Impact of relative estradiol changes during ovarian stimulation on blastocyst formation and live birth in assisted reproductive technology

This study aimed to evaluate the predictive value of relative change in E2 levels during controlled ovarian stimulation (COS) on embryo development and pregnancy outcomes in assisted reproductive technology (ART). We retrospectively analyzed 9,376 patients who underwent their first fresh ART cycle from January 1, 2020, to December 31, 2022. Patients were classified into four groups based on relative change in E2 levels: low response group, moderate response group, moderate-high response group, and high response group. The primary outcomes were blastocyst formation rate, clinical pregnancy rate, and live birth rate, while secondary outcomes included miscarriage rate and ectopic pregnancy rate. Most cycles (96.5%) demonstrated an increase in E2 levels during COS. The blastocyst formation rate significantly increased across the groups (low response group: 0.13, moderate response group: 0.21, moderate-high response group: 0.28, high response group: 0.34; P < 0.001). Multivariable logistic regression showed significantly higher blastocyst formation rates in the moderate response group (adjusted OR = 2.012, 95% CI: 1.687-2.399), moderate-high response group (adjusted OR = 4.613, 95% CI: 3.853-5.523), and high response group (adjusted OR = 11.295, 95% CI: 9.192-13.880) compared to the low response group. Both clinical pregnancy rate and live birth rate were significantly higher in the moderate-high response group and high response group compared to the low response group (clinical pregnancy rate: 54.5% and 61.5% vs. 35.5%, adjusted RR = 1.21 [95% CI: 1.03-1.42] and 1.27 [95% CI: 1.08-1.51]; live birth rate: 44.9% and 52.0% vs. 25.7%, adjusted RR = 1.27 [95% CI: 1.06-1.52] and 1.35 [95% CI: 1.11-1.64]). However, no significant differences were observed in either clinical pregnancy rate or live birth rate between the moderate response group and low response group (clinical pregnancy rate: adjusted RR = 1.07 [95% CI: 0.91-1.25]; live birth rate: adjusted RR = 1.11 [95% CI: 0.92-1.33]). No significant differences in miscarriage rate or ectopic pregnancy rate were observed across the groups. Higher E2 responses were associated with improved embryo development and better pregnancy outcomes.