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

Abstract

Objective: To determine if there is an association between the type of natural cycle frozen embryo transfer (natural cycle 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 received a short-duration of GnRH antagonist (1 amp per day) with low dose gonadotropins (75 IU/day) to delay ovulation to enable more flexible scheduling of the FET were compared with cycles without delay (natural cycle FET group).

Main outcome measure(s): Live birth RESULTS: There were a total of 1,087 natural cycle FETs that met inclusion criteria. The scheduled natural cycle FET protocol was utilized in 114 (10.5%) of these cycles. The mean age was 35 (interquartile range, IQR, 33-38). PGT-A was used in 76.3% (n=87) of scheduled natural cycle and 68.9% (n=670) of natural cycle FET cycles (p=0.11). The scheduled natural cycle FET group had a significantly higher estradiol level (318 vs. 249 pg/mL; p=0.0002) and a lower LH level (5.7 vs. 13.4 mIU/mL) at ovulatory trigger but a comparable peak endometrial thickness (9.4 vs. 9.7 mm) compared to the natural cycle FET group. Overall, there was a significant increase in positive hCG (scheduled natural cycle 81.6% vs natural cycle 64.3%; RR 1.26 (1.15-1.38)) and clinical pregnancy (scheduled natural cycle 68.4% vs natural cycle 57.1%; RR 1.21 (1.06-1.38)) in the scheduled natural cycle group. There was a higher proportion of live births in the scheduled natural cycle group, but this did not reach statistical significance (scheduled natural cycle 57.0% vs natural cycle 49.4%; RR 1.15 (0.97-1.36)). A sub-analysis of PGT-A cycles yielded similar results.

Conclusions: A scheduled natural cycle FET protocol using a short duration of GnRH antagonist along with low dose gonadotropin add-back did not reduce live birth compared to 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.