Frozen Embryo Transfer in Mildly Stimulated Cycles with Letrozole Combined with Estrogen in Women with Unresponsive Thin Endometrium Versus Standard Endometrial Preparation with Estrogen Alone

Infertile women undergoing frozen embryo transfer (FET) cycles may not experience optimal endometrial growth with estrogens alone. Hence, the present study evaluated the clinical effect of mild stimulation with letrozole and estrogens on endometrial growth in comparison to standard endometrial preparation with oral and topical estrogens in infertile women with unresponsive thin endometrium undergoing FET.

It enrolled forty women unresponsive to the first AC-FET cycle who received mild stimulation with letrozole and estrogens as the second LE-FET cycle for endometrial preparation (LE-FET study group) and compared them with 40 historical controls who had received two cycles of AC-FET (AC-FET control group). The study assessed the Responses by optimal endometrial thickness (≥ 7 mm) and clinical pregnancy.

The study found-

• Significantly increased mean endometrial thickness in LE-FET study group than AC-FET control group. 
• Higher clinical pregnancy rate in the study group than in the control group (35% versus 12.5%).

This study suggests that letrozole with estradiol (LE-FET) compared to estradiol alone (AC-FET) for the second cycle greatly augments endometrial thickness and boosts clinical pregnancy rates in women with unresponsive thin endometrium after the first AC-FET cycle with estradiol alone. Adding letrozole to estrogen upfront for FET cycles may improve endometrial receptivity and pregnancy outcomes.

Nagaraja N, Poddar SD, Rai S. et al. Improved Pregnancy Outcomes and Endometrial Receptivity by Thawed Frozen Embryo Transfer in Mildly Stimulated Cycles with Letrozole Combined with Estrogen in Women with Unresponsive Thin Endometrium Compared to Standard Endometrial Preparation with Estrogen Alone: A Retrospective Study. J Obstet Gynecol India. 2023. https://doi.org/10.1007/s13224-023-01813-4