Project description:PurposeTo investigate whether personalized embryo transfer (pET) protocol guided by an endometrial receptivity array (ERA) can improve clinical outcomes of assisted reproduction.MethodsWe searched PubMed, Embase, Web of Science, and the Cochrane library for studies in which analytical comparisons of outcomes of pET and standard embryo transfer (sET) groups were undertaken. The references to the included studies were also manually searched. The primary outcome was clinical pregnancy rate (CPR), and the secondary outcomes were live birth rate (LBR), human chorionic gonadotropin (HCG) positivity, biochemical pregnancy rate (BPR), miscarriage rate (MR), implantation rate (IR), and ongoing pregnancy rate (OPR).ResultsTen studies were included in the meta-analysis, including one randomized controlled trial (RCT) and nine cohort studies. We observed no significant difference in the primary outcome of CPR between the pET and sET groups in unselected patients (RR = 1.07; 95% confidence interval [CI], 0.87-1.30; P = 0.53; I2 = 89%). In terms of secondary outcomes, we likewise noted no significant differences between the groups. Further subgroup analyses indicated that the pET protocol not only significantly reduced the MR for poor-prognosis patients, but it also reduced the CPR in donor cycles, elevated the BPR for good-prognosis patients, non-preimplantation genetic testing (PGT), and programmed cycles, and decreased the proportion of women showing HCG positivity in non-PGT cycles.ConclusionsThis meta-analysis revealed that ERA appears to possess limited guidance in embryo transfer. More high-quality RCTs are therefore needed to investigate the clinical validity and feasibility of ERA in the future.
Project description:BackgroundAbnormal BMI is associated with discouraging IVF outcomes in fresh autologous or oocyte donor cycles, whether or not such a relation also holds true for women undergoing frozen-thawed embryo transfer (FET) remains unknown. In addition, it remains unclear the detrimental effect of abnormal BMI on IVF outcomes occurs at the level of ovary or endometrium.MethodsA retrospective study involved 22,043 first FET cycles of all women who had undergone a freeze-all policy during the period from January 2010 to June 2017. To control for the embryo factor, our analysis was restricted to women with high-quality embryo transfer. The main outcome measure was live birth rate per embryo transfer. The secondary endpoints included rates of implantation, clinical pregnancy, multiple pregnancy, and pregnancy loss. Multivariate logistic regression analysis was performed to detect the independent effect of BMI on live birth rate after adjusting for important confounding variables.ResultsIn the crude analysis, reproductive outcomes were similar between underweight women and normal-weight controls whereas all parameter outcomes were significantly worse in patients with obesity. After adjustment for a number of confounding factors, underweight women had a marginally significant decrease in rates of implantation (adjusted odds ratio (aOR) 0.91; 95% CI 0.85-0.96), clinical pregnancy (aOR 0.91; 95% CI 0.83-0.99), and live birth (aOR 0.91; 95% CI 0.83-0.99) as compared to the women with normal weight. Obesity was significantly associated with decreased implantation (aOR 0.80; 95% CI 0.73-0.87), clinical pregnancy (aOR 0.81; 95% CI 0.71-0.91), and live birth rates (aOR 0.70; 95% CI 0.62-0.80). Moreover, the pregnancy loss rate, both in the first (aOR 1.46; 95% CI 1.15-1.87) and in the second trimester (aOR 2.76; 95% CI 1.67-4.58), was significantly higher in the obesity group than that in the reference group.ConclusionsAmong women undergoing first FET with high-quality embryo transfer, low BMI has limited impact on pregnancy and live birth rates. On the contrary, obesity was associated with worse IVF outcomes. Our findings further highlighted that endometrial receptivity played an important role in the poor reproductive outcomes of women with abnormal weight status.
Project description:INTRODUCTION:Frozen-thawed embryo transfer (FET) has become an increasingly important part of in-vitro fertilisation (IVF) treatment. Currently, there is still no good scientific evidence to support when to perform FET following a stimulated IVF cycle. Since all published studies are retrospective and the findings are contradictory, a randomised controlled study is needed to provide Level 1 evidence to guide the clinical practice. METHODS/ANALYSIS:This is a randomised controlled trial. A total of 724 women undergoing the first FET following ovarian stimulation in IVF will be enrolled and randomised according to a computer-generated randomisation list to either (1) the immediate group in which FET will be performed in the first cycle following the stimulated IVF cycle or (2) the delayed group in which FET will be performed at least in the second cycle following the stimulated IVF cycle. The primary outcome is the ongoing pregnancy defined as a viable pregnancy beyond 12 weeks' gestation. ETHICS AND DISSEMINATION:Ethical approval has been granted by the Ethics Committee of Assisted Reproductive Medicine in Shanghai JiAi Genetics & IVF Institute (JIAI E2017-12) and from the Institutional Review Board of the University of Hong Kong Hospital Authority Hong Kong West Cluster (UW 17-371). A written informed consent will be obtained from each woman before any study procedure is performed, according to good clinical practice. The results of this trial will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER:NCT03201783;Pre-results.
Project description:BackgroundThe optimal time at which to perform a frozen-thawed embryo transfer (FET) following a failed in-vitro fertilization-embryo transfer (IVF-ET) attempt remains elusive to most reproductive experts. Physicians often delay the introduction of FET due to concerns related to potential residual effects of ovarian hyperstimulation which may interfere with the regular menstrual cycle. Moreover, given that most of the published studies on the topic are retrospective and have inconsistent findings, it is crucial to develop evidence-based randomized control guides for clinical practice. Therefore, this well-designed randomized controlled trial (RCT) was conducted to determine whether it is necessary to delay FET for at least one menstrual cycle after the failure of fresh embryo transfer.MethodsInfertile women eligible for IVF-ET were invited to participate in this multicenter, randomized, non-inferiority, parallel-group, unblinded, controlled trial at the academic fertility centers of four public hospitals in Chinese Mainland. Infertile women scheduled to receive their first FET cycle after a failed IVF-ET attempt were randomly assigned to either (a) the immediate FET group in which FET was performed in the first menstrual cycle following the failed IVF-ET cycle (n = 366) or (b) the delayed FET group in which FET was performed in the second or subsequent menstrual cycle following the failed IVF-ET cycle (n = 366). All FET cycles were performed during hormone replacement cycles for endometrial preparation. The primary outcome was the ongoing pregnancy, defined as a detectable fetal heart beat beyond twelve weeks of gestation. Secondary outcomes were other pregnancy-related outcomes, maternal and neonatal complications. Analysis was performed by both intention-to-treat and per-protocol principles.ResultsA total of 646 FETs were completed. The frequency of moderate to severe depression and high stress level prior to FET in delayed FET group were significantly higher than that in immediate FET group (10.6% vs 6.1%, p = 0.039; 30.3% vs 22.4%, p = 0.022, respectively). Immediate FET resulted in a higher frequency of clinical pregnancy than did delayed FET (41.7% vs 34.1%), for a relative risk (RR) of 1.23 (95% confidence interval [CI], 1.00-1.50; p = 0.045). Women who underwent immediate FET also had a lower frequency of biochemical pregnancy loss (11.7% vs. 30.6%), with a RR of 0.28 (95% CI 0.23-0.63, p < 0.001), and a higher frequency of embryo implantation (25.2% vs. 20.2%), with a RR of 1.25 (95% CI 1.01-1.53; p = 0.038). Although the ongoing pregnancy and live birth rates did not differ significantly between the immediate FET and delayed FET groups (37.1% vs 30.3%, RR 1.22, 95% CI 0.99-1.52, p = 0.067; 36.5% vs 30.0%, RR 1.22, 95% CI 0.98-1.52, p = 0.079, respectively), a multivariate logistic regression analysis adjusted for potential confounders such as depression and stress levels revealed that the immediate FET group had a significantly higher ongoing pregnancy and live birth rates than the delayed FET group (odds ratio 0.68, 95% CI 0.47-0.99, p = 0.041; odds ratio 0.67, 95% CI 0.46-0.96, p = 0.031). The risks of maternal and neonatal complications were comparable between the two groups.ConclusionsIn women with a previous failed IVF-ET attempt, immediate FET resulted in higher ongoing pregnancy and live birth rates than delayed FET. These findings warrant caution in the indiscriminate application of a delayed FET strategy when apparent risk of high stress level is perceived.Trial registrationChiCTR2000033313 .
Project description:BackgroundThe E-Freeze trial is a multi-centre randomised controlled trial of fresh versus frozen embryo transfer for women undergoing in vitro fertilisation. This paper describes the statistical analysis plan for the E-Freeze trial.Methods and designE-Freeze is a two-arm parallel-group, multi-centre, individually randomised controlled trial to determine if a policy of freezing embryos, followed by thawed frozen embryo transfer, results in a higher healthy baby rate when compared with the current policy of transferring fresh embryos. Couples undergoing their first, second or third cycle of in vitro fertilisation at fertility centres in the UK were randomised to either fresh or frozen embryo transfer. The primary outcome is a healthy baby, defined as a live singleton baby born at term with an appropriate weight for gestation. This paper describes the statistical analysis plan for the trial, including the analysis principles, definitions of outcomes, methods for primary analysis, pre-specified subgroup analysis and sensitivity analysis. This plan was finalised prior to completion of recruitment to the trial.Trial registrationISRCTN registry: ISRCTN61225414 . Registered on 29 December 2015.
Project description:PURPOSE:This study aimed to clarify the risks of adverse pregnancy outcomes in patients and their offspring after frozen embryo transfer (FET) during an artificial cycle (AC). METHODS:We conducted a retrospective cohort study that included all FET cycles and subsequent deliveries in a single centre between August 2013 and March 2016. Pregnancy, obstetric and neonatal outcomes were compared among patients treated during an AC or a natural cycle with luteal phase support (NC-LPS). Multivariate logistic regression was performed to evaluate the relationship between endometrial preparation schemes and pregnancy, obstetric and neonatal outcomes. RESULTS:AC-FET was not a significant risk factor for clinical pregnancy rate, multiple birth rate or miscarriage rate after adjusting for potential confounders. However, AC-FET was a significant risk factor for ectopic pregnancy rate (adjusted odds ratio (AOR), 1.738; 95% confidence interval (CI), 1.086-2.781) and live birth rate (AOR, 0.709; 95% CI, 0.626-0.802). Regarding obstetric outcomes, AC-FET was found to be associated with an increased risk for hypertension disorder (AOR, 1.780; 95% CI, 1.262-2.510) and caesarean section (AOR, 1.507; 95% CI, 1.195-1.900). In multiples, birth weight (2550 g (2150-2900 g) in AC-FET vs. 2600 g (2350-2900 g) in NC-LPS; P = 0.023), gestational age (36.6 weeks (35.3-37.6 weeks) vs. 37.1 weeks (36.1-37.9 weeks); P < 0.001), and z-score (- 0.5 (- 1.1, - 0.0) vs. - 0.4 (- 1.0, 0.2); P = 0.009) were higher in the NC-LPS group than in the AC-FET group, although there were no differences in these variables among singletons. CONCLUSION:Compared with NC-LPS, AC-FET seemed to have a negative effect on obstetric outcomes.