Estradiol on Trigger Day was Irrelevant to Live Birth Rates of Fresh Cycles but Positively Associated with Cumulative Live Birth Rates: A Multicenter Retrospective Study
Abstract Background: Serum estradiol (E2) level is supraphysiological during controlled ovarian stimulation (COS). However, the impacts of high levels of E2 on the development of preimplantation embryos, live birth rates in fresh and frozen-thawed embryo transfer (FET) cycles, and cumulative live birth rates (CLBR) remain debatable.Methods: This retrospective study included 93,959 oocyte retrieval cycles of 73,794 patients performing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) from 2013 to 2018 in five reproductive centers in China. Patients were categorized according to E2 level on trigger day: <1,000, 1,000-2,000, 2,000-3,000, 3,000-4,000, 4,000-5,000 and ≥5,000 pg/ml. Developments of embryos were evaluated by specific stage embryo rates, fertilization rates and cleavage rates. Generalized linear mixed models and multilevel models were adopted. Univariate and multivariate analysis were performed to adjust for the confounding factors. Results: Compared with the <1,000 pg/ml group, the aMD (95% CI) for the specific stage embryo rates in groups 2-6 were -0.10 (-0.11, -0.10), -0.13 (-0.14, -0.12), -0.14 (-0.15, -0.13), -0.15 (-0.16, -0.15) and -0.14 (-0.15, -0.13), respectively. The adjusted odds ratio (aOR) and 95% confidence interval (CI) of live birth of fresh cycles in the stratified higher E2 groups was 1.03 (0.91, 1.16), 1.06 (0.93, 1.21), 1.03 (0.89, 1.19), 1.02 (0.87, 1.20) and 0.88 (0.75, 1.03), while the aOR (95% CI) for live birth in FET cycles was 1.01 (0.90, 1.14), 1.08 (0.95, 1.22), 1.10 (0.96, 1.27), 1.12 (0.97, 1.29), and 1.20 (1.05, 1.37), respectively. When E2 <14,000 pg/ml, E2 was positively correlated with CLBR, otherwise, E2 was irrelevant to CLBR. Conclusion: High levels of E2 is associated with decreased rates of properly developed embryos. When E2 level is above 5,000 pg/ml on trigger day, the E2 level is associated with increased live birth rates in FET cycles. While the live birth rates in fresh cycles is not impacted. CLBR is positively associated with E2 on trigger day when E2 is <14,000 pg/ml.
