Euploid programmed frozen embryo transfer cycles are associated with a higher live birth rate when estradiol levels more closely mimic physiology.

Objective: To determine whether peak estradiol (E) levels above the usual physiologic range (300-500 pg/mL) will impact programmed frozen embryo transfer (FET) outcomes in an ideal study population of those using good-quality single euploid blastocysts.

Design: Retrospective cohort study.

Setting: University-based clinic.

Patients: Single euploid-programmed FET done at a single academic institution from January 2016 to December 2019. The population was divided into three groups on the basis of peak serum E levels during endometrial preparation: group A (E <300 pg/mL), group B (300-500 pg/mL), and group C (>500 pg/mL). Group B was used as the reference range for statistical analysis.

Intervention: Frozen embryo transfer cycles.

Main Outcome Measures: The primary outcome was the live birth rate (LBR). Secondary outcomes included implantation, biochemical, ectopic, and miscarriage rates.

Results: A total of 750 FET cycles were included in this study. Poisson regression analysis showed a negative impact of higher peak E on the LBR. A decrease in LBR was noted between group C and referent group B (50.2% vs. 63.4%, risk ratio 0.79 [0.68-0.91]) and group A and referent group B (42.5% vs. 63.4%, risk ratio 0.67 [0.46-0.98]). Secondary outcomes were notable for a lower implantation rate when groups A and C were compared with group B and a higher biochemical rate between group C and group B. There was no notable difference between groups in ectopic or miscarriage rates.

Conclusion: Limiting peak serum E levels to 300-500 pg/mL during programmed FET cycles is associated with improved LBRs compared with cycles with peak E levels of <300 pg/mL or >500 pg/mL in an ideal study population.