Elevated estradiol levels in frozen embryo transfer have different effects on pregnancy outcomes depending on the stage of transferred embryos

Supplementation with estradiol (E(2)) is routinely used in frozen embryo transfer (FET) cycles and embryo age plays an important role in conceiving. This study was to compare the effects of serum E(2) levels on pregnancy outcomes between cleavage- and blastocyst-stage FET cycles using hormone replacement therapy. A total of 776 FET cycles (669 couples) performed from January 2016 to December 2019 were included in the present retrospective cohort study. Regarding cleavage-stage embryo transfers, E(2) levels on progesterone initiation day were significantly lower in the ongoing pregnancy/live birth (OP/LB) group than in the non-OP/LB group (214.75 ± 173.47 vs. 253.20 ± 203.30 pg/ml; P = 0.023). In addition, there were downward trends in implantation, clinical pregnancy and OP/LB rates with increasing E(2) levels. However, in blastocyst-stage embryo transfers, such trends were not observed, and E(2) levels were not significant difference between the OP/LB group and the non-OP/LB group (201.66 ± 182.14 vs. 197.89 ± 212.83 pg/ml; P = 0.884). The results suggests that elevated progesterone-initiation-day E(2) levels may negatively affect pregnancy outcomes during artificial cleavage-stage embryo transfers. However, it is not necessary to monitor E(2) levels when transferring blastocysts in artificial FET cycles.