Purpose: To investigate whether the magnitude of estradiol (E2) decline from hCG trigger day to post-retrieval day 2 impacts clinical outcomes of fresh embryo transfers in high responders undergoing GnRH antagonist ovarian stimulation cycles.
Methods: This retrospective cohort study analyzed 1859 fresh embryo transfer cycles (high responders, January 2018-December 2021) under antagonist protocols. Final oocyte maturation was triggered with GnRHa, hCG, or dual trigger. Serum E2 was measured on trigger day and 48 h post-retrieval. Patients were stratified by E2 ratio (post-retrieval day 2/hCG day): low (≤ 0.2, n = 202) vs. high (> 0.2, n = 1657). Multivariate logistic regression compared clinical pregnancy rates (CPR) and live birth rates (LBR) between groups. Given the substantial sample size imbalance between groups (1:8 ratio), we implemented bootstrap adjustment with 1000 replicates to address potential estimation bias.
Results: Mean patient age was 31.0 years; 82.0% involved day 3 transfers. Overall CPR and LBR were 56.2% and 45.2%, respectively. The low E2 ratio group (≤ 0.2) showed significantly reduced CPR (46.5% vs. 57.3%; aOR = 1.38, 95% BCa CI = (0.04, 0.67), bootstrap "p" = 0.031) and LBR (35.6% vs. 46.3%; aOR = 1.42, 95% BCa CI = (0.04, 0.64), bootstrap "p" = 0.028) compared to the high-ratio group (> 0.2).
Conclusion: A post-retrieval E2 ratio ≤ 0.2 predicts significantly decreased CPR and LBR in fresh embryo transfers under GnRH antagonist protocols. This ratio may serve as a clinical criterion for outcome prediction.
Keywords: Antagonist protocol; Estrogen; Fresh embryo transfer; IVF/ICSI; Pregnancy outcomes.
© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.