoplasmic sperm injection cycles (n = 3296) performed in a single IVF centre during the period 2001-2013. Patients in whom ovarian stimulation was performed with gonadotrophins and GnRH analogues. Natural cycles and cycles where stimulation involved the administration of clomiphene were excluded. In order to reflect routine clinical practice, no other exclusion criteria were imposed on this dataset. The primary outcome measure for this study was live birth defined as the delivery of a live infant after 24 weeks of gestation. We compared the association between PE on the day of hCG (defined as P > 1.5 ng/ml) and live birth rates calculated by simple bivariate analyses with that derived from multivariable logistic regression. The multivariable analysis controlled for female age, number of oocytes retrieved, number of embryos transferred, developmental stage of embryos at transfer (cleavage versus blastocyst), whether at least one good-quality embryo was transferred, the woman's body mass index, the total dose of FSH administered during ovarian stimulation and the type of GnRH analogues used (agonists versus antagonists) during ovarian stimulation. In addition, an interaction analysis was performed in order to assess whether the ovarian response (<6, 6-18, >18 oocytes) has a moderating effect on the association of PE on the day of hCG with live birth rates after IVF. Live birth rates were not significantly different between cycles with and those without PE when a bivariate analysis was performed [odds ratio (OR): 0.78, 95% confidence interval (CI): 0.56-1.09]. However, when a multivariable analysis was performed, controlling for the effect of the aforementioned confounders, live birth rates (OR: 0.68, 95% CI: 0.48-0.97) were significantly decreased in the group with PE on the day of hCG. The number of oocytes retrieved was the most potent confounder, causing a 29.4% reduction in the OR for live birth between the two groups compared. Furthermore, a moderating effect of ovarian response on the association between PE and live birth rates was not supported in the present analysis since no interaction was detected between PE and the type of ovarian response (<6, 6-18, >18 oocytes). This is a retrospective analysis of data collected during a 12-year period, and although the effect of the most important confounders was controlled for in the multivariable analysis, the presence of residual bias cannot be excluded. This analysis highlights the need for a multivariable approach when researchers or clinicians aim to evaluate the impact of PE on pregnancy rates in their own clinical setting. Failure to do so might explain why many past studies have failed to identify the detrimental effect of PE in fresh IVF cycles. 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.

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

PubMed

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

2018-03-01

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

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

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.

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.

A fresh look at the freeze-all protocol: a SWOT analysis.

PubMed

Blockeel, Christophe; Drakopoulos, Panagiotis; Santos-Ribeiro, Samuel; Polyzos, Nikolaos P; Tournaye, Herman

2016-03-01

The 'freeze-all' strategy with the segmentation of IVF treatment, namely with the use of a GnRH antagonist protocol, GnRH agonist triggering, the elective cryopreservation of all embryos by vitrification and a frozen-thawed embryo transfer in a subsequent cycle, has become more popular. However, the approach still encounters drawbacks. In this opinion paper, a SWOT (strengths, weaknesses, opportunities and threats) analysis sheds light on the different aspects of this strategy. © 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 of racial disparities in assisted reproductive technology outcomes in black women compared with white women: Society for Assisted Reproductive Technology 1999 and 2000 vs. 2004-2006.

PubMed

Seifer, David B; Zackula, Rosey; Grainger, David A

2010-02-01

To determine trends in assisted reproductive technology (ART) in black and white women by comparing Society for Assisted Reproductive Technology (SART) database outcomes for 2004-2006 with previously reported outcomes for 1999 and 2000. Retrospective, cohort study. The SART member clinics that performed at least 50 cycles of IVF and reported race in more than 95% of cycles. Women receiving 158,693 IVF cycles. In vitro fertilization using nondonor embryos. Live birth rate per cycle started. Reporting of race increased from 52% to 60%. The proportion of black, non-Hispanic (BNH) women increased from 4.6% to 6.5%. For BNH women using fresh embryos and no prior ART, significant increasing trends were observed for older age, male factor, uterine factor, diminished ovarian reserve, and ovulation disorders. The BNH women were 2.5 times more likely to have tubal factor for those cycles with no prior ART. The proportion of live births per cycle started increased across all groups over time, although greater increases occurred for white women. There seems to be widening disparities in IVF outcomes between BNH and white women, perhaps attributable to poor prognostic factors among black women. Race continues to be a marker for prognosis for ART outcomes and should be reported. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Incorporating spirituality in psychosocial group intervention for women undergoing in vitro fertilization: a prospective randomized controlled study.

PubMed

Chan, Celia H Y; Chan, Cecilia L W; Ng, Ernest H Y; Ho, P C; Chan, Timothy H Y; Lee, G L; Hui, W H C

2012-12-01

This study examined the efficacy of a group intervention, the Integrative Body-Mind-Spirit (I-BMS) intervention, which aims at improving the psychosocial and spiritual well-being of Chinese women undergoing their first IVF treatment cycle. The I-BMS intervention facilitates the search of meaning of life in the context of family and childbearing, as well as the letting go of high IVF expectations. A randomized controlled study of 339 women undergoing first IVF treatment cycle in a local Hong Kong hospital was conducted (intervention: n= 172; no-intervention control: n= 167). Assessments of anxiety, perceived importance of childbearing, and spiritual well-being were made at randomization (T(0) ), on the day starting ovarian stimulations (T(1)), and on the day undertaking embryo transfer (T(2)). Comparing T(0) and T(2), interaction analyses showed women who had received the intervention reported lower levels of physical distress, anxiety, and disorientation. They reported being more tranquil and satisfied with their marriage, and saw childbearing as less important compared to women in the control group. These findings suggest that I-BMS intervention was successful at improving the psychosocial and spiritual well-being of women undergoing their first IVF treatment cycle. This study highlights the importance of providing integrative fertility treatment that incorporates psychosocial and spiritual dimensions. ©2011 The British Psychological Society.

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

PubMed

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

2012-09-18

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

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

PubMed Central

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

2011-01-01

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

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.

Comparison of semen quality and outcome of assisted reproductive techniques in Chinese men with and without hepatitis B

PubMed Central

Zhou, Xu-Ping; Hu, Xiao-Ling; Zhu, Yi-Min; Qu, Fan; Sun, Sai-Jun; Qian, Yu-Li

2011-01-01

In this study, we aimed to determine the effects of hepatitis B virus (HBV) infection on sperm quality and the outcome of assisted reproductive technology (ART). A total of 916 men (457 HBV-positive and 459 HBV-negative) seeking fertility assistance from January 2008 to December 2009 at the Women's Hospital in the School of Medicine at Zhejiang University were analysed for semen parameters. Couples in which the men were hepatitis B surface antigen (HBsAg)-seropositive were categorized as HBV-positive and included 587 in vitro fertilisation (IVF) and 325 intracytoplasmic sperm injection (ICSI) cycles from January 2004 to December 2009; negative controls were matched for female age, date of ova retrieval, ART approach used (IVF or ICSI) and randomized in a ratio of 1:1 according to the ART treatment cycles (587 for IVF and 325 for ICSI). HBV-infected men exhibited lower semen volume, lower total sperm count as well as poor sperm motility and morphology (P<0.05) when compared to control individuals. Rates of two-pronuclear (2PN) fertilisation, high-grade embryo acquisition, implantation and clinical pregnancy were also lower among HBV-positive patients compared to those of HBV-negative patients after ICSI and embryo transfer (P<0.05); IVF outcomes were similar between the two groups (P>0.05). Logistic regression analysis showed that HBV infection independently contributed to increased rates of asthenozoospermia and oligozoospermia/azoospermia (P<0.05) as well as decreased rates of implantation and clinical pregnancy in ICSI cycles (P<0.05). Our results suggest that HBV infection in men is associated with poor sperm quality and worse ICSI and embryo transfer outcomes but does not affect the outcome of IVF and embryo transfer. PMID:21399651

[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.

Association between ambient air pollution and pregnancy rate in women who underwent IVF.

PubMed

Choe, S A; Jun, Y B; Lee, W S; Yoon, T K; Kim, S Y

2018-06-01

Are the concentrations of five criteria air pollutants associated with probabilities of biochemical pregnancy loss and intrauterine pregnancy in women? Increased concentrations of ambient particulate matter (PM10), nitrogen dioxide (NO2), carbon monoxide (CO) during controlled ovarian stimulation (COS) and after embryo transfer were associated with a decreased probability of intrauterine pregnancy. Exposure to high ambient air pollution was suggested to be associated with low fertility and high early pregnancy loss in women. Using a retrospective cohort study design, we analysed 6621 cycles of 4581 patients who underwent one or more fresh IVF cycles at a fertility centre from January 2006 to December 2014, and lived in Seoul at the time of IVF treatment. To estimate patients' individual exposure to air pollution, we computed averages of hourly concentrations of five air pollutants including PM10, NO2, CO, sulphur dioxide (SO2) and ozone (O3) measured at 40 regulatory monitoring sites in Seoul for each of the four exposure periods: period 1 (start of COS to oocyte retrieval), period 2 (oocyte retrieval to embryo transfer), period 3 (embryo transfer to hCG test), and period 4 (start of COS to hCG test). Hazard ratios (HRs) from the time-varying Cox-proportional hazards model were used to estimate probabilities of biochemical pregnancy loss and intrauterine pregnancy for an interquartile range (IQR) increase in each air pollutant concentration during each period, after adjusting for individual characteristics. We tested the robustness of the result using generalised linear mixed model, accounting for within-woman correlation. Mean age of the women was 35 years. Average BMI was 20.9 kg/m2 and the study population underwent 1.4 IVF cycles on average. Cumulative pregnancy rate in multiple IVF cycles was 51.3% per person. Survival analysis showed that air pollution during periods 1 and 3 was generally associated with IVF outcomes. Increased NO2 (adjusted HR = 0.93, 95% CI: 0.87, 0.99) and CO (0.94, 95% CI: 0.89, 1.00) during period 1 were associated with decreased probability of intrauterine pregnancy. PM10 (0.92, 95% CI: 0.85, 0.99), NO2 (0.93, 95% CI = 0.86, 1.00) and CO (0.93, 95% CI: 0.87, 1.00) levels during period 3 were also inversely associated with intrauterine pregnancy. Both PM10 (1.17, 95% CI: 1.04 1.33) and NO2 (1.18, 95% CI: 1.03, 1.34) during period 3 showed positive associations with biochemical pregnancy loss. The district-specific ambient air pollution treated as an individual exposure may not represent the actual level of each woman's exposure to air pollution. Smoking, working status, parity or gravidity of women, and semen analysis data were not included in the analysis. This study provided evidence of an association between increased ambient concentrations of PM10, NO2 and CO and reduced probabilities for achieving intrauterine pregnancy using multiple IVF cycle data. Specifically, our results indicated that lower intrauterine pregnancy rates in IVF cycles may be linked to ambient air pollution during COS and the post-transfer period. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013 R1A6A3A04059017, 2016 R1D1A1B03933410 and 2018 R1A2B6004608) and the National Cancer Center of Korea (NCC-1810220-01). The authors report no conflicts of interest. N/A.

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

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

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.

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

Elective oocyte cryopreservation: who should pay?

PubMed

Mertes, Heidi; Pennings, Guido

2012-01-01

Despite the initial reactions of disapproval, more and more fertility clinics are now offering oocyte cryopreservation to healthy women in order to extend their reproductive options. However, so-called social freezing is not placed on an equal footing with 'regular' IVF treatments where public funding is concerned. In those countries or states where IVF patients receive a number of free cycles, we argue that fertilization and transfer cycles of women who proactively cryopreserved their oocytes should be covered. Moreover, when the argument of justice is consistently applied, coverage should also include the expenses of ovarian stimulation, oocyte retrieval and storage. Different modalities are possible: full coverage from the onset, reimbursement in cash or reimbursement in kind, by offering more free transfer cycles.

Effect of Acupuncture vs Sham Acupuncture on Live Births Among Women Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

PubMed

Smith, Caroline A; de Lacey, Sheryl; Chapman, Michael; Ratcliffe, Julie; Norman, Robert J; Johnson, Neil P; Boothroyd, Clare; Fahey, Paul

2018-05-15

Acupuncture is widely used by women undergoing in vitro fertilization (IVF), although the evidence for efficacy is conflicting. To determine the efficacy of acupuncture compared with a sham acupuncture control performed during IVF on live births. A single-blind, parallel-group randomized clinical trial including 848 women undergoing a fresh IVF cycle was conducted at 16 IVF centers in Australia and New Zealand between June 29, 2011, and October 23, 2015, with 10 months of pregnancy follow-up until August 2016. Women received either acupuncture (n = 424) or a sham acupuncture control (n = 424). The first treatment was administered between days 6 to 8 of follicle stimulation, and 2 treatments were administered prior to and following embryo transfer. The sham control used a noninvasive needle placed away from the true acupuncture points. The primary outcome was live birth, defined as the delivery of 1 or more living infants at greater than 20 weeks' gestation or birth weight of at least 400 g. Among 848 randomized women, 24 withdrew consent, 824 were included in the study (mean [SD] age, 35.4 [4.3] years); 371 [45.0%] had undergone more than 2 previous IVF cycles), 607 proceeded to an embryo transfer, and 809 (98.2%) had data available on live birth outcomes. Live births occurred among 74 of 405 women (18.3%) receiving acupuncture compared with 72 of 404 women (17.8%) receiving sham control (risk difference, 0.5% [95% CI, -4.9% to 5.8%]; relative risk, 1.02 [95% CI, 0.76 to 1.38]). Among women undergoing IVF, administration of acupuncture vs sham acupuncture at the time of ovarian stimulation and embryo transfer resulted in no significant difference in live birth rates. These findings do not support the use of acupuncture to improve the rate of live births among women undergoing IVF. anzctr.org.au Identifier: ACTRN12611000226909.

ANDRO-IVF: a novel protocol for poor responders to IVF controlled ovarian stimulation

PubMed Central

Bercaire, Ludmila; Nogueira, Sara MB; Lima, Priscila CM; Alves, Vanessa R; Donadio, Nilka; Dzik, Artur; Cavagna, Mario; Fanchin, Renato

2018-01-01

Objective This study aimed to assess a novel protocol designed to improve poor ovarian response through intra-ovarian androgenization. The endpoints were: number of oocytes and mature oocytes retrieved, fertilization, cancellation and pregnancy rates. Methods This prospective crossover study enrolled poor responders from previous ovarian stimulation cycles submitted to a novel protocol called ANDRO-IVF. The protocol included pretreatment with transdermal AndroGel(r) (Besins) 25 mg, oral letrozole 2.5 mg and subcutaneous hCG 2500 IU; cycle control was performed with estradiol valerate and micronized progesterone; ovarian stimulation was attained with gonadotropins FSH/LH 450 IU, GnRH antagonist and hCG 5000 IU. Results Fourteen poor responders were enrolled. One patient did not meet the inclusion criteria. Thirteen patients previously summited to the standard protocol were offered the ANDRO-IVF Protocol.-Standard Protocol: Mean age: 35.30 years; cancellation rate: 61.53%; mean number of MII oocytes retrieved per patient: 1.8; fertilization rate: 33.33%. Only two patients had embryo transfers, and none got pregnant.-ANDRO-IVF Protocol: Mean age: 35.83 years; cancellation rate: 7.69%; mean number of oocytes retrieved per patient: 5.58, MII oocytes: 3.91. ICSI was performed in 84.61% of the patients and a mean of 1.5 embryos were transferred per patient. Fertilization rate: 62.5%; cumulative pregnancy rate: 16.66%; mean duration of stimulation: 9.77 days. Conclusion ANDRO-IVF allows intra-ovarian androgenization by increasing serum and intra-follicular androgen levels and preventing androgen aromatization. This protocol apparently improved clinical outcomes of poor responders in parameters such as number of oocytes retrieved and clinical pregnancy rates. Further randomized controlled trials are needed to confirm these findings. PMID:29303236

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.

Comparison of clinical outcome and costs with CC + gonadotropins and gnrha + gonadotropins during Ivf/ICSI cycles.

PubMed

Kovacs, Peter; Matyas, Szabolcs; Bernard, l Artur; Kaali, Steven G

2004-06-01

To compare clinical outcome and costs of CC + gonadotropins with GnRHa + gonadotropins during IVF/ICSI cycles. Clinical outcome and expenses of 382 CC + gonadotropin and 964 GnRHa + gonadotropin cycles were compared. Medication costs were calculated on the basis of the mean number of ampoules and the proportion of various gonadotropins. Costs per clinical pregnancy were calculated on the basis of expenses and clinical pregnancy rates. Women in the CC + gonadotropin group were younger, and had fewer follicles, oocytes, embryos, and embryos transferred. Clinical pregnancy rates were higher in the GnRHa group (35.9 % vs 26.2%, p < 0.001). More ampoules of gonadotropins were used in the GnRHa group (24.0 +/- 0.3 vs 20.0 +/- 0.5, p < 0.001). Medication costs per cycle were higher in the GnRHa group (US dollars 357 vs 248). Expenses per pregnancy however were lower in the GnRHa group (USdollars 4197 vs 5335 with IVF; USdollars 5590 vs 7244 with ICSI). When different age subgroups with similar baseline characteristics and stimulation parameters were compared, pregnancy rates were significantly higher in the GnRHa groups. Medication cost per cycle was higher in the GnRHa subgroups, and the expense per pregnancy was lower with GnRHa protocol. Cost per cycle is higher with GnRHa + gonadotropin. However, because of the better performance of the GnRHa + gonadotropin stimulation, the cumulative costs are reduced by the time a clinical pregnancy is achieved.

Determining the need for rescue intracytoplasmic sperm injection in partial fertilisation failure during a conventional IVF cycle.

PubMed

Cao, S; Wu, X; Zhao, C; Zhou, L; Zhang, J; Ling, X

2016-12-01

To explore the need for rescue intracytoplasmic sperm injection (ICSI) in cases of partial fertilisation failure during a conventional in vitro fertilisation cycle, rescue ICSI was performed for cycles with a fertilisation rate of <50%. The data were divided into three groups based on the fertilisation rate: group 1 (0%), group 2 (<25%) and group 3 (>25%). The impact of rescue ICSI on each group was then analysed in terms of ovum fertilisation, embryo development, embryo utilisation and selection of embryos for transfer. Rescue ICSI was performed on 1831 unfertilised oocytes from 313 cycles. The fertilisation rates for group 1, group 2 and group 3 were 74.66, 68.35 and 65.46%, and the rate of polyploidy in the three groups was 8.55, 11.33, and 14.47%. The percentage of embryos that can be transferred from rescue ICSI for group 2 was 38.33%, and this value was higher than those of the other two groups. It is concluded that rescue ICSI is not recommended for patients with an IVF rate of >25% as the procedure is associated with a greater risk and low returns. However, it is feasible to perform rescue ICSI for patients with IVF rates of <25%. © 2016 Blackwell Verlag GmbH.

Thicker endometrial linings are associated with better IVF outcomes: a cohort of 6331 women.

PubMed

Holden, Emily C; Dodge, Laura E; Sneeringer, Rita; Moragianni, Vasiliki A; Penzias, Alan S; Hacker, Michele R

2017-06-18

Our objective was to determine if a correlation exists between endometrial thickness measured on the day of ovulation trigger during an in vitro fertilization (IVF) cycle and pregnancy outcomes among non-cancelled cycles. We performed a retrospective cohort study looking at 6331 women undergoing their first, fresh autologous IVF cycle from 1 May 2004 to 31 December 2012 at Boston IVF (Waltham, MA). Our primary outcome was the risk ratio (RR) of live birth and positive β-hCG. We found that thicker endometrial linings were associated with positive β-hCG and live birth rates. For each additional millimetre of endometrial thickness, we found a statistically significant increased risk of positive β-hCG (adjusted RR: 1.14; 95% CI: 1.09-1.18) and live birth (RR: 1.08; 95% CI: 1.05-1.11). There was no association between endometrial thickness and miscarriage (RR: 0.99; 95% CI: 0.91-1.07). Similar results were seen when categorizing endometrial thickness. Compared with an endometrial thickness >7 to <11 mm, the likelihood of a live birth was significantly higher for an endometrial thickness ≥11 mm (adjusted RR: 1.23; 95% CI: 1.11-1.37) and significantly lower for the ≤7 mm group (adjusted RR: 0.64; 95% CI: 0.45-0.90). In conclusion, thicker endometrial linings were associated with increased pregnancy and live birth rates.

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.

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

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.

Limited importance of pre-embryo pronuclear morphology (zygote score) in assisted reproduction outcome in the absence of embryo cryopreservation.

PubMed

Nicoli, Alessia; Valli, Barbara; Di Girolamo, Roberta; Di Tommaso, Barbara; Gallinelli, Andrea; La Sala, Giovanni B

2007-10-01

To investigate the hypothesis that Z-score criteria represent a reliable predictor of implantation rate and pregnancy outcome in in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles, excluding the possibility of embryo selection before the embryo transfer. Retrospective clinical study. Centre of Reproductive Medicine, Department of Obstetrics and Gynecology, Arcispedale S. Maria Nuova (ASMN), Reggio Emilia, Italy. We analyzed 393 pregnancies obtained by IVF or ICSI cycles. Morphologic evaluations of Z-score in pre-embryos obtained from IVF or ICSI cycles. Evaluations of Z-scores, implantation rate, and clinical pregnancy outcome. We did not find any statistically significant correlation between the Z-score of 1032 embryos transferred in 393 embryo transfers and the implantation rate or the pregnancy outcome. In particular, the best Z-score identified (Z1, 7.2%) did not seem to correlate with embryo implantation rate or pregnancy outcomes any better than those with worse scores (Z2, 6.9% and Z3, 85.9%). Our results seem to confirm that Z-score alone cannot be considered a better tool than standard morphologic criteria for identifying, controlling, or selecting embryos with a better chance of successful ongoing pregnancy.

Association of birth defects with the mode of assisted reproductive technology in a Chinese data-linkage cohort.

PubMed

Yu, Hui-Ting; Yang, Qing; Sun, Xiao-Xi; Chen, Guo-Wu; Qian, Nai-Si; Cai, Ren-Zhi; Guo, Han-Bing; Wang, Chun-Fang

2018-05-01

To evaluate the impact of assisted reproductive technology (ART) on the offspring of Chinese population. Retrospective, data-linkage cohort. Not applicable. Live births resulting from ART or natural conception. None. Birth defects coded according to ICD-10. Births after ART were more likely to be female and multiple births, especially after intracytoplasmic sperm injection (ICSI). ART was associated with a significantly increased risk of birth defects, especially, among singleton births, a significantly increased risk in fresh-embryo cycles after in vitro fertilization (IVF) and frozen-embryo cycles after ICSI. Associations between ART and multiple defects, between ART and gastrointestinal malformation, genital organs malformation, and musculoskeletal malformation among singleton births, and between ART and cardiac septa malformation among multiple births were observed. This study suggests that ART increases the risk of birth defects. Subgroup analyses indicate higher risk for both fresh and frozen embryos, although nonsignificantly for frozen embryos after IVF and for fresh embryos were presented with low power. Larger sample size research is needed to clarify effects from fresh- or frozen-embryo cycles after IVF and ICSI. Copyright © 2018 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

2012-01-01

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

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.

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 2: The predicted hyper responder.

PubMed

Oudshoorn, Simone C; van Tilborg, Theodora C; Eijkemans, Marinus J C; Oosterhuis, G Jur E; Friederich, Jaap; van Hooff, Marcel H A; van Santbrink, Evert J P; Brinkhuis, Egbert A; Smeenk, Jesper M J; Kwee, Janet; de Koning, Corry H; Groen, Henk; Lambalk, Cornelis B; Mol, Ben Willem J; Broekmans, Frank J M; Torrance, Helen L

2017-12-01

Does a reduced FSH dose in women with a predicted hyper response, apparent from a high antral follicle count (AFC), who are scheduled for IVF/ICSI lead to a different outcome with respect to cumulative live birth rate and safety? Although in women with a predicted hyper response (AFC > 15) undergoing IVF/ICSI a reduced FSH dose (100 IU per day) results in similar cumulative live birth rates and a lower occurrence of any grade of ovarian hyperstimulation syndrome (OHSS) as compared to a standard dose (150 IU/day), a higher first cycle cancellation rate and similar severe OHSS rate were observed. Excessive ovarian response to controlled ovarian stimulation (COS) for IVF/ICSI may result in increased rates of cycle cancellation, the occurrence of OHSS and suboptimal live birth rates. In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can be used to predict response to COS. No consensus has been reached on whether ORT-based FSH dosing improves effectiveness and safety in women with a predicted hyper response. Between May 2011 and May 2014, we performed an open-label, multicentre RCT in women with regular menstrual cycles and an AFC > 15. Women with polycystic ovary syndrome (Rotterdam criteria) were excluded. The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. Secondary outcomes included the occurrence of OHSS and cost-effectiveness. Since this RCT was embedded in a cohort study assessing over 1500 women, we expected to randomize 300 predicted hyper responders. Women with an AFC > 15 were randomized to an FSH dose of 100 IU or 150 IU/day. In both groups, dose adjustment was allowed in subsequent cycles (maximum 25 IU in the reduced and 50 IU in the standard group) based on pre-specified criteria. Both effectiveness and cost-effectiveness were evaluated from an intention-to-treat perspective. We randomized 255 women to a daily FSH dose of 100 IU and 266 women to a daily FSH dose of 150 IU. The cumulative live birth rate was 66.3% (169/255) in the reduced versus 69.5% (185/266) in the standard group (relative risk (RR) 0.95 [95%CI, 0.85-1.07], P = 0.423). The occurrence of any grade of OHSS was lower after a lower FSH dose (5.2% versus 11.8%, RR 0.44 [95%CI, 0.28-0.71], P = 0.001), but the occurrence of severe OHSS did not differ (1.3% versus 1.1%, RR 1.25 [95%CI, 0.38-4.07], P = 0.728). As dose reduction was not less expensive (€4.622 versus €4.714, delta costs/woman €92 [95%CI, -479-325]), there was no dominant strategy in the economic analysis. Despite our training programme, the AFC might have suffered from inter-observer variation. Although strict cancellation criteria were provided, selective cancelling in the reduced dose group (for poor response in particular) cannot be excluded as observers were not blinded for the FSH dose and small dose adjustments were allowed in subsequent cycles. However, as first cycle live birth rates did not differ from the cumulative results, the open design probably did not mask a potential benefit for the reduced dosing group. As this RCT was embedded in a larger cohort study, the power in this study was unavoidably lower than it should be. Participants had a relatively low BMI from an international perspective, which may limit generalization of the findings. In women with a predicted hyper response scheduled for IVF/ICSI, a reduced FSH dose does not affect live birth rates. A lower FSH dose did reduce the incidence of mild and moderate OHSS, but had no impact on severe OHSS. Future research into ORT-based dosing in women with a predicted hyper response should compare various safety management strategies and should be powered on a clinically relevant safety outcome while assessing non-inferiority towards live birth rates. This trial was funded by The Netherlands Organization for Health Research and Development (ZonMW, Project Number 171102020). SCO, TCvT and HLT received an unrestricted research grant from Merck Serono (the Netherlands). CBL receives grants from Merck, Ferring and Guerbet. BWJM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. FJMB receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV and Merck Serono for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number: NTR2657. 20 December 2010. 12 May 2011. © 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

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

PubMed

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

2017-05-01

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

A cost-effectiveness analysis of in-vitro fertilization by maternal age and number of treatment attempts.

PubMed

Griffiths, Alison; Dyer, Suzanne M; Lord, Sarah J; Pardy, Chris; Fraser, Ian S; Eckermann, Simon

2010-04-01

The increase in use and costs of assisted reproductive therapies including in-vitro fertilization (IVF) has led to debate over public funding. A decision analytic model was designed to estimate the incremental cost-effectiveness of IVF by additional treatment programmes and maternal age. Data from the Australian and New Zealand Assisted Reproductive Database were used to estimate incremental effects (live birth and other pregnancy outcomes) and costs for cohorts of women attempting up to three treatment programmes. A treatment programme included one fresh cycle and a variable number of frozen cycles dependent on maternal age. The incremental cost per live birth ranged from AU dollars 27 373 and AU dollars 31 986 for women aged 30-33 on their first and third programmes to AU dollars 130 951 and AU dollars 187 515 for 42-45-year-old women on their first and second attempts. Overall, these trends were not affected by inclusions of costs associated with ovarian hyperstimulation syndrome or multiple births. This study suggests that cost per live birth from IVF increases with maternal age and treatment programme number and indicates that maternal age has the much greater effect. This evidence may help decisionmakers target the use of IVF services conditional on societal willingness to pay for live births and equity considerations.

Cycle scheduling for in vitro fertilization with oral contraceptive pills versus oral estradiol valerate: a randomized, controlled trial

PubMed Central

2013-01-01

Background Both oral contraceptive pills (OCPs) and estradiol (E2) valerate have been used to schedule gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles and, consequently, laboratory activities. However, there are no studies comparing treatment outcomes directly between these two pretreatment methods. This randomized controlled trial was aimed at finding differences in ongoing pregnancy rates between GnRH antagonist IVF cycles scheduled with OCPs or E2 valerate. Methods Between January and May 2012, one hundred consecutive patients (nonobese, regularly cycling women 18–38 years with normal day 3 hormone levels and <3 previous IVF/ICSI attempts) undergoing IVF with the GnRH antagonist protocol were randomized to either the OCP or E2 pretreatment arms, with no restrictions such as blocking or stratification. Authors involved in data collection and analysis were blinded to group assignment. Fifty patients received OCP (30 μg ethinyl E2/150 μg levonorgestrel) for 12–16 days from day 1 or 2, and stimulation was started 5 days after stopping OCP. Similarly, 50 patients received 4 mg/day oral E2 valerate from day 20 for 5–12 days, until the day before starting stimulation. Results Pretreatment with OCP (mean±SD, 14.5±1.7 days) was significantly longer than with E2 (7.8±1.9 days). Stimulation and embryological characteristics were similar. Ongoing pregnancy rates (46.0% vs. 44.0%; risk difference, –2.0% [95% CI –21.2% to 17.3%]), as well as implantation (43.5% vs. 47.4%), clinical pregnancy (50.0% vs. 48.0%), clinical miscarriage (7.1% vs. 7.7%), and live birth (42.0% vs. 40.0%) rates were comparable between groups. Conclusions This is the first study to directly compare these two methods of cycle scheduling in GnRH antagonist cycles. Our results fail to show statistically significant differences in ongoing pregnancy rates between pretreatment with OCP and E2 for IVF with the GnRH antagonist protocol. Although the study is limited by its sample size, our results may contribute to a future meta-analysis. An interesting future direction would be to extend our study to women with decreased ovarian reserve, as these are the patients in whom an increase in oocyte yield—due to the hypothetical beneficial effect of steroid pretreatment on follicular synchronization—could more easily be demonstrated. Trial registration ClinicalTrials.gov http://NCT01501448. PMID:24074027

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.

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.

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.

Oocytes with a dark zona pellucida demonstrate lower fertilization, implantation and clinical pregnancy rates in IVF/ICSI cycles.

PubMed

Shi, Wei; Xu, Bo; Wu, Li-Min; Jin, Ren-Tao; Luan, Hong-Bing; Luo, Li-Hua; Zhu, Qing; Johansson, Lars; Liu, Yu-Sheng; Tong, Xian-Hong

2014-01-01

The morphological assessment of oocytes is important for embryologists to identify and select MII oocytes in IVF/ICSI cycles. Dysmorphism of oocytes decreases viability and the developmental potential of oocytes as well as the clinical pregnancy rate. Several reports have suggested that oocytes with a dark zona pellucida (DZP) correlate with the outcome of IVF treatment. However, the effect of DZP on oocyte quality, fertilization, implantation, and pregnancy outcome were not investigated in detail. In this study, a retrospective analysis was performed in 268 infertile patients with fallopian tube obstruction and/or male factor infertility. In 204 of these patients, all oocytes were surrounded by a normal zona pellucida (NZP, control group), whereas 46 patients were found to have part of their retrieved oocytes enclosed by NZP and the other by DZP (Group A). In addition, all oocytes enclosed by DZP were retrieved from 18 patients (Group B). No differences were detected between the control and group A. Compared to the control group, the rates of fertilization, good quality embryos, implantation and clinical pregnancy were significantly decreased in group B. Furthermore, mitochondria in oocytes with a DZP in both of the two study groups (A and B) were severely damaged with several ultrastructural alterations, which were associated with an increased density of the zona pellucida and vacuolization. Briefly, oocytes with a DZP affected the clinical outcome in IVF/ICSI cycles and appeared to contain more ultrastructural alterations. Thus, DZP could be used as a potential selective marker for embryologists during daily laboratory work.

Surgical diminished ovarian reserve after endometrioma cystectomy versus idiopathic DOR: comparison of in vitro fertilization outcome.

PubMed

Roustan, Audrey; Perrin, Jeanne; Debals-Gonthier, Mathias; Paulmyer-Lacroix, Odile; Agostini, Aubert; Courbiere, Blandine

2015-04-01

Does the live birth rate after IVF depend on the etiology of diminished ovarian reserve (DOR)? IVF outcome and live birth rate are significantly impaired in women with DOR caused by a previous cystectomy for endometrioma compared with women with idiopathic DOR. The safety of the surgical treatment of endometriomas is being discussed in terms of damage to ovarian reserve. Several studies have reported a poor response to controlled ovarian stimulation and a significantly impaired IVF outcome in women with DOR consecutive to an endometrioma cystectomy compared with women with tubal factor infertility. Retrospective case-control study conducted in women aged under 40 treated in our Reproductive Medicine Center between January 2010 and January 2014 for a DOR defined by anti-Müllerian hormone level <2 ng/ml. Two groups of patients were selected: group A included patients with a DOR diagnosed after cystectomy(s) for endometrioma(s), group B included patients with an idiopathic DOR. In each group, subgroups of patients 'poor ovarian responders', based on the ESHRE criteria ('Bologna criteria'), have been established. A total of 51 patients in group A were matched to 116 patients in group B, representing respectively 125 and 243 IVF cycles. Among them, 39 patients in group A and 78 patients in group B validated strictly by the Bologna criteria, representing 99 and 189 IVF cycles, respectively. Each patient underwent a controlled ovarian hyperstimulation and IVF with fresh embryo transfer. Primary end-point was the live birth rate. Secondary end-points were the number of retrieved oocytes, fertilization rate, implantation rate, clinical pregnancy rate, spontaneous abortion rate and cycle cancelation rate. Significantly lower pregnancy (11.2% in group A versus 20.6% in group B, P = 0.02) and live birth (7.2 versus 16.9% respectively, P = 0.01) rates per cycle were assessed in women in group A compared with women in group B. The same results were obtained in the Bologna criteria subgroup analysis with a significantly lower pregnancy (9.1 versus 20.1%, P = 0.016) and live birth (5.1 versus 15.3%, P = 0.001) rates per cycle in women in subgroup A compared with women in subgroup B. Patients in group A required significantly higher gonadotrophins doses (2881 IU ± 1111 versus 2526 IU ± 795, P = 0.005), longer ovarian stimulation (10.6 Days ± 2.8 versus 9.9 Days ± 2.4, P = 0.019) and higher cancelation rate for poor response (12 versus 6.2%, P = 0.05). Despite a mean number of retrieved oocytes similar with the group B (5.4 ± 3.1 and 5.1 ± 3.2, NS), and a significantly higher fertilization rate (65.7 versus 47.2%, P < 0.001), women in group A showed a significantly lower implantation rate (7.2 versus 13.5%, P = 0.03). Abortion rate, ectopic pregnancy rate and multiple pregnancy rate were similar in both groups. Data were collected retrospectively using the database of our Department. Sample size is relatively small but our study provides statistically significant evidence that the chances of IVF success are decreased in women with DOR after cystectomy for endometrioma. Further larger series are needed to confirm these findings. To our knowledge, this is the first study evaluating IVF outcome in patients with DOR after cystectomy(s) for endometrioma(s) versus in patients with an idiopathic DOR. In addition to the risk of damaging ovarian reserve, we hypothesize that endometrioma surgery would not have qualitative benefits on results in IVF in patients with DOR. The authors have no competing interests to declare. © 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.

Self-oocyte activation and parthenogenesis: an unusual outcome of a misconducted IVF cycle.

PubMed

Socolov, Razvan; Ebner, Thomas; Gorduza, Vlad; Martiniuc, Violeta; Angioni, Stefano; Socolov, Demetra

2015-07-01

A rare cause of infertility is the lack of fertilisation with the spontaneous activation of oocytes, leading to parthenogenesis. We present such a case. The patient was a G1P0 38-year-old woman of African ethnicity, who requested an in vitro fertilisation (IVF) with donor sperm. She received a stimulation protocol of 75 IU of FSH/LH from day 3 of the cycle, which she interrupted after 2 d, and restarted with the same dosage for another 3 d from day 7, plus one administration of GnRH antagonist in day 10 of the cycle. With a follicle reaching 19 mm on day 11, estradiol of 325 ng/ml, ovulation was induced with hMG 5000 UI, and oocyte pick-up performed at 30 h. One oocyte was retrieved, and good-quality sperms were added to the insemination procedure. No fecundation occurred at 20 h, with the extruded oocyte separated from the granulosa wall. At 40 h and 64 h the aspect was of three cells, one cell with one nucleus, the others with high granulation and no visible nuclei. This case shows an unusual self-activation oocyte in a poorly managed IVF cycle. The patient will be further evaluated, to decide if a better managed stimulation protocol would prevent recurrence.

Effect of women’s age on embryo morphology, cleavage rate and competence—A multicenter cohort study

PubMed Central

Grøndahl, Marie Louise; Christiansen, Sofie Lindgren; Kesmodel, Ulrik Schiøler; Agerholm, Inge Errebo; Lemmen, Josephine Gabriela; Lundstrøm, Peter; Bogstad, Jeanette; Raaschou-Jensen, Morten; Ladelund, Steen

2017-01-01

This multicenter cohort study on embryo assessment and outcome data from 11,744 IVF/ICSI cycles with 104,830 oocytes and 42,074 embryos, presents the effect of women’s age on oocyte, zygote, embryo morphology and cleavage parameters, as well as cycle outcome measures corrected for confounding factors as center, partner’s age and referral diagnosis. Cycle outcome data confirmed the well-known effect of women’s age. Oocyte nuclear maturation and proportion of 2 pro-nuclear (2PN) zygotes were not affected by age, while a significant increase in 3PN zygotes was observed in both IVF and ICSI (p<0.0001) with increasing age. Maternal age had no effect on cleavage parameters or on the morphology of the embryo day 2 post insemination. Interestingly, initial hCG value after single embryo transfer followed by ongoing pregnancy was increased with age in both IVF (p = 0.007) and ICSI (p = 0.001) cycles. For the first time, we show that a woman’s age does impose a significant footprint on early embryo morphological development (3PN). In addition, the developmentally competent embryos were associated with increased initial hCG values as the age of the women increased. Further studies are needed to elucidate, if this increase in initial hCG value with advancing maternal age is connected to the embryo or the uterus. PMID:28422964

Reference values in ovarian response to controlled ovarian stimulation throughout the reproductive period.

PubMed

La Marca, Antonio; Grisendi, Valentina; Spada, Elena; Argento, Cindy; Milani, Silvano; Plebani, Maddalena; Seracchioli, Renato; Volpe, Annibale

2014-01-01

Abstract The age-related decline in ovarian response to gonadotropins has been well known since the beginning of ovarian stimulation in IVF cycles and has been considered secondary to the age-related decline in ovarian reserve. The objective of this study was to establish reference values and to construct nomograms of ovarian response for any specific age to gonadotropins in IVF/ICSI cycles. We analyzed our database containing information on IVF cycles. According to inclusion and exclusion criteria, a total of 703 patients were selected. Among inclusion criteria, there were regular menstrual cycle, treatment with a long GnRH agonist protocol and starting follicle-stimulating hormone (FSH) dose of at least 200 IU per day. To estimate the reference values of ovarian response, the CG-LMS method was used. A linear decline in the parameters of ovarian response with age was observed: the median number of oocytes decreases approximately by one every three years, and the median number of follicles >16 mm by one every eight years. The number of oocytes and growing follicles corresponding to the 5th, 25th, 50th, 75th and 95th centiles has been calculated. This study confirmed the well known negative relationship between ovarian response to FSH and female ageing and permitted the construction of nomograms of ovarian response.

A cost per live birth comparison of HMG and rFSH randomized trials.

PubMed

Connolly, Mark; De Vrieze, Kathleen; Ombelet, Willem; Schneider, Dirk; Currie, Craig

2008-12-01

To help inform healthcare treatment practices and funding decisions, an economic evaluation was conducted to compare the two leading gonadotrophins used for IVF in Belgium. Based on the results of a recently published meta-analysis, a simulated decision tree model was constructed with four states: (i) fresh cycle, (ii) cryopreserved cycle, (iii) live birth and (iv) treatment withdrawal. Gonadotrophin costs were based on highly purified human menopausal gonadotrophin (HP-HMG; Menopur) and recombinant FSH (rFSH) alpha (Gonal-F). After one fresh and one cryopreserved cycle the average treatment cost with HP-HMG was lower than with rFSH (HP-HMG euro3635; rFSH euro4103). The average cost saving per person started on HP-HMG when compared with rFSH was euro468. Additionally, the average costs per live birth of HP-HMG and rFSH were found to be significantly different: HP-HMG euro9996; rFSH euro13,009 (P < 0.0001). HP-HMG remained cost-saving even after key parameters in the model were varied in the probabilistic sensitivity analysis. Treatment with HP-HMG was found to be the dominant treatment strategy in IVF because of improved live birth rates and lower costs. Within a fixed healthcare budget, the cost-savings achieved using HP-HMG would allow for the delivery of additional IVF cycles.

Comparison of GnRH agonist, GnRH antagonist, and GnRH antagonist mild protocol of controlled ovarian hyperstimulation in good prognosis patients.

PubMed

Stimpfel, Martin; Vrtacnik-Bokal, Eda; Pozlep, Barbara; Virant-Klun, Irma

2015-01-01

The reports on how to stimulate the ovaries for oocyte retrieval in good prognosis patients are contradictory and often favor one type of controlled ovarian hyperstimulation (COH). For this reason, we retrospectively analyzed data from IVF/ICSI cycles carried out at our IVF Unit in good prognosis patients (aged <38 years, first and second attempts of IVF/ICSI, more than 3 oocytes retrieved) to elucidate which type of COH is optimal at our condition. The included patients were undergoing COH using GnRH agonist, GnRH antagonist or GnRH antagonist mild protocol in combination with gonadotrophins. We found significant differences in the average number of retrieved oocytes, immature oocytes, fertilized oocytes, embryos, transferred embryos, embryos frozen per cycle, and cycles with embryo freezing between studied COH protocols. Although there were no differences in live birth rate (LBR), miscarriages, and ectopic pregnancies between compared protocols, pregnancy rate was significantly higher in GnRH antagonist mild protocol in comparison with both GnRH antagonist and GnRH agonist protocols and cumulative LBR per cycle was significantly higher in GnRH antagonist mild protocol in comparison to GnRH agonist protocol. Our data show that GnRH antagonist mild protocol of COH could be the best method of choice in good prognosis patients.

Does 45,X/46,XX mosaicism with 6-28% of aneuploidy affect the outcomes of IVF or ICSI?

PubMed

Homer, L; Morel, F; Gallon, F; Le Martelot, M-T; Amice, V; Kerlan, V; De Braekeleer, M

2012-07-01

Several studies have shown an increased frequency of chromosomal aberrations in female partners of couples examined prior to intracytoplasmic sperm injection (ICSI). A retrospective cohort study was performed to determine whether 45,X/46,XX mosaicism affects the outcomes of in vitro fertilization (IVF) or ICSI. Forty-six women with a 45,X/46,XX karyotype with 6-28% of aneuploidy were compared with 59 control women (46,XX), matched for age, from the female population who underwent IVF or ICSI between 1 January 1996 and 31 December 2006 at the Reproductive Medicine Unit at Brest University Hospital. The outcomes of 254 treatment cycles were compared according to patient karyotype. No difference was found in the number of retrieved oocytes (8.9 ± 5.5 vs 8.5 ± 4.7; p=0.56) or the number of mature oocytes (7.4 ± 4.7 vs 6.9 ± 4.2; p=0.49) between the 45,X/46,XX group and the 46,XX group, respectively. Fertilization rates did not differ between the groups for either IVF or ICSI. In addition, no difference was found in the pregnancy rate by cycle (17.4% vs 18.7%, respectively; p=0.87). The percentage of first-trimester miscarriages was similar in both groups (13.6% vs 12.5%, respectively; p=0.51). 45,X/46,XX mosaicism with 6-28% of aneuploidy has no adverse effect on the outcomes of IVF or ICSI among women referred to assisted reproductive technologies. Copyright © 2012 Elsevier Ireland Ltd. 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.

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.

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.

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

[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.

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.

Uterine length and fertility outcomes: a cohort study in the IVF population.

PubMed

Hawkins, L K; Correia, K F; Srouji, S S; Hornstein, M D; Missmer, S A

2013-11-01

What is the relationship between pre-cycle uterine length and IVF outcome (chemical pregnancy, clinical pregnancy, spontaneous abortion and live birth)? Women at extremes of uterine length (<7.0 or >9.0 cm) were less likely to achieve live birth and women with uterine lengths <6.0 cm were also more likely to experience spontaneous abortion. A prospective study of 807 women published in 2000 found that implantation and clinical pregnancy rates were highest in women with uterine lengths between 7.0 and 9.0 cm, though the difference was not significant. The relationship between pre-cycle uterine length and live birth has not been evaluated. A retrospective cohort study of all cycles performed after uterine length measurement at an academic hospital IVF clinic from 2001 to 2012. A total of 8981 fresh cycles were performed in 5120 adult women with normal uterine anatomy. Women with uterine anomalies (unicornuate, bicornuate, septate or uterus exposed to diethylstilbestrol) were excluded and women with fibroids were identified for subanalysis. Uterine length was measured by uterine sounding. Cycles were divided by uterine length into groups: <6.0 cm (very short, n = 76), 6.0-6.9 cm (short, n = 2014), 7.0-7.9 cm (referent, n = 4984), 8.0-8.9 cm (long, n = 1664) and ≥9 cm (very long, n = 243). Multivariate logistic regression (first-cycle analyses) and generalized estimating equations (all-cycle analyses) were adjusted for age, fibroids and ART treatment (assisted hatching, intracytoplasmic sperm injection) to generate relative risk (RR) of cycle outcomes by uterine length. Median uterine length in the IVF population was 7.0 cm (interquartile range 7.0-7.8) and was positively associated with BMI (P < 0.001) and fibroids (P = 0.02). Compared with the referent group, women with uterine lengths <6.0 cm were half as likely to achieve live birth (RR: 0.53; 95% confidence interval (CI): 0.35-0.81) and women with lengths of 6.0-6.9 cm were also less likely (RR: 0.91; CI: 0.85-0.98). Cubic regression spline identified a significant inverse U-shaped association whereby women with uterine lengths <7.0 or >9.0 cm were less likely to achieve live birth. Women with lengths <6.0 cm were also more likely to experience spontaneous abortion (RR: 2.16; CI: 1.23-3.78). Results remained consistent when excluding women with a uterine factor diagnosis (n = 8823), when limiting to the first cycle at our institution (n = 5120) and when further restricting to first-ever cycles (n = 3941). Optimal assessment of uterine length by ultrasound was not feasible due to time and cost limitations, though uterine sounding is a clinically relevant measurement allowing for results with practical implications. Findings from our predominantly Caucasian clinic population may not be generalizable to infertile populations with different ethnic compositions. Reproducibility of results would solidify findings and inform patient counseling in women undergoing IVF. No funding was sought for this investigation. MD declares relationships with UpToDate (royalties) and WINFertlity (consultant).

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.

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.

[Results of requesting a second consecutive sperm ejaculate on the day of oocyte pick-up in assisted reproductive technology].

PubMed

Zhai, Dan-mei; Li, Mu-jun; Jiang, Li; Qin, Ai-ping; Li, Liu-ming; Hang, Fu

2011-05-01

To evaluate the results of requesting a second consecutive sperm ejaculate in order to reduce ICSI cycles by PESA or TESE on the day of oocyte pick-up in assisted reproductive technology (ART). We collected 68 semen samples as a second consecutive ejaculate from 34 men, compared the semen volume and sperm concentration, motility and total count between the first and the second ejaculation, and analyzed the laboratory results and clinical outcomes of fertilization with the mixed sperm. The 34 males ejaculated twice within 4 hours by masturbation, with an interval of 26-183 (94.9 +/- 39.8) minutes between the first and second ejaculation. The volume of the first ejaculate was (2.0 +/- 1.4) ml, significantly higher than that of the second ([1.5 +/- 0.9] ml) (P = 0.007), although the numbers of motile sperm and grade a + b sperm of the first ([40.8 +/- 25.3]% and [30.9 +/- 22.4]%) were significantly lower than those of the second ([52.2 +/- 21.1]% and [39.9 +/- 17.5]%) (P < 0.05). There were no statistically significant differences in the sperm concentration or total sperm count between the two ejaculates (P > 0.05). The ICSI, IVF + ICSI, and IVF cycles were 3, 3 and 28 respectively among the 34 couples undergoing ART. The number of retrieved oocytes, normal fertilization rate, high quality embryo rate and frozen cycles/fresh transfer cycles ratio were 15.5 +/- 8.7, 57.0% (247/433), 58.7% (145/247) and 20/24 for the IVF cycle, 21.7 +/- 8.3, 61.5% (40/65), 67.5% (27/40) and 3/2 for the ICSI cycle, and 10.0 +/- 2.6, 72.4% (21/29), 66.7% (14/21) and 3/3 for the IVF + ICSI cycle. Fourteen live births were achieved out of the 18 pregnancies, including 6 healthy boys and 9 healthy girls. A clinical pregnancy rate of >30% can be achieved by requesting a second consecutive sperm ejaculate on the day of oocyte pick-up in order to collect more sperm and/or increase the total number of motile sperm for ART. And this method can avoid other invasive sperm processing techniques and the need of unnecessary micromanipulative fertilization.

Association between induced abortion history and later in vitro fertilization outcomes.

PubMed

Wang, Yao; Sun, Yun; Di, Wen; Kuang, Yan-Ping; Xu, Bing

2018-06-01

To establish an effective and safe clinical fertility strategy by investigating the relationship between abortion history and pregnancy outcomes of in vitro fertilization (IVF) treatment. In the present retrospective cohort study, data from IVF treatment cycles performed at a reproductive center in China between October 1, 2014, and October 31, 2015, were assessed. Outcomes were compared between women with a history of induced abortion and those without. There were 1532 IVF treatment cycles included; 454 patients had a history of induced abortion and 1078 did not. The spontaneous abortion rate was significantly higher (30/170 [17.6%] vs 41/420 [9.8%]; P=0.002) and the endometrium was significantly thinner (8.8 ± 1.8 vs 9.7 ± 1.8 cm; P=0.001) among patients with a history of induced abortion compared with those without. In a subgroup analysis of patients with a history of induced abortion, women who had undergone surgical abortions had a lower live delivery rate compared with medical abortions (29/76 [38%] vs 101/378 [27%]; P=0.039). Further, women who had a history of more than two surgical abortions had lower live delivery and clinical pregnancy rates (both P<0.05). A history of induced abortion was associated with worse IVF outcomes, especially a history of more than two surgical abortions. © 2018 International Federation of Gynecology and Obstetrics.

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.

Comparison of IVF and ICSI when only few oocytes are available for insemination.

PubMed

Borini, Andrea; Gambardella, Alessia; Bonu, Maria Antonietta; Dal Prato, Luca; Sciajno, Raffaella; Bianchi, Liana; Cattoli, Monica

2009-08-01

The aim of this work was to evaluate the efficiency of IVF and intracytoplasmic sperm injection (ICSI) when few eggs available for insemination. A total of 601 women (group A, mean age 31.2 +/- 2.8 years) who were undergoing a total of 671 assisted reproduction cycles donated their excess oocytes to 694 patients (group B, mean age 41.0 +/- 0.2) for 1606 replacement cycles. Each recipient received three to five eggs. The recipients were divided into two groups depending on the insemination method used (IVF, group B1; or ICSI, group B2); ICSI patients were then subdivided into two further groups based on the semen parameters: B2A adequate for IVF and B2B only suitable for ICSI. The results showed that, when comparing A versus B and B1 versus B2, no significant differences were found in terms of pregnancy (28.0 versus 24.1% and 25.5 versus 21.4%), implantation (15.6 versus 14.9% and 15.9 versus 13.1%) and miscarriage (15.4 versus 20.5% and 17.9 versus 26.3) rates respectively. Comparing subgroups B2A and B2B, no significant differences were found in terms of pregnancy (20.0 versus 21.9%), implantation (14.4 versus 12.7%) and miscarriage rates (18.2 versus 28.6%) respectively. In conclusion, ICSI does not seem to yield better outcomes.

Correlation of Site of Embryo Transfer with IVF Outcome: Analysis of 743 Cycles from a Single Center

PubMed Central

Singh, Neeta; Lata, Kusum; Malhotra, Neena; Vanamail, P.

2017-01-01

Objective: To investigate the influence of site of embryo transfer (ET) on reproductive outcome. Materials and Methods: A retrospective analysis of 743 ultrasound-guided ET in fresh in vitro fertilization (IVF) cycles from a single center over a period of 4 years was conducted. The distance between the fundal endometrial surface and the air bubble was measured, and accordingly, patients were divided into four groups (≤10 mm; >10 and ≤15 mm; >15 and 20 mm; >20 and <25 mm). Setting: Tertiary Assisted Reproductive Technology (ART) center. Patient(s): All patients enrolled in the IVF program undergoing ET. Intervention(s): Controlled ovarian hyperstimulation (OS), IVF, and ET. Main Outcome Measure(s): Cleavage rate and clinical pregnancy rate. Result(s): Clinical pregnancy rate was significantly more in groups 2 and 3 compared to the other groups. Logistic regression analysis showed that one unit increase in embryos transfer will enhance the pregnancy outcome about 3.7 (adjusted odds ratio) times with 95% confidence limits 2.6 to 5.4. Similarly, pregnancy outcome will be 3.1 (95% confidence limits: 1.5–6.4) times higher for distance group >15 and <20 mm compared to less than 10-mm distance group. Ectopic pregnancy rates were similar in all the four groups. Conclusion: The present study demonstrates that site of ET has significant difference on reproductive outcome. PMID:28904498

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

PubMed

Filetto, Juliana N; Makuch, Maria Y

2005-10-01

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

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.

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

PubMed

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

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

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

PubMed Central

Jiang, Shutian; Kuang, Yanping

2017-01-01

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

Sliding scale HCG trigger yields equivalent pregnancy outcomes and reduces ovarian hyperstimulation syndrome: Analysis of 10,427 IVF-ICSI cycles.

PubMed

Gunnala, Vinay; Melnick, Alexis; Irani, Mohamad; Reichman, David; Schattman, Glenn; Davis, Owen; Rosenwaks, Zev

2017-01-01

To evaluate pregnancy outcomes and the incidence of ovarian hyperstimulation syndrome (OHSS) using a sliding scale hCG protocol to trigger oocyte maturity and establish a threshold level of serum b-hCG associated with optimal oocyte maturity. Retrospective cohort. Academic medical center. Fresh IVF cycles from 9/2004-12/2011. 10,427 fresh IVF-ICSI cycles met inclusion criteria. hCG was administered according to E2 level at trigger: 10,000IU vs. 5,000IU vs. 4,000IU vs. 3,300IU vs. dual trigger (2mg leuprolide acetate + 1,500IU hCG). Serum absorption of hCG was assessed according to dose and BMI. Oocyte maturity was analyzed according to post-trigger serum b-hCG. Fertilization, clinical pregnancy, live birth and OHSS rates were examined by hCG trigger dose. Post-trigger serum b-hCG 20-30, 30-40, and 40-50 mIU/mL was associated with reduced oocyte maturity as compared b-hCG >50 (67.8% vs. 71.4% vs. 73.3% vs. 78.9%, respectively, P<0.05). b-hCG 20-50 mIU/mL was associated with a 40.1% reduction in live birth (OR 0.59, 95% CI 0.41-0.87). No differences in IVF outcomes per retrieval were seen for varying doses of hCG or dual trigger when controlling for patient age. The incidence of moderate to severe OHSS was 0.13% (n = 14) and severe OHSS was 0.03% (n = 4) of cycles. Moderate stimulation with sliding scale hCG at trigger and fresh transfer is associated with low rates of OHSS and favorable pregnancy rates. Doses as low as 3,300IU alone or dual trigger with 1,500IU are sufficient to facilitate oocyte maturity.

Sliding scale HCG trigger yields equivalent pregnancy outcomes and reduces ovarian hyperstimulation syndrome: Analysis of 10,427 IVF-ICSI cycles

PubMed Central

Schattman, Glenn; Davis, Owen; Rosenwaks, Zev

2017-01-01

Objective To evaluate pregnancy outcomes and the incidence of ovarian hyperstimulation syndrome (OHSS) using a sliding scale hCG protocol to trigger oocyte maturity and establish a threshold level of serum b-hCG associated with optimal oocyte maturity. Design Retrospective cohort. Setting Academic medical center. Patients Fresh IVF cycles from 9/2004–12/2011. Intervention 10,427 fresh IVF-ICSI cycles met inclusion criteria. hCG was administered according to E2 level at trigger: 10,000IU vs. 5,000IU vs. 4,000IU vs. 3,300IU vs. dual trigger (2mg leuprolide acetate + 1,500IU hCG). Serum absorption of hCG was assessed according to dose and BMI. Main outcome measures Oocyte maturity was analyzed according to post-trigger serum b-hCG. Fertilization, clinical pregnancy, live birth and OHSS rates were examined by hCG trigger dose. Results Post-trigger serum b-hCG 20–30, 30–40, and 40–50 mIU/mL was associated with reduced oocyte maturity as compared b-hCG >50 (67.8% vs. 71.4% vs. 73.3% vs. 78.9%, respectively, P<0.05). b-hCG 20–50 mIU/mL was associated with a 40.1% reduction in live birth (OR 0.59, 95% CI 0.41–0.87). No differences in IVF outcomes per retrieval were seen for varying doses of hCG or dual trigger when controlling for patient age. The incidence of moderate to severe OHSS was 0.13% (n = 14) and severe OHSS was 0.03% (n = 4) of cycles. Conclusions Moderate stimulation with sliding scale hCG at trigger and fresh transfer is associated with low rates of OHSS and favorable pregnancy rates. Doses as low as 3,300IU alone or dual trigger with 1,500IU are sufficient to facilitate oocyte maturity. PMID:28441461

Glycosaminoglycan and transforming growth factor beta1 changes in human plasma and urine during the menstrual cycle, in vitro fertilization treatment, and pregnancy.

PubMed

De Muro, Pierina; Capobianco, Giampiero; Formato, Marilena; Lepedda, Antonio Junior; Cherchi, Gian Mario; Gordini, Laila; Dessole, Salvatore

2009-07-01

To evaluate transforming growth factor beta1 (TGF-beta1) and glycosaminoglycans (GAG) changes in human plasma and urine during the menstrual cycle, IVF-ET, and pregnancy. Prospective clinical study. University hospital. Thirteen women with apparently normal menstrual cycle (group 1); 18 women undergoing IVF-ET (group 2); and 14 low-risk pregnant women (group 3). We assayed plasma and urine concentrations of TGF-beta1, urine content, and distribution of GAG. Blood and urine samples were collected during days 2 to 3, 12 to 13, and 23 to 24 in group 1; in group 2, samples were obtained at menstrual phase, oocyte pick-up day, and 15 days after ET; in group 3, samples were obtained during gestational weeks 10-12, 22-24, and 30-32 and 1 month after delivery. Changes in TGF-beta1 and GAG content. The mean value of total urinary trypsin inhibitor/chondroitin sulfate (UTI/CS) showed a distinct peak at day 12 of the menstrual cycle in the fertile women in whom we monitored the ovulatory period. In the IVF-ET group, GAG distribution and TGF-beta1 levels showed significant differences during the cycle. We observed increased levels of plasma TGF-beta1 15 days after ET. A significant increase of total UTI/CS value with increasing gestation was detected. Transforming growth factor beta1 and GAG levels could represent an additional tool to monitor reproductive events and could be useful, noninvasive markers of ovulation and ongoing pregnancy.

Use of ICSI in IVF cycles in women with tubal ligation does not improve pregnancy or live birth rates.

PubMed

Grimstad, F W; Nangia, Ajay K; Luke, B; Stern, J E; Mak, W

2016-12-01

Does ICSI improve outcomes in ART cycles without male factor, specifically in couples with a history of tubal ligation as their infertility diagnosis? The use of ICSI showed no significant improvement in fertilization rate and resulted in lower pregnancy and live birth (LB) rates for women with the diagnosis of tubal ligation and no male factor. Prior studies have suggested that ICSI use does not improve fertilization, pregnancy or LB rates in couples with non-male factor infertility. However, it is unknown whether couples with tubal ligation only diagnosis and therefore iatrogenic infertility could benefit from the use of ICSI during their ART cycles. Longitudinal cohort of nationally reported cycles in the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System (SART CORS) of ART cycles performed in the USA between 2004 and 2012. There was a total of 8102 first autologous fresh ART cycles from women with the diagnosis of tubal ligation only and no reported male factor in the SART database. Of these, 957 were canceled cycles and were excluded from the final analysis. The remaining cycles were categorized by the use of conventional IVF (IVF, n = 3956 cycles) or ICSI (n = 3189 cycles). The odds of fertilization, clinical intrauterine gestation (CIG) and LB were calculated by logistic regression modeling, and the adjusted odds ratios (AORs) with 95% confidence intervals were calculated by adjusting for the confounders of year of treatment, maternal age, race and ethnicity, gravidity, number of oocytes retrieved, day of embryo transfer and number of embryos transferred. The main outcome measures of the study were odds of fertilization (2PN/total oocytes), clinical intrauterine gestation (CIG/cycle) and live birth (LB/cycle). The fertilization rate was higher in the ICSI versus IVF group (57.5% vs 49.1%); however, after adjustment this trend was no longer significant (AOR 1.14, 0.97-1.35). Interestingly, both odds of CIG (AOR 0.78, 0.70-0.86), and odds of LB were lower (AOR 0.77, 0.69-0.85) in the ICSI group. Plurality at birth, mean length of gestation and birth weight did not differ between the two groups. This was a retrospective study, therefore only the available parameters could be included, with parameters of interest such as smoking status not available for inclusion. Smoking status may have led practitioners to use ICSI to improve pregnancy and LB outcomes. Studies have shown that in the USA there is an increasing usage of ICSI for non-male factor infertility despite a lack of evidence-based benefit. Our study corroborates this increasing use over the last 8 years, specifically in the tubal ligation only patient population. Even after adjusting for multiple confounders, the patients who underwent ICSI had no statistically significant improvement in fertilization rate and actually had a lower likelihood of achieving a clinical pregnancy and LB. Therefore, our data suggest that the use of ICSI in tubal ligation patients has no overall benefit. This study contributes to the body of evidence that the use of ICSI for non-male factor diagnosis does not improve ART outcomes over conventional IVF. None. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2008-02-01

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

[Deep infiltrative endometriosis without digestive involvement, what is the impact of surgery on in vitro fertilization outcomes? A retrospective study].

PubMed

Mounsambote, L; Cohen, J; Bendifallah, S; d'Argent, E Mathieu; Selleret, L; Chabbert-Buffet, N; Ballester, M; Antoine, J M; Daraï, E

2017-01-01

To evaluate the impact of complete removal of endometriosis in case of deep infiltrative endometriosis without digestive involvement, on in vitro fertilization outcomes. Retrospective monocentric study. We included infertile women with deep infiltrative endometriosis without colorectal involvement that underwent IVF. Women were divided in two groups, following their history: "surgery" when they underwent complete endometriosis resection before IVF and "without surgery" when they underwent IVF without endometriosis removal. We analysed IVF outcomes considering pregnancy rates per cycle and cumulative pregnancy rates per patient. We included 72 patients: 35 in the "surgery" group and 37 in the "without surgery" group. Women in the two groups were comparable in terms of baseline characteristics (age, body mass index, anti-Müllerian hormone, antral follicular count), endometriosis localizations and in vitro fertilization parameters. Cumulative pregnancy rates per patient were similar in both groups (40 % in the "surgery" group and 41 % in the "without surgery" group; P=1). Clinical pregnancy rate per cycle were also comparable groups (24 % in the "surgery" group and 28 % in the "without surgery" group; P=0.67). Surgery performed was comparable in women that became pregnant and in women that did not. Age was lower in women that became pregnant (P=0.01) and there were more pregnancy obtained in women under 35 years. In women with deep infiltrative endometriosis without digestive involvement, in vitro fertilization outcomes were not impacted by surgery. Therapeutic choice between IVF or surgery as first-line treatment remains thus questionable and shall be guided by other influencing factors, such as pain symptomatology, age, tubal permeability, ovarian reserve, partner's sperm characteristics and woman's choice. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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.

Overrepresentation of pregnancies conceived by artificial reproductive technology in prenatally identified fetuses with Beckwith-Wiedemann syndrome.

PubMed

Johnson, John P; Beischel, Linda; Schwanke, Corbin; Styren, Katie; Crunk, Amy; Schoof, Jonathan; Elias, Abdallah F

2018-06-24

In vitro fertilization (IVF) has been linked to an increased risk for imprinting disorders in offspring. The data so far have predominantly been retrospective, comparing the rate of IVF conceptions in affected patients with controls. We describe a series of fetuses with omphalocele that were tested for Beckwith-Wiedemann syndrome (BWS) and subsequently ascertained as to whether pregnancies were conceived by assisted reproductive technologies (ART). Fetuses were tested for BWS by Southern blot, PCR based methods, and methylation analysis to identify the imprinting status at primarily the IC2 locus, KCNQ1OT1, as well as IC1, H19/IGF-2. Some fetuses were also tested for uniparental disomy of chromosome 11p. We tested 301 fetuses with omphalocele for BWS. Forty samples were positive. Sixteen were from IVF pregnancies, for an overall rate of 40%. Such as high proportion of IVF pregnancies in a series of BWS-positive fetuses has not been described previously. Possible factors such as twinning and ascertainment bias are discussed. We found about a 20-fold overrepresentation of IVF cases in fetuses with BWS/omphalocele when compared with the rate of ART pregnancies in the USA (p < .0001). Our series provides support for an association of IVF and BWS. Patients should be counseled about these risks and made aware of the availability of prenatal diagnosis for detection.

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.

INVO procedure: minimally invasive IVF as an alternative treatment option for infertile couples.

PubMed

Lucena, Elkin; Saa, Angela M; Navarro, Doris E; Pulido, Carlos; Lombana, Oscar; Moran, Abby

2012-01-01

Intravaginal culture (IVC), also called INVO (intravaginal culture of oocytes), is an assisted reproduction procedure where oocyte fertilization and early embryo development are carried out within a gas permeable air-free plastic device, placed into the maternal vaginal cavity for incubation. In the present study we assessed the outcome of the INVO procedure, using the recently designed INVOcell device, in combination with a mild ovarian stimulation protocol. A total of 125 cycles were performed. On average 6.5 oocytes per cycle were retrieved, and a mean of 4.2 were placed per INVOcell device. The cleavage rate obtained after the INVO culture was 63%. The procedure yielded 40%, 31.2%, and 24% of clinical pregnancy, live birth, and single live birth rates per cycle, respectively. Our results suggest that the INVO procedure is an effective alternative treatment option in assisted reproduction that shows comparable results to those reported for existing IVF techniques.

INVO Procedure: Minimally Invasive IVF as an Alternative Treatment Option for Infertile Couples

PubMed Central

Lucena, Elkin; Saa, Angela M.; Navarro, Doris E.; Pulido, Carlos; Lombana, Oscar; Moran, Abby

2012-01-01

Intravaginal culture (IVC), also called INVO (intravaginal culture of oocytes), is an assisted reproduction procedure where oocyte fertilization and early embryo development are carried out within a gas permeable air-free plastic device, placed into the maternal vaginal cavity for incubation. In the present study we assessed the outcome of the INVO procedure, using the recently designed INVOcell device, in combination with a mild ovarian stimulation protocol. A total of 125 cycles were performed. On average 6.5 oocytes per cycle were retrieved, and a mean of 4.2 were placed per INVOcell device. The cleavage rate obtained after the INVO culture was 63%. The procedure yielded 40%, 31.2%, and 24% of clinical pregnancy, live birth, and single live birth rates per cycle, respectively. Our results suggest that the INVO procedure is an effective alternative treatment option in assisted reproduction that shows comparable results to those reported for existing IVF techniques. PMID:22645435

Optimization of IVF pregnancy outcomes with donor spermatozoa.

PubMed

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

2009-03-01

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

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.

Predicting IVF Outcome: A Proposed Web-based System Using Artificial Intelligence.

PubMed

Siristatidis, Charalampos; Vogiatzi, Paraskevi; Pouliakis, Abraham; Trivella, Marialenna; Papantoniou, Nikolaos; Bettocchi, Stefano

2016-01-01

To propose a functional in vitro fertilization (IVF) prediction model to assist clinicians in tailoring personalized treatment of subfertile couples and improve assisted reproduction outcome. Construction and evaluation of an enhanced web-based system with a novel Artificial Neural Network (ANN) architecture and conformed input and output parameters according to the clinical and bibliographical standards, driven by a complete data set and "trained" by a network expert in an IVF setting. The system is capable to act as a routine information technology platform for the IVF unit and is capable of recalling and evaluating a vast amount of information in a rapid and automated manner to provide an objective indication on the outcome of an artificial reproductive cycle. ANNs are an exceptional candidate in providing the fertility specialist with numerical estimates to promote personalization of healthcare and adaptation of the course of treatment according to the indications. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Preserving and Using Germplasm and Dissociated Embryonic Cells for Conserving Caribbean and Pacific Coral

PubMed Central

Hagedorn, Mary; Carter, Virginia; Martorana, Kelly; Paresa, Malia K.; Acker, Jason; Baums, Iliana B.; Borneman, Eric; Brittsan, Michael; Byers, Michael; Henley, Michael; Laterveer, Michael; Leong, Jo-Ann; McCarthy, Megan; Meyers, Stuart; Nelson, Brian D.; Petersen, Dirk; Tiersch, Terrence; Uribe, Rafael Cuevas; Woods, Erik; Wildt, David

2012-01-01

Coral reefs are experiencing unprecedented degradation due to human activities, and protecting specific reef habitats may not stop this decline, because the most serious threats are global (i.e., climate change), not local. However, ex situ preservation practices can provide safeguards for coral reef conservation. Specifically, modern advances in cryobiology and genome banking could secure existing species and genetic diversity until genotypes can be introduced into rehabilitated habitats. We assessed the feasibility of recovering viable sperm and embryonic cells post-thaw from two coral species, Acropora palmata and Fungia scutaria that have diffferent evolutionary histories, ecological niches and reproductive strategies. In vitro fertilization (IVF) of conspecific eggs using fresh (control) spermatozoa revealed high levels of fertilization (>90% in A. palmata; >84% in F. scutaria; P>0.05) that were unaffected by tested sperm concentrations. A solution of 10% dimethyl sulfoxide (DMSO) at cooling rates of 20 to 30°C/min most successfully cryopreserved both A. palmata and F. scutaria spermatozoa and allowed producing developing larvae in vitro. IVF success under these conditions was 65% in A. palmata and 53% in F. scutaria on particular nights; however, on subsequent nights, the same process resulted in little or no IVF success. Thus, the window for optimal freezing of high quality spermatozoa was short (∼5 h for one night each spawning cycle). Additionally, cryopreserved F. scutaria embryonic cells had∼50% post-thaw viability as measured by intact membranes. Thus, despite some differences between species, coral spermatozoa and embryonic cells are viable after low temperature (−196°C) storage, preservation and thawing. Based on these results, we have begun systematically banking coral spermatozoa and embryonic cells on a large-scale as a support approach for preserving existing bio- and genetic diversity found in reef systems. PMID:22413020

Deleted in malignant brain tumor 1 is secreted in the oviduct and involved in the mechanism of fertilization in equine and porcine species.

PubMed

Ambruosi, Barbara; Accogli, Gianluca; Douet, Cécile; Canepa, Sylvie; Pascal, Géraldine; Monget, Philippe; Moros Nicolás, Carla; Holmskov, Uffe; Mollenhauer, Jan; Robbe-Masselot, Catherine; Vidal, Olivier; Desantis, Salvatore; Goudet, Ghylène

2013-08-01

Oviductal environment affects preparation of gametes for fertilization, fertilization itself, and subsequent embryonic development. The aim of this study was to evaluate the effect of oviductal fluid and the possible involvement of deleted in malignant brain tumor 1 (DMBT1) on IVF in porcine and equine species that represent divergent IVF models. We first performed IVF after pre-incubation of oocytes with or without oviductal fluid supplemented or not with antibodies directed against DMBT1. We showed that oviductal fluid induces an increase in the monospermic fertilization rate and that this effect is canceled by the addition of antibodies, in both porcine and equine species. Moreover, pre-incubation of oocytes with recombinant DMBT1 induces an increase in the monospermic fertilization rate in the pig, confirming an involvement of DMBT1 in the fertilization process. The presence of DMBT1 in the oviduct at different stages of the estrus cycle was shown by western blot and confirmed by immunohistochemical analysis of ampulla and isthmus regions. The presence of DMBT1 in cumulus-oocyte complexes was shown by western blot analysis, and the localization of DMBT1 in the zona pellucida and cytoplasm of equine and porcine oocytes was observed using immunofluorescence analysis and confocal microscopy. Moreover, we showed an interaction between DMBT1 and porcine spermatozoa using surface plasmon resonance studies. Finally, a bioinformatic and phylogenetic analysis allowed us to identify the DMBT1 protein as well as a DMBT1-like protein in several mammals. Our results strongly suggest an important role of DMBT1 in the process of fertilization.

Early experience with gamete intrafallopian transfer (GIFT) and direct intraperitoneal insemination (DIPI).

PubMed Central

Dooley, M; Lim-Howe, D; Savvas, M; Studd, J W

1988-01-01

We present our early experience with gamete intrafallopian transfer (GIFT) and direct intraperitoneal insemination (DIPI) combined with intrauterine insemination (IUI), two recently described methods of assisting conception in patients with patent fallopian tubes. Sixty-nine patients (93 cycles) were entered into the study. Thirty-three patients (51 cycles) entered the DIPI/IUI programme and 36 patients (42 cycles) entered the GIFT programme. The mean age, duration and aetiology of infertility were similar in both groups. In the GIFT programme 12 pregnancies occurred, which is a 29% pregnancy rate per cycle and a 33% pregnancy rate per patient. In the DIPI/IUI programme only 3 pregnancies occurred, being a 6% pregnancy rate per cycle and a 9% pregnancy rate per patient. With the live birth rate of in vitro fertilization (IVF) being 12% per embryo transfer, we conclude that GIFT is more successful than either DIPI/IUI or IVF in patients with patent fallopian tubes. Further controlled studies are required to assess the future role of DIPI/IUI in clinical practice. PMID:3210194

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

PubMed

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

2011-11-01

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

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.

The effect of endometrial scratch on natural-cycle cryopreserved embryo transfer outcomes: a randomized controlled study.

PubMed

Mak, Jennifer Sze Man; Chung, Cathy Hoi Sze; Chung, Jacqueline Pui Wah; Kong, Grace Wing Shan; Saravelos, Sotirios H; Cheung, Lai Ping; Li, Tin-Chiu

2017-07-01

The benefit of endometrial scratch (ES) prior to embryo transfer is controversial. Systemic analysis has confirmed its potential benefit, especially in women with repeated IVF failures, yet most studies have focused on fresh embryo transfer, and its effect on vitrified-warmed embryo transfer (FET) cycles is yet to be explored. We hereby present our prospective, double-blind, randomized controlled study on the evaluation of the implantation and pregnancy rate after ES prior to natural-cycle FET. A total of 299 patients underwent natural-cycle FET and were randomized to receive ES (n = 115) or endocervical manipulation as control (n = 114) prior to FET cycle, and a total of 196 patients had embryo transfer (93 patients in each group). Our study showed no significant difference in the implantation and pregnancy rate, as well as the clinical and ongoing pregnancy or live birth rates between the two groups. It appears that ES does not have any beneficial effect on an unselected group of women undergoing FET in natural cycles. Further studies on its effect in women with recurrent implantation failure after IVF are warranted. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Single versus double embryo transfer: cost-effectiveness analysis alongside a randomized clinical trial.

PubMed

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

2006-08-01

Twin pregnancies after IVF are still frequent and are considered high-risk pregnancies leading to high costs. Transferring one embryo can reduce the twin pregnancy rate. We compared cost-effectiveness of one fresh cycle elective single embryo transfer (eSET) versus one fresh cycle double embryo transfer (DET) in an unselected patient population. Patients starting their first IVF cycle were randomized between eSET and DET. Societal costs per couple were determined empirically, from hormonal stimulation up to 42 weeks after embryo transfer. An incremental cost-effectiveness ratio (ICER) was calculated, representing additional costs per successful pregnancy. Successful pregnancy rates were 20.8% for eSET and 39.6% for DET. Societal costs per couple were significantly lower after eSET (7334 euro) compared with DET (10,924 euro). The ICER of DET compared with eSET was 19,096 euro, meaning that each additional successful pregnancy in the DET group will cost 19,096 euro extra. One cycle eSET was less expensive, but also less effective compared to one cycle DET. It depends on the society's willingness to pay for one extra successful pregnancy, whether one cycle DET is preferred from a cost-effectiveness point of view.

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

PubMed

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

2017-04-01

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

Should luteal phase support be introduced in ovarian stimulation/IUI programmes? An evidence-based review.

PubMed

Cohlen, B J

2009-01-01

World-wide, intrauterine insemination (IUI) is still one of the most applied techniques to enhance the probability of conception in couples with longstanding subfertility. The outcome of this treatment option depends on many confounding factors. One of the confounding factors receiving little attention is the quality of the luteal phase. From IVF studies, it is known that ovarian stimulation causes luteal phase deficiency. Based on the best available evidence, this short review summarizes the indications for mild ovarian stimulation combined with IUI and the optimal stimulation programme. While it has been established that stimulated IVF/intracytoplasmic sperm injection cycles have deficient luteal phases, the question remains whether the quality of the luteal phase when only two or three corpora lutea are present (as is the case in stimulated IUI cycles) is impaired as well. There are too few large non-IVF trials studying luteal phase quality to answer this question. Recently a randomized trial has been published that investigated luteal phase support in an IUI programme. This study is discussed in detail. It is recommended to apply luteal phase support in stimulated IUI cycles only when proven costeffective. Further trials are mandatory to investigate both endometrial and hormonal profile changes in the luteal phase after mild ovarian stimulation, and the cost-effectiveness of luteal support in IUI programmes.

Does elevated progesterone on day of oocyte maturation play a role in the racial disparities in IVF outcomes?

PubMed

Hill, Micah J; Royster, G Donald; Taneja, Mansi; Healy, Mae Wu; Zarek, Shvetha M; Christy, Alicia Y; DeCherney, Alan H; Widra, Eric; Devine, Kate

2017-02-01

The aim of this study was to evaluate if premature progesterone elevation on the last day of assisted reproduction technique stimulation contributes to racial disparities in IVF outcome. A total of 3289 assisted reproduction technique cycles were evaluated in Latino, Asian, African American, and white women. Live birth was more likely in white women (42.6%) compared with Asian (34.8%) and African American women (36.3%), but was similar to Latino women (40.7%). In all racial groups, progesterone was negatively associated with live birth and the negative effect of progesterone persisted when adjusting for confounders. Although the effect of elevated progesterone was similar in all racial groups, the prevalence of elevated progesterone differed. Progesterone > 1.5 ng/ml occurred in only 10.6% of cycles in white women compared with 18.0% in Latino and 20.2% in Asian women. Progesterone > 2 ng/ml occurred in only 2.3% of cycles in white women compared with 6.3% in Latino, 5.9% in Asian and 4.4% in African American women. The increased prevalence of premature elevated progesterone persisted when controlling for IVF stimulation parameters. In conclusion, premature progesterone elevation had a negative effect on live birth in all racial groups studied. The prevalence of elevated progesterone was higher in racial minorities. Published by Elsevier Ltd.

Male adiposity impairs clinical pregnancy rate by in vitro fertilization without affecting day 3 embryo quality.

PubMed

Merhi, Zaher O; Keltz, Julia; Zapantis, Athena; Younger, Joshua; Berger, Dara; Lieman, Harry J; Jindal, Sangita K; Polotsky, Alex J

2013-08-01

Male adiposity is detrimental for achieving clinical pregnancy rate (CPR) following assisted reproductive technologies (ART). The hypothesis that the association of male adiposity with decreased success following ART is mediated by worse embryo quality was tested. Retrospective study including 344 infertile couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles was performed. Cycle determinants included number of oocytes retrieved, zygote PN-score, total number of embryos available on day 3, number of embryos transferred, composite day 3 grade for transferred embryos, composite day 3 grade per cycle, and CPR. Couples with male body mass index (BMI) over 25 kg m(-2) (overweight and obese) exhibited significantly lower CPR compared to their normal weight counterparts (46.7% vs. 32.0% respectively, P = 0.02). No significant difference was observed for any embryo quality metrics when analyzed by male BMI: mean zygote PN-scores, mean composite day 3 grades for transferred embryos or composite day 3 grades per cycle. In a multivariable logistic regression analysis adjusting for female age, female BMI, number of embryos transferred and sperm concentration, male BMI over 25 kg m(-2) was associated with a lower chance for CPR after IVF (OR = 0.17 [95% CI: 0.04-0.65]; P = 0.01) but not after ICSI cycles (OR = 0.88 [95% CI: 0.41-1.88]; P = 0.75). In this cohort, male adiposity was associated with decreased CPR following IVF but embryo quality was not affected. Embryo grading based on conventional morphologic criteria does not explain the poorer clinical pregnancy outcomes seen in couples with overweight or obese male partner. Copyright © 2013 The Obesity Society.

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

PubMed

Gomel, Victor

2015-12-01

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

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

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.

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.

Cost--effectiveness analysis of salpingectomy prior to IVF, based on a randomized controlled trial.

PubMed

Strandell, Annika; Lindhard, Anette; Eckerlund, Ingemar

2005-12-01

In patients with ultrasound-visible hydrosalpinges, salpingectomy prior to IVF increases the chance of a live birth. This study compared the cost-effectiveness of this strategy (intervention) with that of optional salpingectomy after a failed cycle (control). Data from a Scandinavian randomized controlled trial were used to calculate the individual number of treatments and their outcomes. Only patients with ultrasound-visible hydrosalpinges were considered in the main analysis, and a maximum of three fresh cycles were included. The costs for surgical procedures, IVF treatment, medication, complications, management of pregnancy and delivery as well as of early pregnancy losses were calculated from standardized hospital charges. Among the 51 patients in the intervention group, the live birth rate was 60.8% compared with 40.9% in 44 controls. The average cost per patient was 13,943 euro and 12,091 euro, respectively. Thus, the average cost per live birth was 22,823 euro in the intervention group and 29,517 euro in the control group. The incremental cost-effectiveness ratio for adopting the intervention strategy was estimated at 9306 euro. The incremental cost to achieve the higher birth rate of the intervention strategy seems reasonable.

Accurate and noninvasive embryos screening during in vitro fertilization (IVF) assisted by Raman analysis of embryos culture medium Accurate and noninvasive embryos screening during IVF

NASA Astrophysics Data System (ADS)

Shen, A. G.; Peng, J.; Zhao, Q. H.; Su, L.; Wang, X. H.; Hu, J. M.; Yang, J.

2012-04-01

In combination with morphological evaluation tests, we employ Raman spectroscopy to select higher potential reproductive embryos during in vitro fertilization (IVF) based on chemical composition of embryos culture medium. In this study, 57 Raman spectra are acquired from both higher and lower quality embryos culture medium (ECM) from 10 patients which have been preliminarily confirmed by clinical assay. Data are fit by using a linear combination model of least squares method in which 12 basis spectra represent the chemical features of ECM. The final fitting coefficients provide insight into the chemical compositions of culture medium samples and are subsequently used as criterion to evaluate the quality of embryos. The relative fitting coefficients ratios of sodium pyruvate/albumin and phenylalanine/albumin seem act as key roles in the embryo screening, attaining 85.7% accuracy in comparison with clinical pregnancy. The good results demonstrate that Raman spectroscopy therefore is an important candidate for an accurate and noninvasive screening of higher quality embryos, which potentially decrease the time-consuming clinical trials during IVF.

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

PubMed

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

2016-03-01

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

Pituitary-adrenal and sympathetic nervous system responses to psychiatric disorders in women undergoing in vitro fertilization treatment.

PubMed

An, Yuan; Wang, Zhuoran; Ji, Hongping; Zhang, Yajuan; Wu, Kun

2011-08-01

To evaluate whether psychological variables as well as changes in hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) at baseline and in response to a psychosocial stressor affect the chance of achieving pregnancy in women undergoing a first in vitro fertilization (IVF) cycle. Prospective study. Private IVF center. 264 women undergoing IVF or intracytoplasmic sperm injection (ICSI) treatment. Oocyte retrieval after ovarian stimulation. Standardized psychological questionnaires to assess anxiety and depression, and norepinephrine and cortisol in serum or follicular fluid measured by specific assays. Only a trend increase was found in psychological scores during treatment, which did not affect the ongoing pregnancy rates. On the oocyte retrieval day, a statistically significant increase in norepinephrine and cortisol concentrations was found. Lower concentrations of norepinephrine and cortisol, both in serum and follicular fluid, were found in women whose treatments were successful. Concentrations of steroid in serum before treatment and in follicular fluid were positively associated with the State Anxiety scores. Norepinephrine and cortisol concentrations may negatively influence the clinical pregnancy rate in IVF treatment. These biological stress markers could be one of the links in the complex relationship between psychosocial stress and outcome after IVF-ICSI. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2017-08-01

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

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

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

PubMed

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

2018-06-01

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

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

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 1: The predicted poor responder.

PubMed

van Tilborg, Theodora C; Torrance, Helen L; Oudshoorn, Simone C; Eijkemans, Marinus J C; Koks, Carolien A M; Verhoeve, Harold R; Nap, Annemiek W; Scheffer, Gabrielle J; Manger, A Petra; Schoot, Benedictus C; Sluijmer, Alexander V; Verhoeff, Arie; Groen, Henk; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M

2017-12-01

Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI? In women with a predicted poor ovarian response (AFC < 11) undergoing IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day). In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates. However, the existing RCTs on this topic, most of which show no benefit, are underpowered. Between May 2011 and May 2014, we performed an open-label multicentre RCT in women with an AFC < 11 (Dutch Trial Register NTR2657). The primary outcome was ongoing pregnancy achieved within 18 months after randomization and resulting in a live birth. We needed 300 women to assess whether an increased dose strategy would increase the cumulative live birth rate from 25 to 40% (two-sided alpha-error 0.05, power 80%). Women with an AFC ≤ 7 were randomized to an FSH dose of 450 IU/day or 150 IU/day, and women with an AFC 8-10 were randomized to 225 IU or 150 IU/day. In the standard group, dose adjustment was allowed in subsequent cycles based on pre-specified criteria. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. In total, 511 women were randomized, 234 with an AFC ≤ 7 and 277 with an AFC 8-10. The cumulative live birth rate for increased versus standard dosing was 42.4% (106/250) versus 44.8% (117/261), respectively [relative risk (RR): 0.95 (95%CI, 0.78-1.15), P = 0.58]. As an increased dose strategy was more expensive [delta costs/woman: €1099 (95%CI, 562-1591)], standard FSH dosing was the dominant strategy in our economic analysis. Despite our training programme, the AFC might have suffered from inter-observer variation. As this open study permitted small dose adjustments between cycles, potential selective cancelling of cycles in women treated with 150 IU could have influenced the cumulative results. However, since first cycle live birth rates point in the same direction we consider it unlikely that the open design masked a potential benefit for the individualized strategy. Since an increased dose in women scheduled for IVF/ICSI with a predicted poor response (AFC < 11) does not improve live birth rates and is more expensive, we recommend using a standard dose of 150 IU/day in these women. This study was funded by The Netherlands Organisation for Health Research and Development (ZonMW number 171102020). T.C.T., H.L.T. and S.C.O. received an unrestricted personal grant from Merck BV. H.R.V. receives monetary compensation as a member on an external advisory board for Ferring pharmaceutical BV. B.W.J.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. F.J.M.B. receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV (the Netherlands) and Merck Serono (the Netherlands) for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development (Switzerland) and for a research cooperation with Ansh Labs (USA). All other authors have nothing to declare. Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number NTR2657. 20 December 2010. 12 May 2011. © 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

Seasonal variation in assisted conception cycles and the influence of photoperiodism on outcome in in vitro fertilization cycles.

PubMed

Wood, Simon; Quinn, Alison; Troupe, Stephen; Kingsland, Charles; Lewis-Jones, Iwan

2006-12-01

The effect of seasonality and daylight length on mammalian reproduction leading to spring births has been well established, and is known as photoperiodism. In assisted reproduction there is much greater uncertainty as to the effect of seasonality. This was a 4-year retrospective analysis of 2709 standardised cycles of IVF/ICSI. Data was analysed with regard to the 1642 cycles occurring during the months of extended daylight (Apr-Sept) and those 1067 cycles during winter months of restricted light length (Oct-Mar). The results showed that there was significant improvement in assisted conception outcomes in cycles performed in summer (lighter) months with more efficient ovarian stimulation 766iu v880iu/per oocyte retrieved (p=0.006). There was similarly a significantly improved implantation rate per embryo transferred 11.42% vs 9.35% (p=0.011) and greater clinical pregnancy rate 20% vs 15% (p=0.0033) during summer cycles. This study appears to demonstrate a significant benefit of increased daylight length on outcomes of IVF/ICSI cycles. Whilst the exact mechanism of this is unclear, it would seem probable that melatonin may have actions at multiple sites and on multiple levels of the reproductive tract, and may exert a more profound effect on outcomes of assisted conception cycles than has been previously considered.

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

Race matters: a systematic review of racial/ethnic disparity in Society for Assisted Reproductive Technology reported outcomes.

PubMed

Wellons, Melissa F; Fujimoto, Victor Y; Baker, Valerie L; Barrington, Debbie S; Broomfield, Diana; Catherino, William H; Richard-Davis, Gloria; Ryan, Mary; Thornton, Kim; Armstrong, Alicia Y

2012-08-01

To systematically review the reporting of race/ethnicity in Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System (CORS) publications. Systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology of literature published in PubMed on race/ethnicity that includes data from SART CORS. Not applicable. Not applicable. In vitro fertilization cycles reported to SART. Any outcomes reported in SART CORS. Seven publications were identified that assessed racial/ethnic disparities in IVF outcomes using SART data. All reported a racial/ethnic disparity. However, more than 35% of cycles were excluded from analysis because of missing race/ethnicity data. Review of current publications of SART data suggests significant racial/ethnic disparities in IVF outcomes. However, the potential for selection bias limits confidence in these findings, given that fewer than 65% of SART reported cycles include race/ethnicity. Our understanding of how race/ethnicity influences ART outcome could be greatly improved if information on race/ethnicity was available for all reported cycles. Copyright © 2012 American Society for Reproductive Medicine. All rights reserved.

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

PubMed

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

2016-09-01

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

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.

Smoking Decreases Endometrial Thickness in IVF/ICSI Patients.

PubMed

Heger, Anna; Sator, Michael; Walch, Katharina; Pietrowski, Detlef

2018-01-01

Smoking is a serious problem for the health care system. Many of the compounds identified in cigarette smoke have toxic effects on the fertility of both females and males. The purpose of this study was to determine whether smoking affects clinical factors during IVF/ICSI therapy in a single-center reproductive unit. In a retrospective study of 200 IVF/ICSI cycles, endometrial thickness and the outcome of IVF/ICSI therapy were analyzed. Endometrial thickness was significantly lower in smoking patients than in non-smoking patients (10.4 ± 1.5 mm vs. 11.6 ± 1.8 mm). Age was significantly higher in women who failed to conceive. The total dose of gonadotropins administered was significantly lower in pregnant patients and the highest pregnancy rate was achieved with an rFSH protocol. BMI and number of cigarettes smoked did not influence treatment outcomes in this study. We showed that smoking has a negative effect on endometrial thickness on the day of embryo transfer. This may help to further explain the detrimental influence of tobacco smoke on implantation and pregnancy rates during assisted reproduction therapy.

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.

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

PubMed

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

2016-03-01

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

How to personalize ovarian stimulation in clinical practice.

PubMed

Sighinolfi, Giovanna; Grisendi, Valentina; La Marca, Antonio

2017-09-01

Controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles is the starting point from which couple's prognosis depends. Individualization in follicle-stimulating hormone (FSH) starting dose and protocol used is based on ovarian response prediction, which depends on ovarian reserve. Anti-Müllerian hormone levels and the antral follicle count are considered the most accurate and reliable markers of ovarian reserve. A literature search was performed for studies that addressed the ability of ovarian reserve markers to predict poor and high ovarian response in assisted reproductive technology cycles. According to the predicted response to ovarian stimulation (poor- normal- or high- response), it is possible to counsel couples before treatment about the prognosis, and also to individualize ovarian stimulation protocols, choosing among GnRH-agonists or antagonists for endogenous FSH suppression, and the FSH starting dose in order to decrease the risk of cycle cancellation and ovarian hyperstimulation syndrome. In this review we discuss how to choose the best COS therapy, based on ovarian reserve markers, in order to enhance chances in IVF.

Constraining Silicate Weathering Processes in an Active Volcanic Complex: Implications for the Long-term Carbon Cycle

NASA Astrophysics Data System (ADS)

Washington, K.; West, A. J.; Hartmann, J.; Amann, T.; Hosono, T.; Ide, K.

2017-12-01

While analyzing geochemical archives and carbon cycle modelling can further our understanding of the role of silicate weathering as a sink in the long-term carbon cycle, it is necessary to study modern weathering processes to inform these efforts. A recent compilation of data from rivers draining basaltic catchments estimates that rock weathering in active volcanic fields (AVFs) consumes atmospheric CO2 approximately three times faster than in inactive volcanic fields (IVFs), suggesting that the eruption and subsequent weathering of large igneous provinces likely played a major role in the carbon cycle in the geologic past [1]. The study demonstrates a significant correlation between catchment mean annual temperature (MAT) and atmospheric CO2 consumption rate for IVFs. However CO2 consumption due to weathering of AVFs is not correlated with MAT as the relationship is complicated by variability in hydrothermal fluxes, reactive surface area, and groundwater flow paths. To investigate the controls on weathering processes in AVFs, we present data for dissolved and solid weathering products from Mount Aso Caldera, Japan. Aso Caldera is an ideal site for studying the how the chemistry of rivers draining an AVF is impacted by high-temperature water/rock interactions, volcanic ash weathering, and varied groundwater flow paths and residence times. Samples were collected over five field seasons from two rivers and their tributaries, cold groundwater springs, and thermal springs. These samples capture the region's temperature and precipitation seasonality. Solid samples of unaltered volcanic rocks, hydrothermally-altered materials, volcanic ash, a soil profile, and suspended and bedload river sediments were also collected. The hydrochemistry of dissolved phases were analyzed at the University of Hamburg, while the mineralogy and geochemical compositions of solid phases were analyzed at the Natural History Museum of Los Angeles. This work will be discussed in the context of volcanic activity and associated silicate weathering in the geologic past. [1] Li, G., J. Hartmann, L. A. Derry, A. J. West, C.-F. You, X. Long, T. Zhan, L. Li, G. Li, and W. Qiu (2016), Temperature dependence of basalt weathering, Earth Planet. Sci. Lett., 443, 59-69.

[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.

Clinical relevance of combined FSH and AMH observations in infertile women.

PubMed

Gleicher, Norbert; Kim, Ann; Kushnir, Vitaly; Weghofer, Andrea; Shohat-Tal, Aya; Lazzaroni, Emanuela; Lee, Ho-Joon; Barad, David H

2013-05-01

FSH and anti-Müllerian hormone (AMH) are, individually, widely used to assess functional ovarian reserve (FOR) but demonstrate discrepancies in efficacy. How predictive they are combined is unknown. The purpose of this study was to assess predictive values of different FSH and AMH combinations on in vitro fertilization (IVF). FSH and AMH levels in patients were categorized as low, normal, and high, based on age-specific 95% confidence intervals. This allowed for establishment of nine combinations of low, normal, or high FSH/AMH patient categories. With use of various statistical methods, patients in individual categories were then compared in outcomes. We investigated 544 consecutive infertility patients in their first IVF cycles. IVF cycles were managed. Oocyte yields and implantation and pregnancy rates, adjusted for age and fragile X mental retardation 1 (FMR1) genotypes/subgenotypes, were measured. The most notable repeated finding was a strong statistical association of the FSH/AMH high/high category (characterized by abnormally high FSH and AMH levels) with favorable IVF outcomes compared with outcomes for other FSH/AMH variations (4.34 times odds of high oocyte yields and 1.93 times odds of clinical pregnancy). Addition of age to the model only minimally further improved the odds of pregnancy to 2.03 times. The positive association with high oocyte yields, however, turned negative (0.75 times lower yields) with addition of FMR1 to the model for women with FSH/AMH high/high and the het-norm/low FMR1 subgenotype compared with women with the norm FMR1 genotype and other FSH/AMH categories. In the absence of het-norm/low FMR1, abnormally high FSH and AMH, a seemingly contradictory combination, reflects highly beneficial outcomes in IVF compared with the other FSH/AMH categories, suggesting greater importance of FSH in early follicle maturation than currently recognized. The study also confirms adverse outcome effects of het-norm/low FMR1 and, therefore, the gene's importance for reproductive success.

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.

GnRH agonist for final oocyte maturation in GnRH antagonist co-treated IVF/ICSI treatment cycles: Systematic review and meta-analysis

PubMed Central

Youssef, M.A.F.; Abdelmoty, Hatem I.; Ahmed, Mohamed A.S.; Elmohamady, Maged

2015-01-01

Final oocyte maturation in GnRH antagonist co-treated IVF/ICSI cycles can be triggered with HCG or a GnRH agonist. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy and safety of the final oocyte maturation trigger in GnRH antagonist co-treated cycles. Outcome measures were ongoing pregnancy rate (OPR) and ovarian hyperstimulation syndrome (OHSS) incidence. Searches: were conducted in MEDLINE, EMBASE, Science Direct, Cochrane Library, and databases of abstracts. There was a statistically significant difference against the GnRH agonist for OPR in fresh autologous cycles (n = 1024) with an odd ratio (OR) of 0.69 (95% CI: 0.52–0.93). In oocyte-donor cycles (n = 342) there was no evidence of a difference (OR: 0.91; 95% CI: 0.59–1.40). There was a statistically significant difference in favour of GnRH agonist regarding the incidence of OHSS in fresh autologous cycles (OR: 0.06; 95% CI: 0.01–0.33) and donor cycles respectively (OR: 0.06; 95% CI: 0.01–0.27). In conclusion GnRH agonist trigger for final oocyte maturation trigger in GnRH antagonist cycles is safer but less efficient than HCG. PMID:26257931

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

[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.

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)

Effect of simultaneously started clomiphene citrate and gonadotropins in antagonist regimes, on cumulative live births, fresh-cycle live births and cost of stimulation in IVF cycles.

PubMed

Satwik, Ruma; Kochhar, Mohinder

2018-04-11

The aim of the study was to compare simultaneously started clomiphene citrate (CC) and gonadotropins (Gn) with gonadotropins alone in conventional antagonist regimes with respect to fresh-cycle live births, cumulative live births and cost of ovarian stimulation per started cycle. This was a single-center prospective cohort study conducted over 1 year. Women undergoing autologous in vitro fertilization (IVF) treatment in antagonist protocols and who consented to participate in the study were divided into two cohorts. The CC cohort (n = 86) received 50 mg CC for 5 days and individualized Gn daily until the hCG trigger, both starting from day 2 and antagonist daily from day 8 of menstrual cycle. The Gn-only cohort (n = 349) received individualized Gn from day 2 and the antagonist from day 7 of menstrual cycle. IVF outcomes and cost of stimulation were compared between two cohorts across expected ovarian response categories. The CC cohort used a mean lower dose of Gn (1741.38 ± 604.46 vs 1980.54 ± 686.42; MD = -239.16; 95%CI = -348.03 to -189.24; P = 0.003) over fewer days (8.54 ± 1.86 vs 9.25 ± 1.97; MD =-0.71;95% CI = -1.17 to -0.25; P = 0.0026) to achieve similar retrieved oocytes, (9.19 ± 5.92 vs 9.36 ± 6.96; MD = -0.17; 95%CI -1.77 to + 1.43; P = 0.83), positive bhCG rates (40% vs 29.6%, MD = 10.4%; OR = 1.65, 95%CI = 0.95-2.86; P = 0.078) and live births in fresh cycles (32.31% vs 21.30%; MD = 11.01%; OR = 1.76; 95%CI = 0.97-3.19; P = 0.06) and cumulative live births per initiated cycle (30.23% vs 20.34%; MD = 9.89%; OR = 1.697; 95%CI = 0.99-2.88; P = 0.0501). The dose lowering achieved a 28-40% reduction in the cost of stimulation, which was most noticeable in the hyper-responder category for both hMG cycles, (Rs.11 602.3 ± 3365.9 vs 19615 ± 2677.1; MD = -8012.7; %age reduction: 40.8%; P = 0.0007) and recombinant FSH cycles (Rs. 22 459.6 ± 6255.3 vs 33 022.1 ± 9891.2; MD: -10 562; %age reduction: -32%; P = 0.0001). CC started simultaneously with Gn in antagonist regimes helps lower the cost of stimulation without affecting IVF outcomes. © 2018 Japan Society of Obstetrics and Gynecology.

Endometrial Receptivity and its Predictive Value for IVF/ICSI-Outcome

PubMed Central

Heger, A.; Sator, M.; Pietrowski, D.

2012-01-01

Endometrial receptivity plays a crucial role in the establishment of a healthy pregnancy in cycles of assisted reproduction. The endometrium as a key factor during reproduction can be assessed in multiple ways, most commonly through transvaginal grey-scale or 3-D ultrasound. It has been shown that controlled ovarian hyperstimulation has a great impact on the uterine lining, which leads to different study results for the predictive value of endometrial factors measured on different cycle days. There is no clear consensus on whether endometrial factors are appropriate to predict treatment outcome and if so, which one is suited best. The aim of this review is to summarize recent findings of studies about the influence of endometrial thickness, volume and pattern on IVF- and ICSI-treatment outcome and provide an overview of future developments in the field. PMID:25258462

Endometrial Receptivity and its Predictive Value for IVF/ICSI-Outcome.

PubMed

Heger, A; Sator, M; Pietrowski, D

2012-08-01

Endometrial receptivity plays a crucial role in the establishment of a healthy pregnancy in cycles of assisted reproduction. The endometrium as a key factor during reproduction can be assessed in multiple ways, most commonly through transvaginal grey-scale or 3-D ultrasound. It has been shown that controlled ovarian hyperstimulation has a great impact on the uterine lining, which leads to different study results for the predictive value of endometrial factors measured on different cycle days. There is no clear consensus on whether endometrial factors are appropriate to predict treatment outcome and if so, which one is suited best. The aim of this review is to summarize recent findings of studies about the influence of endometrial thickness, volume and pattern on IVF- and ICSI-treatment outcome and provide an overview of future developments in the field.

Innovations 'Out of Place': Controversies Over IVF Beginnings in India Between 1978 and 2005.

PubMed

Bärnreuther, Sandra

2016-01-01

In 1978, the year the first in vitro fertilization (IVF) baby was born in the United Kingdom, a research team in Kolkata reported that it too had successfully produced an IVF baby in India. However, the claim was dismissed at the time, because the experiment was conducted outside authorized institutions and recognized centers of innovation--in short, because it was an innovation 'out of place.' Tracing controversies over the case between 1978 and 2005, I show the importance of space or place in processes of knowledge production and recognition. Further, I explain the initial repudiation and subsequent partial recognition of the claim through shifts in the landscape of legitimate spaces of innovation. By discussing this specific case of the production of science and technology in the Global South, I challenge conventional narratives of diffusion that are prevalent in studies on the worldwide proliferation of reproductive technologies.

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

PubMed

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

2017-03-01

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

Clinical application of a nomogram based on age, serum FSH and AMH to select the FSH starting dose in IVF/ICSI cycles: a retrospective two-centres study.

PubMed

Papaleo, Enrico; Zaffagnini, Stefano; Munaretto, Maria; Vanni, Valeria Stella; Rebonato, Giorgia; Grisendi, Valentina; Di Paola, Rossana; La Marca, Antonio

2016-12-01

To externally validate a nomogram based on ovarian reserve markers as a tool to optimize the FSH starting dose in IVF/ICSI cycles. A two-centres retrospective study including 398 infertile women undergoing their first IVF/ICSI cycle (June 2013-June 2014). IVF data were retrieved from two independent IVF centres in Italy (San Raffaele Hospital, Centre 1; Verona Hospital, Centre 2). A central lab for the routine measurement of AMH and FSH was used for both centres. All women were treated based on physical and hormonal characteristics according to locally adopted protocols. The nomogram was then retrospectively applied to the patients comparing the calculated starting dose to the one actually given. In Centre 1, 64/131 women (48.8%) had an ovarian response below the target. While 45 of these patients were treated with a maximal FSH starting dose (≥225 IU), n=19/131 (14.5%) were treated with a submaximal dose. The vast majority of them (n=17/19) would have received a higher FSH starting dose by using the nomogram. Seventeen patients (n=17/131) had hyper response and about half of them would have been treated with a reduced FSH starting dose according to the nomogram. In Centre 2, 142/267 patients (53.2%) had an ovarian response below the target. While 136 of these were treated with a maximal FSH starting dose (≥225 IU), n=6/267 were treated with a submaximal dose. The majority of them (n=5/6) would have received a higher FSH starting dose. Thirty-two (n=32/267) patients had hyper response and more than half of them would have been treated with a reduced FSH dose. In both Centres, applying the nomogram would have resulted in more appropriate FSH starting doses compared to the the ones actually given based on clinicians choices. The use of an objective algorithm based on patient's age, serum FSH and AMH levels may thus be an effective advice on the selection of the tailored FSH starting dose. Hence, the use of this easily available nomogram could increase the proportion of patients achieving the optimal ovarian response. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Impact of Serum Progesterone Levels on the Results of In Vitro Fertilization Treatments: A Literature Review.

PubMed

Castillo, Jaime Larach Del; Bousamra, Maroun; Fuente, Laura De La; Ruiz-Balda, Jose A; Palomo, Marissa

2015-08-01

The aim of this review is to analyze the relationship between preovulatory progesterone (P) rise and in vitro fertilization (IVF) pregnancy outcomes. It also investigates the sources and effects of rises in progesterone levels, including the underlying mechanisms and potential strategies in preventing its elevation during ovarian stimulation. Progesterone is produced in the early follicular phase in the adrenal gland, which shifts toward the ovaries prior to ovulation. Several factors contribute to the etiology of P level increase including the number of multiple follicles, the overdose of gonadotropins and poor ovarian response. Nowadays, the influence of the preovulatory P rise on IVF outcome remains controversial. Several authors have failed to demonstrate any negative impact, while others reported a detrimental effect associated with the rise of P. It seems that P rise (1.5 ng/ml or 4.77 nmol/l) may have deleterious effects on endometrial receptivity, namely, accelerating the endometrial maturation process that subsequently narrows the period for implantation and thus decreases pregnancy rates. Recent studies have proposed different cutoffs according to the ovarian response, which may be a little high in patients with high response in relation to those of normal response or low response. To prevent a P rise, it might be preferable to use milder stimulation protocols, earlier trigger of ovulation, cryopreservation of all embryos and transfer in the natural cycle.

The Effects of ISM1 Medium on Embryo Quality and Outcomes of IVF/ICSI Cycles.

PubMed

Hassani, Fatemeh; Eftekhari-Yazdi, Poopak; Karimian, Leila; Rezazadeh Valojerdi, Mojtaba; Movaghar, Bahar; Fazel, Mohammad; Fouladi, Hamid Reza; Shabani, Fatemeh; Johansson, Lars

2013-07-01

The aim of this study is to investigate the effect of ISM1 culture medium on embryo development, quality and outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. This study compares culture medium commonly used in the laboratory setting for oocyte recovery and embryo development with a medium from MediCult. We have assessed the effects of these media on embryo development and newborn characteristics. In this prospective randomized study, fertilized oocytes from patients were randomly assigned to culture in ISM1 (MediCult, cycles: n=293) or routine lab culture medium (G-1TM v5; Vitrolife, cycles: n=290) according to the daily media schedule for oocyte retrieval. IVF or ICSI and embryo transfer were performed with either MediCult media or routine lab media. Embryo quality on days 2/3, cleavage, pregnancy and implantation rates, baby take home rate (BTHR), in addition to the weight and length of newborns were compared between groups. There were similar cleavage rates for ISM1 (86%) vs. G-1TM v5 (88%). We observed a significantly higher percentage of excellent embryos in ISM1 (42.7%) compared to G-1TM v5 (39%, p<0.05). Babies born after culture in ISM1 had both higher birth weight (3.03 kg) and length (48.8 cm) compared to G-1TM v5 babies that had a birth weight of 2.66 kg and a length of 46.0 cm (p<0.001 for both). This study suggests that ISM1 is a more effective culture medium in generating higher quality embryos, which may be reflected in the characteristics of babies at birth.

The Effects of ISM1 Medium on Embryo Quality and Outcomes of IVF/ICSI Cycles

PubMed Central

Hassani, Fatemeh; Eftekhari-Yazdi, Poopak; Karimian, Leila; Rezazadeh Valojerdi, Mojtaba; Movaghar, Bahar; Fazel, Mohammad; Fouladi, Hamid Reza; Shabani, Fatemeh; Johansson, Lars

2013-01-01

Background: The aim of this study is to investigate the effect of ISM1 culture medium on embryo development, quality and outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles. This study compares culture medium commonly used in the laboratory setting for oocyte recovery and embryo development with a medium from MediCult. We have assessed the effects of these media on embryo development and newborn characteristics. Materials and Methods: In this prospective randomized study, fertilized oocytes from patients were randomly assigned to culture in ISM1 (MediCult, cycles: n=293) or routine lab culture medium (G-1TM v5; Vitrolife, cycles: n=290) according to the daily media schedule for oocyte retrieval. IVF or ICSI and embryo transfer were performed with either MediCult media or routine lab media. Embryo quality on days 2/3, cleavage, pregnancy and implantation rates, baby take home rate (BTHR), in addition to the weight and length of newborns were compared between groups. Results: There were similar cleavage rates for ISM1 (86%) vs. G-1TM v5 (88%). We observed a significantly higher percentage of excellent embryos in ISM1 (42.7%) compared to G-1TM v5 (39%, p<0.05). Babies born after culture in ISM1 had both higher birth weight (3.03 kg) and length (48.8 cm) compared to G-1TM v5 babies that had a birth weight of 2.66 kg and a length of 46.0 cm (p<0.001 for both). Conclusion: This study suggests that ISM1 is a more effective culture medium in generating higher quality embryos, which may be reflected in the characteristics of babies at birth. PMID:24520472

Paternal Urinary Concentrations of Parabens and Other Phenols in Relation to Reproductive Outcomes among Couples from a Fertility Clinic

PubMed Central

Dodge, Laura E.; Williams, Paige L.; Williams, Michelle A.; Missmer, Stacey A.; Toth, Thomas L.; Calafat, Antonia M.

2015-01-01

Background Human exposure to phenols, including bisphenol A and parabens, is widespread. Evidence suggests that paternal exposure to environmental chemicals may adversely affect reproductive outcomes. Objectives We evaluated associations of paternal phenol urinary concentrations with fertilization rate, embryo quality, implantation, and live birth. Methods Male–female couples who underwent in vitro fertilization (IVF) and/or intrauterine insemination (IUI) cycles in a prospective study of environmental determinants of fertility and pregnancy outcomes were included. The geometric mean of males’ specific gravity–adjusted urinary phenol concentrations measured before females’ cycle was quantified. Associations between male urinary phenol concentrations and fertilization rate, embryo quality, implantation, and live birth were investigated using generalized linear mixed models to account for multiple cycles per couple. Results Couples (n = 218) underwent 195 IUI and 211 IVF cycles. Paternal phenol concentrations were not associated with fertilization or live birth following IVF. In adjusted models, compared with the lowest quartile of methyl paraben, paternal concentrations in the second quartile were associated with decreased odds of live birth following IUI (adjusted odds ratio = 0.19; 95% CI: 0.04, 0.82). Conclusions To our knowledge, these are some of the first data on the association of paternal urinary phenol concentrations with reproduction and pregnancy outcomes. Although these results do not preclude possible adverse effects of paternal paraben exposures on such outcomes, given the modest sample size, further understanding could result from confirmation using a larger and more diverse population. Citation Dodge LE, Williams PL, Williams MA, Missmer SA, Toth TL, Calafat AM, Hauser R. 2015. Paternal urinary concentrations of parabens and other phenols in relation to reproductive outcomes among couples from a fertility clinic. Environ Health Perspect 123:665–671; http://dx.doi.org/10.1289/ehp.1408605 PMID:25767892

Does obesity compromise ovarian reserve markers? A clinician's perspective.

PubMed

Malhotra, Neena; Bahadur, Anupama; Singh, Neeta; Kalaivani, Mani; Mittal, Suneeta

2013-01-01

The aim of the study was to ascertain if increasing body mass index (BMI) adversely affects ovarian reserve among infertile women of Asian origin undergoing in vitro fertilization (IVF). This prospective study on 183 women was carried out in the infertility clinic of All India Institute of Medical Sciences, New Delhi, India. Blood hormonal assay in all patients including follicle-stimulating hormone (FSH), luteinizing hormone (LH) and inhibin B was performed on day 2/3 of a spontaneous cycle. A transvaginal ultrasonographic examination on day 2-5 of the menstrual cycle was done for antral follicle count (AFC) and ovarian volume. A correlation between BMI and ovarian reserve parameters like FSH, LH, inhibin B, antral follicle count and ovarian volume was noted. Age was comparable in the three BMI groups. The mean duration of infertility was 8.38 years. Compared to the normal weight, the overweight and obese women had a statistically significantly low inhibin B (p < 0.0259). The AFC when taken together on both sides was not statistically significant between the groups; however, the overweight and obese women had a significantly low AFC (p < 0.0129) on the right side. Incorporating anti-mullerian hormone, a newer marker for ovarian reserve, may benefit these obese infertile women. Further work is required to elucidate the mechanisms underlying the effect of obesity on inhibin B as a marker of ovarian reserve in infertile women. The best marker to check the ovarian reserve is perhaps the woman's performance during an IVF cycle. However, considering the psychological and financial stress of the procedure, it may seem wise to consider counseling of obese women on their expected performance in the first cycle of IVF through such studies.

Economic Evaluation of Three Frequently Used Gonadotrophins in Assisted Reproduction Techniques in the Management of Infertility in the Netherlands.

PubMed

Fragoulakis, Vassilis; Pescott, Chris P; Smeenk, Jesper M J; van Santbrink, Evert J P; Oosterhuis, G Jur E; Broekmans, Frank J M; Maniadakis, Nikos

2016-12-01

Subfertility represents a multidimensional problem associated with significant distress and impaired social well-being. In the Netherlands, an estimated 50,000 couples visit their general practitioner and 30,000 couples seek medical specialist care for subfertility. We conducted an economic evaluation comparing recombinant human follicle-stimulating hormone (follitropin alfa, r-hFSH, Gonal-F ® ) with two classes of urinary gonadotrophins-highly purified human menopausal gonadotrophin (hp-HMG, Menopur ® ) and urinary follicle-stimulating hormone (uFSH, Fostimon ® )-for ovarian stimulation in women undergoing in vitro fertilization (IVF) treatment in the Netherlands. A pharmacoeconomic model was developed, simulating each step in the IVF protocol from the start of therapy until either a live birth, a new IVF treatment cycle or cessation of IVF, following a long down-regulation protocol. A decision tree combined with a Markov model details progress through each health state, including ovum pickup, fresh embryo transfer, up to two subsequent cryo-preserved embryo transfers, and (ongoing) pregnancy or miscarriage. A health insurer perspective was chosen, and the time horizon was set at a maximum of three consecutive treatment cycles, in accordance with Dutch reimbursement policy. Transition probabilities and costing data were derived from a real-world observational outcomes database (from Germany) and official tariff lists (from the Netherlands). Adverse events were considered equal among the comparators and were therefore excluded from the economic analysis. A Monte Carlo simulation of 5000 iterations was undertaken for each strategy to explore uncertainty and to construct uncertainty intervals (UIs). All cost data were valued in 2013 Euros. The model's structure, parameters and assumptions were assessed and confirmed by an external clinician with experience in health economics modelling, to inform on the appropriateness of the outcomes and the applicability of the model in the chosen setting. The mean total treatment costs were estimated as €5664 for follitropin alfa (95 % UI €5167-6151), €5990 for hp-HMG (95 % UI €5498-6488) and €5760 for uFSH (95 % UI €5256-6246). The probability of a live birth was estimated at 36.1 % (95 % UI 27.4-44.3 %), 33.9 % (95 % UI 26.2-41.5 %) and 34.1 % (95 % UI 25.9-41.8 %) for follitropin alfa, hp-HMG and uFSH, respectively. The costs per live birth estimates were €15,674 for follitropin alfa, €17,636 for hp-HMG and €16,878 for uFSH. Probabilistic sensitivity analysis indicated a probability of 72.5 % that follitropin alfa is cost effective at a willingness to pay of €20,000 per live birth. The probabilistic results remained constant under several analyses. The present analysis shows that follitropin alfa may represent a cost-effective option in comparison with uFSH and hp-HMG for IVF treatment in the Netherlands healthcare system.

Pregnancy outcome in women with endometriosis achieving pregnancy with IVF.

PubMed

Benaglia, Laura; Candotti, Giorgio; Papaleo, Enrico; Pagliardini, Luca; Leonardi, Marta; Reschini, Marco; Quaranta, Lavinia; Munaretto, Maria; Viganò, Paola; Candiani, Massimo; Vercellini, Paolo; Somigliana, Edgardo

2016-12-01

Are women with endometriosis who conceive with IVF at increased risk of preterm birth? Women with endometriosis who conceive with IVF do not face an increased risk of preterm birth. The eutopic endometrium of women with endometriosis has been repeatedly shown to present molecular and cellular alterations. On this basis, it has been hypothesized that pregnancy outcome may be altered in affected women. However, to date, available evidence from epidemiological studies is scanty and conflicting. Data tended to be partly consistent only for an increased risk of preterm birth and placenta previa. Retrospective matched case-control study of women achieving an IVF singleton pregnancy progressing beyond 12 weeks' gestation. Women achieving IVF singleton pregnancies that progressed beyond 12 weeks' gestation at two infertility units were reviewed. Cases were women with a history of surgery for endometriosis and/or with a sonographic diagnosis of the disease at the time of the IVF cycle. Controls were women without current or past evidence of endometriosis who were matched to cases by age (± 6 months), type of cycle (fresh or frozen cycle) and study period. Male factor and unexplained infertility were the most common diagnoses in the control group. Two hundred and thirty-nine women with endometriosis and 239 controls were selected. The main outcome of the study was the rate of preterm birth (birth < 37 weeks' gestation) regardless of the cause. Secondary analyses were performed for the most common obstetrical complications. The rate of preterm birth was similar in the two study groups (14% and 14%, respectively, p = 0.89). The rate of live birth and the incidence of hypertensive disorders, gestational diabetes, small and large for gestational age newborns and neonatal problems also did not differ. In contrast, placenta previa was more common in women with endometriosis than controls (6% versus 1%, respectively; p = 0.006): The adjusted odds ratio was 4.8 (95% confidence interval: 1.4-17.2). As for all observational studies, confounders cannot be totally excluded. Moreover, the retrospective study design exposes the findings to some inaccuracies. For example, the independent role of adenomyosis could not be reliably assessed because this diagnosis is complex and would necessitate a prospective recruitment. Second, the selection of controls may also be a matter of concern because some affected women may have been erroneously included in this group. Third, even if the sample size is significant, it is insufficient for robust subgroup analyses. Finally, it is mandatory to point out that our conclusions are valid for IVF pregnancies only, and specific data from properly designed studies are required to support any inference for natural pregnancies. The results of our study suggest that women with endometriosis conceiving with IVF can be reassured regarding the risk of preterm birth. The observed association with placenta previa requires further investigation and may open a new avenue of research. No external funding was used for this study. None of the authors have any conflict 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.

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

PubMed

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

2017-04-01

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

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

PubMed Central

2011-01-01

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

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

PubMed

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

2018-06-01

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

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

Embryo transfer practices in the United States: a survey of clinics registered with the Society for Assisted Reproductive Technology.

PubMed

Jungheim, Emily S; Ryan, Ginny L; Levens, Eric D; Cunningham, Alexandra F; Macones, George A; Carson, Kenneth R; Beltsos, Angeline N; Odem, Randall R

2010-09-01

To gain a better understanding of factors influencing clinicians' embryo transfer practices. Cross-sectional survey. Web-based survey conducted in December 2008 of individuals practicing IVF in centers registered with the Society for Assisted Reproductive Technology (SART). None. None. Prevalence of clinicians reporting following embryo transfer guidelines recommended by the American Society for Reproductive Medicine (ASRM), prevalence among these clinicians to deviate from ASRM guidelines in commonly encountered clinical scenarios, and practice patterns related to single embryo transfer. Six percent of respondents reported following their own, independent guidelines for the number of embryos to transfer after IVF. Of the 94% of respondents who reported routinely following ASRM embryo transfer guidelines, 52% would deviate from these guidelines for patient request, 51% for cycles involving the transfer of frozen embryos, and 70% for patients with previously failed IVF cycles. All respondents reported routinely discussing the risks of multiple gestations associated with standard embryo transfer practices, whereas only 34% reported routinely discussing single embryo transfer with all patients. Although the majority of clinicians responding to our survey reported following ASRM embryo transfer guidelines, at least half would deviate from these guidelines in a number of different situations. Copyright (c) 2010 American Society for Reproductive Medicine. All rights reserved.

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

PubMed

Mohsen, Iman Abdel; El Din, Rasha Ezz

2013-02-01

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

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.

Do donor oocyte cycles comply with ASRM/SART embryo transfer guidelines? An analysis of 13,393 donor cycles from the SART registry.

PubMed

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

2016-09-01

To analyze donor oocyte cycles in the Society for Assisted Reproductive Technology (SART) registry to determine: 1) how many cycles complied with the 2009 American Society for Reproductive Medicine/SART embryo transfer guidelines; and 2) cycle outcomes according to the number of embryos transferred. For donor oocyte IVF with donor age <35 years, the consideration of single-embryo transfer was strongly recommended. Retrospective cohort study of United States national registry information. Not applicable. A total of 13,393 donor-recipient cycles from 2011 to 2012. Embryos transferred in donor IVF cycles. Percentage of compliant cycles, multiple pregnancy rate. There were 3,157 donor cleavage-stage transfers and 10,236 donor blastocyst transfers. In the cleavage-stage cycles, 88% met compliance criteria. The multiple pregnancy rate (MPR) was significantly higher in the noncompliant cycles. In a subanalysis of compliant cleavage-stage cycles, 91% transferred two embryos and only 9% single embryos. In those patients transferring two embryos, the MPR was significantly higher (33% vs. 1%). In blastocyst transfers, only 28% of the cycles met compliance criteria. The MPR was significantly higher in the noncompliant blastocyst cohort at 53% (compared with 2% in compliant cycles). The majority of donor cleavage-stage transfers are compliant with current guidelines, but the transfer of two embryos results in a significantly higher MPR compared with single-embryo transfer. The majority of donor blastocyst cycles are noncompliant, which appears to be driving an unacceptably high MPR in these cycles. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Obstetric outcomes in women with polycystic ovary syndrome and isolated polycystic ovaries undergoing in vitro fertilization: a retrospective cohort analysis.

PubMed

Wan, Hei Lok Tiffany; Hui, Pui Wah; Li, Hang Wun Raymond; Ng, Ernest Hung Yu

2015-03-01

This retrospective cohort study evaluated the obstetric outcomes in women with polycystic ovary syndrome (PCOS) and isolated polycystic ovaries (PCO) undergoing in vitro fertilization (IVF) treatment. We studied 104 women with PCOS, 184 with PCO and 576 age-matched controls undergoing the first IVF treatment cycle between 2002 and 2009. Obstetric outcomes and complications including gestational diabetes (GDM), gestational hypertension (GHT), gestational proteinuric hypertension (PET), intrauterine growth restriction (IUGR), gestation at delivery, baby's Apgar scores and admission to the neonatal intensive care unit (NICU) were reviewed. Among the 864 patients undergoing IVF treatment, there were 253 live births in total (25 live births in the PCOS group, 54 in the PCO group and 174 in the control group). The prevalence of obstetric complications (GDM, GHT, PET and IUGR) and the obstetric outcomes (gestation at delivery, birth weight, Apgar scores and NICU admissions) were comparable among the three groups. Adjustments for age and multiple pregnancies were made using multiple logistic regression and we found no statistically significant difference among the three groups. Patients with PCO ± PCOS do not have more adverse obstetric outcomes when compared with non-PCO patients undergoing IVF treatment.

Smoking Decreases Endometrial Thickness in IVF/ICSI Patients

PubMed Central

Heger, Anna; Sator, Michael; Walch, Katharina; Pietrowski, Detlef

2018-01-01

Introduction Smoking is a serious problem for the health care system. Many of the compounds identified in cigarette smoke have toxic effects on the fertility of both females and males. The purpose of this study was to determine whether smoking affects clinical factors during IVF/ICSI therapy in a single-center reproductive unit. Material and Methods In a retrospective study of 200 IVF/ICSI cycles, endometrial thickness and the outcome of IVF/ICSI therapy were analyzed. Results Endometrial thickness was significantly lower in smoking patients than in non-smoking patients (10.4 ± 1.5 mm vs. 11.6 ± 1.8 mm). Age was significantly higher in women who failed to conceive. The total dose of gonadotropins administered was significantly lower in pregnant patients and the highest pregnancy rate was achieved with an rFSH protocol. BMI and number of cigarettes smoked did not influence treatment outcomes in this study. Conclusion We showed that smoking has a negative effect on endometrial thickness on the day of embryo transfer. This may help to further explain the detrimental influence of tobacco smoke on implantation and pregnancy rates during assisted reproduction therapy. PMID:29375149

Effect of mood states and infertility stress on patients' attitudes toward embryo transfer and multiple pregnancy.

PubMed

Newton, Christopher; Feyles, Valter; Asgary-Eden, Veronica

2013-08-01

To examine whether mood state or infertility stress influences perceptions of risk, preferences for embryo transfer, or views on multiple pregnancy. Observational cohort study. Hospital-based fertility clinic. One hundred seventy-six women participating in IVF treatment. None. Mood scores, ratings of risk, preference for multiple embryo transfer, and attitudes toward multiple pregnancy. Growing feelings of tension across the cycle corresponded with increases in the perceived riskiness of double-embryo transfer, but there was no change in strength of transfer preferences. Women experiencing negative moods, such as depression, viewed twin and triplet pregnancy as less likely, whereas increasing positive feelings across the cycle were associated with increasing desire for twin pregnancy. Overall, women perceived double- and triple-embryo transfer as less risky by cycle end than at cycle beginning and felt more certain about multiple-embryo transfer. The dyssynchrony observed among changes in mood, perceptions of risk, and transfer preferences challenges assumptions about the way medical risk information influences transfer preferences, and the findings suggest that mood states experienced during an IVF cycle might affect transfer preferences by influencing attitudes toward multiple pregnancy. Additional considerations beyond providing risk information are needed to facilitate effective patient decision making. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Effect of local endometrial injury on pregnancy outcomes in ovum donation cycles.

PubMed

Dain, Lena; Ojha, Kamal; Bider, David; Levron, Jacob; Zinchenko, Viktor; Walster, Sharon; Dirnfeld, Martha

2014-10-01

To evaluate the effect of local endometrial injury (LEI) on clinical outcomes in ovum donation recipients. Retrospective cohort analysis of ovum donation cycles conducted from 2005 to 2012. Two private IVF centers. Total 737 ovum donation cycles. LEI by endometrial "scratch" with the use of a Pipelle catheter. Clinical pregnancy and live birth rates. No statistically significant differences were found in clinical pregnancy rates and live birth rates in cycles subjected to LEI compared with those without. Combination of LEI with fibroid uterus resulted with significantly higher clinical pregnancy rates compared with LEI in normal uterine anatomy. This is the first study done in ovum recipients who underwent LEI by a "scratch" procedure after failed implantation. Unlike most previous reports, which found improved pregnancy rates with the use of "scratch effect" or "minor endometrial injury" after repeated implantation failures in standard IVF with own eggs, we did not find any changes in implantation rates in a population of egg recipients following this procedure. In view of a possible positive effect of LEI in cycles with a previous four or more failures, prospective randomized controlled studies are warranted to better define the target population who may benefit from this intervention. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Paternal urinary concentrations of organophosphate flame retardant metabolites, fertility measures, and pregnancy outcomes among couples undergoing in vitro fertilization.

PubMed

Carignan, Courtney C; Mínguez-Alarcón, Lidia; Williams, Paige L; Meeker, John D; Stapleton, Heather M; Butt, Craig M; Toth, Thomas L; Ford, Jennifer B; Hauser, Russ

2018-02-01

Use of organophosphate flame retardants (PFRs) has increased over the past decade following the phase out of some brominated flame retardants, leading to increased human exposure. We recently reported that increasing maternal PFR exposure is associated with poorer pregnancy outcomes among women from a fertility clinic. Because a small epidemiologic study previously reported an inverse association between male PFR exposures and sperm motility, we sought to examine associations of paternal urinary concentrations of PFR metabolites and their partner's pregnancy outcomes. This analysis included 201 couples enrolled in the Environment and Reproductive Health (EARTH) prospective cohort study (2005-2015) who provided one or two urine samples per IVF cycle. In both the male and female partner, we measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP) and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). The sum of the molar concentrations of the urinary PFR metabolites was calculated. We used multivariable generalized linear mixed models to evaluate the association of urinary concentrations of paternal PFR metabolites with IVF outcomes, accounting for multiple in vitro fertilization (IVF) cycles per couple. Models were adjusted for year of IVF treatment cycle, primary infertility diagnosis, and maternal urinary PFR metabolites as well as paternal and maternal age, body mass index, and race/ethnicity. Detection rates were high for paternal urinary concentrations of BDCIPP (84%), DPHP (87%) and ip-PPP (76%) but low for tb-PPP (12%) and zero for BCIPP (0%). We observed a significant 12% decline in the proportion of fertilized oocytes from the first to second quartile of male urinary ΣPFR and a 47% decline in the number of best quality embryos from the first to third quartile of male urinary BDCIPP in our adjusted models. An 8% decline in fertilization was observed for the highest compared to lowest quartile of urinary BDCIPP concentrations (95% CI: 0.01, 0.12, p-trend=0.06). Using IVF as a model to investigate human reproduction and pregnancy outcomes, we found that paternal urinary concentrations of BDCIPP were associated with reduced fertilization. In contrast to previously reported findings for the female partners, the paternal urinary PFR metabolites were not associated with the proportion of cycles resulting in successful implantation, clinical pregnancy, and live birth. These results indicate that paternal preconception exposure to TDCIPP may adversely impact successful oocyte fertilization, whereas female preconception exposure to ΣPFRs may be more relevant to adverse pregnancy outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Time-lapse monitoring of zona pellucida-free embryos obtained through in vitro fertilization: a retrospective case series.

PubMed

Bodri, Daniel; Kato, Ryutaro; Kondo, Masae; Hosomi, Naoko; Katsumata, Yoshinari; Kawachiya, Satoshi; Matsumoto, Tsunekazu

2015-05-01

To report time-lapse monitoring of human oocytes in which the damaged zona pellucida was removed, producing zona-free (ZF) oocytes that were cultured until the blastocyst stage in time-lapse incubators. Retrospective case series. Private infertility clinic. Infertile patients (n = 32) undergoing minimal ovarian stimulation or natural cycle IVF treatment between October 2012 and June 2014. Intracytoplasmic sperm injection (ICSI) fertilization of ZF oocytes, prolonged embryo culture in time-lapse incubators, elective vitrification, and subsequent single vitrified-thawed blastocyst transfer (SVBT). Rate of fertilization, cleavage and blastocyst development, live-birth rate per SVBT cycle. In spite of advanced maternal age (39 ± 4.2; range, 30-46 years), good fertilization (94%), cleavage (94%), and blastocyst development rates (38%) were reached after fertilization and culturing of ZF oocytes/embryos. All thawed ZF blastocysts survived, and up to this date seven SVBT transfers were performed, yielding three (43%) term live births with healthy newborns. Time-lapse imagery gives a unique insight into the dynamics of embryo development in ZF embryos. Moreover, our case series demonstrate that an oocyte with a damaged zona pellucida that has been removed could be successfully fertilized with ICSI, cultured until blastocyst stage in a time-lapse incubator and vitrified electively for subsequent use. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Essure(®) for management of hydrosalpinx prior to in vitro fertilisation-a systematic review and pooled analysis.

PubMed

Arora, P; Arora, R S; Cahill, D

2014-04-01

Hydrosalpinges in infertile women reduce the success of in vitro fertilisation (IVF) by 50%. Surgical management of hydrosalpinges before IVF improves outcome but these procedures are often contraindicated in women with dense pelvic adhesions. Tubal occlusion achieved by Essure(®) via hysteroscopy provides an alternative. To conduct a systematic review on the efficacy and safety of Essure(®) in the management of hydrosalpinx before IVF. We searched MEDLINE (January 1950 to July 2013), EMBASE (January 1980 to July 2013) and Web of Science (1899 to July 2013). We also searched reference lists of relevant articles and proceedings of relevant international conferences (2000-2013). All types of studies where women with suspected infertility and presence of hydrosalpinx had hysteroscopic tubal occlusion with Essure(®) before IVF. Two authors independently selected studies and extracted data. Where necessary, study authors were contacted for further data. In all, 115 women in 11 studies received Essure(®) , mainly in the outpatient setting where local anaesthesia by paracervical block and/or intravenous sedation was used. Successful placement of Essure(®) was achieved in 96.5% (95% confidence interval [95% CI] 91.1-98.9%) of women and tubal occlusion in 98.1% (95% CI 93.1-99.9%). Subsequent IVF resulted in 38.6% pregnancy rate (95% CI 30.9-46.8%), 27.9% live birth rate (95% CI 21.1-35.8%) and 28.6% combined ongoing pregnancy and live birth rate (95% CI 21.7-36.6%) per embryo transfer. Essure(®) appears to be an effective option for management of hydrosalpinx in women before IVF although evidence from a randomised controlled clinical trial is lacking. © 2014 Royal College of Obstetricians and Gynaecologists.

The effect of cigarette smoking, alcohol consumption and fruit and vegetable consumption on IVF outcomes: a review and presentation of original data.

PubMed

Firns, Sarah; Cruzat, Vinicius Fernandes; Keane, Kevin Noel; Joesbury, Karen A; Lee, Andy H; Newsholme, Philip; Yovich, John L

2015-12-16

Lifestyle factors including cigarette smoking, alcohol consumption and nutritional habits impact on health, wellness, and the risk of chronic diseases. In the areas of in-vitro fertilization (IVF) and pregnancy, lifestyle factors influence oocyte production, fertilization rates, pregnancy and pregnancy loss, while chronic, low-grade oxidative stress may underlie poor outcomes for some IVF cases. Here, we review the current literature and present some original, previously unpublished data, obtained from couples attending the PIVET Medical Centre in Western Australia. During the study, 80 % of females and 70 % of male partners completed a 1-week diary documenting their smoking, alcohol and fruit and vegetable intake. The subsequent clinical outcomes of their IVF treatment such as quantity of oocytes collected, fertilization rates, pregnancy and pregnancy loss were submitted to multiple regression analysis, in order to investigate the relationship between patients, treatment and the recorded lifestyle factors. Of significance, it was found that male smoking caused an increased risk of pregnancy loss (p = 0.029), while female smoking caused an adverse effect on ovarian reserve. Both alcohol consumption (β = 0.074, p < 0.001) and fruit and vegetable consumption (β = 0.034, p < 0.001) had positive effects on fertilization. Based on our results and the current literature, there is an important impact of lifestyle factors on IVF clinical outcomes. Currently, there are conflicting results regarding other lifestyle factors such as nutritional habits and alcohol consumption, but it is apparent that chronic oxidative stress induced by lifestyle factors and poor nutritional habits associate with a lower rate of IVF success.

Improvement in Parenteral Nutrition-Associated Cholestasis With the Use of Omegaven in an Infant With Short Bowel Syndrome.

PubMed

Strang, Brian J; Reddix, Bruce A; Wolk, Robert A

2016-10-01

Parenteral nutrition-associated cholestasis (PNAC) and liver disease have been associated with soybean oil-based intravenous fat emulsions (IVFEs). The benefit of fish oil-based IVFEs in the reversal of parenteral nutrition (PN)-associated liver damage includes allowing for longer PN duration without immediate need for bowel or liver transplantation. The present case involves an infant born with short bowel syndrome (SBS) requiring long-term PN with development of PNAC and subsequent administration of a fish oil-based IVFE. An infant born with SBS was initiated on PN and enteral feeds. After failed enteral progression, bowel lengthening by serial transverse enteroplasty (STEP) resulted in postoperative ileus with delayed enteral feeding for 4 weeks. The administration of long-term PN led to development of PNAC, resulting in initiation of a fish oil-based IVFE. After 4 months, the cholestasis had resolved. Despite the STEP, at 16 months, the child required bowel tapering due to inability to advance enteral feeding. Fish oil-based IVFE was effectively used to reverse PNAC in a child with SBS. Despite early STEP, the patient was not able to tolerate enteral feedings and required bowel tapering. This case illustrates that early surgical intervention did not allow for improved feed tolerance. This resulted in a significant period without enteral nutrition, leading to development of cholestasis. The use of fish oil-based IVFE may permit a longer duration of PN administration without the development of cholestasis or liver disease, allowing for longer time for bowel adaptation prior to the need for surgical intervention. © 2016 American Society for Parenteral and Enteral Nutrition.

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.

External validation of anti-Müllerian hormone based prediction of live birth in assisted conception

PubMed Central

2013-01-01

Background Chronological age and oocyte yield are independent determinants of live birth in assisted conception. Anti-Müllerian hormone (AMH) is strongly associated with oocyte yield after controlled ovarian stimulation. We have previously assessed the ability of AMH and age to independently predict live birth in an Italian assisted conception cohort. Herein we report the external validation of the nomogram in 822 UK first in vitro fertilization (IVF) cycles. Methods Retrospective cohort consisting of 822 patients undergoing their first IVF treatment cycle at Glasgow Centre for Reproductive Medicine. Analyses were restricted to women aged between 25 and 42 years of age. All women had an AMH measured prior to commencing their first IVF cycle. The performance of the model was assessed; discrimination by the area under the receiver operator curve (ROCAUC) and model calibration by the predicted probability versus observed probability. Results Live births occurred in 29.4% of the cohort. The observed and predicted outcomes showed no evidence of miscalibration (p = 0.188). The ROCAUC was 0.64 (95% CI: 0.60, 0.68), suggesting moderate and similar discrimination to the original model. The ROCAUC for a continuous model of age and AMH was 0.65 (95% CI 0.61, 0.69), suggesting that the original categories of AMH were appropriate. Conclusions We confirm by external validation that AMH and age are independent predictors of live birth. Although the confidence intervals for each category are wide, our results support the assessment of AMH in larger cohorts with detailed baseline phenotyping for live birth prediction. PMID:23294733

Impact of endometriosis on in vitro fertilization outcomes: an evaluation of the Society for Assisted Reproductive Technologies Database.

PubMed

Senapati, Suneeta; Sammel, Mary D; Morse, Christopher; Barnhart, Kurt T

2016-07-01

To assess the impact of endometriosis, alone or in combination with other infertility diagnoses, on IVF outcomes. Population-based retrospective cohort study of cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database. Not applicable. A total of 347,185 autologous fresh and frozen assisted reproductive technology cycles from the period 2008-2010. None. Oocyte yield, implantation rate, live birth rate. Although cycles of patients with endometriosis constituted 11% of the study sample, the majority (64%) reported a concomitant diagnosis, with male factor (42%), tubal factor (29%), and diminished ovarian reserve (22%) being the most common. Endometriosis, when isolated or with concomitant diagnoses, was associated with lower oocyte yield compared with those with unexplained infertility, tubal factor, and all other infertility diagnoses combined. Women with isolated endometriosis had similar or higher live birth rates compared with those in other diagnostic groups. However, women with endometriosis with concomitant diagnoses had lower implantation rates and live birth rates compared with unexplained infertility, tubal factor, and all other diagnostic groups. Endometriosis is associated with lower oocyte yield, lower implantation rates, and lower pregnancy rates after IVF. However, the association of endometriosis and IVF outcomes is confounded by other infertility diagnoses. Endometriosis, when associated with other alterations in the reproductive tract, has the lowest chance of live birth. In contrast, for the minority of women who have endometriosis in isolation, the live birth rate is similar or slightly higher compared with other infertility diagnoses. Copyright © 2016. Published by Elsevier Inc.

[Exogenous luteinizing hormone for assisted reproduction techniques in poor response patients].

PubMed

Spremović-Radjenović, Svetlana; Gudović, Aleksandra; Lazović, Gordana

2010-07-01

Two gonadotrophins, two cell theory refers to necessity of both gonadotrophin activities for theca and granulose cells steroidogenesis of dominant follicle. The aim of this study was to determine the influence of recombinant LH in women qualified as poor responders in the first assisted reproduction procedure (IVF), on fertility results, expressed as percentage of clinical pregnancies. The study included 12 women, 35 years and older who were their own controls. The next trial of IVF was with the same dose of recombinant FSH and GnRH agonist, and with the same, long protocol. Recombinant LH was added in the dose of 75 IU from the 2nd to 7th day of the cycle, and 150 IU from the 8th day of the cycle to the aspiration of oocytes. Within the two different protocols: there was no significant difference between LH concentration in 8th and 12th day of cycle; there was no significant difference between E2 concentration on day 2nd and day 8th; there was a significant difference between E2 concentrations on day 12th; endometrial thickness was not significantly different on the day of aspiration, neither was the number of follicles and embryos. In the two patients, clinical pregnancy was detected (pregnancy rate 17%), and they delivered in term. So, a statistically significant difference between the two protocols was in the rate of clinical pregnancies. The patients with low response to a long protocol in IVF procedures had significantly better results according to the clinical pregnancy rate when the recombinant LH was added to recombinant FSH in the stimulation protocol.

Influence of intracervical and intravaginal seminal plasma on the endometrium in assisted reproduction: a double-blind, placebo-controlled, randomized study.

PubMed

Mayer, R B; Ebner, T; Yaman, C; Hartl, J; Sir, A; Krain, V; Oppelt, P; Shebl, O

2015-02-01

To investigate the effect of intracervical and intravaginal application of seminal plasma on the endometrium, as assessed by endometrial/subendometrial vascularization and endometrial volume between the day of oocyte retrieval and the day of embryo transfer in an in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle. This was a double-blind, placebo-controlled, randomized study including patients undergoing a first or second IVF/ICSI cycle. Homologous seminal plasma or placebo (sodium chloride) was injected into the cervix and posterior vaginal fornix just after follicle aspiration. Three-dimensional power Doppler examination was performed 30 min before oocyte retrieval and 30 min before embryo transfer. Main outcome measures were changes in vascularization flow index (VFI), flow index (FI) and vascularization index (VI) of the endometrium/subendometrium using VOCAL™ (Virtual Organ Computer-aided AnaLysis) and endometrial volume. One hundred patients agreed to participate in the study. Twenty-three patients were excluded, mainly as a result of canceled embryo transfer. Data were analyzed from 40 patients receiving seminal plasma and 37 receiving placebo. No significant differences between the two groups were seen in VFI, FI or VI of the endometrium or subendometrium or in endometrial volume on the day of oocyte pick-up and on the day of embryo transfer. Neither endometrial/subendometrial vascularization parameters nor endometrial volume seem to be affected by the application of seminal plasma in patients undergoing their first or second IVF/ICSI cycle. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

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.

The effect of dehydroepiandrosterone (DHEA) supplementation on women with diminished ovarian reserve (DOR) in IVF cycle: Evidence from a meta-analysis.

PubMed

Qin, J C; Fan, L; Qin, A P

2017-01-01

To evaluate the effect of dehydroepiandrosterone (DHEA) therapy on the ovarian response and pregnancy outcome in patients with diminished ovarian reserve (DOR). Eligible studies, published before August 31, 2015, were identified from PubMed, EMBASE, the Cochrane library. Outcome measures were the number of retrieved oocytes, cancellation rate of IVF cycles, clinical pregnancy rate and miscarriage rate. We adopted Revman 5.0 software to pool the data from the eligible studies. A total of 9 studies, four were RCTs, four retrospective studies, one prospective studies, including 540 cases and 668 controls, were available for analysis. The pooled analysis showed that the clinical pregnancy rates were increased significantly in DOR patients who were pre-treated with DHEA (OR=1.47, 95% CI: 1.09-1.99), whereas no differences were found in the number of oocytes retrieved, the cancellation rate of IVF cycles and the miscarriage rate between the cases and controls (WMD= -0.69, 95% CI: -2.18-0.81; OR=0.74, 95% CI: 0.51-1.08; OR=0.34, 95% CI: 0.10-1.24). However, it is worth noting that when data were restricted to RCTs, there was a non-significant difference in the clinical pregnancy rate (OR=1.08, 95% CI: 0.67-1.73). We concluded that DHEA supplementation in DOR patients might improve the pregnancy outcomes. To further confirm this effect, more randomized controlled trials with large sample sizes are needed. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

PubMed

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

2011-11-01

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

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

PubMed

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

2017-06-01

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

Dynamic integrated analysis of DNA methylation and gene expression profiles in in vivo and in vitro fertilized mouse post-implantation extraembryonic and placental tissues.

PubMed

Tan, Kun; Zhang, Zhenni; Miao, Kai; Yu, Yong; Sui, Linlin; Tian, Jianhui; An, Lei

2016-07-01

How does in vitro fertilization (IVF) alter promoter DNA methylation patterns and its subsequent effects on gene expression profiles during placentation in mice? IVF-induced alterations in promoter DNA methylation might have functional consequences in a number of biological processes and functions during IVF placentation, including actin cytoskeleton organization, hematopoiesis, vasculogenesis, energy metabolism and nutrient transport. During post-implantation embryonic development, both embryonic and extraembryonic tissues undergo de novo DNA methylation, thereby establishing a global DNA methylation pattern, and influencing gene expression profiles. Embryonic and placental tissues of IVF conceptuses can have aberrant morphology and functions, resulting in adverse pregnancy outcomes such as pregnancy loss, low birthweight, and long-term health effects. To date, the IVF-induced global profiling of DNA methylation alterations, and their functional consequences on aberrant gene expression profiles in IVF placentas have not been systematically studied. Institute for Cancer Research mice (6 week-old females and 8-9 week-old males) were used to generate in vivo fertilization (IVO) and IVF blastocysts. After either IVO and development (IVO group as control) or in vitro fertilization and culture (IVF group), blastocysts were collected and transferred to pseudo-pregnant recipient mice. Extraembryonic (ectoplacental cone and extraembryonic ectoderm) and placental tissues from both groups were sampled at embryonic day (E) 7.5 (IVO, n = 822; IVF, n = 795) and E10.5 (IVO, n = 324; IVF, n = 278), respectively. The collected extraembryonic (E7.5) and placental tissues (E10.5) were then used for high-throughput RNA sequencing (RNA-seq) and methylated DNA immunoprecipitation sequencing (MeDIP-seq). The main dysfunctions indicated by bioinformatic analyses were further validated using molecular detection, and morphometric and phenotypic analyses. Dynamic functional profiling of high-throughput data, together with molecular detection, and morphometric and phenotypic analyses, showed that differentially expressed genes dysregulated by DNA methylation were functionally involved in: (i) actin cytoskeleton disorganization in IVF extraembryonic tissues, which may impair allantois or chorion formation, and chorioallantoic fusion; (ii) disturbed hematopoiesis and vasculogenesis, which may lead to abnormal placenta labyrinth formation and thereby impairing nutrition transport in IVF placentas; (iii) dysregulated energy and amino acid metabolism, which may cause placental dysfunctions, leading to delayed embryonic development or even lethality; (iv) disrupted genetic information processing, which can further influence gene transcriptional and translational processes. Findings in mouse placental tissues may not be fully representative of human placentas. Further studies are necessary to confirm these findings and determine their clinical significance. Our study is the first to provide the genome-wide analysis of gene expression dysregulation caused by DNA methylation during IVF placentation. Systematic understanding of the molecular mechanisms implicated in IVF placentation can be useful for the improvement of existing assisted conception systems to prevent these IVF-associated safety concerns. This work was supported by grants from the National Natural Science Foundation of China (No. 31472092), and the National High-Tech R&D Program (Nos. 2011|AA100303, 2013AA102506). There was no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The “graying” of infertility services: an impending revolution nobody is ready for

PubMed Central

2014-01-01

Background As demand for infertility services by older women continues to grow, because achievable in vitro fertilization (IVF) outcomes are widely underestimated, most fertility centers do not offer maximal treatment options with use of autologous oocytes. Limited data suggest that clinical IVF outcomes in excess of what the American Society for Reproductive Medicine (ASRM) considers “futile” can, likely, be achieved up to at least age 45 years. Methods In an attempt to point out an evolving demographic trend in IVF, we here report our center’s IVF data for 2010-2012 and national U.S. data for 1997-2010. Though our center’s data are representative of only one IVF center’s patients, they, likely, are unique since they probably represent the most adversely selected IVF patient population ever reported and, thus, are predictive of future demographic trends. In addition we performed a systematic review of the literature on the subject based on PubMed, Medline and Google Scholar searches till year-end 2013. The literature search was performed using key words and phrases relevant to fertility treatments in older women. Results As demonstrated by our center’s patient demographics and national U.S. data, IVF centers are destined to treat increasingly adversely selected patients. Despite our center’s already extremely adversely selected patient population, age-specific IVF cycle outcomes in women above age 40 years, nevertheless, exceeded criteria for “futility” by the ASRM and widely quoted outcome expectations in the literature for patient ages. Age 43 discriminates between better and poorer clinical pregnancy and live birth rates. Conclusions “Graying” of the infertility populations in the developed world, a problem with potentially far-reaching medical and societal consequences, has so far been only insufficiently addressed in the literature. As women’s postmenopausal life spans already exceed postmenarcheal life spans at the start of the 20th century, the “graying” of infertility services can be expected to further accelerate, no longer as in recent decades bringing only women in their 40s into maternity wards but also women in their 50s and 60s. Medicine and society better get ready for this revolution. PMID:25012752

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.

Intent to treat analysis of in vitro fertilization and preimplantation genetic screening versus expectant management in patients with recurrent pregnancy loss.

PubMed

Murugappan, Gayathree; Shahine, Lora K; Perfetto, Candice O; Hickok, Lee R; Lathi, Ruth B

2016-08-01

In an intent to treat analysis, are clinical outcomes improved in recurrent pregnancy loss (RPL) patients undergoing IVF and preimplantation genetic screening (PGS) compared with patients who are expectantly managed (EM)? Among all attempts at PGS or EM among RPL patients, clinical outcomes including pregnancy rate, live birth (LB) rate and clinical miscarriage (CM) rate were similar. The standard of care for management of patients with RPL is EM. Due to the prevalence of aneuploidy in CM, PGS has been proposed as an alternate strategy for reducing CM rates and improving LB rates. Retrospective cohort study of 300 RPL patients treated between 2009 and 2014. Among two academic fertility centers, 112 RPL patients desired PGS and 188 patients chose EM. Main outcomes measured were pregnancy rate and LB per attempt and CM rate per pregnancy. One attempt was defined as an IVF cycle followed by a fresh embryo transfer or a frozen embryo transfer (PGS group) and 6 months trying to conceive (EM group). In the IVF group, 168 retrievals were performed and 38 cycles canceled their planned PGS. Cycles in which PGS was intended but cancelled had a significantly lower LB rate (15 versus 36%, P = 0.01) and higher CM rate (50 versus 14%, P < 0.01) compared with cycles that completed PGS despite similar maternal ages. Of the 130 completed PGS cycles, 74% (n = 96) yielded at least one euploid embryo. Clinical pregnancy rate per euploid embryo transfer was 72% and LB rate per euploid embryo transfer was 57%. Among all attempts at PGS or EM, clinical outcomes were similar. Median time to pregnancy was 6.5 months in the PGS group and 3.0 months in the EM group. The largest limitation is the retrospective study design, in which patients who elected for IVF/PGS may have had different clinical prognoses than patients who elected for expectant management. In addition, the definition of one attempt at conception for PGS and EM groups was different between the groups and can introduce potential confounders. For example, it was not confirmed that patients in the EM group were trying to conceive for each month of the 6-month period. Success rates with PGS are limited by the high incidence of cycles that intend but cancel PGS or cycles that do not reach transfer. Counseling RPL patients on their treatment options should include not only success rates with PGS per euploid embryo transferred, but also LB rate per initiated PGS cycle. Furthermore, patients who express an urgency to conceive should be counseled that PGS may not accelerate time to conception. None. N/A. N/A. N/A. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Reporting in vitro fertilization cycles to the Society for Assisted Reproductive Technology database: where have all the cycles gone?

PubMed

Kulak, David; Jindal, Sangita K; Oh, Cheongeun; Morelli, Sara S; Kratka, Scott; McGovern, Peter G

2016-04-01

To assess the relationship between live birth rates (LBRs) and the incidence of under-reported cycles by IVF clinics. Cohort study. Not applicable. All patients undergoing IVF cycles in the aforementioned clinics. Not applicable. The reporting percentage (RP), defined as number of cycles with reported pregnancy rates divided by total cycles performed. Results from cryopreservation cycles are only presented by SART if an embryo transfer occurs. Thus, RP decreases as incidence of embryo or oocyte banking cycles increases. The LBRs in women aged <35 years were compared between clinics. The median RP of all clinics was 93%-97%. Clinics with RP <80% increased from 2 in 2004 to 30 in 2012. Twenty-one clinics had an RP that fell 2 standard deviations below the mean in any year. Over the 9 years, there was a negative correlation between RP and LBR of -0.17, but for the 21 outlier clinics the correlation increased to -0.26. In 2012 alone, in outlier clinics, for every 10% drop in RP there was an associated rise in LBR of 4.3%; some clinics reported 40% fewer cycles than the median. In clinics with very low RP, the cycles that are reported have higher success rates. Regardless of intent, the reduction of reported data to SART makes it increasingly difficult for clinicians and patients to accurately assess a clinic's success rates. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Clinical and economic analysis of rescue intracytoplasmic sperm injection cycles.

PubMed

Shalom-paz, Einat; Alshalati, Jana; Shehata, Fady; Jimenez, Luis; Son, Weon-Young; Holzer, Hananel; Tan, Seang Lin; Almog, Benny

2011-12-01

To identify clinical and embryological factors that may predict success in rescue intracytoplasmic sperm injection (ICSI) cycles (after total fertilization failure has occurred) and to evaluate the cost effectiveness of rescue ICSI strategy. Additionally, follow-up of 20 rescue ICSI pregnancies is reported. Retrospective analysis of total fertilization failure cycles. University-based tertiary medical center. In total, 92 patients who had undergone conventional in-vitro fertilization (IVF) cycles with total fertilization failure were included. The patients were divided into two subgroups: those who conceived through rescue ICSI and those who did not. The pregnant members of the rescue ICSI subgroup were found to be significantly younger (32.9 ± 4.2 vs. 36.3 ± 4.5, respectively, p = 0.0035,) and to have better-quality embryos than those who did not conceive (cumulative embryo score: 38.3 ± 20.4 vs. 29.3 ± 14.7, p = 0.025). Cost effectiveness analysis showed 25% reduction in the cost per live birth when rescue ICSI is compared to cycle cancellation approach. The pregnancies follow-up did not show adverse perinatal outcome. Rescue ICSI is an option for salvaging IVF cycles complicated by total fertilization failure. Success in rescue ICSI was found to be associated with younger age and higher quality of embryos. Furthermore, the cost effectiveness of rescue ICSI in terms of total fertilization failure was found to be worthwhile.

The Groningen ART cohort study: ovarian hyperstimulation and the in vitro procedure do not affect neurological outcome in infancy.

PubMed

Middelburg, K J; Heineman, M J; Bos, A F; Pereboom, M; Fidler, V; Hadders-Algra, M

2009-12-01

Due to the growing number of children born following assisted reproduction technology, even subtle changes in the children's health and development are of importance to society at large. The aim of the present study was to evaluate the specific effects of ovarian hyperstimulation and the in vitro procedure on neurological outcome in 4-18-month-old children. In this prospective assessor-blinded cohort study, we included singletons born following controlled ovarian hyperstimulation in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) (COH-IVF; n = 68) or modified natural cycle-IVF/ICSI (MNC-IVF; n = 57) or naturally conceived singletons of subfertile couples (NC; n = 90). Children were assessed with standardized, age-specific and sensitive neurological assessments (TINE and Hempel assessment) at 4, 10 and 18 months. Neurological examination resulted in a neurological optimality score (NOS), a fluency score and a clinical neurological classification. Fluency of movements is easily affected by neurological dysfunction and is therefore a sensitive measure for minimal changes in neuromotor development. The NOS and the fluency score were similar in COH-IVF, MNC-IVF and NC children. None of the children showed major neurological dysfunction and rates of minor neurological dysfunction at the three ages were not different between the three conception groups. We found no effects of ovarian hyperstimulation or the in vitro procedure itself on neurological outcome in children aged 4-18 months. The findings of our study are reassuring, nevertheless it should be kept in mind that subtle neurodevelopmental disorders may emerge when children grow older. Continuation of follow-up in older and larger groups of children is therefore still needed.

An ICSI rate of 90% minimizes complete failed fertilization and provides satisfactory implantation rates without elevating fetal abnormalities.

PubMed

Yovich, John L; Conceicao, Jason L; Marjanovich, Nicole; Ye, Yun; Hinchliffe, Peter M; Dhaliwal, Satvinder S; Keane, Kevin N

2018-05-22

IVF cycles utilizing the ICSI technique for fertilization have been rising over the 25 years since its introduction, with indications now extending beyond male factor infertility. We have performed ICSI for 87% of cases compared with the ANZARD average of 67%. This retrospective study reports on the outcomes of 1547 autologous ART treatments undertaken over a recent 3-year period. Based on various indications, cases were managed within 3 groupings - IVF Only, ICSI Only or IVF-ICSI Split insemination where oocytes were randomly allocated. Overall 567 pregnancies arose from mostly single embryo transfer procedures up to December 2016, with 402 live births, comprising 415 infants and a low fetal abnormality rate (1.9%) was recorded. When the data was adjusted for confounders such as maternal age, measures of ovarian reserve and sperm quality, it appeared that IVF-generated and ICSI-generated embryos had a similar chance of both pregnancy and live birth. In the IVF-ICSI Split model, significantly more ICSI-generated embryos were utilised (2.5 vs 1.8; p < 0.003) with productivity rates of 67.8% for pregnancy and 43.4% for livebirths per OPU for this group. We conclude that ART clinics should apply the insemination method which will maximize embryo numbers and the first treatment for unexplained infertility should be undertaken within the IVF-ICSI Split model. Whilst ICSI-generated pregnancies are reported to have a higher rate of fetal abnormalities, our data is consistent with the view that the finding is not due to the ICSI technique per se. Copyright © 2018 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.

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

Surrogate in vitro fertilization outcome in typical and atypical forms of Mayer-Rokitansky-Kuster-Hauser syndrome.

PubMed

Raziel, A; Friedler, S; Gidoni, Y; Ben Ami, I; Strassburger, D; Ron-El, R

2012-01-01

The genital malformations in Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) are frequently accompanied by associated malformations whose forms were recently classified as typical (isolated uterovaginal aplasia/hypoplasia) and atypical (the addition of malformations in the ovary or renal system). The aim of this study was to compare the surrogate IVF performance of women with typical and atypical forms including their chances of achieving pregnancy. The follow-up data on a total of 102 cycles of surrogate IVF in 27 MRKH patients treated in our department between 2000 and 2010 were analysed. Twenty patients with the typical form who underwent 72 IVF cycles were compared with seven patients with the atypical form who underwent 30 IVF cycles. The various examined parameters of these intended mothers were age, hormonal profile during controlled ovarian hyperstimulation and laboratory outcome. The mean number of gonadotrophin ampoules needed for stimulation and treatment duration was significantly higher in the atypical form (3600 ± 1297IU for 13 ± 2.3 days versus 2975 ± 967 IU for 11.6 ± 1.6 days, P≤ 0.01). Serum estradiol and progesterone levels measured on the hCG administration day were similar. A significantly higher mean number of follicles 12.6 ± 6 versus 8.9 ± 5.4, P≤ 0.03, metaphase II (MII) oocytes 8.7 ± 5.1 versus 6.7 ± 4.8, P≤ 0.05, fertilizations 6 ± 3.6 versus 4.4 ± 3.3, P≤ 0.03 and cleaving embryos 5.7 ± 3.8 versus 4.1 ± 3.3, P≤ 0.01 were available in patients with the typical form compared with those with the atypical form, respectively. There was no significant difference in fertilization rate, cleavage rate or the mean number of transferred embryos. Embryo quality of the transferred ones and pregnancy rate per cycle were also similar between the two groups. Women with the typical form of MRKH needed fewer gonadotrophins and for a shorter duration for ovarian hyperstimulation. The mean number of follicles, oocytes, MII oocytes, fertilizations and cleaving embryos was higher among women with the typical form. Pregnancy rates were similar since the available number and quality of transferred embryos to the surrogate mother were not affected.

Predicting Live Birth, Preterm Delivery, and Low Birth Weight in Infants Born from In Vitro Fertilisation: A Prospective Study of 144,018 Treatment Cycles

PubMed Central

Nelson, Scott M.; Lawlor, Debbie A.

2011-01-01

Background The extent to which baseline couple characteristics affect the probability of live birth and adverse perinatal outcomes after assisted conception is unknown. Methods and Findings We utilised the Human Fertilisation and Embryology Authority database to examine the predictors of live birth in all in vitro fertilisation (IVF) cycles undertaken in the UK between 2003 and 2007 (n = 144,018). We examined the potential clinical utility of a validated model that pre-dated the introduction of intracytoplasmic sperm injection (ICSI) as compared to a novel model. For those treatment cycles that resulted in a live singleton birth (n = 24,226), we determined the associates of potential risk factors with preterm birth, low birth weight, and macrosomia. The overall rate of at least one live birth was 23.4 per 100 cycles (95% confidence interval [CI] 23.2–23.7). In multivariable models the odds of at least one live birth decreased with increasing maternal age, increasing duration of infertility, a greater number of previously unsuccessful IVF treatments, use of own oocytes, necessity for a second or third treatment cycle, or if it was not unexplained infertility. The association of own versus donor oocyte with reduced odds of live birth strengthened with increasing age of the mother. A previous IVF live birth increased the odds of future success (OR 1.58, 95% CI 1.46–1.71) more than that of a previous spontaneous live birth (OR 1.19, 95% CI 0.99–1.24); p-value for difference in estimate <0.001. Use of ICSI increased the odds of live birth, and male causes of infertility were associated with reduced odds of live birth only in couples who had not received ICSI. Prediction of live birth was feasible with moderate discrimination and excellent calibration; calibration was markedly improved in the novel compared to the established model. Preterm birth and low birth weight were increased if oocyte donation was required and ICSI was not used. Risk of macrosomia increased with advancing maternal age and a history of previous live births. Infertility due to cervical problems was associated with increased odds of all three outcomes—preterm birth, low birth weight, and macrosomia. Conclusions Pending external validation, our results show that couple- and treatment-specific factors can be used to provide infertile couples with an accurate assessment of whether they have low or high risk of a successful outcome following IVF. Please see later in the article for the Editors' Summary PMID:21245905

Fibroids and in-vitro fertilization: which comes first?

PubMed

Rackow, Beth W; Arici, Aydin

2005-06-01

There is no consensus about the impact of uterine fibroids on fertility. This review explores past and recent studies that investigated the effects of submucosal, intramural, and subserosal fibroids on in-vitro fertilization (IVF) outcomes. We discuss the importance of proper evaluation of the uterus and endometrial cavity, and current options for optimal fibroid management in patients desiring fertility. Several studies have reviewed the data on fibroids and infertility, further exploring this potential relationship. Two recent studies investigated reproductive outcomes before and after myomectomy, and IVF outcomes based on fibroid size and location. Both studies concluded that fibroids can impair reproductive outcomes. Several papers thoroughly reviewed medical and surgical management options for patients with fibroids and desired fertility. Although several medical therapies may reduce fibroid volume or decrease menorrhagia, myomectomy remains the standard of care for future fertility. Recent data identified an increased rate of pregnancy complications after uterine artery embolization compared with laparoscopic myomectomy. A new procedure, magnetic resonance imaging-guided focused ultrasound ablation, shows promise for the management of symptomatic fibroids, and possibly for the management of fibroids prior to pregnancy. As with embolization, more data are needed to evaluate postprocedure fertility and pregnancy outcomes. Fibroid location, followed by size, is the most important factor determining the impact of fibroids on IVF outcomes. Any distortion of the endometrial cavity seriously affects IVF outcomes, and myomectomy is indicated in this situation. Myomectomy should also be considered for patients with large fibroids, and for patients with unexplained unsuccessful IVF cycles.

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

PubMed

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

2009-03-01

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

Enough is enough! Patients who do not conceive on 600IU/day of gonadotropins show no improvement from an additional 150IU of LH activity

PubMed Central

Maguire, Marcy; Csokmay, John; Segars, James; Payson, Mark; Armstrong, Alicia

2010-01-01

Studies have suggested that supplemental LH improves outcomes in ART cycles. In this retrospective review, an additional 150IU of LH activity did not improve ART outcomes in women undergoing a second round of IVF/ICSI following an initial failed cycle employing 600IU of gonadotropins. PMID:20850732

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2017-04-04

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

[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.

Three pro-nuclei (3PN) incidence factors and clinical outcomes: a retrospective study from the fresh embryo transfer of in vitro fertilization with donor sperm (IVF-D)

PubMed Central

Li, Mingzhao; Zhao, Wanqiu; Xue, Xia; Zhang, Silin; Shi, Wenhao; Shi, Juanzi

2015-01-01

Objectives: The aim of this study was to explore the main factors of 3PN incidence and determine whether the presence of 3PN could lead to a worse pregnancy outcome. Methods: This study included 508 IVF-D (in vitro fertilization with donor sperm) cycles from January 2013 to September 2014. The patients were divided into three groups as follows: group 1 included patients with no 3PN zygotes, group 2 included patients with 1%-25% 3PN zygotes and group 3 included patients with > 25% 3PN zygotes. Results: We observed that more retrieved oocytes and higher HCG day peak E2 value could result in 3PN incidence more easily. When the 3PN zygotes rate was > 25%, the percentages of normal fertilization (68.4% and 66.3% and 46.4%, P < 0.001), day 3 grade I+II embryos (41.2% and 38.6% and 25.8%, P < 0.001), day 3 grade I+II+III embryos (68.7% and 65.2% and 61.4%, P = 0.032) and implantation rates (52.1% and 50.8% and 45.4%, P = 0.026) were significantly lower than that in the other two groups respectively. The pregnancy rate was lower in 3PN > 25% group than that in the other two groups but there was no significant difference (65.2% and 66.7% and 55.6%, P = 0.266). The cleavage (98.3% and 97.2% and 98.2%, P = 0.063) and early abortion (7.1% and 8.0% and 8.6%, P = 0.930) rate were identical among three groups. Conclusions: More retrieved oocytes and higher HCG day peak E2 value could result in 3PN incidence more easily. Interestingly, normal fertilization rate, day-3 grade I+II embryos rate, day-3 grade I+II+III embryos rate and implantation rate were significantly lower in IVF-D cycles with a 3PN incidence of > 25%. The number of day-3 grade I+II embryos might be a key factor for pregnancy in IVF-D cycles with a 3PN incidence of > 25%. PMID:26550358

South Asian women with polycystic ovary syndrome exhibit greater sensitivity to gonadotropin stimulation with reduced fertilization and ongoing pregnancy rates than their Caucasian counterparts.

PubMed

Palep-Singh, M; Picton, H M; Vrotsou, K; Maruthini, D; Balen, A H

2007-10-01

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome. In vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) is required for PCOS cases that are refractory to standard ovulation induction or have co-existing infertility factors in women with PCOS and Tubal factor subfertility. Assess ethnic variations in response to IVF/ICSI treatment. Observational Comparative study in a University hospital fertility clinic in women with PCOS and Tubal factor subfertility. Women with PCOS (Asians: AP=104; Caucasians: CP=220) and those with tubal factor infertility seeking fertility treatment were assessed (Asians: AC=84; Caucasians: CC=200). Six hundred and eight fresh IVF or ICSI cycles using long protocol of GnRHa suppression and resulting in a fresh embryo transfer were compared. The primary endpoint was to assess the dose of gonadotropins used in the cycles. The secondary outcomes were: total number of oocytes retrieved, fertilization and ongoing clinical pregnancy rates. We found that the South Asian women presented at a younger age for the management of sub-fertility. An extended stimulation phase and Caucasian ethnicity showed an inverse correlation with the number of oocytes retrieved in the PCOS subgroup. Caucasian ethnicity was associated with a higher fertilization rate however increase in body mass index (BMI) and the laboratory technique of IVF appeared to have a negative impact on fertilization rates in the PCOS subgroup. Commencing down regulation on day 1 of the cycles was negatively associated with fertilization rates in the tubal group. In terms of clinical pregnancy rates, the Caucasian PCOS had a 2.5 times (95% CI: 1.25-5) higher chance of an ongoing clinical pregnancy as compared with their Asian counterpart. Also, a unit increase in the basal FSH concentration reduced the odds of pregnancy by 18.6% (95% CI: 1.8-32.6%) in the PCOS group. The Asian PCOS have a greater sensitivity to gonadotropin stimulation with lower fertilization and ongoing clinical pregnancy rates as compared with their Caucasian counterparts.

Semen molecular and cellular features: these parameters can reliably predict subsequent ART outcome in a goat model

PubMed Central

Berlinguer, Fiammetta; Madeddu, Manuela; Pasciu, Valeria; Succu, Sara; Spezzigu, Antonio; Satta, Valentina; Mereu, Paolo; Leoni, Giovanni G; Naitana, Salvatore

2009-01-01

Currently, the assessment of sperm function in a raw or processed semen sample is not able to reliably predict sperm ability to withstand freezing and thawing procedures and in vivo fertility and/or assisted reproductive biotechnologies (ART) outcome. The aim of the present study was to investigate which parameters among a battery of analyses could predict subsequent spermatozoa in vitro fertilization ability and hence blastocyst output in a goat model. Ejaculates were obtained by artificial vagina from 3 adult goats (Capra hircus) aged 2 years (A, B and C). In order to assess the predictive value of viability, computer assisted sperm analyzer (CASA) motility parameters and ATP intracellular concentration before and after thawing and of DNA integrity after thawing on subsequent embryo output after an in vitro fertility test, a logistic regression analysis was used. Individual differences in semen parameters were evident for semen viability after thawing and DNA integrity. Results of IVF test showed that spermatozoa collected from A and B lead to higher cleavage rates (0 < 0.01) and blastocysts output (p < 0.05) compared with C. Logistic regression analysis model explained a deviance of 72% (p < 0.0001), directly related with the mean percentage of rapid spermatozoa in fresh semen (p < 0.01), semen viability after thawing (p < 0.01), and with two of the three comet parameters considered, i.e tail DNA percentage and comet length (p < 0.0001). DNA integrity alone had a high predictive value on IVF outcome with frozen/thawed semen (deviance explained: 57%). The model proposed here represents one of the many possible ways to explain differences found in embryo output following IVF with different semen donors and may represent a useful tool to select the most suitable donors for semen cryopreservation. PMID:19900288

Experiences of physical activity during pregnancy resulting from in vitro fertilisation: an interpretative phenomenological analysis.

PubMed

Walker, Chloe; Mills, Hayley; Gilchrist, Angela

2017-09-01

To explore the qualitative experiences and decision-making processes surrounding physical activity (PA) for women who have undergone IVF treatment. PA during pregnancy is safe for both mother and fetus in the majority of cases, including for women who have undergone in vitro fertilisation (IVF) treatment; however, there is a paucity of research into decision-making and PA in this population. Eight women, who had undergone successful IVF treatment and were currently pregnant or had given birth within the last two years, participated in semi-structured interviews about their experiences of infertility and PA during pregnancy. Interview transcripts were analysed using interpretative phenomenological analysis. Three superordinate themes emerged from the data: 'navigating away from childlessness and towards motherhood', 'negotiating a safe passage' and 'balancing the challenges of pregnancy with the needs of the self'. Ten subthemes indicated the processes adopted to navigate experiences of infertility, the IVF process, and subsequent decision-making about PA during pregnancy. PA during pregnancy was experienced as a way to soothe the self and control the experience of pregnancy; however, this was mediated by concerns about safety and physical limitations on PA. Limitations of the study are considered, as well as implications for clinical practice and directions for future research.

The carriers of the A/G-G/G allelic combination of the c.2039 A>G and c.-29 G>A FSH receptor polymorphisms retrieve the highest number of oocytes in IVF/ICSI cycles.

PubMed

Allegra, Adolfo; Marino, Angelo; Raimondo, Stefania; Maiorana, Antonio; Gullo, Salvatore; Scaglione, Piero; Volpes, Aldo; Alessandro, Riccardo

2017-02-01

The objective of this study was the elucidation of the possible role of the single-nucleotide polymorphisms (SNP) at position -29 and 2039 of the FSH receptor gene (FSHR) as independent predictive markers of ovarian response. Indeed, the tailoring of reproductive treatments is crucial for both maximizing the success of IVF patients and obtaining a reduction in hypo- or hyper-response rates. This prospective, observational study analyzed the association of -29 and 2039 FSHR polymorphisms with the number of retrieved oocytes in 140 patients attending an IVF/ICSI cycle for severe male factors (≤5,000,000 spermatozoa/mL) or tubal factors at the ANDROS Day Surgery Clinic, Palermo, Italy. The results of this study demonstrate that the genetic combination of A/G for polymorphism c.2039 A>G with G/G for polymorphism c.-29 G>A is significantly associated with the highest number of collected oocytes (p = 0.03). This association was significant even after controlling for the effect of other clinical variables. The A/G-G/G allelic variant, identified as an independent variable, if confirmed in a larger number of patients, could be considered as a new genetic biomarker, which could increase the efficacy of prediction models for ovarian stimulation.

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

NASA Astrophysics Data System (ADS)

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

2014-03-01

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

Time to next pregnancy in spontaneous pregnancies versus treatment cycles in fertile patients with recurrent pregnancy loss.

PubMed

Perfetto, Candice O; Murugappan, Gayathree; Lathi, Ruth B

2015-01-01

The current standard of care for management of patients with recurrent pregnancy loss is expectant management. However, the emotional impact of pregnancy losses and the urgency to conceive often leads couples to consider a variety of fertility treatments. The objective of this study is to report the time to next pregnancy and subsequent live birth and miscarriage rates in fertile patients with recurrent pregnancy loss (RPL) who choose to attempt spontaneous conception compared to those that opt to pursue fertility treatment. Retrospective cohort study of one hundred and fifty-eight fertile RPL patients treated at a university-based fertility center. Patients were followed for a minimum of 6 months. Patients were encouraged to attempt spontaneous conception, but allowed to initiate fertility treatments (ovarian stimulation, insemination, IVF or PGS) according to their preferences. Main outcome measures were time to next pregnancy and pregnancy outcome. For those patients who achieved a spontaneous conception, 88% conceived within 6 months, with a median time of 2 months and range of 1-10 months. Patients using IUI, IVF and PGS conceived in a median of 3, 4 and 5 months, respectively. The live birth rate and clinical miscarriage rate was not improved with any fertility treatment. In the fertile RPL patient population, there does not appear to be a benefit to proceeding directly with fertility treatment. Patients should be encouraged to attempt spontaneous conception for at least 6 months.

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

[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.

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

PubMed

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

2016-09-01

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

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.

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

PubMed Central

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

2010-01-01

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

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.

Re-evaluation of post-wash sperm is a helpful tool in the decision to perform in vitro fertilisation or intracytoplasmic sperm injection.

PubMed

Wiser, A; Ghetler, Y; Gonen, O; Piura, E; Berkovits, A; Itskovich, A; Rom, T; Shulman, A

2012-04-01

The aim of this study was to find discriminatory parameters, based on sperm characteristics on the day of ovum pickup, that can help guide the decision to perform either intracytoplasmic sperm injection (ICSI) or in vitro fertilisation (IVF). We evaluated 112 cycles fertilised with both regular and ICSI insemination during the same cycle. A total of 112 cycles were analysed. In 62 cycles, fertilisation was obtained with both ICSI and IVF, and in 50 cycles, fertilisation was obtained by ICSI alone. The sperm samples were re-evaluated after the preparation process. The mean initial total motile sperm count (TMSC) was 66.3 × 10(6) ± 47.5 in the group that underwent both methods and 23.1 × 10(6) ± 20.4 in the ICSI only group (P < 0.05). After sperm preparation, the mean post-wash TMSC was 4.4 × 10(6) ± 3.4 and 1.06 × 10(6) ± 0.9 respectively (P < 0.05). A cutoff of 1.5 × 10(6) or fewer sperm after preparation as an indicator for ICSI has a sensitivity of 80% and a specificity of 77%. Re-evaluation of TMSC can prevent unexpected fertilisation failure. Fewer than 1.5 million TMSC after wash should be considered an indication for ICSI fertilisation. © 2011 Blackwell Verlag GmbH.

Pregnancy outcomes decline in recipients over age 44: an analysis of 27,959 fresh donor oocyte in vitro fertilization cycles from the Society for Assisted Reproductive Technology.

PubMed

Yeh, Jason S; Steward, Ryan G; Dude, Annie M; Shah, Anish A; Goldfarb, James M; Muasher, Suheil J

2014-05-01

To use a large and recent national registry to provide an updated report on the effect of recipient age on the outcome of donor oocyte in vitro fertilization (IVF) cycles. Retrospective cohort study. United States national registry for assisted reproductive technology. Recipients of donor oocyte treatment cycles between 2008 and 2010, with cycles segregated into five age cohorts: ≤34, 35 to 39, 40 to 44, 45 to 49, and ≥50 years. None. Implantation, clinical pregnancy, live-birth, and miscarriage rates. In donor oocyte IVF cycles, all age cohorts ≤39 years had similar rates of implantation, clinical pregnancy, and live birth when compared with the 40- to 44-year-old reference group. Patients in the two oldest age groups (45 to 49, ≥50 years) experienced statistically significantly lower rates of implantation, clinical pregnancy, and live birth compared with the reference group. Additionally, all outcomes in the ≥50-year-old group were statistically significantly worse than the 45- to 49-year-old group, demonstrating progressive decline with advancing age. Recent national registry data suggest that donor oocyte recipients have stable rates of pregnancy outcomes before age 45, after which there is a small but steady and significant decline. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

HMG versus rFSH for ovulation induction in developing countries: a cost-effectiveness analysis based on the results of a recent meta-analysis.

PubMed

Al-Inany, Hesham G; Abou-Setta, Ahmed M; Aboulghar, Mohamed A; Mansour, Ragaa T; Serour, Gamal I

2006-02-01

Both cost and effectiveness should be considered conjointly to aid judgments about drug choice. Therefore, based on the results of a recent published meta-analysis, a Markov model was developed to conduct a cost-effectiveness analysis for estimation of the cost of an ongoing pregnancy in IVF/intracytoplasmic sperm injection (ICSI) cycles. In addition, Monte Carlo micro-simulation was used to examine the potential impact of assumptions and other uncertainties represented in the model. The results of the study reveal that the estimated average cost of an ongoing pregnancy is 13,946 Egyptian pounds (EGP), and 18,721 EGP for a human menopausal gonadotrophin (HMG) and rFSH cycle respectively. On performing a sensitivity analysis on cycle costs, it was demonstrated that the rFSH price should be 0.61 EGP/IU to be as cost-effective as HMG at the price of 0.64 EGP/IU (i.e. around 60% reduction in its current price). The difference in cost between HMG and rFSH in over 100,000 cycles would result in an additional 4565 ongoing pregnancies if HMG was used. Therefore, HMG was clearly more cost-effective than rFSH. The decision to adopt a more expensive, cost-ineffective treatment could result in a lower number of cycles of IVF/ICSI treatment undertaken, especially in the case of most developing countries.

Oocyte-triggering day progesterone levels and endometrial appearance in normoresponders undergoing IVF/ICSI cycles: a hypothesis and a study protocol.

PubMed

Siristatidis, Charalampos; Drakopoulos, Panagiotis; Vogiatzi, Paraskevi; Karageorgiou, Vasilios; Daskalakis, George

2018-05-16

In this report, we propose a study protocol capable of improving IVF outcomes in subfertile women with expected normal ovarian response. This proposal derives from conflicting published data and observations in our daily practice, concerning the negative impact of progesterone (P4) elevation at the day of oocyte triggering on pregnancy outcomes. Our hypothesis points to the combination of two previous "suspects" of reduced success after assisted reproduction techniques (ART) - the endometrium ultrasonographic parameters and P4 elevation at the day of oocyte triggering on their impact on pregnancy outcomes. Up-to-the minute data show that, there is a different impact of elevated P4 in fresh, frozen and donor cycles, whereas there are plenty of reports pointing to a different endometrial gene expression on different P4 measurements. Gaps in the literature are linked with a variation of the measurements of P4, its cycle-to-cycle reproducibility, the different cut-off levels used, the impact of various protocols of ovarian stimulation and the limitations of systematic reviews originating from the initial studies. Our hypothesis states that the combination of P4 values and endometrial ultrasound parameters at the day of oocyte triggering can affect clinical pregnancy rates in normal responders undergoing ART.

Successful outcomes achieved in assisted reproduction cycles using sperm with high levels of high DNA stainability.

PubMed

Speyer, Barbara E; Pizzey, Arnold R; Abramov, Benjamin; Saab, Wael; Doshi, Alpesh; Sarna, Urvashi; Harper, Joyce C; Serhal, Paul

2015-01-01

The sperm chromatin structure assay (SCSA) has been proposed as a useful addition to the battery of tests routinely used to explore semen quality and hence to give an indication of the likelihood of a successful pregnancy. As usually performed at present, the assay yields two main sperm variables, the DNA fragmentation index (DFI) and the high DNA stainability (HDS). In the present study 275 patients undergoing 215 in vitro fertilization (IVF) and 215 intracytoplasmic sperm injection (ICSI) cycles were studied with the purpose of defining the clinical significance of HDS in IVF and ICSI cycles. Using the Spearman correlation test there were no significant statistical relationships between %HDS and fertilization rate, rate of embryo growth, blastocyst rate, implantation rate, or live birth rate. Rate of pregnancy loss showed a negative relationship significant at the 0.05 level which is unexplained. It is not known whether the normal practice of using processed sperm for fertilization plays any part in this lack of a negative effect of HDS level upon the stages of the cycle. A total of 16 patients with HDS levels >28% had an average live birth rate of 47.8% and an average pregnancy loss of 8.7%, which compared favourably with the group of patients as a whole.

Female age, serum antimüllerian hormone level, and number of oocytes affect the rate and number of euploid blastocysts in in vitro fertilization/intracytoplasmic sperm injection cycles.

PubMed

La Marca, Antonio; Minasi, Maria Giulia; Sighinolfi, Giovanna; Greco, Pierfrancesco; Argento, Cindy; Grisendi, Valentina; Fiorentino, Francesco; Greco, Ermanno

2017-11-01

To study the relative role of female age and ovarian reserve, measured through serum antimüllerian hormone (AMH) in determining the rate and number of euploid blastocysts in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Retrospective analysis of cycles performed in 2014-2015. Tertiary referral IVF center. A total of 578 infertile couples undergoing IVF/ICSI and preimplantation genetic screening (PGS) analysis. All embryos were cultured and biopsied at the blastocyst stage. The method involved whole-genome amplification followed by array comparative genome hybridization. Serum AMH was measured by means of the modified Beckman Coulter AMH Gen II assay. The rate and number of euploid blastocysts and their correlation with ovarian reserve and response to stimulation. The mean (±SD) age of patients was 37.6 ± 4.1 years, and the mean number of blastocysts per patient was 3.1 ± 2. The total number of blastocysts available to the analysis was 1,814, and 36% of them were euploid after PGS. Age and serum AMH were significantly and independently related to the rate of euploid blastocysts available for patients. As an effect of the cohort size, the number of mature oocytes positively affected the total number of euploid blastocysts per patient. A strong positive age-independent relationship between AMH level and the rate of euploid blastocysts was found. This confirms that the measurement of ovarian reserve by means of AMH has high relevance when counseling infertile patients. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Assisted reproductive medicine in Poland --Fertility and Sterility Special Interest Group of the Polish Gynaecological Society (SPiN PTG) 2012 report.

PubMed

Janicka, Anna; Spaczyńiski, Robert Z; Kurzawa, Rafał

2015-12-01

The aim of this report is to present data concerning results and complications related to infertility treatment using assisted reproductive technology (ART) and insemination (IUI) in Poland in 2012. The report was prepared by the Fertility and Sterility Special Interest Group of the Polish Gynaecological Society (SPiN PTG), based on individual data provided by fertility clinics. Reporting was voluntary data were not subject to external verification. The report presents the availability and the structure of infertility treatment services, the number of procedures performed, their effectiveness and the most common complications. In 2014, 34 Polish fertility clinics provided information to the report, presenting data from 2012. The total number of reported treatment cycles using ART was 17,116 (incl. 10,714 fresh IVF/ICSI) and 14,727 IUI. The clinical pregnancy rate per cycle was on average 33.7% for fresh IVF/ICSI and 13.3% for IUI. The prevalence of multiple births was 15.7% and 6.2%, in case of IVF/ICSI and IUI methods respectively The most frequent complication in the course of treatment using ART was ovarian hyperstimulation syndrome (OHSS)--severe OHSS constituted 0.68% of all stimulated cycles. The SPiN PTG report shows the average effectiveness and safety of ART and was the only proof of responsibility and due diligence of fertility centres in Poland. However, due to the lack of a central register of fertility clinics, facultative participation in the report as well as incomplete information on pregnancy and delivery rate, the collected data do not reflect the full spectrum of Polish reproductive medicine.

Elective single embryo transfer with cryopreservation improves the outcome and diminishes the costs of IVF/ICSI.

PubMed

Veleva, Zdravka; Karinen, Petri; Tomás, Candido; Tapanainen, Juha S; Martikainen, Hannu

2009-07-01

Although elective single embryo transfer (eSET) minimizes the multiple birth rate after in vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI), there remain concerns in many countries that it is less effective and more expensive than conventional double embryo transfer (DET). We compared the clinical outcome achieved in the years 1995-1999, in which eSET was rarely used (4.2% of women, DET period) with that of the years 2000-2004, in which eSET was more widely used (46.2%, eSET period). In the DET period, 826 women had 1359 fresh embryo cycles followed by 589 frozen-thawed embryo transfer (FET) cycles. In the eSET period, 684 women had 1027 fresh and 683 FET cycles. The cumulative term live birth rate/woman was the primary clinical outcome measure. An incremental cost-effectiveness ratio of a term live birth was also calculated based on hospital charges and medication prices of IVF/ICSI treatment. The cumulative pregnancy rate/oocytes pickup (38.2 versus 33.1%, P = 0.01), cumulative live birth rate/oocytes pickup (28.0 versus 22.5%, P = 0.002) and cumulative live birth rate/woman (41.7 versus 36.6%, P = 0.04) were all higher in the eSET period than in the DET period. The cumulative multiple birth rate was significantly lower in the eSET period than in the DET period (8.9 versus 19.6%, P < 0.0001). A term live birth in the eSET period was 19 889 euros less expensive than in the DET period. This study shows that eSET with cryopreservation is more effective and less expensive than DET and should be adopted as a treatment of choice.

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.

Risk of placenta praevia is linked to endometrial thickness in a retrospective cohort study of 4537 singleton assisted reproduction technology births.

PubMed

Rombauts, L; Motteram, C; Berkowitz, E; Fernando, S

2014-12-01

Is endometrial thickness measured prior to embryo transfer associated with placenta praevia? Following IVF, the risk of placenta praevia is increased 4-fold in women with an endometrial thickness of >12 mm compared with women with an endometrial thickness of <9 mm. Placenta praevia is a serious complication of pregnancy with adverse maternal and neonatal outcomes. Placenta praevia is 2- to 6-fold more likely to occur following IVF treatment but it remains unknown what factors contribute to that increased risk. Retrospective cohort study involving 4007 women who had 4537 singleton assisted reproduction technology (ART) births occurring between January 2006 and June 2012 with no loss to follow-up. The primary outcome measure was the diagnosis of placenta praevia, made by the treating obstetrician on a transvaginal ultrasound in the third trimester. Women who had singleton births following single embryo transfer performed at Monash IVF in Melbourne, Australia were included. Of the 4537 cycles leading to a singleton ART birth, 2951 were stimulated cycles with fresh embryo transfers; 355 were hormone replacement therapy frozen embryo transfers and 1231 were natural cycles with frozen embryo transfers. The dataset was analysed using binary logistic general estimating equations to calculate odds ratios for placenta praevia adjusted (aOR) for known confounders. The study groups did not differ significantly in age, BMI and aetiologies of infertility prior to IVF treatment. When compared with stimulated cycles, placenta praevia was less common in women undergoing natural cycles with frozen embryo transfers (OR 0.44, 95% confidence interval (CI) 0.27-0.70, P < 0.01) but hormone replacement therapy frozen embryo transfer cycles were not associated with a lower risk (OR 0.89, 95% CI 0.48-1.63). After adjusting for confounders, smoking (aOR 2.58, 95% CI 1.07-6.24, P = 0.04, endometriosis (aOR 2.01, 95% CI 1.21-3.33, P < 0.01) and endometrial thickness remained statistically significant as independent risk factors for placenta praevia. Compared with women with an endometrial thickness of <9 mm, women with an endometrial thickness of 9-12 mm had an aOR of 2.02 (95% CI 1.12-3.65, P = 0.02) and women with an endometrial thickness >12 mm had an aOR of 3.74 (95% CI 1.90-7.34, P < 0.01). These differences remained statistically significant after performing a sensitivity analysis limited to women with no previous births. The study is retrospective in nature, not all confounders may have been accounted for and details on previous intrauterine surgery, a known risk factor, were not available. In addition, ultrasound assessments were carried out by several highly trained operators measuring the endometrial thickness, the main independent variable, in a two-dimensional plane and some inter-observer variability may therefore be present. The findings of a higher risk of placenta praevia in patients with endometriosis and in those that smoke are in agreement with the current literature on natural conception. There have so far been no reports of an association between endometrial thickness and placenta praevia after ART. This novel finding warrants further study to elucidate the underlying cause of the association and to assess how to minimize harm to IVF patients and their offspring. The fact that the observed increased risk is not linked to the type of embryo transfer (fresh/frozen) but to the type of endometrial preparation, suggests that the risk of placenta praevia in ART can be reduced by considering an elective frozen embryo transfer in a natural cycle, especially given the growing evidence that this strategy also provides a number of other maternal and neonatal benefits. No funding was required for this study. L.R. has a minority shareholding in Monash IVF and has received unconditional research and educational grants from MSD, Merck-Serono and Ferring. L.R. serves on an advisory board for MSD and Ferring. © 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.

Characterization and comparative analyses of transcriptomes for in vivo and in vitro produced peri-implantation conceptuses and endometria from sheep

PubMed Central

WEI, Xia; XIAOLING, Zhang; KAI, Miao; RUI, Wang; JING, Xu; MIN, Guo; ZHONGHONG, Wu; JIANHUI, Tian; XINYU, Zhang; LEI, An

2016-01-01

An increasing number of reports indicate that in vitro fertilization (IVF) is highly associated with long‑term side effects on embryonic and postnatal development, and can sometimes result in embryonic implant failure. While high‑throughput gene expression analysis has been used to explore the mechanisms underlying IVF-induced side effects on embryonic development, little is known about the effects of IVF on conceptus–endometrial interactions during the peri-implantation period. Using sheep as a model, we performed a comparative transcriptome analysis between in vivo (IVO; in vivo fertilized followed by further development in the uterus) and in vitro produced (IVP; IVF with further culture in the incubator) conceptuses, and the caruncular and intercaruncular areas of the ovine endometrium. We identified several genes that were differentially expressed between the IVO and IVP groups on day 17, when adhesion between the trophoblast and the uterine luminal epithelium begins in sheep. By performing Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found that, in the conceptus, differentially expressed genes (DEGs) were associated mainly with functions relating to cell binding and the cell cycle. In the endometrial caruncular area, DEGs were involved in cell adhesion/migration and apoptosis, and in the intercaruncular area, they were significantly enriched in pathways of signal transduction and transport. Thus, these DEGs are potential candidates for further exploring the mechanism underlying IVF/IVP-induced embryonic implant failure that occurs due to a loss of interaction between the conceptus and endometrium during the peri-implantation period. PMID:26946921

Association between preconception maternal beverage intake and in vitro fertilization outcomes.

PubMed

Machtinger, Ronit; Gaskins, Audrey J; Mansur, Abdallah; Adir, Michal; Racowsky, Catherine; Baccarelli, Andrea A; Hauser, Russ; Chavarro, Jorge E

2017-12-01

To study whether maternal intake of beverage type affects IVF outcomes. A prospective study. Tertiary, university-affiliated center. Three hundred forty women undergoing IVF from 2014 through 2016 for infertility as well as for pregenetic diagnosis for autosomal recessive diseases were enrolled during ovarian stimulation and completed a questionnaire describing their usual beverage consumption. None. IVF outcomes were abstracted from medical records. Total caffeine intake was estimated by summing the caffeine content for specific beverages multiplied by frequency of intake. Associations between specific types of beverages and IVF outcomes were analyzed using Poisson and logistic regression models adjusting for possible confounders. Higher intake of sugared soda was associated with lower total, mature, and fertilized oocytes and top-quality embryos after ovarian stimulation. Women who consumed sugared soda had, on average, 1.1 fewer oocytes retrieved, 1.2 fewer mature oocytes retrieved, 0.6 fewer fertilized oocytes, and 0.6 fewer top-quality embryos compared with women who did not consume sugared soda. Furthermore, compared with women who did not drink sugared soda, the adjusted difference in percent of cycles resulting in live birth for women consuming 0.1-1 cups/day and >1 cup/day were -12% and -16%, respectively. No associations were found between consumption of coffee, caffeine, or diet sodas and IVF outcome. Sugared beverages, independent of their caffeine content, may be a bigger threat to reproductive success than caffeine and caffeinated beverages without added sugar. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Women's perspectives regarding subcutaneous injections, costs and live birth rates in IVF.

PubMed

Musters, A M; de Bekker-Grob, E W; Mochtar, M H; van der Veen, F; van Mello, N M

2011-09-01

The addition of recombinant LH (rLH) to controlled ovarian hyperstimulation (COH) shows a beneficial effect on ongoing pregnancy rates in poor responder women, with an increase of ongoing pregnancy rate. Next to this possible beneficial effect, there are two potential drawbacks of adding rLH to COH; women have to administer extra injections, and daily rLH injections generate additional costs. We therefore investigated women's perspectives on an additional injection of rLH with respect to live birth rates (LBR) and out-of-pocket costs in a discrete choice experiment. Women eligible for IVF were asked to choose between treatments that differed in LBR after one IVF cycle, the amount of self-administered injections and out-of-pocket costs or reimbursement. The relative weights that women place on these attributes were estimated with a logistic regression model. To test for heterogeneity of preferences among women, patient characteristics were included in the model. Two-hundred and thirty-four women were asked to participate in the study. In total, 223 women responded (response rate 95%) and 206 questionnaires were analysed. An increase of one daily injection did not alter women's treatment preference. LBR and costs did have a significant (P < 0.001) impact on women's choice of IVF treatment. Patient characteristics significantly influenced the effect of costs on women's preferences. One extra daily injection will not cause a woman to refrain from a certain IVF treatment. However, to compensate for the out-of-pocket costs of this extra daily injection, the expected LBR should at least be 6%.

Poor response cycles: when should we cancel? Comparison of outcome between egg collection, intrauterine insemination conversion, and follow-up cycles after abandonment.

PubMed

Nicopoullos, James D M; Abdalla, Hossam

2011-01-01

To determine optimal management with one or two mature follicles after stimulation. Retrospective analysis. Lister fertility clinic. A total of 1,350 IVF/intracytoplasmic sperm injection cycles (7.3% of total) during 1998-2009 were found to have one or two mature follicles. Group 1 (n = 807) comprised those who proceeded to vaginal egg collection (VEC) (59.8%; outcome per egg collection), group 2 (n=248) those who converted to IUI (18.4%; outcome per insemination) and group 3 (n=259) those who abandoned the current cycle (21.9%; outcome per abandoned cycle in first subsequent cycle). Live birth rate, clinical pregnancy rate, and biochemical pregnancy rate. Biochemical pregnancy rates of 13.1%, 4.9%, and 9.7%, clinical pregnancy rates of 8.1%, 3.6%, and 7.2%, and ongoing pregnancy rates of 6.8%, 2.0%, and 5.5% were achieved in groups 1, 2, and 3, respectively. All pregnancy outcomes were significantly higher after VEC (group 1) than for those converted to IUI (group 2), and all pregnancy outcomes were higher with borderline significance in group 3 vs. group 2. There was no significant difference in outcome between groups 1 and 3. Our data suggest that for such poor responders, proceeding to VEC may represent their best chance of successful outcome. Conversion to IUI offers the poorest outcome, and despite the potential for improvements in cycle protocol, abandoning and a further attempt does not improve outcome (using abandoned cycle as the denominator). Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

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.

Percentage of Blastulation on the Number and Function of Metaphase II Oocytes.

PubMed

Chadid, Martha L; Carpio, Jorge; Valdivieso, Pedro; Zambrano, Milton; García-Ferreyra, Javier; Valdivieso-Mejía, Pedro

2015-08-01

Establish the number of metaphase II oocytes that are needed for optimum blastulation rate and to achieve a better rate of gestation. Retrospective study. Women diagnosed with infertility. There were 110 women submitted to IVF/ICSI, excluding third day transfers and those with canceled cycles. After controlled ovarian stimulation, cultivation continued to blastocysts. Average age of the patients: 33.41. IVF technique: 73 patients, 66.4%; ICSI: 37 patients, 33.6%. Pregnancy: gestation: 57.3%; Non-gestation: 42.7%. Mean number of oocytes in metaphase II: 7.5. The gestation rate coincides with the center's results (50-60%), reached with 7 mature oocytes. Mean blastulation rate was 39.2%.

Uterine adenomyosis and in vitro fertilization outcome: a systematic review and meta-analysis.

PubMed

Vercellini, Paolo; Consonni, Dario; Dridi, Dhouha; Bracco, Benedetta; Frattaruolo, Maria Pina; Somigliana, Edgardo

2014-05-01

Is adenomyosis associated with IVF/ICSI outcome in terms of clinical pregnancy rate? In a meta-analysis of published data, women with adenomyosis had a 28% reduction in the likelihood of clinical pregnancy at IVF/ICSI compared with women without adenomyosis. Estimates of the effect of adenomyosis on IVF/ICSI outcome are inconsistent. A systematic literature review and meta-analysis were conducted. A Medline search was performed to identify all the comparative studies published from January 1998 to June 2013 in the English language literature on IVF/ICSI outcome in women with and without adenomyosis. Two authors independently performed the literature screening, scrutinized articles of potential interest, selected relevant studies and extracted data. Studies were categorized based on research design. Of the 17 articles assessed in detail, 9 were finally selected based on diagnosis of adenomyosis at magnetic resonance imaging or transvaginal ultrasonography. The quality of studies was evaluated by means of the Newcastle-Ottawa scale. A total of 1865 women were enrolled in the 9 selected studies, 665 of whom in 4 prospective observational studies, and 1200 in 5 retrospective studies. The dichotomous data for clinical pregnancy and secondary outcomes were expressed as risk ratios (RR) with 95% confidence intervals (CIs) and were combined in a meta-analysis using the random-effects model. The heterogeneity Cochrane's Q and the I(2) statistics were calculated. Egger's approach to testing the significance of funnel plot asymmetry was also used. The clinical pregnancy rate achieved after IVF/ICSI was 123/304 (40.5%) women with adenomyosis versus 628/1262 (49.8%) in those without adenomyosis. The RR of clinical pregnancy ranged from 0.37 (95% CI, 0.15-0.92) to 1.20 (95% CI, 0.58-2.45), with a significant heterogeneity among studies (I(2) = 56.8%, P = 0.023). Pooling of the results yielded a common RR of 0.72 (95% CI, 0.55-0.95). A funnel plot showed no indication of asymmetry among studies (Egger's test, P = 0.696). In a meta-regression model, no association was observed between prevalence of endometriosis and the likelihood of clinical pregnancy. Three studies reported the pregnancy rate per cycle. The common RR was 0.71 (95% CI, 0.51-0.98; I(2) = 78.1%, P = 0.010). The RR observed in a study with donated oocytes was 0.90 (95% CI, 0.75-1.08). The number of miscarriages per clinical pregnancy was reported in seven studies. A miscarriage was observed in 77/241 women with adenomyosis (31.9%) and in 97/687 in those without adenomyosis (14.1%). The RR of miscarriage ranged from 0.57 (95% CI, 0.15-2.17) to 18.00 (95% CI, 4.08-79.47) (I(2) = 67.7%, P = 0.005). Pooling of the results yielded a common RR of 2.12 (95% CI, 1.20-3.75). Qualitative and quantitative heterogeneity among studies was high. At sensitivity analysis, I(2) statistic regarding the main outcome was reduced under the 50% threshold removing one trial, but the resulting confidence interval crossed unity. Also the confidence interval of the common RR of the four studies reporting only one IVF/ICSI cycle included unity. Only part of the studies could be included in the assessment of secondary outcomes. Adenomyosis appears to impact negatively on IVF/ICSI outcome owing to reduced likelihood of clinical pregnancy and implantation, and increased risk of early pregnancy loss. Screening for adenomyosis before embarking on medically assisted reproductive procedures should be encouraged. The potentially protective role of long down-regulation protocols needs further evaluation. In future studies on the association between adenomyosis and IVF/ICSI outcome, a matched case-control design should be adopted, live birth should be the default primary outcome and only the results regarding the first cycle should be considered. None.

A retrospective evaluation of prognosis and cost-effectiveness of IVF in poor responders according to the Bologna criteria.

PubMed

Busnelli, Andrea; Papaleo, Enrico; Del Prato, Diana; La Vecchia, Irene; Iachini, Eleonora; Paffoni, Alessio; Candiani, Massimo; Somigliana, Edgardo

2015-02-01

Do the Bologna criteria for poor responders successfully identify women with poor IVF outcome? The Bologna criteria effectively identify a population with a uniformly low chance of success. Women undergoing IVF who respond poorly to ovarian hyper-stimulation have a low chance of success. Even if improving IVF outcome in this population represents a main priority, the lack of a unique definition of the condition has hampered research in this area. To overcome this impediment, a recent expert meeting in Bologna proposed a new definition of poor responders ('Bologna criteria'). However, data supporting the relevance of this definition in clinical practice are scanty. Retrospective study of women undergoing IVF-ICSI between January 2010 and December 2012 in two independent infertility units. Women could be included if they fulfilled the definition of poor ovarian response (POR) according to Bologna criteria prior to initiation of the cycle. Women were included only for one cycle. The main outcome was the live birth rate per started cycle. The perspective of the cost analysis was the one of the health provider. Three-hundred sixty-two women from two independent Infertility Units were selected. A binomial distribution model was used to calculate the 95% CI of the rate of success. Characteristics of women who did and did not obtain a live birth were compared. A logistic regression model was used to adjust for confounders. The economic analysis included costs for pharmacological compounds and for the IVF procedure. The benefits were estimated on quality-adjusted life years (QALY). To develop the model, we used the local life-expectancy tables, we applied a 3% discount of life years gained and we used a 0.07 improvement in quality of life associated with parenthood. Sensitivity analyses were performed varying the improvement of the quality of life and including/excluding the male partner. The reference values for cost-effectiveness were the Italian and the local (Lombardy) gross domestic product (GDP) pro capita per year in the studied period and the upper and lower limits suggested by NICE. Overall, 23 women had a live birth (6%, 95% CI: 4-9%), in line with the previous evidence. This proportion did not significantly differ in the different subgroups of poor responders. Positive predictive factors of success were previous deliveries (adjusted OR = 3.0, 95% CI: 1.1-8.7, P = 0.039) and previous chemotherapy (adjusted OR = 13.9, 95% CI: 2.5-77.2, P = 0.003). Age, serum AMH, serum FSH and antral follicle count were not significantly associated with live birth. The total cost per live birth was 87 748 Euros, corresponding to 49 919 Euros per QALY. This is above both the limits suggested by NICE for cost-effectiveness and the Italian and local GDP pro capita. Sensitivity analyses mainly support the robustness of the conclusion. We lack a control group and we cannot thus exclude that an alternative definition of poor responders may be equally if not more valid. Moreover, independent validations are warranted prior to concluding that IVF is not cost-effective. Women should thus not be denied treatment based on our findings. Noteworthy, there is also not yet a consensus on the most appropriate economic model to be used. We recommend the use of the Bologna criteria when designing future studies on poor responders. Large multi-centred international studies are now required to draw definite conclusions on the economic profile of IVF in this situation. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The value of delaying hCG administration to enable maturation of medium-sized follicles in patients undergoing superovulation for IVF/ICSI.

PubMed

Awonuga, Awoniyi O; Wheeler, Karen; Thakur, Mili; Jeelani, Roohi; Diamond, Michael P; Puscheck, Elizabeth E

2018-02-01

The purpose of the study is to determine whether continued stimulation of mature follicles to allow "catch up" growth of medium-sized follicles in assisted reproductive technology compromises the clinical pregnancy (CPR) and live birth (LBR) rates in IVF/ICSI cycles. This retrospective cohort study reviewed 200 first IVF ± ICSI cycles out of a total of 340 cycles with complete data. Women underwent stimulation protocols with gonadotropins (Gn) and GnRH antagonist. Treatment cycles were divided into two groups (Gp): hCG administration delayed despite the presence of two mature follicles, defined as ≥ 18 mm [Gp1, n = 79] and hCG administration given when there were two mature follicles [Gp2, n = 121]. The patients in Gp1 were significantly younger than those in Gp2 [32.9 (4.5) vs. 34.3 (4.8), p = 0.04] and needed a median of one more day of superovulation before ovulation was triggered with hCG. The extra days was associated with the use of 450 [75-2025] more Gn, such that at the time the hCG was administered, patient's in group 1 had developed significantly greater number of follicles ≥ 18 mm [mean (SD), 4.9 (1.8) vs. 3.4 (1.7), p < 0.0001]. The clinical pregnancy (48.1 vs. 38.0%, [OR (95% CI)] [1.6 (1.0-2.5), p = 0.09]) and live birth (43.0 vs. 35.5%, [1.4 (0.9-2.3), p = 0.21]) rates per cycle started were not significantly different between the two groups. Forward stepwise logistic regression showed that only maternal age (p = 0.04) influenced clinical pregnancy rates (OR = 0.88, CI 0.78-0.99) and only the number of days for superovulation influenced live birth rates (OR = 0.65, CI 0.486-0.869). This study demonstrated that delaying hCG administration to allow further growth of the medium-sized follicles added further days of superovulation and cost without improvement in CPR and LBR.

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.

Complex chromosomal rearrangement-a lesson learned from PGS.

PubMed

Frumkin, Tsvia; Peleg, Sagit; Gold, Veronica; Reches, Adi; Asaf, Shiri; Azem, Foad; Ben-Yosef, Dalit; Malcov, Mira

2017-08-01

The aim of the study is to report a case of non-diagnosed complex chromosomal rearrangement (CCR) identified by preimplantation genetic screening (PGS) followed by preimplantation genetic diagnosis (PGD) which resulted in a pregnancy and delivery of healthy offspring. A 29-year-old woman and her spouse, both diagnosed previously with normal karyotypes, approached our IVF-PGD center following eight early spontaneous miscarriages. PGS using chromosomal microarray analysis (CMA) was performed on biopsied trophectoderm. Fluorescence in situ hybridization (FISH), as well as re-karyotype, were performed on metaphase derived from peripheral blood of the couple. Subsequently, in the following PGD cycle, a total of seven blastocysts underwent CMA. A gain or loss at three chromosomes (3, 7, 9) was identified in six out of seven embryos in the first PGS-CMA cycle. FISH analysis of parental peripheral blood samples demonstrated that the male is a carrier of a CCR involving those chromosomes; this was in spite of a former diagnosis of normal karyotypes for both parents. Re-karyotype verified the complex translocation of 46,XY,t (3;7;9)(q23;q22;q22). Subsequently, in the following cycle, a total of seven blastocysts underwent PGD-CMA for the identified complex translocation. Two embryos were diagnosed with balanced chromosomal constitution. A single balanced embryo was transferred and pregnancy was achieved, resulting in the birth of a healthy female baby. PGS employing CMA is an efficient method to detect unrevealed chromosomal abnormalities, including complicated cases of CCR. The combined application of array CGH and FISH technologies enables the identification of an increased number of CCR carriers for which PGD is particularly beneficial.

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

PubMed

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

2016-03-01

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

Successful twin delivery following transmyometrial embryo transfer in a patient with a false uterine cavity.

PubMed

Muñoz, Manuel; Galindo, Noemí; Pérez-Cano, Inmaculada; Cruz, María; García-Velasco, Juan Antonio

2014-02-01

A successful pregnancy is the greatest goal for reproductive medicine. The probability that pregnancy occurs during a cycle of assisted reproduction is a function of multiple factors, of which embryo transfer is one of the most critical steps in these treatments. This article reports a case of successful pregnancy and twin delivery by transmyometrial embryo transfer after IVF in a woman with a neocavity parallel to the uterine cavity, which prevented the transfer of embryos to the correct place. The patient first went to another fertility centre where embryo transfer was impossible to perform because the cervix could not be canalized. Subsequently in this study clinic, after considering the difficulty of inserting a catheter into the endometrial cavity, a trial transfer was performed, which discovered a false route parallel to endometrial cavity. Following a first cycle in which conventional transcervical embryo transfer was performed, a transmyometrial embryo transfer was carried out and the patient became pregnant with twins. In cases where transcervical embryo transfer is very difficult or impossible to perform, the value of transmyometrial transfer is self-evident. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

GnRH Agonist Trigger and LH Activity Luteal Phase Support versus hCG Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles-A Systematic PRISMA Review and Meta-analysis.

PubMed

Haahr, Thor; Roque, Matheus; Esteves, Sandro C; Humaidan, Peter

2017-01-01

The use of GnRH agonist (GnRHa) for final oocyte maturation trigger in oocyte donation and elective frozen embryo transfer cycles is well established due to lower ovarian hyperstimulation syndrome (OHSS) rates as compared to hCG trigger. A recent Cochrane meta-analysis concluded that GnRHa trigger was associated with reduced live birth rates (LBRs) in fresh autologous IVF cycles compared to hCG trigger. However, the evidence is not unequivocal, and recent trials have found encouraging reproductive outcomes among couples undergoing GnRHa trigger and individualized luteal LH activity support. Thus, the aim was to compare GnRHa trigger followed by luteal LH activity support with hCG trigger in IVF patients undergoing fresh embryo transfer. We conducted a systematic review and meta-analysis of randomized trials published until December 14, 2016. The population was infertile patients submitted to IVF/ICSI cycles with GnRH antagonist cotreatment who underwent fresh embryo transfer. The intervention was GnRHa trigger followed by LH activity luteal phase support (LPS). The comparator was hCG trigger followed by a standard LPS. The critical outcome measures were LBR and OHSS rate. The secondary outcome measures were number of oocytes retrieved, clinical and ongoing pregnancy rates, and miscarriage rates. A total of five studies met the selection criteria comprising a total of 859 patients. The LBR was not significantly different between the GnRHa and hCG trigger groups (OR 0.84, 95% CI 0.62, 1.14). OHSS was reported in a total of 4/413 cases in the GnRHa group compared to 7/413 in the hCG group (OR 0.48, 95% CI 0.15, 1.60). We observed a slight, but non-significant increase in miscarriage rate in the GnRHa triggered group compared to the hCG group (OR 1.85; 95% CI 0.97, 3.54). GnRHa trigger with LH activity LPS resulted in comparable LBRs compared to hCG trigger. The most recent trials reported LBRs close to unity indicating that individualization of the LH activity LPS improved the luteal phase deficiency reported in the first GnRHa trigger studies. However, LPS optimization is needed to further limit OHSS in the subgroup of normoresponder patients (<14 follicles ≥ 11 mm). CRD42016051091.

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

PubMed

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

2017-01-01

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

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

PubMed

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

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

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.

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.

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.

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.

A randomized controlled trial investigating the use of a predictive nomogram for the selection of the FSH starting dose in IVF/ICSI cycles.

PubMed

Allegra, Adolfo; Marino, Angelo; Volpes, Aldo; Coffaro, Francesco; Scaglione, Piero; Gullo, Salvatore; La Marca, Antonio

2017-04-01

The number of oocytes retrieved is a relevant intermediate outcome in women undergoing IVF/intracytoplasmic sperm injection (ICSI). This trial compared the efficiency of the selection of the FSH starting dose according to a nomogram based on multiple biomarkers (age, day 3 FSH, anti-Müllerian hormone) versus an age-based strategy. The primary outcome measure was the proportion of women with an optimal number of retrieved oocytes defined as 8-14. At their first IVF/ICSI cycle, 191 patients underwent a long gonadotrophin-releasing hormone agonist protocol and were randomized to receive a starting dose of recombinant (human) FSH, based on their age (150 IU if ≤35 years, 225 IU if >35 years) or based on the nomogram. Optimal response was observed in 58/92 patients (63%) in the nomogram group and in 42/99 (42%) in the control group (+21%, 95% CI = 0.07 to 0.35, P = 0.0037). No significant differences were found in the clinical pregnancy rate or the number of embryos cryopreserved per patient. The study showed that the FSH starting dose selected according to ovarian reserve is associated with an increase in the proportion of patients with an optimal response: large trials are recommended to investigate any possible effect on the live-birth rate. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

The Impact of Immediate Verbal Feedback on the Improvement of Swimming Technique

PubMed Central

Zatoń, Krystyna; Szczepan, Stefan

2014-01-01

The present research attempts to ascertain the impact of immediate verbal feedback (IVF) on modifications of stroke length (SL). In all swimming styles, stroke length is considered an essential kinematic parameter of the swimming cycle. It is important for swimming mechanics and energetics. If SL shortens while the stroke rate (SR) remains unchanged or decreases, the temporal-spatial structure of swimming is considered erroneous. It results in a lower swimming velocity. Our research included 64 subjects, who were divided into two groups: the experimental – E (n=32) and the control – C (n=32) groups. A pretest and a post-test were conducted. The subjects swam the front crawl over the test distance of 25m at Vmax. Only the E group subjects were provided with IVF aiming to increase their SL. All tests were filmed by two cameras (50 samples•s-1). The kinematic parameters of the swimming cycle were analyzed using the SIMI Reality Motion Systems 2D software (SIMI Reality Motion Systems 2D GmbH, Germany). The movement analysis allowed to determine the average horizontal swimming velocity over 15 meters. The repeated measures analysis of variance ANOVA with a post-hoc Tukey range test demonstrated statistically significant (p<0.05) differences between the two groups in terms of SL and swimming velocity. IVF brought about a 6.93% (Simi method) and a 5.09% (Hay method) increase in SL, as well as a 2.92% increase in swimming velocity. PMID:25114741

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.

Volatile organic compounds and good laboratory practices in the in vitro fertilization laboratory: the important parameters for successful outcome in extended culture.

PubMed

Agarwal, Nupur; Chattopadhyay, Ratna; Ghosh, Sanghamitra; Bhoumik, Arpita; Goswami, S K; Chakravarty, Baidyanath

2017-08-01

This study aims to describe the role of implementing good laboratory practices to improve in vitro fertilization (IVF) outcomes which are of great interest for practitioners dealing with infertility. Certain modifications were introduced in May 2015 in our IVF laboratory like high-efficiency particulate air CODA system, steel furniture instead of wooden, use of new disinfectants like oosafe, and restriction of personnel entry along with avoidance of cosmetics like perfume to improve pregnancy rates. Volatile organic compound (VOC) meter reading was monitored at two time points and five different places in the laboratory to compare the embryonic development parameters before (group A: July 2014-April 2015) and after (group B: July 2015-April 2016) remodeling. The IVF outcomes from 1036 cycles were associated in this study. Reduction in VOC meter readings, enhanced air quality, improvement in blastocyst formation rate, implantation, and clinical pregnancy rate were observed in the laboratory after implementation of new facilities. Results illustrated that the attention must be focused on potential hazards which expose laboratories to elevated VOC levels. Blastocyst formation rate increased around 18%. Implantation rate, clinical pregnancy rate, and live birth rate increased by around 11, 10, and 8%, respectively. In conclusion, with proper engineering and material selection, we have been able to reduce chemical contamination and adverse effects on culture with optimized IVF results. None.

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

PubMed

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

2007-06-27

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

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.

Comparison of a Web-Based Teaching Tool and Traditional Didactic Learning for In Vitro Fertilization Patients: A Preliminary Randomized Controlled Trial.

PubMed

Vause, Tannys Dawn Reiko; Allison, David J; Vause, Tricia; Tekok-Kilic, Ayda; Ditor, David S; Min, Jason K

2018-05-01

The objective of this prospective RCT was to compare the efficacy of a web-based teaching tool to traditional didactic teaching in IVF patients. Forty women undergoing their first IVF cycle were randomly allocated to an interactive web-based teaching session or a nurse-led didactic teaching session. The primary outcome measure was participant knowledge regarding the IVF process, risks, and logistics assessed before and after the respective teaching session. Secondary outcomes included patient stress, assessed before and after the respective teaching session, and patient satisfaction, assessed following the respective teaching session and on the day of embryo transfer (following implementation of the teaching protocol). Both groups demonstrated similar and significant improvements in knowledge and stress after exposure to their respective teaching sessions. The web-based group was significantly more satisfied than the didactic teaching group. Web-based teaching was also shown to be equally effective for participants of high versus low income and education status for knowledge, stress, and satisfaction. This study provides preliminary support for the use of web-based teaching as an equally effective tool for increasing knowledge and reducing stress compared to traditional didactic teaching in IVF patients, with the added benefit of increased patient satisfaction. Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

[Health economic consequences of the choice of follicle stimulating hormone alternatives in IVF treatment].

PubMed

Poulsen, Peter Bo; Højgaard, Astrid; Quartarolo, Jens Piero

2007-04-02

There is a choice between two types of hormones for stimulation of the follicles in IVF treatment - recombinant FSH and the urine-derived menotrophin. A literature review by NICE (2004) in the United Kingdom documented that the two types of hormones were equally effective and safe, which is why it was recommended to use the cheaper urine-derived hormone. Based on the EISG study (European and Israeli Study Group), the aim was to analyse the health economic consequences of the choice between the two types of hormone in IVF treatment in Denmark. In a prospective cost-effectiveness analysis (health care sector perspective), menotrophin and recombinant FSH (Gonal-F) were compared. Differences in costs were compared with differences in effects of the two alternatives. The total costs for the average patient are lower when using menotrophin compared with recombinant FSH. Furthermore, the cost per clinical pregnancy was lower with menotrophin compared with recombinant FSH hormone. Menotrophin is therefore less expensive both for the patient as well as for the health care sector. The use of menotrophin instead of recombinant FSH can result in savings of up to DKK 16 million on the drug budget--savings that could finance 1,400 additional IVF cycles. The analysis shows that urine-derived menotrophin is a cost-effective alternative to recombinant FSH with a potential for considerable savings for patients as well as the public drug budget.

Investigating the effect of ethnicity on IVF outcome.

PubMed

Dhillon, Rima K; Smith, Paul P; Malhas, Rosamund; Harb, Hoda M; Gallos, Ioannis D; Dowell, Ken; Fishel, Simon; Deeks, Jon J; Coomarasamy, Aravinthan

2015-09-01

Success rates for IVF among women from different ethnic groups have been inconclusive. In this study, the relationship between ethnicity and IVF outcome was investigated. Results of a cohort study analysing 13,473 first cycles were compared with the results of meta-analysed data from 16 published studies. Adjustment was made for age, body-mass index, cause of infertility, duration of infertility, previous live birth, previous spontaneous abortion and number of embryos transferred. Black and South Asian women were found to have lower live birth rates compared with White women: Black versus White (OR 0.42 [0.25 to 0.70]; P = 0.001); South Asian versus White (OR 0.80 [0.65t o 0.99]; P = 0.04). Black women had significantly lower clinical pregnancy rates compared with White women (OR 0.41 [0.25 to 9 0.67]; P < 0.001). The meta-analysed results also showed that Black and South Asian women had statistically significant reduced odds of live birth (OR 0.62 [0.55 to 0.71); P < 0.001 and OR 0.66 [0.52 to 0.85); P = 0.001, respectively). Black and South Asian women seem to have the poorest outcome, which is not explained by the commonly known confounders. Future research needs to investigate the possible explanations for this difference and improve IVF outcome for all women. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Abnormally fertilized oocytes can result in healthy live births: improved genetic technologies for preimplantation genetic testing can be used to rescue viable embryos in in vitro fertilization cycles.

PubMed

Capalbo, Antonio; Treff, Nathan; Cimadomo, Danilo; Tao, Xin; Ferrero, Susanna; Vaiarelli, Alberto; Colamaria, Silvia; Maggiulli, Roberta; Orlando, Giovanna; Scarica, Catello; Scott, Richard; Ubaldi, Filippo Maria; Rienzi, Laura

2017-12-01

To test whether abnormally fertilized oocyte (AFO)-derived blastocysts are diploid and can be rescued for clinical use. Longitudinal-cohort study from January 2015 to September 2016 involving IVF cycles with preimplantation genetic testing for aneuploidy (PGT-A). Ploidy assessment was incorporated whenever a blastocyst from a monopronuclear (1PN) or tripronuclear zygote (2PN + 1 smaller PN; 2.1 PN) was obtained. Private IVF clinics and genetics laboratories. A total of 556 women undergoing 719 PGT-A cycles. Conventional chromosome analysis was performed on trophectoderm biopsies by quantitative polymerase chain reaction. For AFO-derived blastocysts, ploidy assessment was performed on the same biopsy with the use of allele ratios for hetorozygous SNPs analyzed by means of next-generation sequencing (1:1 = diploid; 2:1 = triploid; loss of heterozygosity = haploid). Balanced-diploid 1PN- and 2.1PN-derived blastocysts were transferred in the absence of normally fertilized transferable embryos. Ploidy constitution and clinical value of AFO-derived blastocysts in IVF PGT-A cycles. Of the 5,026 metaphase II oocytes injected, 5.2% and 0.7% showed 1PN and 2.1PN, respectively. AFOs showed compromised embryo development (P<.01). Twenty-seven AFO-derived blastocysts were analyzed for ploidy constitution. The 1PN-derived blastocysts were mostly diploid (n = 9/13; 69.2%), a few were haploid (n = 3/13; 23.1%), and one was triploid (n = 1/13; 7.7%). The 2.1PN-derived blastocysts were also mostly diploid (n = 12/14; 85.7%), and the remainder were triploid. Twenty-six PGT-A cycles resulted in one or more AFO-derived blastocysts (n = 26/719; 3.6%). Overall, eight additional balanced-diploid transferable embryos were obtained from AFOs. In three cycles, the only balanced-diploid blastocyst produced was from an AFO (n = 3/719; 0.4%). Three AFO-derived live births were achieved: one from a 1PN zygote and two from 2.1PN zygotes. Enhanced PGT-A technologies incorporating reliable ploidy assessment provide an effective tool to rescue AFO-derived blastocysts for clinical use. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Review: MicroRNAs in assisted reproduction and their potential role in IVF failure.

PubMed

Siristatidis, Charalampos; Vogiatzi, Paraskevi; Brachnis, Nikos; Liassidou, Aspasia; Iliodromiti, Zoe; Bettocchi, Stefano; Chrelias, Charalampos

2015-01-01

MicroRNAs (miRNAs) have recently emerged as important regulators of gene expression stability. In the endometrium, miRNAs are involved in the dynamic changes associated with the menstrual cycle, implicated in implantation and in reproductive disorders. We performed a review in an attempt to assess the potential biological pathways linking altered miRNAs profiles with in vitro fertilisation (IVF) failure. Crucially, as miRNAs appear to have a significant role in the course of reproduction, they are excellent research candidates with the potential to enable a better understanding over the underlying molecular activities that prevent implantation and further progression of the embryo. Further steps include in-depth pathway mapping of the implantation process and the characterization of the respective miRNAs and associated links. The efficiency of any intervention should determine whether miRNA profiling could possibly be adopted in routine practice to substantially improve the diagnostic accuracy and, in parallel, the directed treatment of the next-generation IVF. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Embryo quality is the main factor affecting cumulative live birth rate after elective single embryo transfer in fresh stimulation cycles.

PubMed

Niinimäki, Maarit; Veleva, Zdravka; Martikainen, Hannu

2015-11-01

The study was aimed to evaluate which factors affect the cumulative live birth rate after elective single embryo transfer in women younger than 36 years. Additionally, number of children in women with more than one delivery per ovum pick-up after fresh elective single embryo transfer and subsequent frozen embryo transfers was assessed. Retrospective cohort study analysing data of a university hospital's infertility clinic in 2001-2010. A total of 739 IVF/ICSI cycles with elective single embryo transfer were included. Analyses were made per ovum pick-up including fresh and subsequent frozen embryo transfers. Factors affecting cumulative live birth rates were examined in uni- and multivariate analyses. A secondary endpoint was the number of children born after all treatments. In the fresh cycles, the live birth rate was 29.2% and the cumulative live birth rate was 51.3%, with a twin rate of 3.4%. In the multivariate analysis, having two (odds ratio (OR) 1.73; 95% confidence interval (CI) 1.12-2.67) or ≥3 top embryos (OR 2.66; 95% CI 1.79-3.95) was associated with higher odds for live birth after fresh and frozen embryo cycles. Age, body mass index, duration of infertility, diagnosis or total gonadotropin dose were not associated with the cumulative live birth rate. In cycles with one top embryo, the cumulative live birth rate was 40.2%, whereas it was 64.1% in those with at least three top embryos. Of women who had a live birth in the fresh cycle, 20.4% had more than one child after all frozen embryo transfers. Among women with three or more top embryos after ovum pick-up, 16.1% gave birth to more than one child. The cumulative live birth rate in this age group varies from 40% to 64% and is dependent on the quality of embryos. Women with three or more top embryos have good chance of having more than one child per ovum pick-up without elevated risk of multiple pregnancies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

IVF outcome is optimized when embryos are replaced between 5 and 15 mm from the fundal endometrial surface: a prospective analysis on 1184 IVF cycles

PubMed Central

2013-01-01

Background Some data suggest that the results of human in vitro fertilization (IVF) may be affected by the site of the uterine cavity where embryos are released. It is not yet clear if there is an optimal range of embryo-fundus distance (EFD) within which embryos should be transferred to optimize IVF outcome. Methods The present study included 1184 patients undergoing a blind, clinical-touch ET of 1–2 fresh embryos loaded in a soft catheter with a low amount of culture medium. We measured the EFD using transvaginal US performed immediately after ET, with the aim to assess (a) if EFD affects pregnancy and implantation rates, and (b) if an optimal EFD range can be identified. Results Despite comparable patients’ clinical characteristics, embryo morphological quality, and endometrial thickness, an EFD between 5 and 15 mm allowed to obtain significantly higher pregnancy and implantation rates than an EFD above 15 mm. The abortion rate was much higher (although not significantly) when EFD was below 5 mm than when it was between 5 and 15 mm. Combined together, these results produced an overall higher ongoing pregnancy rate in the group of patients whose embryos were released between 5 and 15 mm from the fundal endometrial surface. Conclusions The site at which embryos are released affects IVF outcome and an optimal EFD range exists; this observations suggest that US-guided ET could be advantageous vs. clinical-touch ET, as it allows to be more accurate in releasing embryos within the optimal EFD range. PMID:24341917

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

PubMed

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

2018-06-20

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

Predictive Modeling of Implantation Outcome in an In Vitro Fertilization Setting: An Application of Machine Learning Methods.

PubMed

Uyar, Asli; Bener, Ayse; Ciray, H Nadir

2015-08-01

Multiple embryo transfers in in vitro fertilization (IVF) treatment increase the number of successful pregnancies while elevating the risk of multiple gestations. IVF-associated multiple pregnancies exhibit significant financial, social, and medical implications. Clinicians need to decide the number of embryos to be transferred considering the tradeoff between successful outcomes and multiple pregnancies. To predict implantation outcome of individual embryos in an IVF cycle with the aim of providing decision support on the number of embryos transferred. Retrospective cohort study. Electronic health records of one of the largest IVF clinics in Turkey. The study data set included 2453 embryos transferred at day 2 or day 3 after intracytoplasmic sperm injection (ICSI). Each embryo was represented with 18 clinical features and a class label, +1 or -1, indicating positive and negative implantation outcomes, respectively. For each classifier tested, a model was developed using two-thirds of the data set, and prediction performance was evaluated on the remaining one-third of the samples using receiver operating characteristic (ROC) analysis. The training-testing procedure was repeated 10 times on randomly split (two-thirds to one-third) data. The relative predictive values of clinical input characteristics were assessed using information gain feature weighting and forward feature selection methods. The naïve Bayes model provided 80.4% accuracy, 63.7% sensitivity, and 17.6% false alarm rate in embryo-based implantation prediction. Multiple embryo implantations were predicted at a 63.8% sensitivity level. Predictions using the proposed model resulted in higher accuracy compared with expert judgment alone (on average, 75.7% and 60.1%, respectively). A machine learning-based decision support system would be useful in improving the success rates of IVF treatment. © The Author(s) 2014.

Single embryo transfer and IVF/ICSI outcome: a balanced appraisal.

PubMed

Gerris, Jan M R

2005-01-01

This review considers the value of single embryo transfer (SET) to prevent multiple pregnancies (MP) after IVF/ICSI. The incidence of MP (twins and higher order pregnancies) after IVF/ICSI is much higher (approximately 30%) than after natural conception (approximately 1%). Approximately half of all the neonates are multiples. The obstetric, neonatal and long-term consequences for the health of these children are enormous and costs incurred extremely high. Judicious SET is the only method to decrease this epidemic of iatrogenic multiple gestations. Clinical trials have shown that programmes with >50% of SET maintain high overall ongoing pregnancy rates ( approximately 30% per started cycle) while reducing the MP rate to <10%. Experience with SET remains largely European although the need to reduce MP is accepted worldwide. An important issue is how to select patients suitable for SET and embryos with a high putative implantation potential. The typical patient suitable for SET is young (aged <36 years) and in her first or second IVF/ICSI trial. Embryo selection is performed using one or a combination of embryo characteristics. Available evidence suggests that, for the overall population, day 3 and day 5 selection yield similar results but better than zygote selection results. Prospective studies correlating embryo characteristics with documented implantation potential, utilizing databases of individual embryos, are needed. The application of SET should be supported by other measures: reimbursement of IVF/ICSI (earned back by reducing costs), optimized cryopreservation to augment cumulative pregnancy rates per oocyte harvest and a standardized format for reporting results. To make SET the standard of care in the appropriate target group, there is a need for more clinical studies, for intensive counselling of patients, and for an increased sense of responsibility in patients, health care providers and health insurers.

The effects of superovulation with gonadotropins on autoantibody levels in patients undergoing assisted reproductive cycles.

PubMed

Ashrafi, Mahnaz; Amirchaghmaghi, Elham; Arabipoor, Arezoo; Vesali, Samira; Salman-Yazdi, Reza

2018-04-25

To evaluate the effect of controlled ovarian stimulation (COH) with gonadotropins on the serum levels of autoantibodies in the women who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles and to compare basal levels of these autoantibodies between groups according to history of COH. This prospective cohort study was performed from October 2014 to March 2016 in the Royan Institute. The volunteered infertile women with regard to the inclusion criteria, who underwent IVF/ICSI cycles, were recruited. The COH was performed according to standard long GnRH agonist protocol. The mean levels of the autoantibodies including anti-nuclear, anti-smooth muscle, anti-ovarian, anti-mitochondrial, anti β 2 -glycoprotein I, anti-parietal cell and anti-follicle-stimulating hormone antibodies were measured at three time points: on the 3-5 days of the menstrual cycle, 1 week after starting of COH and the ovum pick-up (OPU) day. Of all participants (n = 189), 73 women had history of COH (group B) and 116 women did not have such history (group A). The analysis indicated that the autoantibodies changes during COH were similar in both groups. COH has no significant impact on the level of autoantibodies during the stimulation cycle. Multiple logistic regression analysis showed that the serum levels of anti-smooth muscle antibody on OPU day was the positive predictive factors for live birth following ART cycles in the studied population. No significant effect of COH on the studied autoantibodies by the time of OPU was found but further studies are required to interpret these results.

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.

Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice.

PubMed

La Marca, Antonio; Sunkara, Sesh Kamal

2014-01-01

The main objective of individualization of treatment in IVF is to offer every single woman the best treatment tailored to her own unique characteristics, thus maximizing the chances of pregnancy and eliminating the iatrogenic and avoidable risks resulting from ovarian stimulation. Personalization of treatment in IVF should be based on the prediction of ovarian response for every individual. The starting point is to identify if a woman is likely to have a normal, poor or a hyper response and choose the ideal treatment protocol tailored to this prediction. The objective of this review is to summarize the predictive ability of ovarian reserve markers, such as antral follicle count (AFC) and anti-Mullerian hormone (AMH), and the therapeutic strategies that have been proposed in IVF after this prediction. A systematic review of the existing literature was performed by searching Medline, EMBASE, Cochrane library and Web of Science for publications in the English language related to AFC, AMH and their incorporation into controlled ovarian stimulation (COS) protocols in IVF. Literature available to May 2013 was included. The search generated 305 citations of which 41 and 25 studies, respectively, reporting the ability of AMH and AFC to predict response to COS were included in this review. The literature review demonstrated that AFC and AMH, the most sensitive markers of ovarian reserve identified to date, are ideal in planning personalized COS protocols. These sensitive markers permit prediction of the whole spectrum of ovarian response with reliable accuracy and clinicians may use either of the two markers as they can be considered interchangeable. Following the categorization of expected ovarian response to stimulation clinicians can adopt tailored therapeutic strategies for each patient. Current scientific trend suggests the elective use of the GnRH antagonist based regimen for hyper-responders, and probably also poor responders, as likely to be beneficial. The selection of the appropriate and individualized gonadotrophin dose is also of paramount importance for effective COS and subsequent IVF outcomes. Personalized IVF offers several benefits; it enables clinicians to give women more accurate information on their prognosis thus facilitating counselling especially in cases of extremes of ovarian response. The deployment of therapeutic strategies based on selective use of GnRH analogues and the fine tuning of the gonadotrophin dose on the basis of potential ovarian response in every single woman can allow for a safer and more effective IVF practice.

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.

Low versus high volume of culture medium during embryo transfer: a randomized clinical trial.

PubMed

Sigalos, George Α; Michalopoulos, Yannis; Kastoras, Athanasios G; Triantafyllidou, Olga; Vlahos, Nikos F

2018-04-01

The aim of this prospective randomized control trial was to evaluate if the use of two different volumes (20-25 vs 40-45 μl) of media used for embryo transfer affects the clinical outcomes in fresh in vitro fertilization (IVF) cycles. In total, 236 patients were randomized in two groups, i.e., "low volume" group (n = 118) transferring the embryos with 20-25 μl of medium and "high volume" group (n = 118) transferring the embryos with 40-45 μl of medium. The clinical pregnancy, implantation, and ongoing pregnancy rates were compared between the two groups. No statistically significant differences were observed in clinical pregnancy (46.8 vs 54.3%, p = 0.27), implantation (23.7 vs 27.8%, p = 0.30), and ongoing pregnancy (33.3 vs 40.0%, p = 0.31) rates between low and high volume group, respectively. Higher volume of culture medium to load the embryo into the catheter during embryo transfer does not influence the clinical outcome in fresh IVF cycles. NCT03350646.

Single embryo transfer - state of the art.

PubMed

De Neubourg, Diane; Gerris, Jan

2003-12-01

Every practitioner active in the field of assisted reproduction treatment is aware of the risks and complications related to twin and higher-order multiple pregnancies. Introduction of single embryo transfer (SET) into IVF/intracytoplasmic sperm injection (ICSI) is one of the possible ways of reducing the rate of twin pregnancy. Careful selection of patients, in combination with elective SET, has been shown to decrease the twin pregnancy rate while maintaining a stable ongoing pregnancy rate. The combination of a woman younger than 38 years of age, in her first or second IVF/ICSI cycle and with an embryo with a high implantation potential is the key to successful SET. This article will discuss embryo selection and patient selection and review the data published on SET. In the Centre for Reproductive Medicine at Middelheim Hospital, 39% of all transfers in 2002 were SET; the ongoing pregnancy rate remained stable at 30.6%. The twin (multiple) pregnancy rate declined to 11.7%. Particular attention should be drawn to the augmenting effect of the pregnancy rate of frozen-thawed cycles. Health economic data available so far subscribe the plea for SET.

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

Gestational surrogacy.

PubMed

Brinsden, Peter R

2003-01-01

Gestational surrogacy is a treatment option available to women with certain clearly defined medical problems, usually an absent uterus, to help them have their own genetic children. IVF allows the creation of embryos from the gametes of the commissioning couple and subsequent transfer of these embryos to the uterus of a surrogate host. The indications for treatment include absent uterus, recurrent miscarriage, repeated failure of IVF and certain medical conditions. Treatment by gestational surrogacy is straightforward and follows routine IVF procedures for the commissioning mother, with the transfer of fresh or frozen-thawed embryos to the surrogate host. The results of treatment are good, as would be expected from the transfer of embryos derived from young women and transferred to fit, fertile women who are also young. Clinical pregnancy rates achieved in large series are up to 40% per transfer and series have reported 60% of hosts achieving live births. The majority of ethical or legal problems that have arisen out of surrogacy have been from natural or partial surrogacy arrangements. The experience of gestational surrogacy has been largely complication-free and early results of the follow-up of children, commissioning couples and surrogates are reassuring. In conclusion, gestational surrogacy arrangements are carried out in a few European countries and in the USA. The results of treatment are satisfactory and the incidence of major ethical or legal complications has been limited. IVF surrogacy is therefore a successful treatment for a small group of women who would otherwise not be able to have their own genetic children.

Effects of previous ovarian surgery for endometriosis on the outcome of assisted reproduction treatment.

PubMed

Geber, Selmo; Ferreira, Daniela Parreiras; Spyer Prates, Luis Felipe Víctor; Sales, Liana; Sampaio, Marcos

2002-01-01

Endometriosis affects 2-50% of women at reproductive age. Surgery is an option for treatment, but there is no convincing evidence that it promotes a significant improvement in fertility. Also, the removal of ovarian endometrioma might lead to a reduction in the follicular reserve and response to stimulation. Therefore, the aim of this study was to evaluate the effect of previous ovarian surgery for endometriosis on the ovarian response in assisted reproduction treatment cycles and its pregnancy outcome. A total of 61 women, with primary infertility and previously having undergone ovarian surgery for endometriosis, who had received 74 IVF/intracytoplasmic sperm injection (ICSI) cycles, were studied (study group). A further 74 patients with primary infertility who underwent 77 IVF/ICSI cycles within#10; the same period of time, at the same clinic and without previous ovarian surgery or endometriosis were studied as a control group. Patients were matched for age and treatment performed. Patients 35 years with previous ovarian surgery needed more ampoules for ovulation induction (P = 0.017) and had fewer follicles and oocytes than women in the control group (P = 0.001). Duration of folliculogenesis was similar in both groups, as was fertilization rate. A total of 10 patients achieved pregnancy in the study group (34.5%) and 14 (48.3%) in the control group. Although a lower pregnancy rate was observed in patients who had undergone previous ovarian surgery, this difference was not statistically significant (P = 0.424). In conclusion, ovarian surgery for the treatment of endometriosis reduces the ovarian outcome in IVF/ICSI cycles in women >35 years old, and might also decrease pregnancy rates. Therefore, for infertile patients, non-surgical treatment might be a better option to avoid reduction of the ovarian response.

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.

Culture media influenced laboratory outcomes but not neonatal birth weight in assisted reproductive technology.

PubMed

Yin, Tai-lang; Zhang, Yi; Li, Sai-jiao; Zhao, Meng; Ding, Jin-li; Xu, Wang-ming; Yang, Jing

2015-12-01

Whether the type of culture media utilized in assisted reproductive technology has impacts on laboratory outcomes and birth weight of newborns in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) was investigated. A total of 673 patients undergoing IVF/ICSI and giving birth to live singletons after fresh embryo transfer on day 3 from Jan. 1, 2010 to Dec. 31, 2012 were included. Three types of culture media were used during this period: Quinn's Advantage (QA), Single Step Medium (SSM), and Continuous Single Culture medium (CSC). Fertilization rate (FR), normal fertilization rate (NFR), cleavage rate (CR), normal cleavage rate (NCR), good-quality embryo rate (GQER) and neonatal birth weight were compared using one-way ANOVA and χ (2) tests. Multiple linear regression analysis was performed to determine the impact of culture media on laboratory outcomes and birth weight. In IVF cycles, GQER was significantly decreased in SSM medium group as compared with QA or CSC media groups (63.6% vs. 69.0% in QA; vs. 71.3% in CSC, P=0.011). In ICSI cycles, FR, NFR and CR were significantly lower in CSC medium group than in other two media groups. No significant difference was observed in neonatal birthweight among the three groups (P=0.759). Multiple linear regression analyses confirmed that the type of culture medium was correlated with FR, NFR, CR and GQER, but not with neonatal birth weight. The type of culture media had potential influences on laboratory outcomes but did not exhibit an impact on the birth weight of singletons in ART.

Projecting the potential impact of the Cap-Score™ on clinical pregnancy, live births, and medical costs in couples with unexplained infertility.

PubMed

Babigumira, Joseph B; Sharara, Fady I; Garrison, Louis P

2018-01-01

The Cap-Score™ was developed to assess the capacitation status of men, thereby enabling personalized management of unexplained infertility by choosing timed intrauterine insemination (IUI), versus immediate in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in individuals with a low Cap-Score™. The objective of this study was to estimate the differences in outcomes and costs comparing the use of the Cap-Score™ with timed IUI (CS-TI) and the standard of care (SOC), which was assumed to be three IUI cycles followed by three IVF-ICSI cycles. We developed and parameterized a decision-analytic model of management of unexplained infertility for women based on data from the published literature. We calculated the clinical pregnancy rates, live birth rates, and medical costs comparing CS-TI and SOC. We used Monte Carlo simulation to quantify uncertainty in projected estimates and performed univariate sensitivity analysis. Compared to SOC, CS-TI was projected to increase the pregnancy rate by 1-26%, marginally reduce live birth rates by 1-3% in couples with women below 40 years, increase live birth rates by 3-7% in couples with women over 40 years, reduce mean medical costs by $4000-$19,200, reduce IUI costs by $600-$1370, and reduce IVF costs by $3400-$17,800, depending on the woman's age. The Cap-Score™ is a potentially valuable clinical tool for management of unexplained infertility because it is projected to improve clinical pregnancy rates, save money, and, depending on the price of the test, increase access to treatment for infertility.

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.

Genetic and clinical predictors of ovarian response in assisted reproductive technology

NASA Astrophysics Data System (ADS)

Wiweko, B.; Damayanti, I.; Suryandari, D.; Natadisastra, M.; Pratama, G.; Sumapraja, K.; Meutia, K.; Iffanolia, P.; Harzief, A. K.; Hestiantoro, A.

2017-08-01

Several factors are known to influence ovarian response to rFSH stimulation such as age, antral follicle count (AFC), and basal FSH level, Mutation of allele Ser680Asn in FSHR gene was responsible to ovarian resistance toward exogenous FSH. The aim of this study is to develop a prediction model of ovarian response to COS in IVF. This study was a prospective cohort study. One hundred and thirteen women undergoing their first cycle of IVF in Yasmin IVF Clinic Jakarta were recruited to this study. Clinical datas included were age, BMI, and AFC. Basal FSH and E2 as well as serum AMH was measured from peripheral blood taken at second day of cycle. Bsr-1 enzyme is used to identify the polymorphism in exon 10 position 680 with RFLP technique. Three genotype polymorphism, Asn/Asn (255 bp ribbon), Asn/Ser (97 bp and 158 bp), and Ser/Ser (97 bp, 158 bp, and 255 bp). AFC has the highest predictor for ovarian response with AUC 0.922 (CI 95% 0.833-1.000). AMH also showed high predicting value (AUC 0.843 CI 95% 0.663-1.000). The multivariate analysis revealed combination of AFC, AMH, age, and basal FSH is a good model for ovarian response prediction (AUC=0.97). No significant relation between Asn/Asn, Asn/Ser, or Ser/Ser genotype FSHR polymorphism with ovarian response (p = 0.866) and total dose of rRSH (p = 0.08). This study showed that model combination of AFC, AMH, patient’s age and basal FSH are very good to predict number of mature oocytes.

Effect of high ovarian response on the expression of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in peri-implantation endometrium in IVF women

PubMed Central

Xu, Li-Zhen; Gao, Min-Zhi; Yao, Li-Hua; Liang, A-Juan; Zhao, Xiao-Ming; Sun, Zhao-Gui

2015-01-01

Objective: To investigate the effect of ovarian stimulation on the expression of EG-VEGF mRNA and protein in peri-implantation endometrium in women undergoing IVF and its relation with endometrial receptivity (ER). Design: Prospective laboratory study. Setting: University hospital. Patients: Eighteen women in stimulated cycles (SC) as study subjects and 18 women in natural cycles (NC) as controls. Women in SC group were classified with two subgroups, high ovarian response (SC1, n=9) with peak serum E2>5,000 pg/mL and moderate ovarian response (SC2, n=9) with peak serum E2 1,000-5,000 pg/mL. Intervention(s): Endometrial biopsies were collected 6 days after ovulation in NC or after oocyte retrieval in SC. Main outcome measure(s): Endometrium histological dating was observed with HE staining. EG-VEGF mRNA expression levels determined by real-time polymerase chain reaction analysis, and protein levels by immunohistochemistry. Results: All endometrial samples were in the secretory phase. The endometrial development in SC1 was 1 to 2 days advanced to NC, and with dyssynchrony between glandular and stromal tissue. Immunohistochemistry analysis showed that EG-VEGF protein was predominantly expressed in the glandular epithelial cells and endothelial cells of vessels, and also presented in the stroma. The image analysis confirmed that both the gland and stroma of endometrium in SC1 had a significantly lower EG-VEGF protein expression than that in SC2 and NC endometrium. Moreover, EG-VEGF mRNA levels were significantly lower in SC1 than in NC. Both EG-VEGF protein and mRNA levels had no significant difference between SC2 and NC. Conclusion: Decreased expression of EG-VEGF in the peri-implantation is associated with high ovarian response, which may account for the impaired ER and lower implantation rate in IVF cycles. PMID:26464631

Effect of high ovarian response on the expression of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in peri-implantation endometrium in IVF women.

PubMed

Xu, Li-Zhen; Gao, Min-Zhi; Yao, Li-Hua; Liang, A-Juan; Zhao, Xiao-Ming; Sun, Zhao-Gui

2015-01-01

To investigate the effect of ovarian stimulation on the expression of EG-VEGF mRNA and protein in peri-implantation endometrium in women undergoing IVF and its relation with endometrial receptivity (ER). Prospective laboratory study. University hospital. Eighteen women in stimulated cycles (SC) as study subjects and 18 women in natural cycles (NC) as controls. Women in SC group were classified with two subgroups, high ovarian response (SC1, n=9) with peak serum E2>5,000 pg/mL and moderate ovarian response (SC2, n=9) with peak serum E2 1,000-5,000 pg/mL. Endometrial biopsies were collected 6 days after ovulation in NC or after oocyte retrieval in SC. Endometrium histological dating was observed with HE staining. EG-VEGF mRNA expression levels determined by real-time polymerase chain reaction analysis, and protein levels by immunohistochemistry. All endometrial samples were in the secretory phase. The endometrial development in SC1 was 1 to 2 days advanced to NC, and with dyssynchrony between glandular and stromal tissue. Immunohistochemistry analysis showed that EG-VEGF protein was predominantly expressed in the glandular epithelial cells and endothelial cells of vessels, and also presented in the stroma. The image analysis confirmed that both the gland and stroma of endometrium in SC1 had a significantly lower EG-VEGF protein expression than that in SC2 and NC endometrium. Moreover, EG-VEGF mRNA levels were significantly lower in SC1 than in NC. Both EG-VEGF protein and mRNA levels had no significant difference between SC2 and NC. Decreased expression of EG-VEGF in the peri-implantation is associated with high ovarian response, which may account for the impaired ER and lower implantation rate in IVF cycles.

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."

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.

Overt leptin response to controlled ovarian hyperstimulation negatively correlates with pregnancy outcome in in vitro fertilization--embryo transfer cycle.

PubMed

Chakrabarti, Jana; Chatterjee, Ratna; Goswami, Sourendrakanta; Chakravarty, Baidyanath; Kabir, Syed Nazrul

2012-05-01

A critical body mass of adipose tissue is essential for the normal development of female reproductive functions. Leptin, an adipocyte-derived hormone encoded by the 'Ob' gene has been proposed as a peripheral signal indicating the adequacy of nutritional status for reproductive functions. It is reported as a direct regulator of gametogenic and steroidogenic potential of ovary. Though leptin is widely present in reproductive tissues, its relationship to reproductive hormones is still poorly understood. Present investigation attempts to explore ovarian response to secretory profile of leptin and its impact on pregnancy outcome in women undergoing controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer (IVF-ET). Patients enrolled for IVF-ET underwent pituitary-ovarian suppression by 'Long Protocol' GnRH-agonist downregulation followed by ovarian stimulation. Sera were procured at different phases of IVF-ET for the assay of estradiol, progesterone, human chorionic gonadotropin, and for leptin. Ovarian follicular fluids were also assayed for leptin. Luteinized granulosa cells were cultured in vitro to evaluate their steroidogenic potential. Statistical analyses were done by student's t-test, ANOVA, and Chi-square tests as applicable. All results were expressed as Mean ± SE. P values < 0.05 were considered significant. Positive correlation was observed between serum and ovarian follicular fluid leptin. A negative correlation was noted between the serum leptin levels and endometrial thickness. Elevated leptin response may exert adverse impacts on pregnancy success during IVF-ET possibly by modulating uterine receptivity.

A direct healthcare cost analysis of the cryopreserved versus fresh transfer policy at the blastocyst stage.

PubMed

Papaleo, Enrico; Pagliardini, Luca; Vanni, Valeria Stella; Delprato, Diana; Rubino, Patrizia; Candiani, Massimo; Viganò, Paola

2017-01-01

A cost analysis covering direct healthcare costs relating to IVF freeze-all policy was conducted. Normal- and high- responder patients treated with a freeze-all policy (n = 63) compared with fresh transfer IVF (n = 189) matched by age, body mass index, duration and cause of infertility, predictive factors for IVF (number of oocytes used for fertilization) and study period, according to a 1:3 ratio were included. Total costs per patient (€6952 versus €6863) and mean costs per live birth were similar between the freeze-all strategy (€13,101, 95% CI 10,686 to 17,041) and fresh transfer IVF (€15,279, 95% CI 13,212 to 18,030). A mean per live birth cost-saving of €2178 (95% CI -1810 to 6165) resulted in a freeze-all strategy owing to fewer embryo transfer procedures (1.29 ± 0.5 versus 1.41 ± 0.7); differences were not significant. Sensitivity analysis revealed that the freeze-all strategy remained cost-effective until the live birth rate is either higher or only slightly lower (≥-0.59%) in the freeze-all group compared with fresh cycles. A freeze-all policy does not increase costs compared with fresh transfer, owing to negligible additional expenses, i.e. vitrification, endometrial priming and monitoring, against fewer embryo transfer procedures required to achieve pregnancy. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

The Experience of Chinese Couples Undergoing In Vitro Fertilization Treatment: Perception of the Treatment Process and Partner Support.

PubMed

Ying, Li-Ying; Wu, Lai Har; Loke, Alice Yuen

2015-01-01

Couples undergoing In Vitro Fertilization (IVF) Treatment suffer as dyads from the stressful experience of the painful treatment and the fear that the IVF cycle will fail. They are likely to report that their marital relationship has become unstable due to the prolonged period of treatment. This is a qualitative study that was conducted to explore the experiences that Chinese couples have had with IVF treatment, especially their perceptions of the process and the support between couples. The interviews revealed that couples suffered from the process, experiencing physical and emotional pain, struggling with the urgency and inflexibility of bearing a child, and experiencing disturbances in their daily routines and work. The participants described how they endured the hardships as a couple and how it affected their relationship. The couples felt that sharing feelings and supporting each other contribute to psychological well-being and improves the marital relationship. They also identified some unfavorable aspects in their partner relationship. They were ambivalent about receiving social support from friends and family members. With the couples indicating that the support that they received from each other affected their experience during the treatment process, it is suggested that a supportive intervention that focuses on enhancing the partnership of the couples and dealing with their inflexibility on the issue of bearing a child might result in improvements in the psychological status and marital relationship of infertile couples undergoing IVF treatment.

The Experience of Chinese Couples Undergoing In Vitro Fertilization Treatment: Perception of the Treatment Process and Partner Support

PubMed Central

Ying, Li-Ying; Wu, Lai Har; Loke, Alice Yuen

2015-01-01

Background Couples undergoing In Vitro Fertilization (IVF) Treatment suffer as dyads from the stressful experience of the painful treatment and the fear that the IVF cycle will fail. They are likely to report that their marital relationship has become unstable due to the prolonged period of treatment. Methods This is a qualitative study that was conducted to explore the experiences that Chinese couples have had with IVF treatment, especially their perceptions of the process and the support between couples. Results The interviews revealed that couples suffered from the process, experiencing physical and emotional pain, struggling with the urgency and inflexibility of bearing a child, and experiencing disturbances in their daily routines and work. The participants described how they endured the hardships as a couple and how it affected their relationship. The couples felt that sharing feelings and supporting each other contribute to psychological well-being and improves the marital relationship. They also identified some unfavorable aspects in their partner relationship. They were ambivalent about receiving social support from friends and family members. Conclusions With the couples indicating that the support that they received from each other affected their experience during the treatment process, it is suggested that a supportive intervention that focuses on enhancing the partnership of the couples and dealing with their inflexibility on the issue of bearing a child might result in improvements in the psychological status and marital relationship of infertile couples undergoing IVF treatment. PMID:26431545

Endometrial fluid associated with Essure implants placed before in vitro fertilization: Considerations for patient counseling and surgical management

PubMed Central

Walsh, David J; Jones, Christopher A; Wood, Samuel H

2015-01-01

Essure (Bayer) received approval from the U.S. Food and Drugs Administration as a permanent non-hormonal contraceptive implant in November 2002. While the use of Essure in the management of hydrosalpinx prior to in vitro fertilization (IVF) remains off-label, it has been used specifically for this purpose since at least 2007. Although most published reports on Essure placement before IVF have been reassuring, clinical experience remains limited, and no randomized studies have demonstrated the safety or efficacy of Essure in this context. In fact, no published guidelines deal with patient selection or counseling regarding the Essure procedure specifically in the context of IVF. Although Essure is an irreversible birth control option, some patients request the surgical removal of the implants for various reasons. While these patients could eventually undergo hysterectomy, at present no standardized technique exists for simple Essure removal with conservation of the uterus. This article emphasizes new aspects of the Essure procedure, as we describe the first known association between the placement of Essure implants and the subsequent development of fluid within the uterine cavity, which resolved after the surgical removal of both devices. PMID:26473113

Further evidence that culture media affect perinatal outcome: findings after transfer of fresh and cryopreserved embryos.

PubMed

Nelissen, Ewka C; Van Montfoort, Aafke P; Coonen, Edith; Derhaag, Josien G; Geraedts, Joep P; Smits, Luc J; Land, Jolande A; Evers, Johannes L; Dumoulin, John C

2012-07-01

We have previously shown that the medium used for culturing IVF embryos affects the birthweight of the resulting newborns. This observation with potentially far-reaching clinical consequences during later life, was made in singletons conceived during the first IVF treatment cycle after the transfer of fresh embryos. In the present study, we hypothesize that in vitro culture of embryos during the first few days of preimplantation development affects perinatal outcome, not only in singletons conceived in all rank order cycles but also in twins and in children born after transfer of frozen embryos. Furthermore, we investigated the effect of culture medium on gestational age (GA) at birth. Oocytes and embryos from consecutive treatment cycles were alternately assigned to culture in either medium from Vitrolife or from Cook. Data on a cohort of 294 live born singletons conceived after fresh transfer during any of a patient's IVF treatment cycles, as well as data of 67 singletons conceived after frozen embryo transfer (FET) and of 88 children of 44 twin pregnancies after fresh transfer were analysed by means of multiple linear regression. In vitro culture in medium from Cook resulted in singletons after fresh transfer with a lower mean birthweight (adjusted mean difference, 112 g, P= 0.03), and in more singletons with low birthweight (LBW) <2500 g (P= 0.006) and LBW for GA ≥ 37 weeks (P= 0.015), when compared with singletons born after culture in medium from Vitrolife AB. GA at birth was not related to the medium used (adjusted difference, 0.05 weeks, P = 0.83). Among twins in the Cook group, higher inter-twin mean birthweight disparity and birthweight discordance were found. Z-scores after FET were -0.04 (± 0.14) in the Cook group compared with 0.18 (± 0.21) in the Vitrolife group (P> 0.05). Our findings support our hypothesis that culture medium influences perinatal outcome of IVF singletons and twins. A similar trend is seen in case of singletons born after FET. GA was not affected by culture medium. These results indicate that in vitro culture might be an important factor explaining the poorer perinatal outcome after assisted reproduction technology (ART). Further research is needed to confirm this culture medium-induced effect in humans and to provide more insight into whether it is caused by epigenetic disturbance of imprinted genes in fetal or placental tissues. Moreover, embryo culture media and their effects need to be investigated thoroughly to select the best embryo culture medium in order to minimize or prevent short-term risks and maybe even long-term disease susceptibility.

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.

Elevated progesterone on the trigger day does not impair the outcome of Human Menotrophins Gonadotrophin and Medroxyprogesterone acetate treatment cycles

NASA Astrophysics Data System (ADS)

Lu, Xuefeng; Chen, Qiuju; Fu, Yonglun; Ai, Ai; Lyu, Qifeng; Kuang, Yan Ping

2016-08-01

To demonstrate the incidence and effects of elevated progesterone (P) on the trigger day on the outcome of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles using Medroxyprogesterone acetate (MPA) co-treated with Human Menotrophins Gonadotrophin (hMG + MPA), we performed a retrospective analysis including 4106 IVF/ICSI cycles. The cycles were grouped according to the P level on the trigger day: <1 ng/mL, between 1-1.5 ng/ml (including 1), between 1.5-2 ng/mL (including 1.5), and ≥2 ng/mL. The primary outcome measure was live birth rate. The prevalence of P level categories was 12.93% (531/4106), 2.92% (120/4106), and 1.92% (79/4106) in women with P between 1-1.5 ng/mL, between 1.5-2 ng/mL, and ≥2 ng/mL, respectively. The mean stimulation duration, total hMG dose, serum follicle stimulating hormone (FSH), estrogen(E2) on the trigger day and the number of oocytes in patients with elevated P were significantly higher than patients with P < 1 ng/mL (P < 0.05). However, there were no significant differences in the oocyte retrieval rates, fertilization rates, implantation rates, clinical pregnancy rates and live birth rates between the groups based on frozen embryo transfer (FET). We concluded that elevated P on the trigger day had no negative effect on the final outcome of the hMG + MPA treatment cycles based on FET.

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

PubMed

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

2017-01-01

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

Increased AIF-1-mediated TNF-α expression during implantation phase in IVF cycles with GnRH antagonist protocol.

PubMed

Xu, Bufang; Zhou, Mingjuan; Wang, Jingwen; Zhang, Dan; Guo, Feng; Si, Chenchen; Leung, Peter C K; Zhang, Aijun

2018-06-12

Is allograft inflammatory factor-1 (AIF-1), a cytokine associated with inflammation and allograft rejection, aberrantly elevated in in vitro fertilization (IVF) cycles with gonadotropin-releasing hormone (GnRH) antagonist protocol with potential effects on endometrial receptivity? Our findings indicated AIF-1 is increased in IVF cycles with GnRH antagonist protocol and mediates greater TNF-α expression during implantation phase, which may be unfavorable for embryo implantation. Studies have shown that GnRH antagonist protocol cycles have lower implantation and clinical pregnancy rates than GnRH agonist long protocol cycles. Endometrial receptivity but not embryo quality is a key factor contributing to this phenomenon; however, the mechanism is still unknown. Implantation and pregnancy rates were studied in 238 patients undergoing their first cycle of IVF/ICSI between 2012 and 2014. Forty of these patients opted to have no fresh embryo replacement and were divided into two equal groups: (i) GnRH antagonist protocol and (ii) GnRH agonist long protocol, group 3 included 20 infertile women with a tubal factor in untreated cycles. During the same interval, endometrial tissues were taken from 18 infertile women with a tubal factor in the early proliferative phase, late proliferative phase, and mid-secretory phase of the menstrual cycle (n = 6/group). Microarray analysis, RT-qPCR, Western blot analysis, immunohistochemistry were used to investigate the expression levels of AIF-1 and the related cytokines (TNF-α, IL1β, IL1RA, IL6, IL12, IL15 and IL18). The effect of AIF-1 on uterine receptivity was modeled using in vitro adhesion experiments (coculture of JAR cells and Ishikawa cells). The expression of AIF-1 was the highest in early proliferative phase, decreasing thereafter in the late proliferative phase, and almost disappearing in the mid-secretory phase, indicating that low AIF-1 expression might be important for embryo implantation during implantation phase. Microarray results revealed that AIF-1 was upregulated in the antagonist group compared with the control group (fold change [FC] = 3.75) and the agonist (FC = 2.20) group. The raw microarray data and complete gene expression table were uploaded to GEO under the accession number of GSE107914. Both the mRNA and protein expression levels of AIF-1 and TNF-α were the higher in the antagonist group than in the other two groups (P < 0.05) which did not differ significantly (P > 0.05). The protein levels of TNF-α in both Ishikawa cells and primary endometrial cells were significantly increased (P < 0.05) at 96 h after transfection with the AIF-1 expression vector, indicating that TNF-α was mediated by AIF-1 in endometrial cells. Overexpression of AIF-1 in Ishikawa cells inhibited adhesion of JAR cells to them. Thus, increased AIF-1 might inhibit adhesion during implantation via raised TNF-α. The sample size of the microarray was small, which might weaken the accuracy of our results; however, the sample size of RT-qPCR and the Western blotting assays were sufficient to compensate for this deficiency in our study. In addition, the aberrant AIF-1 and thus TNF-α expression is one of many factors that may contribute to limiting implantation success. Therefore, further extensive in vitro mechanistic and in vivo animal studies are needed to assess the actual functional impact of this pathway. Anti-TNF-α therapy might mitigate the adverse effects of GnRH antagonist on endometrial receptivity and improve the implantation rate in GnRH antagonist protocols in IVF. This work was supported by grants from the National Natural Science Foundation of China, Grant numbers 81771656 and 81370763; Clinical research special fund of Chinese Medical Association, Grant number 16020480664; Shanghai Jiao Tong University Medicine-Engineering Fund, Grant number YG2017ZD11 and YG2017MS57; and the Merck-Serono China Research Fund for Fertility Agreement. P.C.K.L. is supported by a Canadian Institutes of Health Research Foundation Scheme Grant 143317. None of the authors has any competing interests.

Increased risk of large-for-gestational age birthweight in singleton siblings conceived with in vitro fertilization in frozen versus fresh cycles.

PubMed

Luke, Barbara; Brown, Morton B; Wantman, Ethan; Stern, Judy E; Toner, James P; Coddington, Charles C

2017-02-01

Children born from fresh in vitro fertilization (IVF) cycles are at greater risk of being born smaller and earlier, even when limited to singletons; those born from frozen cycles have an increased risk of large-for-gestational age (LGA) birthweight (z-score ≥1.28). This analysis sought to overcome limitations in other studies by using pairs of siblings, and accounting for prior cycle outcomes, maternal characteristics, and embryo state and stage. Pairs of singleton births conceived with IVF and born between 2004 and 2013 were identified from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database, matched for embryo stage (blastocyst versus non-blastocyst) and infant gender, categorized by embryo state (fresh versus frozen) in 1st and 2nd births (four groups). The data included 7795 singleton pairs. Birthweight z-scores were 0.00-0.04 and 0.24-0.26 in 1st and 2nd births in fresh cycles, and 0.25-0.34 and 0.50-0.55 in frozen cycles, respectively. LGA was 9.2-9.8 and 14.2-15.4% in 1st and 2nd births in fresh cycles, and 13.1-15.8 and 20.8-21.0% in 1st and 2nd births in frozen cycles. The risk of LGA was increased in frozen cycles (1st births, adjusted odds ratios (AOR) 1.74, 95% CI 1.45, 2.08; and in 2nd births when the 1st birth was not LGA, AOR 1.70, 95% CI 1.46, 1.98 for fresh/frozen and 1.40, 1.11, 1.78 for frozen/frozen). Our results with siblings indicate that frozen embryo state is associated with an increased risk for LGA. The implications of these findings for childhood health and risk of obesity are unclear, and warrant further investigation.

Is the type of gonadotropin-releasing hormone suppression protocol for ovarian hyperstimulation associated with ectopic pregnancy in fresh autologous cycles for in vitro fertilization?

PubMed

Londra, Laura; Moreau, Caroline; Strobino, Donna; Bhasin, Aarti; Zhao, Yulian

2016-09-01

To evaluate the association between different ovarian hyperstimulation protocols and ectopic pregnancy (EP) in in vitro fertilization (IVF) cycles in fresh autologous embryo transfer cycles in the United States between 2008 and 2011 as reported to the Society of Assisted Reproductive Technology (SART). Historical cohort study. Not applicable. None. None. All autologous cycles that resulted in a clinical pregnancy after a fresh, intrauterine embryo transfer and described characteristics of cycles according to protocol were included: luteal GnRH agonist, GnRH agonist flare, or GnRH antagonist. Multivariate logistic regression was conducted to investigate the association between type of protocol and EP. Among 136,605 clinical pregnancies, 2,645 (1.94%) were EP. Ectopic pregnancy was more frequent with GnRH antagonist (2.4%) cycles than with GnRH agonist flare (2.1%) or luteal GnRH agonist (1.6%) cycles. After adjusting for maternal and treatment characteristics, the GnRH antagonist and the GnRH agonist flare protocols were associated with increased odds of EP (adjusted odds ratio [aOR] 1.52; 95% confidence interval [CI], 1.39-1.65; and aOR 1.25; 95% CI, 1.09-1.44, respectively) compared with luteal GnRH agonist. Analysis of differences in the factors related to EP in luteal GnRH agonist versus GnRH antagonist protocols indicated that diminished ovarian reserve was associated with an increased risk of EP in luteal GnRH agonist but not in GnRH antagonist cycles. The type of protocol used during ovarian hyperstimulation in fresh autologous cycles was associated with EP. This finding suggests a role for extrapituitary GnRH on the tubal and uterine environment during ovarian hyperstimulation treatment for IVF. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Is endometrioma-associated damage to ovarian reserve progressive? Insights from IVF cycles.

PubMed

Benaglia, Laura; Castiglioni, Marta; Paffoni, Alessio; Sarais, Veronica; Vercellini, Paolo; Somigliana, Edgardo

2017-10-01

The relation between endometriomas and damage to ovarian reserve remains controversial. In this study, we hypothesized that this damage may not be present at the time of endometrioma formation but may conversely gradually develop over time. To investigate the possibility of a time-related detrimental effect of endometriomas on ovarian reserve, we retrospectively selected 29 women with unilateral cysts who underwent at least two IVF cycles at least 6 months apart and evaluated ovarian responsiveness over time. Women were excluded if they conceived, developed new endometriomas or necessitated new medical or surgical therapies for endometriosis during the interval between the two cycles, RESULTS: The mean±SD of the diameter of the endometriomas was 26±8mm. Most women (n=25) had only one endometrioma. In the first cycle, the number of developing follicles in the affected and contralateral intact gonads was 4.9±2.5 and 5.9±2.4, respectively (p=0.10). In the second cycle, it was 5.0±2.9 and 6.0±2.8, respectively (p=0.13). The median (Interquartile Range) proportion of follicles developing in the affected ovaries in the first and second cycles was 44% (31-58%) and 44% (35-55%), respectively (p=0.97). Subgroup analyses according to the duration of the time interval between the two assessments, the dimension of the endometriomas and the history of previous surgery for endometriosis did not show subgroups at significant risk of time-related damage. We failed to observe an endometrioma-related reduction of ovarian responsiveness with time. However, evidence from larger series obtained in women carrying larger cysts and enrolled for longer time period of time are required for a definitive conclusion. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2017-01-01

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

Cell adhesion molecules and in vitro fertilization.

PubMed

Simopoulou, Maria; Nikolopoulou, Elena; Dimakakos, Andreas; Charalabopoulos, Konstantinos; Koutsilieris, Michael

2014-01-01

This review addresses issues regarding the need in the in vitro fertilization (IVF) field for further predictive markers enhancing the standing embryo selection criteria. It aims to serve as a source of defining information for an audience interested in factors related to the wide range of multiple roles played by cell adhesion molecules (CAMs) in several aspects of IVF ultimately associated with the success of an IVF cycle. We begin by stressing the importance of enriching the standing embryo selection criteria available aiming for the golden standard: "extract as much information as possible focusing on non-invasive techniques" so as to guide us towards selecting the embryo with the highest implantation potential. We briefly describe the latest trends on how to best select the right embryo, moving closer towards elective single embryo transfer. These trends are: frozen embryo transfer for all, preimplantation genetic screening, non-invasive selection criteria, and time-lapse imaging. The main part of this review is dedicated to categorizing and presenting published research studies focused on the involvement of CAMs in IVF and its final outcome. Specifically, we discuss the association of CAMs with conditions and complications that arise from performing assisted reproductive techniques, such as ovarian hyperstimulation syndrome, the state of the endometrium, and tubal pregnancies, as well as the levels of CAMs in biological materials available in the IVF laboratory such as follicular fluid, trophectoderm, ovarian granulosa cells, oocytes, and embryos. To conclude, since CAMs have been successfully employed as a diagnostic tool in several pathologies in routine clinical work, we suggest that their multi-faceted nature could serve as a prognostic marker in assisted reproduction, aiming to enrich the list of non-invasive selection and predictive criteria in the IVF setting. We propose that in light of the well-documented involvement of CAMs in the developmental processes of fertilization, embryogenesis, implantation, placentation, and embryonic development, further studies could contribute significantly to achieving a higher quality of treatment and management of infertility. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Abnormal vaginal microbiota may be associated with poor reproductive outcomes: a prospective study in IVF patients.

PubMed

Haahr, T; Jensen, J S; Thomsen, L; Duus, L; Rygaard, K; Humaidan, P

2016-04-01

What is the diagnostic performance of qPCR assays compared with Nugent scoring for abnormal vaginal microbiota and for predicting the success rate of IVF treatment? The vaginal microbiota of IVF patients can be characterized with qPCR tests which may be promising tools for diagnosing abnormal vaginal microbiota and for prediction of clinical pregnancy in IVF treatment. Bacterial vaginosis (BV) is a common genital disorder with a prevalence of approximately 19% in the infertile population. BV is often sub-clinical with a change of the vaginal microbiota from being Lactobacillus spp. dominated to a more heterogeneous environment with anaerobic bacteria, such as Gardnerella vaginalis and Atopobium vaginae. Few studies have been conducted in infertile women, and some have suggested a negative impact on fecundity in the presence of BV. A cohort of 130 infertile patients, 90% Caucasians, attending two Danish fertility clinics for in vitro fertilization (IVF) treatment from April 2014-December 2014 were prospectively enrolled in the trial. Vaginal swabs from IVF patients were obtained from the posterior fornix. Gram stained slides were assessed according to Nugent's criteria. PCR primers were specific for four common Lactobacillus spp., G. vaginalis and A. vaginae. Threshold levels were established using ROC curve analysis. The prevalence of BV defined by Nugent score was 21% (27/130), whereas the prevalence of an abnormal vaginal microbiota was 28% (36/130) defined by qPCR with high concentrations of Gardnerella vaginalis and/or Atopobium vaginae. The qPCR diagnostic approach had a sensitivity and specificity of respectively 93% and 93% for Nugent-defined BV. Furthermore, qPCR enabled the stratification of Nugent intermediate flora. Eighty-four patients completed IVF treatment. The overall clinical pregnancy rate was 35% (29/84). Interestingly, only 9% (2/22) with qPCR defined abnormal vaginal microbiota obtained a clinical pregnancy (P = 0.004). Although a total of 130 IVF patients were included in the study, a larger sample size is needed to draw firm conclusions regarding the possible adverse effect of an abnormal vaginal microbiota in relation to the clinical pregnancy rate and other reproductive outcomes. Abnormal vaginal microbiota may negatively affect the clinical pregnancy rate in IVF patients. If a negative correlation between abnormal vaginal microbiota and the clinical pregnancy rate is corroborated, patients could be screened and subsequently treated for abnormal vaginal microbiota prior to fertility treatment. This study was funded by The AP Møller Maersk Foundation for the advancement of Medical Science and Hospital of Central Jutland Research Fund, Denmark. No competing interests. The project was registered at clinicaltrials.gov (file number NCT02042352). © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Patient-reported vision-related quality of life differences between superior and inferior hemifield visual field defects in primary open-angle glaucoma.

PubMed

Cheng, Hui-Chen; Guo, Chao-Yu; Chen, Mei-Ju; Ko, Yu-Chieh; Huang, Nicole; Liu, Catherine Jui-ling

2015-03-01

Previous studies have found that glaucoma is associated with impaired patient-reported vision-related quality of life (pVRQOL) but few, to our knowledge, have assessed how the visual field (VF) defect location impacts the pVRQOL. To investigate the associations of VF defects in the superior vs inferior hemifields with pVRQOL outcomes in patients with primary open-angle glaucoma. Prospective cross-sectional study at a tertiary referral center from March 1, 2012, to January 1, 2013, including patients with primary open-angle glaucoma who had a best-corrected visual acuity in the better eye equal to or better than 20/60 and reliable VF tests. The pVRQOL was assessed by a validated Taiwanese version of the 25-item National Eye Institute Visual Function Questionnaire. Reliable VF tests obtained within 3 months of enrollment were transformed to binocular integrated VF (IVF). The IVF was further stratified by VF location (superior vs inferior hemifield). The association between each domain of the 25-item National Eye Institute Visual Function Questionnaire and superior or inferior hemifield IVF was determined using multivariable linear regression analysis. The analysis included 186 patients with primary open-angle glaucoma with a mean age of 59.1 years (range, 19-86 years) and IVF mean deviation (MD) of -4.84 dB (range, -27.56 to 2.17 dB). In the multivariable linear regression analysis, the MD of the full-field IVF showed positive associations with near activities (β = 0.05; R2 = 0.20; P < .001), vision-specific role difficulties (β = 0.04; R2 = 0.19; P = .01), vision-specific dependency (β = 0.04; R2 = 0.20; P < .001), driving (β = 0.05; R2 = 0.24; P < .001), peripheral vision (β = 0.03; R2 = 0.18; P = .02), and composite scores (β = 0.04; R2 = 0.27; P = .005). Subsequent analysis showed that the MD of the superior hemifield IVF was associated only with near activities (β = 0.04; R2 = 0.21; P < .001) while the MD of the inferior hemifield IVF was associated with general vision (β = 0.04; R2 = 0.12; P = .01), vision-specific role difficulties (β = 0.04; R2 = 0.20; P = .01), and peripheral vision (β = 0.03; R2 = 0.17; P = .03). Superior hemifield IVF was strongly associated with difficulty with near activities. Inferior hemifield IVF impacted vision-specific role difficulties and general and peripheral vision. The impact of a VF defect on a patient's pVRQOL may depend not only on its severity, but also on its hemifield location.

Natural conception rates in couples with unexplained or mild male subfertility scheduled for fertility treatment: a secondary analysis of a randomized controlled trial.

PubMed

van Eekelen, R; Tjon-Kon-Fat, R I; Bossuyt, P M M; van Geloven, N; Eijkemans, M J C; Bensdorp, A J; van der Veen, F; Mol, B W; van Wely, M

2018-05-01

What is the natural conception rate over the course of 12 months in couples with unexplained or mild male subfertility who are scheduled for fertility treatment and have a predicted unfavourable prognosis for natural conception? The natural conception rate over the course of 12 months in couples who were allocated to treatment was estimated to be 24.5% (95% CI: 20-29%). After starting treatment, couples often perceive unsuccessful cycles as evidence of definitive failure even though they are still able to conceive naturally in between and after treatment. The magnitude of the natural conception rate for couples who chose to commence treatment is unknown, as is whether the calculated prognosis before commencing treatment is still applicable. We performed a secondary analysis of a randomized controlled trial including couples with unexplained or mild male subfertility and an unfavourable prognosis for natural conception. Couples were allocated to either three cycles IVF with single embryo transfer (SET), six cycles of IVF in a modified natural cycle (MNC) or six cycles of IUI with controlled ovarian hyperstimulation (IUI-COH). The detailed data collection in this trial allowed us to study the conception rates in periods that couples were not receiving treatment. We split the dataset into periods during which couples were treated and periods during which they were not treated. Couples could conceive naturally in the periods before, in between and after treatment cycles. The outcome was ongoing pregnancy, thus natural conception rate refers to natural conception leading to ongoing pregnancy. We performed a Cox proportional hazards analysis with female age, duration of subfertility and a time-varying covariate with four categories: IVF-SET, IVF-MNC, IUI-COH and no treatment. We used this Cox model to estimate the natural conception rate over 12 months of no treatment. Out of 602 included couples, there were 342 ongoing pregnancies, of which 77 (23%) resulted from natural conception. The estimated natural conception rate over 12 months was 24.5% (95% CI: 20-29%) on cohort level. Estimated rates for female age varying between 18 and 38 years and duration of subfertility between 1 and 3 years ranged from 22 to 35%. We considered couples at risk for natural conception when not receiving treatment, whereas they might not have had periovulatory sexual intercourse. As couples were scheduled for treatment, it is possible that these couples were less inclined to try to conceive naturally, potentially leading to an underestimation of their natural conception rate if they kept trying to conceive. Couples with unexplained subfertility who are about to start fertility treatment, still have about a one in four chance of ongoing pregnancy due to natural conception over 12 months. This information can add to the counselling of couples who commenced fertility treatment after failed cycles and to emphasize not to cease their natural attempts. The INeS trial was supported by a grant from ZonMW, the Dutch Organization for Health Research and Development (120620027), and a grant from Zorgverzekeraars Nederland, the Dutch association of health care insurers (09-003). The funders had no role in study design, collection, analysis and interpretation of the data. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck and Guerbet. No other potential conflicts of interest reported. The INeS trial was registered at the Dutch trial registry (NTR 939).

Fresh versus frozen embryo transfers in assisted reproduction.

PubMed

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

2017-03-28

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

What do consistently high-performing in vitro fertilization programs in the U.S. do?

PubMed

Van Voorhis, Bradley J; Thomas, Mika; Surrey, Eric S; Sparks, Amy

2010-09-01

To identify common clinical and laboratory practices among consistently high-performing IVF programs. Questionnaire study of selected IVF programs. Academic and private practice IVF programs. Ten of 12 programs identified as having consistently high singleton delivery rates per cycle. None. Common clinical practices. Common clinical practices identified among these programs included testing all patients for ovarian reserve, endometrial defects, and hydrosalpinges; use of a mixed LH and FSH stimulation protocol with step-down dosing; and use of ultrasound guidance for ET. Common laboratory practices included selective use of intracytoplasmic sperm injection, group culture of embryos in microdrops, and use of blastocyst ET in selected cases. Common laboratory features included good air quality using filtration and heated stages for oocyte and embryo work. Although a number of factors were identified in this best-practices questionnaire, programs often differed in many aspects of care. However, high-performing programs cited experience of physicians, embryologists, and staff members as well as consistency of approach, attention to detail, and good communication as being vital to excellent outcomes. Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2001-03-01

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

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.

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.

Desperately seeking parenthood: neonatal nurses reflect on parental anguish.

PubMed

Green, Janet; Darbyshire, Philip; Adams, Anne; Jackson, Debra

2015-07-01

This paper aims to explore the ways in which neonatal nurses understand the experience of parents who have experienced infertility, conceived a baby via in vitro fertilisation and delivered an extremely premature infant. The chance of a poor long-term outcome for the baby is significant; therefore, parental anguish plays out in the neonatal intensive care. Current literature suggests that infertility is a significant issue for ageing women and many couples experience multiple cycles of invitro-fertilisation (IVF) treatment to achieve a pregnancy. Babies conceived through IVF are more likely to have genetic disorders, and be born prematurely. When the baby is born through IVF and is also born extremely prematurely, it creates a crisis situation for the parents. This paper will focus on the parental anguish of achieving a pregnancy through IVF to see the baby born extremely prematurely (defined as ≤ 24-week gestation). It will examine parental anguish from caregiver perspective of the neonatal nurse who supports the parents through this very difficult time. This study used interviews with neonatal nurses, and drew insights from interpretative phenomenology. This research used a combination of a questionnaire and a series of interviews in a qualitative study informed by phenomenology. The analysis of the interview data involved the creation of key themes following extensive coding of thematic statements and the analysis of the emerging themes. This paper outlines the neonatal nurses' understanding of parental anguish and overwhelming sadness in parents whose baby was conceived by IVF, and was also born extremely prematurely. The theme of 'seeking parenthood' was synthesised from two sub-themes - 'longing for a baby' and 'the desperation to become parents'. This study identified that neonatal nurses bear witness to parental anguish as their hopes of taking home a live baby might not be realised. The time, effort and money required to achieve a pregnancy does not mean that the baby will be spared the outcomes of extreme prematurity and the risk factors associated with IVF. The parents may be left empty handed. Therefore, the word precious becomes a metaphor for the IVF baby as the neonatal team try desperately to give the parents their much longed baby. Delayed child bearing has an impact on fertility, with maternal age having the most impact on the ability to conceive. Babies conceived through IVF technologies have a higher risk of genetic abnormalities and being born prematurely, and this will impact on the neonatal intensive care availability. Extreme prematurity and IVF can significantly impact on the baby's outcome. Witnessing parental anguish can be a major source of stress for the neonatal nurses. Neonatal nurses need to develop strategies not only to help the parents but also to prevent the parents' overwhelming sadness from affecting their ability to function in the neonatal intensive care unit. © 2015 John Wiley & Sons Ltd.

Number of embryos for transfer following in-vitro fertilisation or intra-cytoplasmic sperm injection.

PubMed

Pandian, Z; Bhattacharya, S; Ozturk, O; Serour, G I; Templeton, A

2004-10-18

The traditional reliance on the transfer of multiple embryos during in vitro fertilisation (IVF) in order to maximise the chance of pregnancy, has resulted in increasing rates of multiple pregnancies. Women undergoing IVF had a 20 - fold increased risk of twins and 400 - fold increased risk of higher order pregnancies (Martin 1998). The maternal and perinatal morbidity and mortality as well as national health service costs associated with multiple pregnancies is significantly high in comparison with singleton births (Luke 1992; Callahan 1994; Goldfarb 1996). Single embryo transfer is now being considered as an effective means of reducing this iatrogenic complication. This systematic review evaluates the effectiveness of elective two embryo transfer in comparison with single and more than two embryo transfer following IVF and ICSI (intra cytoplasmic sperm injection) treatment. The aim of this review is to determine, whether in couples who undergo IVF/ICSI: (1) the elective transfer of two embryos improves the probability of livebirth compared with: (a) Single embryo transfer, (b) Three embryo transfer or (c) Four embryo transfer.(2) the elective transfer of three embryos improves the probability of livebirth compared with: (a) Single embryo transfer, or (b) Four embryo transfer, We searched the Cochrane Menstrual Disorders and Subfertility Group's trials register (searched June 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), MEDLINE (1970 to 2003), EMBASE (1985 to 2003) and reference lists of articles. We also handsearched relevant conference proceedings and contacted researchers in the field. Only randomised controlled trials were included. Two reviewers independently assessed eligibility and quality of trials. We found no studies that compared a policy of transferring multiple embryos on one cycle versus a policy of cryo- preservation and transfer of a single embryo over multiple cycles. We also found no trials comparing transfer of two versus three embryos. Three small, poorly reported trials compared transfer of two versus one embryo in a single cycle, and one small, poorly reported trial compared transfer of two versus four embryos in a single cycle. The clinical pregnancy rate per woman/couple associated with two embryo transfer was significantly higher compared to single embryo transfer (OR 2.08, 95% CI 1.24 to 3.50; test for overall effect p = 0.006). The live birth rate per woman/couple associated with two embryo transfer was also significantly higher than that associated with single embryo transfer (OR 1.90, 95% CI 1.12 to 3.22, test for overall effect p=0.02). The multiple pregnancy rate was significantly lower in women who had single embryo transfer (OR 9.97, 95% CI 2.61 to 38.19; p = 0.0008). The effectiveness of double embryo transfer versus four embryo transfer was tested in a single trial. There was no statistically significant differences in the clinical pregnancy rate (OR 0.75, 95% CI 0.26 to 2.16; p=0.6), and multiple pregnancy rates (OR 0.44. 95% CI 0.10 to 1.97; p = 0.28) between the two groups. The livebirth rate in the four embryo transfer group was higher compared to the two embryo transfer group, but the results were not statistically significant (OR 0.35, 95% CI 0.11 to 1.05; p = 0.06). The results of this systematic review suggest that live birth and pregnancy rates following single embryo transfer are lower than those following double embryo transfer as are the chances of multiple pregnancy including twins. As such, it is unlikely that the conclusions are robust enough to catalyse a change in clinical practice. The studies included are limited by their small sample size, so that even large differences might be hidden. Cumulative livebirth rates are seldom reported. The data were inadequate to draw conclusions about single embryo transfer and first frozen single embryo transfer (1FZET) or subsequent single frozen embryo transfers. Until more evidence is available single embryo transfer may not be the preferred choice for all patients undergoing IVF/ICSI. Clinicians may need to individualise protocols for couples based on their risks of multiple pregnancy. A definitive pragmatic, large multi centre randomised controlled trial comparing single embryo versus double embryo transfer in terms of clinical and cost effectiveness as well as acceptability is required. The primary outcome measured should be cumulative livebirth per woman/couple.

Does a strategy to promote shared decision-making reduce medical practice variation in the choice of either single or double embryo transfer after in vitro fertilisation? A secondary analysis of a randomised controlled trial.

PubMed

Brabers, Anne E M; van Dijk, Liset; Groenewegen, Peter P; van Peperstraten, Arno M; de Jong, Judith D

2016-05-06

The hypothesis that shared decision-making (SDM) reduces medical practice variations is increasingly common, but no evidence is available. We aimed to elaborate further on this, and to perform a first exploratory analysis to examine this hypothesis. This analysis, based on a limited data set, examined how SDM is associated with variation in the choice of single embryo transfer (SET) or double embryo transfer (DET) after in vitro fertilisation (IVF). We examined variation between and within hospitals. A secondary analysis of a randomised controlled trial. 5 hospitals in the Netherlands. 222 couples (woman aged <40 years) on a waiting list for a first IVF cycle, who could choose between SET and DET (ie, ≥2 embryos available). SDM via a multifaceted strategy aimed to empower couples in deciding how many embryos should be transferred. The strategy consisted of decision aid, support of IVF nurse and the offer of reimbursement for an extra treatment cycle. Control group received standard IVF care. Difference in variation due to SDM in the choice of SET or DET, both between and within hospitals. There was large variation in the choice of SET or DET between hospitals in the control group. Lower variation between hospitals was observed in the group with SDM. Within most hospitals, variation in the choice of SET or DET appeared to increase due to SDM. Variation particularly increased in hospitals where mainly DET was chosen in the control group. Although based on a limited data set, our study gives a first insight that including patients' preferences through SDM results in less variation between hospitals, and indicates another pattern of variation within hospitals. Variation that results from patient preferences could be potentially named the informed patient rate. Our results provide the starting point for further research. NCT00315029; Post-results. 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/

Predictive value of serum progesterone level on β-hCG check day in women with previous repeated miscarriages after in vitro fertilization.

PubMed

Kim, Yong Jin; Shin, Jung Ho; Hur, Jun Yong; Kim, Hoon; Ku, Seung-Yup; Suh, Chang Suk

2017-01-01

To evaluate the predictive value of the progesterone level at the beta-human chorionic gonadotropin (β-hCG) check day for ongoing pregnancy maintenance in in vitro fertilization (IVF) cycles in women with previous unexplained repeated miscarriages. One hundred and forty-eight women, with visible gestational sac after IVF, were recruited in this observational study. All subjects had unexplained recurrent miscarriages in more than two previous IVF cycles. The progesterone level at the β-hCG check day (i.e. 14 days after oocyte retrieval) was assessed. The area under the curve (AUC) of the progesterone level was evaluated to predict the ongoing pregnancy or miscarriage outcomes. The overall ongoing pregnancy rate was 60.8% (90/148). The cut-off value with β-hCG levels higher than 126.5 mIU/mL and with progesterone levels higher than 25.2 ng/mL could be the predictive factors for ongoing pregnancy maintenance (AUC = 0.788 and 0.826; sensitivity = 0.788 and 0.723; specificity = 0.689 and 0.833; P < 0.0001 and P < 0.0001, respectively). The miscarriage rates were 19.5% (15/77) in the women with β-hCG > 126.5 mIU/mL and 13.0% (10/77) in those with > 25.2 ng/mL. In the comparison of the ROC curves between both values, a similar significance was found. The subjects with β-hCG > 126.5 mIU/mL and progesterone > 25.2 ng/mL showed higher ongoing pregnancy rates [98.0% (49/50) vs. 41.8% (41/98)] than those with β-hCG ≤ 126.5 mIU/mL or progesterone ≤ 25.2 ng/mL. The progesterone level at 14 days after oocyte retrieval can be a good predictive marker for ongoing pregnancy maintenance in women with repeated IVF failure with miscarriage, together with the β-hCG level. The combined cut-off value of progesterone > 25.2 ng/mL and β-hCG > 126.5 mIU/mL may suggest a good prognosis.

Parthenogenic Blastocysts Derived from Cumulus-Free In Vitro Matured Human Oocytes

PubMed Central

McElroy, Sohyun L.; Byrne, James A.; Chavez, Shawn L.; Behr, Barry; Hsueh, Aaron J.; Westphal, Lynn M.; Reijo Pera, Renee A.

2010-01-01

Background Approximately 20% of oocytes are classified as immature and discarded following intracytoplasmic sperm injection (ICSI) procedures. These oocytes are obtained from gonadotropin-stimulated patients, and are routinely removed from the cumulus cells which normally would mature the oocytes. Given the ready access to these human oocytes, they represent a potential resource for both clinical and basic science application. However culture conditions for the maturation of cumulus-free oocytes have not been optimized. We aimed to improve maturation conditions for cumulus-free oocytes via culture with ovarian paracrine/autocrine factors identified by single cell analysis. Methodology/Principal Finding Immature human oocytes were matured in vitro via supplementation with ovarian paracrine/autocrine factors that were selected based on expression of ligands in the cumulus cells and their corresponding receptors in oocytes. Matured oocytes were artificially activated to assess developmental competence. Gene expression profiles of parthenotes were compared to IVF/ICSI embryos at morula and blastocyst stages. Following incubation in medium supplemented with ovarian factors (BDNF, IGF-I, estradiol, GDNF, FGF2 and leptin), a greater percentage of oocytes demonstrated nuclear maturation and subsequently, underwent parthenogenesis relative to control. Similarly, cytoplasmic maturation was also improved as indicated by development to blastocyst stage. Parthenogenic blastocysts exhibited mRNA expression profiles similar to those of blastocysts obtained after IVF/ICSI with the exception for MKLP2 and PEG1. Conclusions/Significance Human cumulus-free oocytes from hormone-stimulated cycles are capable of developing to blastocysts when cultured with ovarian factor supplementation. Our improved IVM culture conditions may be used for obtaining mature oocytes for clinical purposes and/or for derivation of embryonic stem cells following parthenogenesis or nuclear transfer. PMID:20539753

Culture media for human pre-implantation embryos in assisted reproductive technology cycles.

PubMed

Youssef, Mohamed M A; Mantikou, Eleni; van Wely, Madelon; Van der Veen, Fulco; Al-Inany, Hesham G; Repping, Sjoerd; Mastenbroek, Sebastiaan

2015-11-20

Many media are commercially available for culturing pre-implantation human embryos in assisted reproductive technology (ART) cycles. It is unknown which culture medium leads to the best success rates after ART. To evaluate the safety and effectiveness of different human pre-implantation embryo culture media in used for in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) cycles. We searched the Cochrane Menstrual Disorders and Subfertility Group's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the National Research Register, the Medical Research Council's Clinical Trials Register and the NHS Center for Reviews and Dissemination databases from January 1985 to March 2015. We also examined the reference lists of all known primary studies, review articles, citation lists of relevant publications and abstracts of major scientific meetings. We included all randomised controlled trials which randomised women, oocytes or embryos and compared any two commercially available culture media for human pre-implantation embryos in an IVF or ICSI programme. Two review authors independently selected the studies, assessed their risk of bias and extracted data. We sought additional information from the authors if necessary. We assessed the quality of the evidence using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methods. The primary review outcome was live birth or ongoing pregnancy. We included 32 studies in this review. Seventeen studies randomised women (total 3666), three randomised cycles (total 1018) and twelve randomised oocytes (over 15,230). It was not possible to pool any of the data because each study compared different culture media.Only seven studies reported live birth or ongoing pregnancy. Four of these studies found no evidence of a difference between the media compared, for either day three or day five embryo transfer. The data from the fifth study did not appear reliable.Six studies reported clinical pregnancy rate. One of these found a difference between the media compared, suggesting that for cleavage-stage embryo transfer, Quinn's Advantage was associated with higher clinical pregnancy rates than G5 (odds ratio (OR) 1.56; 95% confidence interval (CI) 1.12 to 2.16; 692 women). This study was available only as an abstract and the quality of the evidence was low.With regards to adverse effects, three studies reported multiple pregnancies and six studies reported miscarriage. None of them found any evidence of a difference between the culture media used. None of the studies reported on the health of offspring.Most studies (22/32) failed to report their source of funding and none described their methodology in adequate detail. The overall quality of the evidence was rated as very low for nearly all comparisons, the main limitations being imprecision and poor reporting of study methods. An optimal embryo culture medium is important for embryonic development and subsequently the success of IVF or ICSI treatment. There has been much controversy about the most appropriate embryo culture medium. Numerous studies have been performed, but no two studies compared the same culture media and none of them found any evidence of a difference between the culture media used. We conclude that there is insufficient evidence to support or refute the use of any specific culture medium. Properly designed and executed randomised trials are necessary.

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.

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.

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.