Abstract
BACKGROUND: To evaluate the impact of estradiol levels of hCG day (E2-hCG) on pregnancy outcomes in fresh embryo transfer (ET) cycles following antagonist protocol. METHODS: The retrospective study includes 3192 fresh ET cycles under antagonist protocol at Xiangya Hospital from October 2020 to July 2024. We evaluated the association of E2-hCG and pregnancy outcomes by generalized additive models adjusted for confounders. The turning point of E2-hCG is detected by segmentation regression. Pregnancy outcomes were compared across different E2-hCG ranges. RESULTS: We detect a curved inverted U-shaped relationship between E2-hCG level and pregnancy outcomes. The pregnancy rates increased with the increase of E2-hCG levels, reaching the highest pregnancy rate at about 2400 pg/ml (turning point), and then the pregnancy rate decreased with the increase of E2-hCG levels. Based on the smooth curves, we divided the E2-hCG levels into three groups include E2-hCG < 1500 pg/ml, 1500 ≤ E2-hCG ≤ 4000 pg/mL, and E2-hCG > 4000 pg/ml. 1500 ≤ E2-hCG ≤ 4000 pg/mL increased 30% BPR (OR 1.30, 95%CI 1.07 ~ 1.56, p-value = 0.007) and 28% CPR (OR 1.28, 95%CI 1.07 ~ 1.54, p-value = 0.008) compared to E2-hCG < 1500 pg/mL. However, E2-hCG > 4000 pg/mL did not significantly increase BPR (OR 1.13, 95%CI 0.80 ~ 1.60, p-value = 0.50) and CPR (OR 1.07, 95%CI 0.76 ~ 1.50, p-value = 0.71) compared to E2-hCG < 1500 pg/mL. CONCLUSIONS: For fresh ET under antagonist protocol, hCG day’s estradiol levels have an inverted U-shaped effect on pregnancy outcomes, with the highest pregnancy rate at a level of about 2400 pg/ml. We can get an ideal pregnancy rate when E2-hCG ranges from 1500 to 4000 pg/ml compared to E2-hCG < 1500 pg/ml or E2-hCG > 4000 pg/ml. Pregnancy outcomes are not significantly different between E2-hCG < 1500 pg/ml and E2-hCG > 4000 pg/ml groups. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12884-025-07929-x.