Effectiveness of progesterone supplementation in women presenting low progesterone levels on the day of frozen embryo transfer: a randomised controlled trial

INTRODUCTION: Progesterone is an essential hormone involved in the process of implantation and pregnancy maintenance. Evidence from recent studies has supported the importance of serum progesterone level around the time of embryo transfer in hormonal replacement therapy frozen embryo transfer cycles and recommended the need for individualised luteal support. Low progesterone around the time of embryo transfer is found to be associated with decreased rate of pregnancy after frozen embryo transfer. This single-centre, longitudinal, randomised, interventional controlled study aims to compare the rate of ongoing pregnancy between two groups of women with progesterone level below 10 ng/mL on the day of frozen embryo transfer: the study group using 800 mg vaginal micronised progesterone supplemented with 50 mg intramuscular progesterone per day and the control group using only 800 mg vaginal micronised progesterone. METHODS AND ANALYSIS: We enrol patients who are undergoing frozen embryo transfers with blastocyst-stage or cleavage-stage embryos and who satisfy the inclusion and exclusion criteria. After signing the informed consent, participants are randomised into two groups: the study group using vaginal micronised progesterone supplemented with progesterone intramuscular 50 mg per day and the control group using only vaginal micronised progesterone. Randomisation will be performed using R software at a 1:1 allocation ratio. Sequentially numbered, opaque sealed envelopes are used for allocation. The primary outcome is the rate of ongoing pregnancy. To demonstrate a difference of 10% with regard to rate of ongoing pregnancy, at least 370 participants per arm are required (type I error α=0.05, power=0.8). Assuming a dropout rate of 10%, a total of 824 patients (412 per group) will be invited. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of Tu Du Hospital on 17 May 2021 (reference number: 1251/QĐ-BVTD). All participants provide informed consent before being enrolled in the study. The results of our study will be submitted to reproductive medicine conferences and journals. TRIAL REGISTRATION NUMBER: NCT04897269.