Live Birth Rate In Women Research Articles

P–633 lifestyle intervention prior to IVF does not improve embryo utilization rate and cumulative live birth rate in women with obesity

Abstract Study question Does lifestyle intervention prior to in vitro fertilization (IVF) improve embryo utilization rate (EUR) and cumulative live birth rate (CLBR) in women with obesity? Summary answer A six-month lifestyle intervention preceding IVF improved neither EUR, nor CLBR in women with obesity. What is known already A randomized controlled trial (RCT) evaluating the efficacy of a low caloric liquid formula diet (LCD) preceding IVF in women with obesity was unable to demonstrate an effect of LCD on embryo quality and live birth rate. In that study, only one fresh embryo transfer (ET) or, in case of freeze-all strategy, the first transfer with frozen-thawed embryos was reported. We hypothesized that any effect on embryo quality of a lifestyle intervention in women with obesity undergoing IVF treatment is better revealed by EUR and CLBR after transfer of fresh and frozen-thawed embryos. Study design, size, duration This is a nested cohort study within an RCT. The LIFEstyle study examined whether a six-month lifestyle intervention prior to assisted reproductive technology (ART) in women with obesity improved live birth rate, compared to prompt ART within 24 months after randomization. In the original study, 577 women with obesity and infertility were assigned to a lifestyle intervention followed by ART (N = 290) or to prompt ART (N = 287) between 2009 and 2012. Participants/materials, setting, methods The first IVF cycle with successful oocyte retrieval was included, resulting in 51 participants in the intervention group and 72 in the control group. EUR was defined as the proportion of inseminated/injected oocytes that could be transferred or cryopreserved as an embryo. Analysis was performed per cycle and per oocyte/embryo. CLBR was defined as the percentage of participants with at least one live birth from the first fresh and subsequent frozen-thawed ET(s). Main results and the role of chance The overall mean age was 31.64 years, and the mean BMI was 35.40 ± 3.21 kg/m2 in the intervention group, and 34.86 ± 2.86 kg/m2 in the control group (P = 0.33). The mean difference of weight change at six months between the two groups was in favor of the intervention group (mean difference in kg: –3.14, 95% CI: –5.73 – –0.56). The median (Q25; Q75) of EUR was 33.3% (12.5; 60.0) in the intervention group and 33.3% (16.7; 50.0) in the control group in the per cycle analysis (adjusted B: 2.7%, 95% CI: –8.6 – 14.0). In the per oocyte/embryo analysis, in total 280 oocytes were injected or inseminated in the intervention group, 113 were utilized (transferred or cryopreserved embryos, EUR = 40.4%); in the control group EUR was 30.8% (142/461). The lifestyle intervention did not significantly improve EUR (adjusted OR: 1.36, 95% CI: 0.94 – 1.98) in the per oocyte/embryo analysis taking into account the interdependency of the oocytes per participant. CLBR was not significantly different between the intervention group and the control group after adjusting for type of infertility (male factor and unexplained) and smoking (27.5% vs 22.2%, adjusted OR: 1.03, 95% CI: 0.43 – 2.47). Limitations, reasons for caution This study is a nested cohort study within an RCT, and no power calculation was performed. The randomization was not stratified for indicated treatment. The limited absolute weight loss and the short duration of the lifestyle intervention might be insufficient to affect EUR and CLBR. Wider implications of the findings: Our data do not support the hypothesis of a beneficial effect of lifestyle intervention on embryo quality and CLBR after IVF in women with obesity. Trial registration number NTR 1530

P–590 Women with hypothalamic hypogonadism have lower live birth rates following frozen embryo transfer

Abstract Study question How do live birth rates differ in anovulatory women with polycystic ovary syndrome and hypothalamic hypogonadism compared to normo-ovulatory women undergoing fresh or frozen embryo transfer? Summary answer Live birth rates are similar among all groups undergoing fresh embryo transfer but are significantly lower in women with hypothalamic hypogonadism undergoing frozen embryo transfer. What is known already Conflicting data exist regarding pregnancy outcomes in patients with tubal factor infertility versus polycystic ovary syndrome (PCOS). Some studies demonstrate higher pregnancy and live birth rates for women with PCOS undergoing fresh embryo transfer, but other studies demonstrate no difference. Women with PCOS have higher live birth rates than those with tubal factor infertility when undergoing frozen embryo transfer. Fewer data are available regarding IVF outcomes in women with hypothalamic hypogonadism (HH) and tubal factor infertility. Several studies report comparable live birth rates with fresh embryo transfer, but there are no data on frozen embryo transfer outcomes. Study design, size, duration Retrospective cohort study of all fresh and frozen autologous embryo transfers performed for patients with oligo-anovulation (PCOS, n = 380 and HH, n = 39) and normo-ovulation (tubal factor infertility, n = 315) from 1/1/2012 to 6/30/2019. A total of 734 transfers from 653 patients were analyzed. Participants/materials, setting, methods Transfer outcomes, including implantation, miscarriage, clinical pregnancy and live birth rates, were assessed in fresh and frozen embryo transfer cycles. Adjusted relative risks (RR) and 95% confidence intervals (CI) were calculated adjusting for age, BMI, stimulation protocol, number of embryos transferred, embryo quality, endometrial stripe thickness and day of transfer. Poisson regression was used for counts and with an offset for ratios. Generalized estimating equations were used to account for patients contributing multiple cycles. Main results and the role of chance For fresh embryo transfer cycles, live birth rates are similar among patients with tubal factor infertility, PCOS and HH (29.5% vs. 37.9% vs. 35.9%, respectively, aRR 1.15 95% CI: 0.91–1.44 and aRR 1.23 95% CI: 0.81–2.00, respectively). When evaluating frozen embryo transfer cycles, patients with HH have lower live birth rates than patients with tubal factor infertility (26.5% vs. 42.6%, aRR 0.54 95% CI: 0.33–0.88) and patients with PCOS (26.5% vs. 46.7%, aRR 0.55 95% CI: 0.34–0.88). Additionally, patients with HH have higher chemical pregnancy rates and miscarriage rates than patients with tubal factor infertility (26.5% vs. 13.0% and 17.7% vs. 6.5%, respectively, RR 2.71 95% CI: 1.27–5.77 and RR 2.03 95% CI: 1.05–3.80, respectively). Point biserial correlation showed no significant correlation between live birth and endometrial stripe thickness in HH patients undergoing frozen embryo transfer (r = 0.028, p-value 0.876). Limitations, reasons for caution This study is limited by its retrospective nature and the small sample size of women with hypothalamic hypogonadism. Additionally, these data represent outcomes from a single academic center, so generalizability of our findings may be limited. Wider implications of the findings: Lower live birth rates for HH patients undergoing frozen embryo transfer cycles are not correlated with endometrial stripe thickness. This may be due to absent gonadotropin signaling on endometrial receptors. A prospective randomized trial of HH patients to modified natural versus programmed frozen embryo transfer would best support this hypothesis. Trial registration number Not applicable

O-001 Delay in IVF treatment up to 180 days does not affect pregnancy outcomes in women with diminished ovarian reserve

textIn clinical practice, infertility treatment delays can occur due to medical, logistical, or financial reasons. Concerns over treatment delays were brought to the forefront in March 2020 when the SARS-CoV-2 pandemic prompted both the ESHRE and ASRM to recommend the suspension of new infertility treatment cycles. At the time, little was known about the risk of viral transmission on reproductive health and necessary medical resources urgently needed to be reallocated to the front lines of the pandemic. These society recommendations were met with resistance from some clinicians and patients that raised valid concerns about whether delaying IVF treatment for a few months could negatively affect pregnancy outcomes.To help answer this question, we designed a retrospective cohort study to assess whether a delay up to 180 days in initiating IVF treatment affects pregnancy outcomes in infertile women with diminished ovarian reserve. This population was selected because their treatment outcomes were the most likely to affected by treatment delays due to the continuous decline in ovarian reserve over time. Infertile women treated at our IVF center were included if they had diminished ovarian reserve and started an ovarian stimulation cycle within 180 days of their initial consultation that resulted in an oocyte retrieval with planned fresh embryo transfer between 1 January 2012 and 31 December 2018. Diminished ovarian reserve was defined as an anti-Mŭllerian hormone (AMH) < 1.1 ng/mL.In total, 1,790 patients met inclusion criteria (1,115 immediate and 675 delayed treatment). Each patient had one included cycle and no subsequent data from additional frozen embryo transfer cycles were included. Since all cycle outcomes evaluated were from fresh embryo transfers, no genetically tested embryos were included. Patients were grouped by whether their cycle started 1-90 days after presentation (immediate) or 91-180 days (delayed). The primary outcome was live birth (≥24 weeks of gestation). A subgroup analysis of more severe forms of diminished ovarian reserve was performed to evaluate outcomes for patients with an AMH < 0.5 and for patients >40 years old with an AMH < 1.1 ng/mL (Bologna criteria for diminished ovarian reserve). Logistic regression analysis, adjusted a priori for patient age, was used to estimate the odds ratio (OR) with a 95% CI. All pregnancy outcomes were additionally adjusted for the number of embryos transferred.The mean ± SD number of days from presentation to IVF start was 50.5 ± 21.9 (immediate) and 128.8 ± 25.9 (delayed). After embryo transfer, the live birth rate was similar between groups (immediate: 23.9%; delayed: 25.6%; OR 1.08, 95% CI 0.85-1.38). Additionally, a similar live birth rate was observed in a subgroup analysis of patients with an AMH < 0.5 ng/mL (immediate: 18.8%; delayed: 19.1%; OR 0.99, 95% CI 0.65-1.51) and in patients >40 years old with an AMH < 1.1 ng/mL (immediate: 12.3%; delayed: 14.7%; OR 1.21, 95% CI 0.77-1.91).Overall, we observed that a delay in initiating IVF treatment up to 180 days does not affect the live birth rate for women with diminished ovarian reserve when compared to women who initiate IVF treatment within 90 days of presentation. This observation persisted for patients who in the highest-risk categories for poor response to ovarian stimulation. Providers and patients should be reassured that when a short-term treatment delay is deemed necessary for medical, logistical, or financial reasons, treatment outcomes will not be negatively affected.

P–426 Uterine Natural Killer Cells in Recurrent Miscarriage and Implantation Failure: An Updated Systematic Review and Meta-analysis

Abstract Study question Do women with recurrent miscarriage (RM) or implantation failure (RIF) have different levels of uterine Natural Killer (NK) cells compared to fertile controls? Summary answer Women with RIF but not RM are associated with significantly higher levels of CD56+ uterine NK cells compared to controls. What is known already Uterine NK cells (uNK) are different from peripheral NK cells (pNK) and are important in early pregnancy for development of the placenta. The association between uNK and RM/RIF is less clear, but dysfunction of uNK is believed to result in early pregnancy failure. Previous systematic reviews by Seshadri (2014) and Tang (2013) on infertile and RM patients showed no significant difference in uNK levels and highlighted need for further studies. Since, many prospective studies have been published and therefore warrant an updated systematic review. On the other hand, evidence for correlation between uNK and pNK is sparse and needs clarification. Study design, size, duration We have conducted a systematic review and meta-analysis to evaluate three outcomes. The primary outcome was the difference of uNK level in RM/RIF compared to controls. The secondary outcome was livebirth rate in women with RM/RIF with high compared to normal uNK level, and the tertiary outcome was correlation between uNK and pNK in RM/RIF. Participants/materials, setting, methods The electronic database search included MEDLINE, EMBASE, Web of Science and bibliographies from included articles from inception to December 2020 using a combination of MESH and keywords. Search, screen, and data extraction were performed by two reviewers independently. Quality assessment was conducted with ROBINS-I and meta-analysis with Revman 5.3. Out of 4636 studies screened, 43 studies (2539 women) and 3 studies each (598 and 77 women) were analysed for primary, secondary and tertiary outcomes respectively. Main results and the role of chance Our meta-analysis showed that CD56+ uNK were significantly higher in women with RIF but not RM compared to controls (SMD 0.60; 95% CI 0.12–1.08]. Subgroup analysis in RM patients showed no significant difference whether definition of 2 or 3 previous RM was used, in primary/secondary RM compared to controls, or in primary versus secondary RM. CD56+ uNK were significantly higher in RM/RIF when sampled during mid-luteal phase [SMD 0.56; 95% CI 0.19–0.93] but not in the early pregnancy decidua. Interestingly, there was significant difference in CD56+ uNK when analysed by immunohistochemistry [SMD 0.50; CI 0.05–0.94] but not by flow cytometry, and when CD56+ uNK were reported as percentage over total endometrial cells [SMD 0.58; 95% CI 0.10–1.07]. Further subgroup analysis showed significant difference in CD16 + [SMD 0.54; 95% CI 0.18–0.89] but not in CD56+CD16-, CD56+CD16+ or CD57. For pregnancy outcome, there was no significant difference in livebirth rate in RM/RIF patients with high uNK compared to normal uNK [RR 1.06, 95% CI 0.86–1.30]. Mean uNK level in RM patients with subsequent miscarriage was not significantly higher than subsequent livebirth. Finally, the pooled correlation between CD56 pNK and CD56 uNK (r = 0.42; 95% CI –0.04–0.73] was not significant in RM/RIF patients. Limitations, reasons for caution The meta-analysis is limited by quality of some of the studies. Some data were presented in median that was transformed to mean which may result in data skew. Other confounding factors e.g. maternal age, fetal karyotype, number of previous miscarriages and variable definition of controls may contribute to bias. Wider implications of the findings: Clinical interpretation of uNK level needs to be treated with caution because there is significant heterogeneity in method of analysis. There may be a role for uNK measurement in RIF patients however further studies to understand pathophysiology underlying elevated uNK is warranted before recommending it as a diagnostic tool. Trial registration number N/A

Impact of maternal depression and anxiety-related disorders on live birth rate in women with recurrent pregnancy loss

It is unknown whether depression and anxiety-related conditions associate with poor perinatal outcomes, especially live birth rates, among women diagnosed with recurrent pregnancy loss. We performed a retrospective cohort study using the Japanese Medical Data Centre Claims Database and identified women diagnosed with recurrent pregnancy loss. Live birth rates were compared as the primary outcome between patients with and without depression and/or anxiety-related disorders. A stabilised inverse probability of treatment weight analysis using propensity scores was also performed to assess the association. Among 5,517 eligible patients, there were 804 (14.6%) women who had depression and/or anxiety-related disorders during treatment for recurrent pregnancy loss during pregnancy. The overall live birth rates differed significantly between the groups according to the Kaplan–Meier method and log-rank test (p = 0.011). However, Cox proportional-hazards regression model and stabilised inverse probability of treatment weight analysis showed no statistically significant association between depressive disorders and live birth rates. The current study showed that approximately 15% of patients diagnosed with recurrent pregnancy loss develop depressive disorders. After accounting for variables, we found no independent association between depressive disorders after recurrent pregnancy losses and low live birth rates.

Intrauterine injection of HCG before embryo transfer: a parallel, double-blind randomized trial

Research questionDoes intrauterine administration of HCG before embryo transfer improve live birth rate during IVF cycles? DesignA parallel, randomized controlled trial conducted between July 2018 and February 2020. Infertile women (n = 181) scheduled for fresh or vitrified–warmed embryo transfer after IVF carried out for any indication were randomized in a 1:1 ratio to receive either HCG (500 IU in 0.1 ml of tissue culture media) or culture media (0.1 ml of tissue culture media) via intrauterine injection 4 min before embryo transfer. In both groups, an intrauterine insemination catheter was used for administering the medication. Primary outcome was live birth, with ongoing pregnancy and clinical pregnancy as secondary outcomes. Analysis was based on intention-to-treat principle. ResultsBaseline and cycle characteristics were comparable between the two groups. In the control group, one woman with a confirmed clinical pregnancy was lost to follow-up. Live birth rates were 24% (22/90) in the HCG group versus 19% (17/90) in the control group (RR 1.29, 95% CI 0.74 to 2.27). Clinical pregnancy and ongoing pregnancy rates were 34% versus 26% (RR 1.31, 95% CI 0.84 to 2.04) and 24% versus 19% (RR 1.29, 95% CI 0.74 to 2.27) in the HCG and the control groups, respectively. ConclusionIntrauterine injection of HCG before embryo transfer did not improve live birth rates in women undergoing IVF. As the study was designed to detect a 20% difference between groups, a smaller, clinically important difference could not be ruled out. Treatment outcomes were lower than expected in the control group.

PGT-A: who and when? Α systematic review and network meta-analysis of RCTs.

Wide controversy is still ongoing regarding efficiency of preimplantation genetic testing for aneuploidy (PGT-A). This systematic review and meta-analysis, aims to identify the patient age group that benefits from PGT-A and the best day to biopsy. A systematic search of the literature was performed on MEDLINE/PubMed, Embase and Cochrane Central Library up to May 2020. Eleven randomized controlled trials employing PGT-A with comprehensive chromosomal screening (CCS) on Day-3 or Day-5 were eligible. PGT-A did not improve live-birth rates (LBR) per patient in the general population (RR:1.11; 95%CI:0.87-1.42; n=1513; I2=75%). However, PGT-A lowered miscarriage rate in the general population (RR:0.45; 95%CI:0.25-0.80; n=912; I2=49%). Interestingly, the cumulative LBR per patient was improved by PGT-A (RR:1.36; 95%CI:1.13-1.64; n=580; I2=12%). When performing an age-subgroup analysis PGT-A improved LBR in women over the age of 35 (RR:1.29; 95%CI:1.05-1.60; n=692; I2=0%), whereas it appeared to be ineffective in younger women (RR:0.92; 95%CI:0.62-1.39; n=666; I2=75%). Regarding optimal timing, only day-5 biopsy practice presented with improved LBR per ET (RR: 1.37; 95% CI: 1.03-1.82; I2=72%). PGT-A did not improve clinical outcomes for the general population, however PGT-A improved live-birth rates strictly when performed on blastocyst stage embryos of women over the 35-year-old mark.

Comparison of pregnancy outcomes using a time-lapse monitoring system for embryo incubation versus a conventional incubator in in vitro fertilization: An age-stratification analysis.

ObjectiveThe aim of this study was to compare the pregnancy outcomes of in vitro fertilization with embryo transfer between embryos cultured in a time-lapse monitoring system (TLS) and those cultured in a conventional incubator (CI).MethodsThe medical records of 250 fertilized embryos from 141 patients undergoing infertility treatment with assisted reproductive technology at a tertiary hospital from June 2018 to May 2020 were reviewed. The study population was divided into TLS and CI groups at a 1 to 1 ratio (125 embryos per group). The primary outcome was the live birth rate. ResultsThe TLS group had a significantly higher clinical pregnancy rate (46.4% vs. 27.2%, p=0.002), implantation rate (27.1% vs. 12.0%, p=0.004), and live birth rate (32.0% vs. 18.4%, p=0.013) than the CI group. Furthermore, subgroup analyses of the clinical pregnancy rate and live birth rate in the different age groups favored the TLS group. However, this difference only reached statistical significance in the live birth rate in women aged over 40 years and the clinical pregnancy rate in women aged 35–40 years (p=0.048 and p=0.031, respectively). The miscarriage rate, cleavage rate, and blastocyst rate were comparable.ConclusionTLS application improved the live birth rate, implantation rate, and clinical pregnancy rate, particularly in the advanced age group in this study, while the other reproductive outcomes were comparable. Large randomized controlled trials are needed to further explore the ramifications of these findings, especially in different age groups.

Effect of Dexamethasone Co-Treatment During Ovarian Stimulation in Women of Different Reproductive Age With Elevated Early Follicular Phase Progesterone Level: a Prospective Longitudinal Study.

The aim of this paper was to estimate the effect of dexamethasone during ovarian stimulation in women of different reproductive age with elevated early follicular phase progesterone level undergoing fresh IVF cycle. This study is a prospective longitudinal analysis of consecutive women who underwent fresh IVF cycles at a single center, between January 2012 to December 2013. Women with early follicular phase progesterone above 0.50 ng/ml, assessed in day 0 or day 5 of stimulation, were included. Study group (n = 113) included women who underwent dexamethasone supplementation until the day of triggering. Women who did not undergo dexamethasone treatment formed the control group (n = 109). We further stratified our study population according to age ranges: (1) ≤ 34 years, (2) between 35 and 39 years, and (3) ≥ 40 years. Significantly lower progesterone levels were observed in study than in control group (0.59 ± 0.21 vs 0.94 ± 0.42, p < 0.001). Such difference is not observed in women above 39 years old. Higher, albeit not significant, live birth rate was detected in the study versus control group, considering the overall population. In women ≤ 34 years old, a significantly higher live birth rate was observed in women who underwent dexametasone treatment than in the control group (67.5% vs 47.2%, p = 0.04). Conversely, live birth rates were similar between groups in women above 34 years old. Our data suggest that dexamethasone helps to modulate progesterone levels during the follicular phase and might improve live birth rate of women below 34 years old.

Impact of thyroid cancer treatment on assisted reproductive technology outcomes in women with infertility

PurposeWe investigated the effect of different surgical procedures and radioactive iodine treatment (RAIT) on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes and evaluated whether possible risk factors, including age, thyroid-stimulating hormone (TSH) levels, and thyroid antibody positivity, were associated with adverse IVF/ICSI outcomes.MethodsThis retrospective study included 76 women with infertility who had received thyroid cancer (TC) treatment among 137,698 infertile women who underwent IVF/ICSI cycles at the Peking University Third Hospital between 2010 and 2019. Clinical pregnancy and live birth rates were assessed.ResultsWe found that the clinical pregnancy and live birth rates in women who underwent partial thyroidectomy were 7- and 6-fold higher, respectively, than those in women who underwent total thyroidectomy. We observed no significant differences in the clinical pregnancy and live birth rates between the RAIT and non-RAIT groups, even after adjusting for age, TSH levels, surgical treatment, and thyroid antibody positivity. Multivariate logistic regression analysis showed that age and TSH levels were not associated with decreased clinical pregnancy and live birth rates. Women with thyroid antibody positivity had significantly lower clinical pregnancy and live birth rates than women without thyroid antibody positivity.ConclusionOur study showed lower clinical pregnancy and live birth rates in women who underwent total thyroidectomy than in women who underwent partial thyroidectomy. Thyroid antibody positivity is an important risk factor for adverse IVF/ICSI outcomes in women who have received TC treatment.

Progestogens for preventing miscarriage: a network meta-analysis.

Progestogens for preventing miscarriage: a network meta-analysis.

AMH Highly Correlates With Cumulative Live Birth Rate in Women with Diminished Ovarian Reserve Independent of Age.

Antimüllerian hormone (AMH) level is strongly associated with ovarian response in assisted reproductive technology (ART) cycles but is a poor predictor of live birth. It is unknown whether AMH is associated with cumulative live birth rates (CLBRs) in women with diminished ovarian reserve (DOR). To examine the association between serum AMH and CLBR among women with DOR undergoing ART. Retrospective analysis of Society for Assisted Reproductive Technology Clinic Outcome Reporting System database 2014-16. A total of 34 540 index retrieval cycles of women with AMH <1 ng/mL. The main outcome measure was cumulative live birth. A total of 34 540 (25.9%) cycles with AMH <1 ng/mL out of 133 442 autologous index retrieval cycles were analyzed. Cycles with preimplantation genetic testing or egg/embryo banking were excluded. Data were stratified according to AMH and, age and regression analysis of AMH and CLBR was performed for each age stratum. Multiple logistic regression demonstrated that AMH is an independent predictor of CLBR (odds ratio [OR] 1.39, 95% CI 1.18-1.64). Serum AMH was strongly associated with number of oocytes retrieved, embryos cryopreserved, mean number of cumulative embryos transferred, and percentage of cycles that had an embryo transfer. Linear regression analysis demonstrated that AMH highly correlated with CLBR in each age stratum. Serum AMH is highly correlated with CLBR in women with DOR independent of age. The addition of AMH to current age-based prognostication counseling particularly in women with DOR would provide more informative and personalized CLBR prediction prior to ART.

Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI)).

Failure of implantation and conception may result from inability of the blastocyst to escape from its outer coat, which is known as the zona pellucida. Artificial disruption of this coat is known as assisted hatching and has been proposed as a method for improving the success of assisted conception by facilitating embryo implantation. To determine effects of assisted hatching (AH) of embryos derived from assisted conception on live birth and multiple pregnancy rates. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register (until May 2020), the Cochrane Central Register of Controlled Trials (CENTRAL; until May 2020), in the Cochrane Library; MEDLINE (1966 to May 2020); and Embase (1980 to May 2020). We also searched trial registers for ongoing and registered trials (http://www.clinicaltrials.gov - a service of the US National Institutes of Health; http://www.who.int/trialsearch/Default.aspx - The World Health Organization International Trials Registry Platform search portal) (May 2020). Two review authors identified and independently screened trials. We included randomised controlled trials (RCTs) of AH (mechanical, chemical, or laser disruption of the zona pellucida before embryo replacement) versus no AH that reported live birth or clinical pregnancy data. We used standard methodological procedures recommended by Cochrane. Two review authors independently performed quality assessments and data extraction. We included 39 RCTs (7249 women). All reported clinical pregnancy data, including 2486 clinical pregnancies. Only 14 studies reported live birth data, with 834 live birth events. The quality of evidence ranged from very low to low. The main limitations were serious risk of bias associated with poor reporting of study methods, inconsistency, imprecision, and publication bias. Five trials are currently ongoing. We are uncertain whether assisted hatching improved live birth rates compared to no assisted hatching (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.92 to 1.29; 14 RCTs, N = 2849; I² = 20%; low-quality evidence). This analysis suggests that if the live birth rate in women not using assisted hatching is about 28%, the rate in those using assisted hatching will be between 27% and 34%. Analysis of multiple pregnancy rates per woman showed that in women who were randomised to AH compared with women randomised to no AH, there may have been a slight increase in multiple pregnancy rates (OR 1.38, 95% CI 1.13 to 1.68; 18 RCTs, N = 4308; I² = 48%; low-quality evidence). This suggests that if the multiple pregnancy rate in women not using assisted hatching is about 9%, the rate in those using assisted hatching will be between 10% and 14%. When all of the included studies (39) are pooled, the clinical pregnancy rate in women who underwent AH may improve slightly in comparison to no AH (OR 1.20, 95% CI 1.09 to 1.33; 39 RCTs, N = 7249; I² = 55%; low-quality evidence). However, when a random-effects model is used due to high heterogeneity, there may be little to no difference in clinical pregnancy rate (P = 0.04). All 14 RCTs that reported live birth rates also reported clinical pregnancy rates, and analysis of these studies illustrates that AH may make little to no difference in clinical pregnancy rates when compared to no AH (OR 1.07, 95% CI 0.92 to 1.25; 14 RCTs, N = 2848; I² = 45%). We are uncertain about whether AH affects miscarriage rates due to the quality of the evidence (OR 1.13, 95% CI 0.82 to 1.56; 17 RCTs, N = 2810; I² = 0%; very low-quality evidence). This update suggests that we are uncertain of the effects of assisted hatching (AH) on live birth rates. AH may lead to increased risk of multiple pregnancy. The risks of complications associated with multiple pregnancy may be increased without evidence to demonstrate an increase in live birth rate, warranting careful consideration of the routine use of AH for couples undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). AH may offer a slightly increased chance of achieving a clinical pregnancy, but data quality was of low grade. We are uncertain about whether AH influences miscarriage rates.

Assisted reproductive technology outcomes in women with a chronic viral disease.

The aim of this study was to evaluate the cumulative live birth rate in women undergoing in-vitro fertilization/intracytoplasmic-sperm-injection (IVF/ICSI) according to the type of chronic viral infection [HIV, hepatitis-B virus (HBV) and hepatitis-C virus (HCV)]. A cohort study. A tertiary-care university hospital. Women with a chronic viral illness HIV, HBV or HCV- were followed until four IVF/ICSI cycles had been completed, until delivery or until discontinuation of the treatment before the completion of four cycles. The primary outcome was the cumulative live birth rate after up to four IVF/ICSI cycles. A total of 235 women were allocated to the HIV-infected group (n = 101), the HBV-infected group (n = 114) and the HCV-infected group (n = 20). The cumulative live birth rate after four cycles was significantly lower in the HIV-infected women than in those with HBV [39.1%, 95% confidence interval (95% CI): 17.7-60.9 versus 52.8%, 95% CI: 41.6-65.5, respectively; P = 0.004]. Regarding the obstetrical outcomes, the mean birth weight was lower in the HIV-infected women than in those with HBV or HCV. Multivariate analysis indicated that the age, the anti-Müllerian hormone and the number of cycles performed were significantly associated with the chances of a live birth. HIV-infected women had lower cumulative live birth rate than women with chronic hepatitis, and this was due to less favourable ovarian reserve parameters. These findings underscore the need to better inform practitioners and patients regarding fertility issues and the importance of early fertility assessment. However, larger studies are necessary to gain more in-depth knowledge of the direct impact of HIV on live birth rates.

Clinical outcomes analysis of infertile women with unicornuate uterus in IVF-ET

PurposeTo explore the pregnancy outcomes, and neonatal status, arising from embryo transfer in unicornual uterine infertility patients. MethodsWe analyzed 2499 cycles of clinical data from in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) from 1st May 2016 to 1st May 2018 in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University, including 109 women with unicornuate uterus (the observation group) and 2390 women with normally shaped uterus (the control group). ResultsThere were no significant differences in embryo implantation rate, clinical pregnancy rate or miscarriage rate (41.88 % VS 42.36 %, P = 0.904; 48.62 % VS 55.94 %, P = 0.133; 11.01 % VS 8.99 %, P = 0.474) between the two groups. The live birth rate in the observation group was lower than that in the control group (35.78 % VS 45.82 %, P = 0.040). The fetal birth weight of the observation group was lower than that of the control group among single-born live births (3009.12 ± 430.59 g VS 3413.40 ± 492.25 g, P = 0.017), but the differences were not observed in the sex ratio at birth, premature birth rate, low birth weight infant (LBW) rate and macrosomia rate (P > 0.05). The fetal birth weight of the observation group was lower than that of the control group among twins live births (2480.00 ± 190.32 g VS 2606.02 ± 471.59 g), but the difference between the groups did not reach statistical significance (P > 0.05)．Logistic regression analysis showed that age, number of embryos transplanted and uterine morphology were independent influencing factors of live birth. ConclusionCompared with women with normal uterus, the live birth rate of women with unicornuate uterus is low, and the birth weight of newborns with single birth is reduced.

A rare case of extensive placenta accreta in twin pregnancy after GnRH agonist treatment of adenomyosis

BackgroundAdenomyosis remains an enigma for the reproductive endocrinologist. It is thought to contribute to sub-fertility, and its only curative treatment is hysterectomy. However, studies have documented increased live birth rates in women with adenomyosis who were treated with gonadotropin releasing hormone agonist (GnRHa).CaseHere we present a case of a 52-year-old woman with adenomyosis who had three failed frozen embryo transfers (FETs) prior to initiating a 6-month trial of GnRHa. GnRHa therapy resulted in a decrease in uterine size from 11.5 × 7.9 × 7.0 cm to 7.8 × 6.2 × 5.9 cm and a decrease in the junctional zone (JZ) thickness from 19 to 9 mm. Subsequently, she underwent her fourth FET, which resulted in live birth of twins. The delivery was complicated by expansive accretas of both placentas requiring cesarean hysterectomy. The final pathology of the placentas demonstrated an extensive lack of decidualized endometrium that was even absent outside the basal plate.ConclusionsGnRHa therapy in patients with adenomyosis may improve implantation rates after FET. Previous molecular studies indicate that genetic variance in the expression of the gonadotropin releasing hormone receptor (GnRHR) could explain the expansive lack of decidualized endometrium after GnRHa therapy. Further investigations are needed to determine if GnRHa therapy contributes to the pathologic process of placenta accreta.

Endometrial preparation with etanercept increased embryo implantation and live birth rates in women suffering from recurrent implantation failure during IVF

Recurrent implantation failure (RIF), defined as ≥3 failed in vitro fertilization (IVF) cycles with the accumulated transfer of at least five embryos, plague many infertile women. The exact cause is unknown; however, evidence supports the immune system, specifically the Tumor Necrosis Factor (TNF) pathway. Etanercept (a TNFα antagonist) has been shown to improve pregnancy rates in women with rheumatoid arthritis or endometriomas; therefore, this study aimed to determine the effectiveness of etanercept for IVF in RIF women. Eighty-three RIF women were recruited from the Ingenes Institute in Mexico City for this single-arm, prospective study. All patients underwent a similar IVF protocol and received etanercept (4 × 25 mg every 72 h) after endometrial preparation, if applicable, and at embryo transfer. IVF endpoints assessed were embryo implantation (h-βCG >10 mg/dL at Day 14), the presence of a gestational sac, live birth, and birth weight. All women reported no side-effects associated with the etanercept treatment. 75.9 % of the cohort achieved embryo implantation, 74.7 % developed gestational sacs, and the ongoing pregnancy/live birth rate was at 62.7 %. However, 56.7 % of the live births were preterm (<37 weeks) and 60.5 % of the births were underweight (<2500 g). When stratified by fresh or frozen cycles or by the ova source (patient versus donor), the results were not significantly different with respect to the implantation rate, formation of gestational sacs, and the live birth rate. Here, we showed that using etanercept during endometrial preparation improves IVF outcomes in RIF women.

Association between endometrial indoleamine 2,3-dioxygenase expression level and pregnancy outcomes in women undergoing first in vitro fertilization treatment

BackgroundIndoleamine 2,3-dioxygenase (IDO) has been reported to play a key role in placental development during normal pregnancy. However, the question of whether endometrial IDO expression affects in vitro fertilization (IVF) pregnancy outcomes remains unclear. The current study was undertaken to investigate whether there was any association between endometrial IDO immunohistochemical staining and IVF treatment outcome.MethodsThis retrospective study was designed to compare pregnancy outcomes among women with different endometrial IDO expression levels under their first IVF treatment. A total of 140 women undergoing their IVF treatment were selected from January 2017 to December 2017. Endometrial samples were collected during mid-luteal phase before IVF cycle. The endometrial IDO expression levels were analyzed by immunohistochemistry, and compared between women who were pregnant or not. A logistic regression analysis was performed to determine the impact of endometrial IDO staining on live birth.ResultsNo significant differences in the endometrial IDO immunohistochemical staining were found between women who had clinical pregnancy and those who failed (P>0.05). However, the endometrial IDO staining was significantly higher among women who had live birth compared with those who had no live birth (P=0.031). Additionally, after adjusting for differences in maternal age, BMI and duration of gonadotropin stimulation, women with higher IDO expression level had an increased live birth rate (adjusted odds ratio [aOR] 2.863, 95% confidence interval [CI] 1.180-6.947).ConclusionsHigher endometrial IDO expression level during mid-luteal phase is associated with an increased live birth rate in women undergoing their first IVF treatment.

Dual Trigger with Gonadotropin-releasing Hormone Agonist and Human Chorionic Gonadotropin Improves Live Birth Rate for Women with Expected Normal Ovarian Response in Gonadotropin Releasing Hormone Antagonist Cycles: Retrospective Study

Objective: To evaluate and compare cycle outcomes following triggering final oocyte maturation with dual trigger of concomitant gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (hCG) administration versus hCG alone for women with expected normal ovarian response that underwent antagonist cycles with intracytoplasmic sperm injection (ICSI). Material and Methods: Women with expected normal ovarian response that underwent GnRH antagonist cycles with ICSI between January 2010 and April 2020 were evaluated in this retrospective cohort study. A total of 2,443 patients were included. Dual trigger was used for oocyte maturation in 637 cycles whereas hCG alone was used for triggering in 1,806 women. Cycles with dual trigger were assigned to study group and cycles with hCG alone are taken as controls. Results: Number of retrieved oocytes (14.08±3.58 vs. 13.15±3.61), number of metaphase 2 oocytes (9.77±3.08 vs. 8.06±3.14), fertilization rate (0.75±0.19 vs. 0.69±0.19), implantation rate (0.43±0.48 vs. 0.35±0.50) and clinical pregnancy rate (49.9% vs. 40.6%) were significantly higher in dual trigger group in comparison to hCG alone group. Higher number of good quality embryos were obtained in dual trigger group (85.7% vs. 76.3%). Live birth rate was significantly increased in dual trigger group in comparison to hCG only trigger group (45.1% vs. 36.7%). Multivariate logistic regression analysis showed dual trigger is a significant factor in predicting live birth deliveries (odds ratio 1.426, 95% confidence interval 1.185-1.716). Conclusion: Dual-triggering appears to improve embryo quality, increase implantation rates, clinical pregnancy rates and live birth rates in women with expected normal ovarian response that underwent GnRH antagonist cycles.

Efficacy of tamoxifen for infertile women with thin endometrium undergoing frozen embryo transfer: a meta-analysis

Background: This study aims to compare the effect of tamoxifen (TMX) vs. other regimens on endometrial thickness (EMT), clinical pregnancy, implantation, miscarriage, and live birth rates in women with thin endometrium undergoing frozen-thawed embryo transfer (FET). Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and CINAHL from inception to November 2020 and cross-checked the references of relevant articles. We included randomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs) to compare TMX with other regimens for endometrium preparation in women with thin endometrium undergoing FET. We pooled weighted mean differences (WMD) with 95% confidence intervals (CI) for continuous variables (EMT) and odds ratios (OR) with 95% CI for binary variables (i.e., clinical pregnancy rate, implantation rate, and first trimester miscarriage rate). Results: An RCT and three controlled trials (2 before-after and 1 retrospective controlled trials) were included in the final review. One study including 154 women and comparing TMX-FET with natural cycle (NC)—FET showed a significant increase in EMT in the TMX cycle (7.87 ± 1.48 mm vs. 6.11 ± 0.98 mm, P &lt; 0.05). Three studies compared the EMT in the TMX and the hormone replacement treatment (HRT) cycles. The pooled analysis showed beneficial effect of TMX on EMT (WMD = 2.06, 95% CI = 1.86–2.27, P &lt; 0.00001). An RCT and a retrospective controlled trial compared TMX and ovulation induction (OI) with Letrozole/human menopause gonadotropin (hMG) for endometrium preparation in women with thin endometrium undergoing FET. No significant difference in clinical pregnancy rates (OR = 1.03, 95% CI = 0.71–1.51), implantation rate (OR = 1.03, 95% CI = 0.76–1.38), or miscarriage rate (OR = 0.91, 95% CI = 0.40–2.06) was observed. No significant difference in EMT was found between TMX and OI with Letrozole/hMG in the included studies. Conclusions: In women with thin endometrium undergoing FET, the use of TMX may result in improved EMT than other regimens. At present, evidence supporting the preferred use of TMX over other regimens as clinical pregnancy rate, implantation rate, or the first trimester miscarriage rate is insufficient.