Association between clinical and IVF laboratory parameters and miscarriage after single euploid embryo transfers

Background The goal of this study was to investigate which factors, excluding embryo aneuploidies, are associated with miscarriage in patients who have undergone a single euploid blastocyst transfer. Methods Retrospective, observational and multicenter study with 2832 patients undergoing preimplantational genetic testing for aneuploidies (PGT-A) due to repeated implantation failure, recurrent pregnancy loss, advanced maternal age or severe male factor were transferred one single euploid embryo. Results One of the main findings was a significant relationship between body mass index (BMI) and miscarriage rates (13.4% in underweight women, 12.1% in normal weight, 14.5% in overweight, and 19.2% in obese women, odds ratio [OD] 1.04; 95% confidence interval [CI], 1.01–1.07 p = 0.006). Endometrial thickness (OD 0.65; 95%, 0.52–0.77 p = 0.04) and type of endometrial preparation (natural cycle or hormone replacement cycle) (OD 0.77; 95%, 0.52–0.77, p = 0.04) were also associated with miscarriage rates. Conclusions BMI was strongly associated to miscarriage rates. We also observed a weaker association with endometrial thickness and with the type of endometrial preparation (natural cycle or hormone replacement cycle). None of the other studied variables (biopsy day, maternal and male age, duration of infertility, cycle length, previous miscarriages, previous live births, previous In Vitro Fertilization (IVF) cycles, endometrial pattern and/or diagnosis) were associated with miscarriage rates.

Retrospective cohort study on preparation regimens for frozen embryo transfer

Objective: To examine the pregnancy outcomes from frozen embryo transfer (FET) cycles using different endometrial preparation regimens, compared to ovulation induction with letrozole (letrozole OI). Design: Retrospective cohort study. Setting: Fertility centre in Sydney, Australia. Patient(s): 6060 frozen embryo transfer cycles. Interventions: Cycles were stratified into one of four ways to achieve endometrial preparation. These were either a natural, letrozole OI, OI with follicle stimulating hormone (FSH OI) or a programmed cycle. Main Outcome Measure(s): The primary outcome was live birth rate per embryo transfer (LBR). Secondary outcomes included clinical pregnancy and biochemical pregnancy rates, adverse events including miscarriage, ectopic pregnancy, stillbirth, neonatal death and multiple births. Ovarian stimulation parameters were also analysed including time taken to reach the luteal phase and the number of blood or urine tests required for monitoring of the cycle. Results: The LBR following letrozole OI cycles was higher when compared to natural cycles (OR 1.27 (1.07 – 1.49)) and programmed cycles (OR 2.36 (1.67 – 3.34)). There was no significant difference between letrozole OI and FSH OI LBR (OR 0.99 (0.76 – 1.28)). An improved LBR with letrozole OI compared to natural cycles was maintained when only women with a normal length cycle were considered (OR 1.44 (1.10 – 1.89)). There was a significant reduction in miscarriage rates when letrozole OI was compared to programmed cycles (OR 0.46 (0.26 – 0.83)). Conclusion(s): The use of letrozole OI for endometrial preparation in an FET cycle may be associated with higher LBR and lower miscarriage rate, compared to using a programmed cycle.

Is Human Chorionic Gonadotropin Trigger Beneficial for Natural Cycle Frozen-Thawed Embryo Transfer?

Objective: The aim of this study is to investigate, in ovulatory patients, whether there is a difference in reproductive outcomes following frozen-thawed embryo transfer (FET) in natural cycles (NC) compared to modified natural cycles (mNC).Methods: This retrospective cohort study, performed at the public tertiary fertility clinic, involved all infertile patients undergoing endometrial preparation prior to FET in NC and mNC from January, 2017 to November, 2020. One thousand hundred and sixty-two patients were divided into two groups: mNC group (n = 248) had FET in a NC after ovulation triggering with human chorionic gonadotropin (hCG); NC group (n = 914) had FET in a NC after spontaneous ovulation were observed. The primary outcome was live birth rate. All pregnancy outcomes were analyzed by propensity score matching (PSM) and multivariable logistic regression analyses.Results: The NC group showed a higher live birth rate [344/914 (37.6%) vs. 68/248 (27.4%), P = 0.003; 87/240 (36.3%) vs. 66/240 (27.5%), P = 0.040] than the mNC group before and after PSM analysis. Multivariable analysis also showed mNC to be associated with a decreased likelihood of live birth compared with NC [odds ratio (OR) 95% confidence interval (CI) 0.71 (0.51–0.98), P = 0.039].Conclusion: For women with regular menstrual cycles, NC-FET may have a higher chance of live birth than that in the mNC-FET cycles. As a consequence, it's critical to avoid hCG triggering as much as possible when FETs utilize a natural cycle strategy for endometrial preparation. Nevertheless, further more well-designed randomized clinical trials are still needed to determine this finding.

Effect of different endometrial preparation protocols on pregnancy outcomes in frozen- embryo transfer cycles: a retrospective cohort study

Background Owing to the crucial role the endometrium plays in embryo implantation, the four main endometrial preparation protocols have become important factors in the study of pregnancy outcomes in the FET cycles. Previous studies have shown that the best of these four protocols remains controversial for women undergoing FET. Methods A total of 10333 FET cycles from January 2018 to December 2018 were analyzed in this study. They were categorized into four groups according to endometrial preparation regimen: natural cycles (Group NC,n = 815), hormone replacement therapy cycles (Group HRT ,n = 6434), GnRH agonist artificial cycles (Group GAC,n = 1392) and ovarian stimulation cycles (Group OC, n = 1692). All patients were followed up for at least 1 year. Pregnancy outcomes were compared between the four groups and multiple logistic regression models were used to adjust for the effects of confounding factors. Results The ectopic pregnancy rate (P = 0.627) and miscarriage rate (P = 0.164) were not statistically significant between the four groups. Moreover, biochemical pregnancy rate, clinical pregnancy rate and live birth rate in the NC group were not statistically significant compared to the other three groups. After adjusting for covariates, multiple logistic regression analysis showed no statistical significance in pregnancy outcomes in the HRT, GAC and OC groups compared to the NC group.And the adjusted OR for live births was 0.988 (95 % CI0.847-1.152) for the HRT group, 0.955 (95 % CI0.795-1.146) for the GAC group,0.898 (95 % CI0.754-1.070) for the OC group. Conclusions Our study showed that natural cycles have similar pregnancy outcomes in terms of clinical pregnancy and live birth to the other three endometrial preparation options. As it has other advantages, the natural cycle protocol can therefore be the recommended option for endometrial preparation in the FET population.

Hormone replacement therapy may increase the risk of early miscarriage during frozen embryo transfer cycles in patients with a history of cesarean section: a retrospective cohort study

Objective: To investigate the efficacies of three cycle regimens in women receiving FET with a history of CS: natural cycle (NC) treatment, hormone replacement therapy (HRT) and treatment with gonadotropin-releasing hormone agonist (GnRH-a) + HRT). Design: Retrospective cohort study. Setting: University-affiliated center. Population: Patients (N = 6,159) with a history of CS who fulfilled the inclusion criteria were enrolled in the study from January 2014 to December 2019. Methods: Reproductive outcomes of patients in the NC (n = 4,306) versus HRT (n = 1,007) versus GnRH-a + HRT groups (n = 846) were compared. Main Outcome Measure: The main outcome measure was the live birth rate per embryo transfer (ET). Results: The unadjusted odds of the miscarriage rate of singleton pregnancies were also significantly higher in the HRT-group compared with the NC-group (25.5% versus 20.4%, respectively). After adjusting for possible confounding factors, the early miscarriage rate and the miscarriage rate of singleton pregnancies remained significantly higher in the HRT-group than the NC-group. The clinical pregnancy rates in the NC-, HRT- and GnRH-a + HRT-groups of women with a history of CS was 48.8%, 48% and 47.1%, respectively, and the live birth rates were 37%, 34.1% and 35.7%, respectively. Conclusion(s): In women undergoing FET with a history of CS, HRT for endometrial preparation was associated with a higher early miscarriage rate, albeit after statistical adjustment for confounding factors. Funding: The National Science Foundation of China (81501328). Key Words: Caesarean section, endometrial preparation, frozen embryo transfer, miscarriage

A Novel Promising Endometrial Preparation Protocol for Frozen-Thawed Embryo Transfer: A Randomized Controlled Trial

BackgroundIn recent years frozen-thawed embryo transfer (FET) has played an increasingly important role in ART, but there is limited consensus on the most effective method of endometrial preparation (EP) for FET. Inspired by significantly higher implantation rate and clinical pregnancy rate of the depot GnRH-a protocol, we proposed a novel EP protocol named down-regulation ovulation-induction (DROI) aimed to improve pregnancy outcomes of FET.MethodsThis was a single-center, randomized controlled pilot trial. A total of 307 patients with freeze-all strategy scheduled for first FET were enrolled in the study. A total 261 embryos were transferred in DROI-FET group including 156 patients and 266 embryos were transferred in mNC-FET group including 151 patients. Reproductive outcomes were compared between the two groups.ResultsThe basic characteristics of patients, and the average number, quality and stage of embryos transferred were comparable between the two groups. Our primary outcome, implantation rate(IR) in DROI-FET group, was significantly higher than that of the mNC-FET group (54.41% versus 35.71%, P<0.01). The clinical pregnancy rate (CPR) and ongoing pregnancy rate (OPR) in DROI-FET group was also higher than that in mNC-FET group (69.87% versus 50.33%, P<0.01; 64.10% versus 42.38%, P<0.01).Conclusion(s)Compared to existing endometrial preparation methods, the DROI protocol might be the more efficient and promising protocol.