Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 11:14:e66579.
doi: 10.2196/66579.

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

Alexandra Churchill  1   2 , Ektoras Georgiou  1   3   4 , Veronica Abruzzo  1 , Alex Polyakov  1   3   5 , Wan Tinn Teh  1   3   6
Affiliations

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

Alexandra Churchill et al. JMIR Res Protoc. .

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

International registered report identifier (irrid): PRR1-10.2196/66579.

Keywords: fertility care; frozen embryo transfer; in vitro fertilization; infertility; progesterone-modified natural cycle protocol; reproductive health.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: None declared.

Figures

Figure 1
Figure 1
Visual representation of the patient journey with P4mNFET protocol. FET: frozen embryo transfer; hCG: human chorionic gonadotropin; P4: progesterone; P4mNFET: progesterone-modified natural cycle protocol for frozen embryo transfer; TVUS: transvaginal ultrasound.
See this image and copyright information in PMC

References

    1. Alteri A, Arroyo G, Baccino G, Craciunas L, De Geyter C, Ebner T, Koleva M. ESHRE guideline on the number of embryos to transfer during IVF/ICSI. European Society of Human Reproduction and Embryology. 2024. [2025-04-01]. https://www.eshre.eu/Guidelines-and-Legal/Guidelines/Embryo-transfer . - PMC - PubMed
    1. VARTA: 2023 annual report. VARTA. 2023. [2025-04-01]. https://www.varta.org.au/sites/default/files/2023-11/7093_VARTA_AR2023_s... .
    1. Ghobara T, Gelbaya TA, Ayeleke RO. Cycle regimens for frozen-thawed embryo transfer. Cochrane Database Syst Rev. 2017 Jul 05;7(7):CD003414. doi: 10.1002/14651858.CD003414.pub3. https://europepmc.org/abstract/MED/28675921 - DOI - PMC - PubMed
    1. Mumusoglu S, Polat M, Ozbek IY, Bozdag G, Papanikolaou EG, Esteves SC, Humaidan P, Yarali H. Preparation of the endometrium for frozen embryo transfer: a systematic review. Front Endocrinol (Lausanne) 2021;12:688237. doi: 10.3389/fendo.2021.688237. https://europepmc.org/abstract/MED/34305815 - DOI - PMC - PubMed
    1. von Versen-Höynck Frauke, Schaub AM, Chi Y, Chiu K, Liu J, Lingis M, Stan Williams R, Rhoton-Vlasak A, Nichols WW, Fleischmann RR, Zhang W, Winn VD, Segal MS, Conrad KP, Baker VL. Increased preeclampsia risk and reduced aortic compliance with in vitro fertilization cycles in the absence of a corpus luteum. Hypertension. 2019 Mar;73(3):640–649. doi: 10.1161/HYPERTENSIONAHA.118.12043. https://europepmc.org/abstract/MED/30636552 - DOI - PMC - PubMed

LinkOut - more resources