Modified versions of natural frozen embryo transfers do not impact live births

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

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.

Four commonly used modified natural, stimulated, and natural FET protocols were evaluated, including: a true natural cycle with no modifications; vaginal progesterone supplementation only; human chorionic gonadotropin (hCG) trigger and vaginal progesterone supplementation; and aromatase inhibitor, hCG trigger, and vaginal progesterone supplementation. Protocol 4, hCG and vaginal progesterone protocol, was the reference group because it was the most commonly used protocol, making up 42.5% of included cycles.

Live births per FET.

A total of 4,806 cycles from 3,517 individual patients were included. The live birth per transfer for all FET cycles was 51.6% (2,480/4,806 cycles). The reference group that received hCG trigger and VP had an incidence of live birth of 53.4% (1,090/2,042 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 (adjusted relative risk [95% confidence interval]: 0.89 [0.62-1.28]), after adjusting for confounders.

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