Dual Impact of Estradiol Fluctuations in the Final Three Days on IVF/ICSI Outcomes: A Retrospective Cohort Analysis

How do dynamic changes in serum estradiol (E2) and progesterone (P) concentrations during controlled ovarian hyperstimulation (COS) affect oocyte retrieval and embryo outcomes? What clinical factors drive estradiol elevation in the final three days of stimulation?.

This single-center retrospective study included 486 first-cycle patients with normal ovarian function undergoing a long protocol in early follicular phase, with fresh embryo transfer. Serum E2 and P concentrations were measured at four time points: the gonadotropin initiation day, four days post-initiation, two days before the hCG trigger, and the day of hCG administration, with different stages, grouped patients by median hormone changes into high-growth and low-growth. Primary and secondary endpoints were ovarian stimulation and pregnancy outcomes, respectively. logistic regressions identified factors associated with estradiol elevation during the last three days of stimulation.

High-growth groups had higher oocyte retrieval rates but lower transferable embryo rates. Multivariate analysis identified higher AFCs and mid-cycle estradiol increase as a protective factor (p<0.01). Conversely, higher BMI, higher initial Gn dose (>300 IU) and prolonged stimulation duration were linked to poorer outcomes (p<0.01).

Dynamic E2/P monitoring provides actionable insights for COS management. Elevated E2 in the late stimulation phase, driven by AFC and mid-cycle hormonal surge, correlates with oocyte yield but requires caution due to reduced embryo utilization. Clinically, excessive gonadotropin dosing and prolonged stimulation should be avoided to optimize outcomes. These findings support personalized hormone adjustment protocols to balance efficacy and safety in ART cycles.