Serial estradiol levels before progesterone administration and on the day of day-3 frozen embryo transfer in artificial cycles may be associated with pregnancy outcomes

To evaluate whether serum estradiol levels measured before progesterone administration and on the day of embryo transfer are associated with pregnancy outcomes in day-3 frozen embryo transfer in artificial cycles. A retrospective cohort study included patients receiving day-3 frozen embryo transfer in artificial cycles between 2018 and 2024 categorized into four groups: pre-progesterone estradiol ≥500 pg/mL (group A, n = 69) or <500 pg/mL (group B, n = 261) and embryo transfer day estradiol ≥200 pg/mL (group C, n = 119) or <200 pg/mL (group D, n = 211). Subgroup analyses were conducted for double-high group (pre-progesterone estradiol ≥500 pg/mL and embryo transfer day estradiol ≥200 pg/mL), estradiol fluctuation group, and double-low groups (pre-progesterone estradiol <500 pg/mL and embryo transfer day estradiol <200 pg/mL) to evaluate combined effects. Main outcomes were biochemical pregnancy, implantation, clinical pregnancy, live birth, and miscarriage rates. Group A exhibited lower biochemical pregnancy (36.2 % vs. 52.1 %, p<0.05) and miscarriage rate (20.0 % vs. 42.6 %, p<0.05) than group B. Group C showed lower biochemical pregnancy (38.7 % vs. 54.5 %, p<0.05) and miscarriage rate (26.1 % vs. 44.3 %, p<0.05) than group D. Double-low group demonstrated higher biochemical pregnancy (55.4 % vs 36.0 %; p<0.05) and implantation rate (30.8 % vs. 16.0 %, p<0.05) than double-high group. Double-low group exhibited the highest miscarriage rate (46.3 %, 25.7 %, and 22.2 % for double-low, estradiol fluctuation, and double-high group, p<0.05), suggesting the potential role of estradiol levels in implantation and early pregnancy. High estradiol levels in day-3 frozen embryo transfer in artificial cycles may affect pregnancy outcomes. Serial estradiol monitoring may provide a more comprehensive assessment of estrogen's role in early pregnancy.