Frozen Embryo Transfer Protocol Performance in Untested Frozen Embryo Transfers

Objective: To evaluate the association between frozen embryo transfer (FET) protocol and fetal heartbeat rate after transfer of frozen embryos that were not biopsied for preimplantation genetic testing. Design: Retrospective cohort study. Materials and Methods: A total of 712 single frozen embryo transfers without preimplantation genetic testing performed at a single private fertility practice in Cincinnati, Ohio between January 1, 2024 and December 1, 2025 were analyzed. Three FET protocols were evaluated. Protocol 1 consisted of hormone replacement with 2 mg oral estradiol three times daily and 200 mg micronized vaginal progesterone three times daily. Protocol 2 consisted of hormone replacement with 2 mg oral estradiol three times daily, 200 mg micronized vaginal progesterone three times daily, and 50 mg intramuscular progesterone every third day. Protocol 3 consisted of modified natural FET without letrozole using trigger with 250 µg choriogonadotropin alfa and luteal support with 200 mg micronized vaginal progesterone once daily. The primary outcome was fetal heartbeat rate per embryo transfer. Results: Protocol Cycles (n) Clinical Pregnancy Rate 95% CI Protocol 1 218 47% 45%–54% Protocol 2 260 50% 44%–56% Protocol 3 234 57% 50%–63% Expected live birth rates based on age at oocyte retrieval and day of embryo cryopreservation were similar across groups (36.7%, 36.6%, and 36.3%, respectively). Fetal heartbeat rate was not significantly associated with FET protocol when all groups were compared (p=0.11). On subgroup analysis, clinical pregnancy rates were significantly higher in protocol 3 compared with protocol 1 (p=0.048). Comparisons involving other groups were not statistically significant. Conclusions: Modified natural FET without letrozole demonstrated the highest fetal heartbeat rates at this center.