Introduction: Polycystic ovary syndrome (PCOS) is the leading cause of female infertility, affecting approximately 5–10% of women of reproductive age (1). In these patients, reduced expression of growth differentiation factor-9 (GDF-9), bone morphogenetic protein-15 (BMP-15), and miR-320 has been associated with impaired ovulation and embryo development (2, 3). Empagliflozin (EMPA), a sodium–glucose cotransporter 2 (SGLT2) inhibitor, may indirectly regulate the expression of these genes by improving insulin resistance (4) and reducing inflammation (5), thereby enhancing oocyte quality. Therefore, the present study aimed to evaluate the effects of empagliflozin on the expression levels of GDF-9, BMP-15, and miR-320 in granulosa cells of women with PCOS. Methods: In this randomized study, 40 women with PCOS were assigned to two groups. Empagliflozin (25 mg) or placebo (25 mg ORS solution) was administered for eight weeks. Treatment started two months before the ovulation cycle and continued until the day of oocyte retrieval. Gene expression levels of GDF-9, BMP-15, and miR-320 in granulosa cells were measured using real-time PCR. Data were analyzed using the Independent T-test, and differences were considered statistically significant at P<0.05. Results: The mean expression levels of GDF-9 (P<0.001), BMP-15 (P<0.001), and miR-320 in granulosa cells were significantly higher in the empagliflozin group (P<0.001) compared to the placebo group. Conclusion: Our findings suggest that empagliflozin may play an important role in improving oocyte quality and embryo development, likely through upregulation of GDF-9, BMP-15, and miR-320 expression, ultimately enhancing fertility outcomes.
