Does estradiol orally and vaginally administered together impact live birth and neonatal outcomes in artificial frozen-thawed embryo transfer cycles: a retrospective cohort study

Abstract

Background: Previous studies have demonstrated that newborns from fresh embryo transfer have higher risk of small for gestation (SGA) rate than those from frozen-thawed embryo transfer (FET). It is suggested that supraphysiologic serum estradiol in controlled ovarian stimulation (COS) is one of reasons. Our study aims to investigate whether exogenous estradiol delivered regimens have an impact on live birth rate and neonatal outcomes in hormone replacement (HRT)-FET cycles. Methods: This was a retrospective study involving patients undergoing their first FET with HRT endometrium preparation followed by the transfer of two cleavage-staged embryos, comparing estradiol administered orally and vaginally (OVE group) versus estradiol administered orally (OE group) from January 2015 to December 2018 at our center. A total of 792 patients fulfilled the criteria, including 228 live birth singletons. The live birth rate was the primary outcome measure. Secondary outcome measures included clinical pregnancy rate, singleton birthweight, large for gestational age (LGA) rate, SGA rate, preterm delivery rate. Results: Patients in OVE group achieved higher serum estradiol level with more days of estradiol treatment. No difference in live birth (Adjusted OR 1.327; 95%CI 0.982, 1.794, p = 0.066) and clinical pregnancy rate (Adjusted OR 1.278; 95%CI 0.937, 1.743, p = 0.121) was found between OVE and OE groups. Estradiol route did not affect singletons birth weight (β = -30.962, SE = 68.723, p = 0.653), the odds of LGA (Adjusted OR 1.165; 95%CI 0.545, 2.490, p = 0.694), the odds of SGA (Adjusted OR 0.569; 95%CI 0.096, 3.369, p = 0.535) or the preterm delivery (Adjusted OR 0.969; 95%CI 0.292, 3.214, p = 0.959). Conclusion: Estrogen taken orally and vaginally together did not change live birth rate and singleton neonatal outcomes compared to estrogen taken orally, but was accompanied with relative higher serum E2 level and potential maternal undesirable risks.