Background: Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility, usually characterized by anovulation due to hormonal imbalances, including excessive luteinizing hormone (LH), normal level of follicle-stimulating hormone (FSH), insufficient gonadotropin secretion, hyperandrogenism, and the presence of polycystic ovarian morphology. Metformin is the most commonly prescribed medication for managing reproductive issues linked to insulin resistance in PCOS and is widely used to regulate menstrual cycles. Objective: In this study, the effects of metformin on the levels of LH, FSH, testosterone, and estradiol hormones were investigated to predict reproductive function in women with PCOS. Materials and Methods: This experimental study was a randomized, double-blind clinical trial conducted at the Qom University Jahad Infertility Treatment Center, Qom, Iran on 40 women with PCOS who were candidates for intracytoplasmic sperm injection. Participants were selected based on the Rotterdam criteria and ultrasound findings anti-Mullerian hormone levels, LH/FSH ratio, normal thyroid function and prolactin. Patients with systemic diseases, endocrine disorders or taking drugs affecting metabolism were excluded. Randomization was performed using colored cards (white: placebo, black: metformin). The metformin group (n = 20) received 1500 mg of metformin daily and the placebo group (n = 20) received 25 mg of ORS solution, both for 8 wk. Treatment began 2 months before the ovulation cycle and continued until the day oocyte retrieval. Finally, the levels of LH, FSH, testosterone and estradiol in serum and follicular fluid were measured by enzyme-linked immunosorbent assay. Results: In the metformin group, a significant decrease in the mean serum LH level (p = 0.000) and the mean follicular fluid LH level (p = 0.028) was observed compared with the placebo group. Similarly, the serum FSH level in the metformin group was significantly lower than in the placebo group (p = 0.005). However, the difference in follicular fluid FSH level between the 2 groups was not statistically significant (p = 0.074). Serum estradiol levels did not show a significant difference between the metformin and placebo groups (p = 0.810). In contrast, follicular fluid estradiol levels were significantly reduced in the metformin group compared with the placebo group (p = 0.001). There was no significant difference in serum testosterone levels (p = 0.954) or follicular fluid testosterone levels (p = 0.910). Conclusion: Based on the results of this study, metformin reduced serum and follicular fluid LH levels in PCOS women. Therefore, metformin can reduce the LH to FSH ratio in serum and follicular fluid of these women and improve the quality of oocytes and embryos in PCOS women. In addition, metformin caused an abnormal decrease in androgenic markers, including estradiol and testosterone. Therefore, by reducing androgens, it is possible to improve the follicular growth environment, leading to increased oocyte quality.
