Antioxidants Improve Reproductive Health in Women With Ovarian Aging

Objectives: Ovarian aging is a major factor for female subfertility. Multiple antioxidants have been applied in different clinical scenarios to delay aging, but their effects in the ovarian aging are still unclear. Therefore, we performed a meta-analysis to evaluate the effectiveness and safety of antioxidants on fertility in women with ovarian aging. Methods: PubMed, CENTRAL, Embase and ClinicalTrials.gov were searched from inception to September 2023, without language restrictions. Randomized controlled trials (RCTs) evaluating the effects of antioxidants in women with ovarian aging were included. Risk of bias and quality of evidence (QoE) were assessed according to the Cochrane Collaboration's tool and the GRADE system. The random-effects model was used to pool the odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals. Results: A total of 22 RCTs with 2779 participants were included. The results showed that use of antioxidants not only significantly increased the number of retrieved oocytes and high-quality embryos but also reduced the dose of gonadotropin, which contributed to an improved clinical pregnancy rate, although uncertain effects on the live birth rate were observed. No evidence suggested an association between antioxidants and adverse events. According to the subgroup analysis, in terms of antioxidant types, CoQ10 tended to be more effective than melatonin, myo-inositol and vitamins. With regard to different dose settings, a better effect was observed with a lower dose. Based on subgroup analysis of CoQ10, the optimal treatment regimen for improving pregnancy rate was 30 mg/d for three months before the ovarian stimulation cycle, and women with diminished ovarian reserve clearly benefited from the treatment, especially those at young reproductive age (< 35 years old). Conclusions: Antioxidants could be considered as an effective and safe complementary therapy for women with ovarian aging, especially CoQ10. Appropriate antioxidant treatment should be offered from a low dose according to patients' age and ovarian reserve. Funding Sources: This work is supported by the Project funded by National Natural Science Foundation of China (82305305), China Postdoctoral Science Foundation (2023M733981) and the Natural Science Foundation of Hunan Province (2023JJ40799).