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Association between serum estradiol levels on the hCG trigger day and euploid blastocyst rate in preimplantation genetic testing cycles: a retrospective cohort study

Year: 2026

Type: article

Abstract: Background: While serum estradiol (E2) predicts ovarian response and endometrial receptivity, its role in embryonic development remains unclear. This study assessed the association between E2 levels on the day of human chorionic gonadotropin (hCG) trigger and the euploid blastocyst rate (EBR) in preimplantation genetic testing (PGT) cycles. Methods: This retrospective study included 3,082 couples who underwent PGT between 2017 and 2022, comprising 18,036 oocytes and 5,009 blastocysts screened using next-generation sequencing. Oocytes were stratified into tertiles based on serum E2 levels on the hCG trigger day: Group 1 (<3149 pg/mL), Group 2 (3149-4725.66 pg/mL), and Group 3 (≥4725.67 pg/mL). Associations between serum E2 levels and both blastocyst formation rate (BFR) and EBR were assessed using univariate stratified analyses and multivariable generalized estimating equation (GEE) models (crude, Model I, Model II) accounting for patient-level clustering. Restricted cubic spline (RCS) analysis with three knots, collinearity diagnostics (variance inflation factor, VIF), and formal E2 × total gonadotropin (Gn) dose interaction tests were additionally performed. Results: Univariate stratified analyses showed subgroup-specific patterns: higher E2 generally correlated with lower blastocyst formation rate (BFR) yet higher EBR. In fully adjusted GEE Model II, E2 was not associated with BFR (Group3 vs Group1: aOR 1.050, 95%CI 0.910-1.212, P = 0.502; P-trend=0.653), while high E2 was associated with higher EBR (aOR 1.295, 95%CI 1.028-1.631, P = 0.028; P-trend=0.047). RCS revealed no significant overall E2-BFR (P-overall=0.107; P-nonlinearity=0.055) or E2-EBR associations (P-overall=0.100; P-nonlinearity=0.119), although the EBR curve showed an upward high-E2 trend consistent with tertile results. No multicollinearity was detected (all VIF <6, range 1.137-5.399), and no significant E2-Gn interactions existed (all P>0.05). Sensitivity analysis excluding oocyte number yielded consistent EBR estimates (aOR 1.232, 95%CI 1.006-1.508, P = 0.044). Conclusion: In PGT cycles, elevated hCG-trigger-day E2 was not associated with BFR but was modestly associated with higher EBR. These observational findings require prospective validation and should not be interpreted as evidence of a causal or protective effect of E2 on embryonic chromosomal integrity.

Source: Frontiers in Endocrinology

DOI: 10.3389/fendo.2026.1935196