Relative estradiol response during controlled ovarian stimulation and cycle-level blastocyst formation after IVF/ICSI: a retrospective cohort study

The clinical interpretation of relative serum estradiol response during controlled ovarian stimulation remains uncertain. We assessed its association with the cycle-level probability of obtaining at least one eligible blastocyst and, secondarily, with pregnancy outcomes after IVF/ICSI. This retrospective cohort study included 9146 women, each contributing her first recorded ovarian-stimulation IVF/ICSI cycle between January 2020 and December 2022. The E2 response ratio was calculated as (trigger-day E2 minus basal E2)/basal E2 and categorized into quartiles. The primary outcome was cycle-level blastocyst success, defined as at least one eligible blastocyst. The primary association was estimated using robust Poisson regression with prespecified pretreatment covariates; logistic regression was retained as a sensitivity analysis. Clinical pregnancy and live birth were analysed among 4191 fresh embryo-transfer cycles. Among 9146 first ovarian-stimulation cycles, 5060 (55.3%) achieved cycle-level blastocyst success. Success increased from 15.1% in Q1 to 89.2% in Q4. In the pretreatment-adjusted robust Poisson model, relative risks were 2.03 (95% CI 1.82–2.25), 2.78 (2.50–3.08) and 3.02 (2.72–3.35) for Q2, Q3 and Q4 versus Q1, respectively. Logistic and trimmed-distribution sensitivity analyses showed the same graded direction. Associations with clinical pregnancy and live birth were modest and conditional on fresh embryo transfer. Higher E2 response was associated with a greater cycle-level probability of obtaining at least one eligible blastocyst. The finding may reflect ovarian responsiveness and the number of developmental opportunities within a cycle; it does not establish an embryo-level or causal effect of E2. Pregnancy-outcome associations require cautious interpretation.