Abstract
BACKGROUND: Elevated estradiol (E(2)) levels are an inevitable outcome of the controlled ovulation hyperstimulation. However, the effect of this change on pregnancy is still uncertain. Our study aimed to analyze the impact of increased serum E(2) at the day of human chorionic gonadotropin (hCG) administration on the clinical outcomes of women with fresh embryo transfer (ET) cycles. METHODS: This study included 3,009 fresh ET cycles from October 2015 to September 2021. Based on the stage of embryos transferred, these cycles were categorized into the cleavage group and blastocyst group. Both groups were then divided into four sets according to E(2) levels when hCG was administered: set 1 (E(2) ≤ 2,000 pg/ml), set 2 (E(2) = 2,001-3,000 pg/ml), set 3 (E(2) = 3,001-4,000 pg/ml), and set 4 (E(2) > 4,000 pg/ml). The primary outcome was the clinical pregnancy rate (CPR). Binary logistics regression analysis was established to explore the association between CPR and E2 levels. Specifically, the threshold effect of serum E2 on CPR was revealed using the two-piecewise linear regression analyses. RESULTS: The multivariate regression model in the cleavage group showed that patients' CPR in set 4 was 1.59 times higher than those in reference set 1, but the statistical difference was insignificant (P = 0.294). As for the blastocyst group, patients in set 4 had a lower CPR with adjusted ORs of 0.43 (P = 0.039) compared to patients in set 1. The inflection point for the blastocyst group was 39.7 pg/dl according to the results of the two-piecewise linear regression model. When E(2) levels were over the point, the CPR decreased by 17% with every 1 pg/dl increases in serum E(2) (adjusted OR = 0.83, 95% CI [0.72-0.96], P = 0.012). CONCLUSIONS: Elevated E(2) levels (>39.7 pg/dl) on hCG trigger day were associated with decreased CPR in patients with fresh blastocyst ET. However, it had no similar effect on the CPR of patients with fresh cleavage-stage ET.