Effect of alpha-lipoic acid supplementation on polycystic ovary syndrome clinical outcome in infertile females treated with letrozole: a randomized controlled trial.

Non-responsive cycles during ovulation induction with letrozole (LZ) often necessitate the use of human menopausal gonadotropin (HMG), which may be associated with undesirable adverse effects. Therefore, strategies to improve the therapeutic outcomes of LZ are needed. This trial aimed to evaluate the impact of combining alpha-lipoic acid (ALA) with LZ on ovulation induction in women with polycystic ovary syndrome (PCOS). This randomized controlled trial included 151 infertile women with PCOS who were randomly allocated to either the LZ group (n = 76) or the ALA group (n = 75). The LZ group received LZ (2.5-7.5 mg) with lifestyle modification for up to three treatment cycles or until pregnancy occurred. The ALA group received the same regimen in addition to ALA (1800 mg/day), which was discontinued on the day of human chorionic gonadotropin (HCG) injection in ovulatory patients. Ovulation and pregnancy rates were assessed, along with hormonal parameters. Ovulation per cycle was significantly higher in the ALA group [153/166 (92.2%)] compared with the LZ group [146/203 (71.9%)] (P = 0.035). Moreover, pregnancy per cycle was significantly higher in the ALA group than in the LZ group (P = 0.033). Although serum estradiol, mid-luteal progesterone, and endometrial thickness showed numerically higher values in the ALA group, the differences between the groups were not statistically significant after Bonferroni adjustment. The addition of ALA to LZ improved ovulation and pregnancy outcomes and was associated with favorable metabolic and hormonal effects in women with PCOS.