Authors' reply Re: Supraphysiological estradiol level in ovarian stimulation cycles affects the birthweight of neonates conceived through subsequent frozen-thawed cycles: a retrospective study.

Abstract

Objective To investigate whether supraphysiological estradiol (E2 ) in controlled ovarian stimulation (COS) cycles affects the subsequent frozen-thawed embryo transfer (FET) in terms of the neonatal birthweight. Design Retrospective cohort study. Setting University affiliated hospital. Population In all, 2066 patients undergoing FET cycles that resulted in live singleton births between July 2011 and Dec 2016. Interventions None. Methods Multivariable linear regression and logistic regression was used to evaluate the association between peak E2 and birthweight outcomes. Main outcome measures Birthweight, z-score adjusted for gender and gestational age, and incidence of small-for-gestational-age (SGA) and low birthweight (LBW) in singleton neonates derived from FET cycles. Results Adjusted for confounding factors, both the absolute birthweight and the z-score of singletons following FET were negatively associated with peak E2 levels in COS. In comparison with the referent category (E2 ≤1500 pg/ml), the categories with E2 >3000 pg/ml had a significantly lower z-score. The difference (95% CI) in estimated marginal mean of birthweights between referent category and highest E2 (>8000 pg/ml) category was 104.57 g (18.13-181.06). Multiple logistic regression analyses showed that the adjusted odds ratio (95% CI) for SGA and LBW in term singletons comparing patients with E2 >3000 pg/ml with those with E2 ≤3000 pg/ml was 2.44 (1.37-4.34) and 2.32 (1.01-5.40), respectively. Conclusions Peak E2 levels in COS cycles are negatively associated with the birthweight of singletons conceived through subsequent FET cycles. Tweetable abstract The birthweight following FET is affected by previous COS cycle.