Modified Versions of Natural Frozen Embryo Transfers Do Not Impact Live Births

Courtney Hargreaves; Wendy Craig; Denny Sakkas; Thomas L Toth; Denis Vaughan

doi:10.1016/j.fertnstert.2025.06.036

Modified Versions of Natural Frozen Embryo Transfers Do Not Impact Live Births

Fertil Steril. 2025 Jun 28:S0015-0282(25)00541-2. doi: 10.1016/j.fertnstert.2025.06.036. Online ahead of print.

Authors

Courtney Hargreaves¹, Wendy Craig², Denny Sakkas³, Thomas L Toth⁴, Denis Vaughan⁴

Affiliations

¹ Department of Obstetrics and Gynecology, Maine Medical Center, Portland, ME, USA. Electronic address: courtneyjhargreaves@gmail.com.
² MaineHealth Institute for Research, Portland, ME, USA; Tufts University School of Medicine, Boston, MA.
³ Boston IVF - IVIRMA Global Research Alliance, Waltham, MA, USA.
⁴ Boston IVF - IVIRMA Global Research Alliance, Waltham, MA, USA; Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA, USA.

PMID: 40588150
DOI: 10.1016/j.fertnstert.2025.06.036

Abstract

Objective: To evaluate the effect of protocol modifications to "natural" frozen embryo transfer (FET) cycles on live birth DESIGN: Retrospective cohort study.

Subjects: Patients undergoing natural, modified natural, and stimulated single FETs between January 2014 and December 2021 in a single university affiliated fertility clinic in the United States.

Exposure: Four commonly used modified natural, stimulated, and natural FET protocols were evaluated, including: 1. A true natural cycle with no modifications 2. vaginal progesterone supplementation only 3. Human chorionic gonadotropin (hCG) trigger and vaginal progesterone supplementation 4. Aromatase inhibitor, hCG trigger, and vaginal progesterone supplementation. Protocol 3, HVP, was the reference group as it was the most commonly used protocol making up 42.5% of included cycles.

Main outcome measures: Live births per FET.

Results: 4806 cycles from 3517 individual patients were included. The live birth per transfer for all FET cycles was 51.6% (2480/4806 cycles). The reference group that received hCG trigger and VP had an incidence of live birth of 53.4% (1090/2042 cycles). All three study protocols had similar live births. Although the group that did not have modifications had the lowest percentage of live births (41.3%), this was not significantly different from the reference group (aRR (95% CI): 0.89 (0.62-1.28)), after adjusting for confounders.

Conclusion: In a large cohort of patients live births per FET was similar among commonly used variations in modified natural FET cycles. These results allow for the modification of natural cycles without impacting live births and enables shared decision making between patient and provider.

Keywords: frozen embryo transfer; modified natural cycle; single embryo transfer.