Feasibility of a Progesterone-Modified Natural Protocol for Frozen Embryo Transfer: Protocol for a Pilot Cohort Study

TL;DR

This study explores a new frozen embryo transfer protocol using progesterone to improve implantation timing and reduce monitoring.

Contribution

The novel progesterone-modified natural cycle protocol for FET is evaluated for feasibility and clinical outcomes.

Findings

The primary outcome will assess the presence of a corpus luteum on ultrasound during embryo transfer.

Secondary outcomes include clinic visits, biochemical, and clinical pregnancy rates.

The study will serve as a pilot for a future randomized controlled trial.

Abstract

With the existence of various frozen embryo transfer (FET) methods currently used in the field of assisted reproductive technologies, the debate surrounding which of these is superior remains. All FET protocols aim to prime the endometrium and time embryo transfer during the window of implantation. Current methods include the true natural cycle FET (tNFET), modified natural cycle FET, artificial cycle FET, and ovulation induction. Each of these harbors, distinct advantages and disadvantages, namely, surrounding the timing of transfer and flexibility conferred through this process. More recently, a newer approach has been used whereby the need to monitor or trigger ovulation is circumvented, with luteal phase support commenced once a certain follicle diameter and endometrial thickness criteria are met but before ovulation. However, the research into this protocol has certain important limitations that our study seeks to address.

This study aims to assess the feasibility of a progesterone-modified natural cycle protocol for FET. The primary outcome will be the presence of a corpus luteum on ultrasound scans on the day of embryo transfer. The secondary outcomes will include the number of clinic visits required per patient undergoing the protocol, biochemical pregnancy rate, and clinical pregnancy rate.

We will conduct a prospective cohort study, recruiting 20 women undertaking FET at the Public Fertility Care of The Royal Women’s Hospital in Melbourne, Australia. These women will be matched to a control group who have undergone the tNFET protocol within the preceding 12 months of the study start date.

This project received ethics approval on July 17, 2024, with commencement of the study in September 2024, aiming for a duration of completion of 9 months. The completion of the follow-up and submission of the study for publication are anticipated for September 2025.

After this preliminary study, the aim would be to progress to a noninferiority randomized controlled trial to compare the progesterone-modified natural cycle protocol for FET to the tNFET.

PRR1-10.2196/66579

Figures