Use of antioxidants does not improve fertility in men trying to conceive

1. In a cohort of men trying to conceive, the use of antioxidants did not significantly improve pregnancy rates compared to a placebo.

2. In the “optimal treatment window,” pregnancy rates were significantly lower in the antioxidant group compared to the placebo group.

Evidence Rating Level: 1 (Excellent) 

Study Rundown: Infertility affects around 10% of the population worldwide, with male factors contributing to equally as many cases. Current fertility treatment options for men are costly and invasive, creating yet another barrier to desired reproductive outcomes. Oxidative stress, caused by an imbalance between reactive oxygen species (ROS) and antioxidant defences, has previously been proposed as a contributing factor to male infertility through damage to sperm DNA. To address this, over-the-counter antioxidants have been marketed as fertility aids, despite a lack of clinical evidence. Given the increase in antioxidant usage for male infertility, this randomized clinical trial sought to assess whether antioxidant treatment improves semen quality and pregnancy rates. 

There was no significant difference in ongoing pregnancy rates within 6 months between the antioxidant group and the placebo group, suggesting there is no significant benefit in achieving ongoing pregnancy. However, when narrowing in on the most optimal treatment window, there was a signicantly lower pregnancy rate in the antioxidant group compared to the placebo. Ultimately this evidence hinders against the use of antioxidants for male infertility. The study was unable to include subfertile men due to insufficient sample size, limiting the generalizability of the results. Despite this limitation, this study found that there is no significant evidence for antioxidant use in male infertility but rather supports against it. 

Click here to read the study in JAMA Network Open 

Relevant Reading: Antioxidant Supplementation on Male Fertility—A Systematic Review  

In-Depth [Randomized Clinical Trial]: 

Patients were eligible to participate in the study if they were aged 18-50, with female partners aged 18-43, who were unable to conceive after one year of unprotected intercourse and were recommended expectant management, intrauterine insemination (IUI), in vitro fertilization (IVF), or intracytoplasmic sperm injection (ICSI). A total of 1171 patients (median [IQR] age, 34 [31-38] years) met eligibility criteria and were randomized, with 590 in the antioxidant supplementation group, and 580 in the placebo group. Within the 6 month period, the pregnancy rate was not statistically different among the groups (193 of 571 patient [33.8%] vs 208 od 55 patients [37.5%]; adjusted odds ratio [AOR], 0.85 [95% CI, 0.66-1.09]; P=.20). Between 4 and 6 months of treatment, which aligns with the typical 72-day sperm development cycle, the antioxidant group had a significantly lower ongoing pregnancy rate compared to the placebo group (69 of 446 [15.5%] vs 95 of 442 [21.5%]; AOR, 0.66 [95% CI, 0.47-0.94]; P = .02). There was no significant differences in fertilization rate and embryo utilization rate among couples treated with IVF or ICSI. In conclusion, this randomized clinical trial found no evidence to support the use of antioxidant supplementation in men seeking fertility. 

Image: PD

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