Effects of the duration of estrogen therapy on live birth rate in HRT cycles: protocol for a randomized, controlled, non-inferiority study

Abstract

Abstract Background Hormone-replacement therapy (HRT) is usually used before frozen-thawed embryo transfer (FET) in women undergoing assisted reproduction. Estrogen is used first in the HRT cycle to stimulate endometrial proliferation, followed by combined estrogen and progesterone therapy to imitate the secretory phase of the endometrium. The progesterone is continued until 8–10 weeks of gestation when the placenta begins the function of luteal support. However, to date, there has been no comprehensive evaluation of the recommended duration of estrogen treatment in the HRT cycle. Prolonged estrogen use can contribute to increased risk of metabolic, coagulation, and neurological outcomes as well as mammary gland diseases. Methods The present protocol outlines a proposed single-center, prospective, randomized, controlled, non-inferiority trial. The trial will include clinically pregnant women between 20 and 40 years of age with singleton pregnancies resulting from FET during a hormone replacement cycle. The goal of the trial is to determine whether the live birth rates are impacted by the duration of oral estradiol valerate supplementation (6 vs 10 weeks). The live birth rate will be the primary study outcome, while secondary outcomes include maternal morbidity and neonatal outcomes at birth. Adverse events will be monitored and recorded during the trial. Discussion We do not expect to observe any differences in live birth rates, obstetric, or pediatric outcomes when oral estrogen supplementation is discontinued at 6 versus 10 weeks of pregnancy. The clinical data obtained from this trial may provide evidence for improving luteal support guidelines for women undergoing HRT cycles. Trial registration The study has been approved by the Ethics Committee of the Third Affiliated Hospital of Guangzhou Medical University, and will be performed according to the Good Clinical Practices guidelines. The protocol has been registered on ClinicalTrials.gov (No: ChiCTR2100041917).