Antioxidants and Fertility in Women with Ovarian Aging: A Systematic Review and Meta-Analysis

Abstract

Ovarian aging is a major factor for female subfertility. Multiple antioxidants have been applied in different clinical scenarios, but their effects on fertility in women with ovarian aging are still unclear. To address this, a meta-analysis was performed to evaluate the effectiveness and safety of antioxidants on fertility in women with ovarian aging. A total of 20 randomized clinical trials with 2617 participants were included. The results showed that use of antioxidants not only significantly increased the number of retrieved oocytes and high-quality embryo rates but also reduced the dose of gonadotropin, contributing to higher clinical pregnancy rates. According to the subgroup analysis of different dose settings, better effects were more pronounced with lower doses; in terms of antioxidant types, coenzyme Q10 (CoQ10) tended to be more effective than melatonin, myo-inositol, and vitamins. When compared with placebo or no treatment, CoQ10 showed more advantages, whereas small improvements were observed with other drugs. In addition, based on subgroup analysis of CoQ10, the optimal treatment regimen of CoQ10 for improving pregnancy rate was 30 mg/d for 3 mo before the controlled ovarian stimulation cycle, and women with diminished ovarian reserve clearly benefited from CoQ10 treatment, especially those aged <35 y. Our study suggests that antioxidant consumption is an effective and safe complementary therapy for women with ovarian aging. Appropriate antioxidant treatment should be offered at a low dose according to the patient's age and ovarian reserve. This study was registered at PROSPERO as CRD42022359529.

Keywords: CoQ10; antioxidants; clinical pregnancy; high-quality embryo; oocyte; ovarian aging.

FIGURE 1

Flow chart of study selection for the systematic review and meta-analysis.

FIGURE 2

Forest plots of clinical pregnancy rate. Antioxidant versus placebo or no treatment (control). CI, confidence interval; M-H, Mantel–Haenszel.

FIGURE 3

Forest plots of oocyte and embryo quality. Antioxidant versus placebo or no treatment (control): (A) number of retrieved oocytes, (B) number of high-quality embryos and (C) high-quality embryo rate. CI, confidence interval; IV, inverse variance; M-H, Mantel–Haenszel; SD, standard deviation.

FIGURE 4

Forest plots of gonadotropin dose. Antioxidant versus placebo or no treatment (control). CI, confidence interval; IV, inverse variance; SD, standard deviation.

FIGURE 5

Funnel plots of clinical pregnancy rate (A), number of retrieved oocytes (B), and number of high-quality embryos (C). MD, mean difference; OR, odds ratio; SE, standard error.