Evaluating antioxidants in male infertility

This trial looked at whether antioxidant supplements improve male infertility. It found that antioxidants did not improve semen parameters, natural conception, or birth rates.

Male infertility is the sole cause of 20-30% of infertility cases and contributes to half of the cases. Male infertility may be caused by sperm which do not move normally, cannot interact with the egg normally to fertilize it, or have damage to their DNA (genetic material). Reactive oxygen species (ROS) are reactive molecules that can cause these kinds of changes to sperm. Lowering levels of ROS may improve male infertility.

Antioxidants are molecules that can neutralize ROS. Studies have found that antioxidant supplements may improve male infertility. However, most of these studies have been with a small number of men, or have had other design flaws such as not comparing antioxidants to a placebo (inactive pill). Also, these studies have focused on in vitro fertilization and other forms of assisted reproduction (AR). It is unclear whether antioxidants can improve male infertility and natural conception.

This study included 174 heterosexual couples with male infertility. The female partners had normal fertility. The men were randomly assigned to receive an antioxidant supplement or placebo. The supplement contained selenium, carnitine, zinc, folic acid, lycopene, and vitamins C, D, and E. 144 of the couples completed the study. The couples were followed for 6 months.

During the first three months, sperm count improved significantly more for men taking placebo compared to those taking antioxidants (1.6 million increase vs.10.6 million decrease). Men taking placebo also had a significantly improved sperm concentration (2.4 million/mL increase vs. 4.0 million/mL decrease). There was no difference in sperm shape, movement, or DNA damage between groups. Subgroups of patients, such as those with a low sperm concentration, also had no benefit from antioxidants.

In the first 3 months, couples tried to conceive naturally using at-home ovulation predictor tests. A similar number of couples in both groups became pregnant through intercourse (9% vs. 9%). From months 4 – 6, the female partners used clomiphene citrate (Clomid), a medication to stimulate ovulation. The couples also underwent intrauterine insemination (IUI), in which sperm are injected directly into the uterus. Slightly more couples became pregnant in the placebo group through medication and IUI (21% vs. 12%).

This study found that antioxidant supplements do not improve sperm parameters or increase birth rates in couples with male infertility.

According to the authors, this is the largest well-designed trial of antioxidant supplements for male factor infertility and non-AR conception as of 2020. Its conclusion is different from reviews that analyzed smaller studies.