Efficacy and Safety of Vaginal Estradiol Hemihydrate as an Adjunct to Oral Estradiol Valerate in Hormone Replacement Therapy-Frozen Embryo Transfer (HRT-FET) Cycles: A Retrospective Study

Objective: To evaluate the efficacy and safety of vaginal estradiol hemihydrate as an adjunct to oral estradiol valerate in improving endometrial thickness and pregnancy outcomes in the hormone replacement therapy-frozen embryo transfer (HRT-FET) cycle. Materials and methods: This retrospective observational study was conducted at Kamala Polyclinic and Nursing Home, Mumbai, India, and included women aged 25-42 years undergoing HRT-FET treatment cycles between May and July 2024. Only those patients were included in this study whose endometrial thickness was <8 mm after administering oral estradiol valerate 12 mg OD for 12 to 15 days and who achieved a clinically adequate endometrium after co-treatment with vaginal estradiol hemihydrate 2 mg twice daily for two to three days. The study endpoints were measured as an increase in endometrial thickness, clinical pregnancy rate, and safety. Results: Mean (SD) endometrial thickness increased significantly from 7.47 (0.97) mm to 8.68 (1.34) mm after vaginal supplementation (p < 0.001). The clinical pregnancy rate was 50%. No adverse events were reported. Conclusion: In this study, administration of estradiol hemihydrate by vaginal route as an adjuvant helped to increase the endometrial thickness and was associated with higher clinical pregnancy in women with a thin endometrium following orally administered estradiol valerate alone.