Effect of hCG day’s estradiol levels on pregnancy outcomes following GnRH antagonist protocol: a retrospective study of 3192 fresh embryo transfer cycles

To evaluate the impact of estradiol levels of hCG day (E2-hCG) on pregnancy outcomes in fresh embryo transfer (ET) cycles following antagonist protocol. 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. 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. 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.