Impact of Estradiol Levels on Pregnancy Outcomes in Programmed Frozen-Thawed Single Euploid Blastocyst Transfers: A Prospective Cohort Study

Abstract

Background: To Frozen Embryo transfer cycles allow for better synchronization between the embryo and the endometrium, potentially improving implantation rates. Additionally, the use of preimplantation genetic testing for aneuploidy (PGT-A) to select euploid embryos has further enhanced the success rates of FET. Estradiol (E2) plays a critical role in preparing the endometrium for embryo implantation during FET cycles. Both insufficient and supraphysiological levels of estradiol can lead to impaired endometrial receptivity, potentially reducing the chances of successful implantation and pregnancy. Euploid embryos, being genetically normal, have a higher potential for implantation and live birth, however there is a paucity of data on the optimal estradiol levels required for achieving the best pregnancy outcomes, particularly in cycles involving the transfer of euploid embryos.Aim: To investigate the impact of serum estradiol (E2) levels on the day of embryo transfer (ET) on clinical pregnancy outcomes in women undergoing frozen embryo transfer cycles.Methods: A prospective cohort study was conducted from April to December 2024, involving 203 women undergoing single euploid blastocyst transfers at two IVF centers in Alexandria, Egypt. Participants were stratified into four groups based on the percentile of serum E2 levels on the day of ET. Endometrial preparation followed a programmed cycle protocol using estradiol valerate and progesterone. Clinical pregnancy, implantation, and miscarriage rates were analyzed.Results: The highest clinical pregnancy rate (62%) was observed in Group 3 (299.0–396.0pg/mL), though the difference was not statistically significant (p= 0.081). Group 4 (>396.0pg/mL) had the highest positive pregnancy test rate (69.4%, p= 0.045). Implantation rates were highest in Group 3 (60.8%, p= 0.180), while miscarriage rates did not differ significantly across groups (p= 0.749). Multivariate regression analysis revealed no significant impact of age, previous IVF attempts, endometrial thickness, or hormonal levels on clinical pregnancy rates. ROC curve analysis confirmed that serum E2 levels on the day of ET had no predictive value for clinical pregnancy (AUC= 0.520, p= 0.629).Conclusion: ThisSerum E2 levels on the day of ET, while essential for endometrial preparation, are not a strong predictor of clinical pregnancy outcomes in programmed frozen-thawed euploid blastocyst transfer cycles. Embryo quality and uterine receptivity may play more critical roles in determining success.