Live birth after letrozole as an adjunct to follicle-stimulating hormone versus follicle-stimulating hormone alone for ovarian stimulation in in vitro fertilisation cycles—study protocol for a randomised controlled trial

INTRODUCTION: In vitro fertilisation (IVF) is an effective infertility treatment but the live birth rate remains unsatisfactory. Ovarian stimulation by follicle-stimulating hormone (FSH) is routinely used in IVF and the resulting high serum estradiol levels may impair oocyte/embryo quality and endometrial receptivity. Letrozole, an aromatase inhibitor, can reduce serum estradiol levels following ovarian stimulation. We aim to test the hypothesis that co-treatment with letrozole reduces supraphysiological serum estradiol levels and improves endometrial receptivity, leading to a higher live birth rate of IVF. We are conducting a randomised controlled trial (RCT) to evaluate whether letrozole as an adjunct to FSH in IVF is superior to FSH alone in the live birth rate of fresh embryo transfer. METHODS/DESIGN: This is an open-label randomised controlled superiority trial being performed in two assisted reproduction centres in China. Infertile women who have antral follicle count (AFC) before ovarian stimulation or on day 5 of ovarian stimulation ≥15 are randomly allocated in a 1:1 ratio to receive either letrozole and FSH or FSH alone in a GnRH antagonist protocol. Recruited women follow the standard operating procedures of the two centres. The primary outcome is the live birth rate of the fresh embryo transfer. Stimulation parameters, maternal side effects and obstetric and perinatal complications are secondary outcomes. The planned sample size is 900, i.e. 450 per group. DISCUSSION: The present study is the first multicentre randomised study to compare the live birth rate of the fresh embryo transfer following ovarian stimulation by letrozole and FSH versus FSH alone in women with anticipated high ovarian responses. TRIAL REGISTRATION: ClinicalTrials.gov NCT02912988. Registered on September 23, 2016. This trial protocol is version 2.0.