Do antioxidants help male fertility?

“Antioxidants may help improve male fertility, early research suggests,” reported BBC News. It said that a review of studies found that a woman was more likely to have a pregnancy or live birth if her male partner took certain vitamins or other antioxidants, including vitamin E, L-carnitine, zinc and magnesium.

The news story is based on a systematic review of 34 randomised controlled trials in 2,876 couples having fertility treatments such as IVF. The findings suggest that in many cases of unexplained subfertility, men who take antioxidant supplements may increase the couple’s chances of conceiving and carrying a pregnancy to term.

However, further research is needed, despite this being a high quality review. The findings on live births in particular need confirmation, as this was the result of combining only three trials in a total of 214 couples, among whom there were 20 live births. The findings on pregnancy rates came from 15 trials including 964 couples, among whom there were 96 pregnancies.

The review did not draw any conclusions about which, if any, antioxidant might be most effective (or at what dose) and says more research comparing different antioxidants is needed.

Where did the story come from?

The study was carried out by researchers from The Cochrane Collaboration, an international, non-profit organisation that publishes high quality systematic reviews of healthcare research. The study was published in the Cochrane Database of Systematic Reviews. No external funding was supplied.

The study was reported accurately by the BBC, which included comments from external experts.

What kind of research was this?

This was a systematic review of previous randomised controlled trials (RCTs), which examined whether antioxidant supplements affect the rate of live births or pregnancies in couples having fertility treatments, where subfertility was unexplained or the man was known to be subfertile. A systematic review of RCTs is considered the “gold standard” in research methodology. It aims to identify, appraise, select and combine all high quality research evidence relevant to a specific question.

The researchers say that in couples where the cause of subfertility is a male factor (such as low sperm count), 30% to 80% of cases are thought to be due to the damaging effects of oxidative stress on sperm. In theory, this is when molecules containing reactive oxygen (called reactive oxygen species) overcome the semen’s “natural antioxidant defences” to cause cell damage. Increased levels of these molecules are thought to be due to several factors including pesticides, pollution, alcohol, smoking and poor diet.

Antioxidants can reduce oxidative damage, say the researchers, and are widely available and inexpensive compared to other fertility treatments. However, studies of whether antioxidants can improve outcomes for subfertile couples have had mixed findings and there is not much evidence of their benefits. The aim of this review was to collect and appraise the evidence base to answer this question.

What did the research involve?

The researchers carried out a search for randomised controlled trials comparing antioxidant supplements with placebo, no treatment or another antioxidant. The supplements had to be taken orally by the male partner in a couple seeking fertility treatment. All trials that compared any type or dose of antioxidant, taken singly or combined, with a placebo, an alternative antioxidant or no treatment were included. Trials that were not fully randomised were excluded.

The trials included couples with unexplained subfertility or where the man had been identified as having fertility problems. They looked at live birth rates in these trials, and also pregnancy rates, miscarriage, stillbirth rate and sperm quality. They also looked for adverse effects associated with antioxidant supplements.

The search was carried out using standardised methods, and included electronic databases, handsearches of conference abstracts, trial registers, sources of unpublished literature and reference lists. The researchers also asked experts in the field for any relevant research.

What were the basic results?

The search found 34 relevant trials with a total of 2,876 couples. All of these were assessed for risk of bias and the relevant data extracted. The figures for live birth, pregnancy rates and other outcomes were combined in a meta-analysis, using standard tools. The researchers used standard methods to carry out a statistical analysis. The main findings are described below.

Live birth: three trials reported live births. Couples where the men took oral antioxidants had a significant increase in live birth rate (pooled odds ratio (OR) 4.85, 95% confidence interval (CI) 1.92 to 12.24) compared with couples where the men took control pills. This result was based on 20 live births from a total of 214 couples.

Pregnancy rate: 15 trials recorded pregnancies, in which there were 96 pregnancies in 964 couples. Couples where men took antioxidants had a significant increase in pregnancy rate compared to control couples (pooled OR 4.18, 95% CI 2.65 to 6.59).

The researchers noted the following:

• None of the studies reported evidence of harmful side effects from taking antioxidants.
• Antioxidant use did not appear to be associated with any increase in the chance of miscarriage.
• None of the trials reported on stillbirths.
• There were not enough studies to combine and compare the effectiveness of different antioxidants. From the results they had however, the researchers say that one antioxidant did not appear to have any more effect on pregnancy rates than any other.
• Analysis of sperm concentrations (i.e. the numbers of sperm in a certain volume of ejaculate) at nine months showed that men taking antioxidants had more antioxidants than the controls, a difference that was statistically significant.

How did the researchers interpret the results?

The researchers say that among couples trying to conceive, use of an antioxidant supplement by the man may improve his partner’s chances of conceiving. However, they say further research is needed to substantiate their conclusions and to compare the effectiveness of different antioxidants.

Conclusion

Cochrane reviews like this are carried out using stringent, high quality methods and tend to be considered as reliable indications of the existing evidence. The results of this review suggest that antioxidant supplements taken by men who are subfertile could increase the chances for couples who are undergoing fertility treatment of a pregnancy and live birth.

However, as the authors point out, the numbers that were included were small: only three trials, with a combined total of 214 couples, reported on live births, of which there were 20. In addition, only 15 of 34 trials that fulfilled the search criteria actually reported on pregnancy outcomes. As such, further research is needed to confirm the results.

As the authors also note, the quality of the methods used in some trials was unclear, and this could undermine the overall findings. For example, in about three-quarters of the studies reviewed it is unclear how the men were allocated to receiving either the antioxidant treatment or a placebo, and whether this was blinded or not.

It is important to note that the research did not look at whether taking antioxidants improves male fertility in the general population. Couples undergoing fertility treatment, or who are concerned about their fertility and interested in antioxidant supplements, are advised to consult their doctor.