Non-Linear Association Between Serum Estradiol Decline and Clinical Outcomes in IVF/ICSI Cycles: A Retrospective Cohort Study.

BACKGROUND: The impact of changes in estradiol (E2) levels prior to human chorionic gonadotropin (hCG) administration during controlled ovarian hyperstimulation (COH) on pregnancy and live birth outcomes remains poorly understood. OBJECTIVE: To study association between serum estradiol decline and clinical outcomes in IVF/ICSI cycles. MATERIALS AND METHODS: In this retrospective cohort study, we analyzed clinical data from 1113 patients at our reproductive center between January 2016 and December 2017. Peripheral blood samples were collected to measure baseline follicle-stimulating hormone (FSH), luteinizing hormone (LH), and E2, as well as those hormone levels on both stimulation initiation day and hCG administration day. E2 decline was defined as any transient decrease in serum E2 between consecutive measurements (typically 2-3 days apart) during COH, calculated as a percentage change. RESULTS: Participants were stratified into pregnancy (n = 744) and non-pregnancy (n = 369) groups based on clinical outcomes, and further categorized into live birth (n = 677) and non-live birth (n = 436) groups. The mean age of participants was 31.07 ± 4.11 years, with a median infertility duration of 3.00 years (interquartile range: 2.00-5.00). The mean (standard deviation, SD) numbers of previous pregnancies and miscarriages were 0.83 (1.15) and 0.51 (0.89), respectively. Baseline E2, FSH, and LH levels were 171.30 (402.11) pg/mL, 6.90 (1.04) IU/L, and 5.25 (4.04) IU/L, respectively. The mean (SD) change in serum E2 levels on hCG administration day was 2.15 (3.07). Multivariate analysis revealed that a decline in E2 levels was an independently associated with reduced chances of achieving clinical pregnancy (OR = 0.622, 95% CI: 0.424~0.910, P = 0.015). Furthermore, sensitivity analysis also suggested 75-100% decrease in E2 levels was significantly associated with adverse live birth (OR = 0.158, 95% CI: 0.050~0.494, P = 0.001). Our analysis also revealed significant non-linear dose-response association between decreasing E2 levels and adverse pregnancy outcomes by restricted cubic splines. CONCLUSION: A decrease in serum E2 levels before hCG administration was negatively associated with clinical pregnancy and live birth rates in IVF/ICSI cycles, and decreased serum E2 levels exhibited a dose-response relationship with both pregnancy and live birth outcomes.