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.

Context: Infertile women undergoing frozen embryo transfer (FET) cycles may not show optimal endometrial growth with estrogens alone. Aim: To evaluate 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. Settings and design: Retrospective observational case-control study. Material and methods: Forty women unresponsive to first AC-FET cycle were given mild stimulation with letrozole and estrogens as second LE-FET cycle for endometrial preparation (LE-FET study group) and compared with 40 historical controls who had received two cycles of AC-FET (AC-FET control group). Responses were assessed by optimal endometrial thickness (≥ 7 mm) and clinical pregnancy. Statistical analysis: Descriptive statistics were elaborated by mean ± SD and percentages. Results were expressed by mean ± SD, unpaired t test for difference in endometrial thickness, chi square and Fisher exact test to compare the difference in pregnancy among both groups. Results: Mean endometrial thickness was significantly increased in LE-FET study group (6.68 ± 2.09 mm) versus AC-FET control group (5.35 ± 1.90 mm). Higher clinical pregnancy rate was noted in study group as compared to control group (35% versus 12.5%). Conclusion: This study suggests that letrozole with estradiol (LE-FET) compared to estradiol alone (AC-FET) for second cycle significantly increased endometrial thickness and improved clinical pregnancy rates in women with unresponsive thin endometrium after first AC-FET cycle with estradiol alone. Addition of letrozole to estrogen upfront for FET cycles may enhance endometrial receptivity and might improve pregnancy outcomes.