High estradiol levels in fresh embryo transfer cycles are not associated with detrimental impact on birth outcomes.

Abstract

There is an unclear relationship between estradiol levels and fresh embryo transfer (ET) outcomes. We determined the relationship between estradiol on the day of trigger, in fresh ET cycles without premature progesterone elevation, and good birth outcomes (GBO). We identified autologous fresh ET cycles from 2015 to 2021 at multiple clinics in the USA. Patients with recurrent pregnancy loss, uterine factor, and elevated progesterone on the day of trigger (progesterone > 2ng/mL or 3-day area under the curve > 4.5ng/mL) were excluded. The primary outcome was GBO (singleton, term, live birth with appropriate weight). Log-binomial generalized estimating equations determined the likelihood of outcomes. Of 17,608 fresh ET cycles, 5025 (29%) yielded GBO. Cycles with estradiol 4000pg/mL had a greater likelihood of GBO compared to cycles < 1000pg/mL (aRR = 1.32, 95% CI 1.13-1.54). Pairwise comparisons of estradiol between < 1000pg/mL versus 1000-1999pg/mL and 1000-1999pg/mL versus 2000-2999pg/mL revealed a higher likelihood of GBO with higher estradiol (aRR 0.83, 95% CI 0.73-0.95; aRR 0.91, 95% CI 0.85-0.97, respectively). Comparisons amongst more elevated estradiol levels revealed that the likelihood of GBO remained similar between groups (2000-2999pg/mL versus 3000-3999pg/mL, aRR 1.04, 95% CI 0.97-1.11; 3000-3999pg/mL versus 4000pg/mL, aRR 0.96, 95% CI 0.9-1.04). In fresh ET cycles, higher estradiol levels were associated with an increased prevalence of GBO until estradiol 2000-2999pg/mL, thereafter plateauing. In fresh ET candidates, elevated estradiol levels should not preclude eligibility though premature progesterone rise, and risk of ovarian hyperstimulation syndrome must still be considered.