Adding short-duration gonadotropin-releasing hormone antagonist and gonadotropin to natural cycle frozen embryo transfer allowed scheduling of transfer day without compromising live birth.

OBJECTIVE

To determine whether there is an association between the type of natural cycle frozen embryo transfer (FET) (scheduled vs. traditional) and live birth outcomes.

DESIGN

Retrospective cohort of all natural cycle FETs across a single network of fertility clinics in the United States.

SUBJECTS: All natural cycle FETs performed in ovulatory patients between January 2019 and April 2022.

EXPOSURE: Scheduled natural cycle FET cycles that received a short-duration of gonadotropin-releasing hormone antagonist (1 ampule/d) with low-dose gonadotropins (75 IU/d) to delay ovulation to enable more flexible scheduling of the FET were compared with cycles without delay.

MAIN OUTCOME MEASURES: Live birth.

RESULTS

There were a total of 1,087 natural cycle FETs that met the inclusion criteria. The scheduled natural cycle FET protocol was used in 114 (10.5%) of these cycles. The mean age was 35 (interquartile range, 33-38) years. Preimplantation genetic testing for aneuploidy was used in 76.3% (n = 87) of scheduled natural cycle FET cycles and 68.9% (n = 670) of natural cycle FET cycles. The scheduled natural cycle FET group had a significantly higher estradiol level (318 vs. 249 pg/mL) and a lower luteinizing hormone level (5.7 vs. 13.4 mIU/mL) at ovulatory trigger but a comparable peak endometrial thickness (9.4 vs. 9.7 mm) compared with the natural cycle FET group. Overall, there was a significant increase in the rates of positive human chorionic gonadotropin (scheduled natural cycle, 81.6%, vs. natural cycle, 64.3%; relative risk [RR], 1.26 [95% confidence interval {CI}, 1.15-1.38]) and clinical pregnancy (scheduled natural cycle, 68.4%, vs. natural cycle, 57.1%; RR, 1.21 [95% CI, 1.06-1.38]) in the scheduled natural cycle group. There were a higher proportion of live births in the scheduled natural cycle group; however, this did not reach statistical significance (scheduled natural cycle, 57.0%, vs. natural cycle, 49.4%; RR, 1.15 [95% CI, 0.97-1.36]). A subanalysis of preimplantation genetic testing for aneuploidy cycles yielded similar results.

CONCLUSION

A scheduled natural cycle FET protocol using a short duration of gonadotropin-releasing hormone antagonist along with low-dose gonadotropin add-back did not reduce live birth compared with traditional natural cycle FET cycles. These results suggest that this is an alternative FET protocol that may serve as a viable strategy to provide flexibility in scheduling the day of FET while still allowing a patient to undergo a natural cycle protocol. This protocol modification may enable more clinics to offer natural cycle FET.