Direct warming and rehydration method in frozen embryo transfer: study protocol for a pragmatic, multi-center, double-blinded, two-arm randomized controlled trial

BACKGROUND: Embryo cryopreservation through vitrification is widely used to store surplus embryos for future transfer. Traditional multi-step warming methods are both time-consuming and costly. This study evaluates the clinical outcomes and the effectiveness of a novel direct warming method for frozen embryo transfer (FET) in comparison to the conventional multi-step method. METHODS: This is a pragmatic, two-arm, double-blinded randomized controlled trial (RCT) comparing the new direct warming method with the conventional multi-step method. Participants undergoing FET will be randomly assigned to either the direct warming method or the conventional warming protocol. The primary outcomes are the clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR), the live birth rate (LBR), miscarriage rate, and cost-effectiveness. Secondary outcomes include identifying clinical differences among various brands of warming media, embryo storage devices, and embryo culture media through subgroup analyses. A sample size of 578 participants is planned, allowing for a 5% loss to follow-up. DISCUSSION: Preliminary studies have shown that the direct warming method offers comparable or slightly higher live birth rates than conventional methods. Moreover, it significantly reduces thawing time and associated costs, offering a faster, cost-effective option for FET. This trial has the potential to improve accessibility to ART by reducing procedural costs and increasing efficiency without compromising clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT06741748. Registered on 19 November 2024.