Comparative study between three endometrial preparation protocols for frozen-thawed embryo transfer cycles in regularly ovulating women

Abstract

Background: In recent years, with the continuous technical advancement in cryopreservation techniques, frozen embryo transfer (FET) has become mainstream and a viable alternative to fresh embryo transfer. Despite the upward trend in FET, the most optimal priming strategy of the endometrium before FET remains controversial. For ages, the hormone replacement treatment (HRT) cycle protocol has been favored as the first-line regimen for endometrial priming in FET; however, nowadays some patients and physicians may opt for other protocols rather than using high-dose hormones with their potential adverse risks. Objective: The aim of this work is to compare three endometrial preparation protocols for FET; either by HRT cycles, ovulation induction (OI) cycles with aromatase inhibitors (AI), or modified natural cycles (mNC). Methods: This prospective randomized clinical trial included 120 patients preparing for FET. Partipants were randomized into three equal groups according to the protocol of endometrial preparation. Group A underwent HRT protocol by daily 6 mg oral Estradiol valerate, followed by daily 800 mg vaginal progesterone (P4). Group B underwent OI protocol, using 2.5 mg Letrozole, twice daily, for 5 days. Group C underwent mNC protocol, using 5000 IU human chorionic gonadotropin (hCG) as a trigger for ovulation. Results: there were no significant differences between the three groups regarding number of days before FET, mean endometrial thickness, or reproductive outcomes. In normo-ovulatory women, there was a trend toward improved reproductive outcomes in the mNC group regarding implantation, clinical pregnancy, and ongoing pregnancy rates; nevertheless neither of these outcomes reached a statistical significance.  Conclusion: In normo-ovulatory women, there was a trend toward improved reproductive outcomes in the mNC group, so we recommend the mNC protocol for endometrial preparation before FET as the protocol of choice in these women.