John: Hello, I'm John Hilton, editor of the Cochrane Editorial unit. Up to one in four couples planning a baby may have difficulty conceiving. Several interventions are available that might help and Cochrane keeps many of these under review. In July 2017, the Cochrane Review of antioxidants for female subfertility was updated and we asked one of the authors, Dr Rebecca Mackenzie-Proctor from the Auckland City Hospital in New Zealand to tell us about the rationale for the review and the latest evidence.

Rebecca: Some causes of subfertility among women are associated with the adverse effects of oxidative stress and, so, antioxidant drugs would be expected to counteract these negative impacts of oxygen free radicals, by acting as free radical scavengers. We did our review to test this idea and found 50 randomised trials in which some women took an oral antioxidant supplement, while others were allocated to either a control group or an alternative antioxidant. This adds 22 studies to the review since its last version in 2013 and allows us to draw some new conclusions about the benefits of these drugs, based on data from the six and a half thousand women who were undergoing assisted reproduction techniques across the trials.
We were most interested in the effects on live birth but few trials provided information on this, and we could only use data from 8 trials. This showed a significant increase in live birth rates, with just over twice the likelihood of a live birth for women taking antioxidants, suggesting increases in the percentage chance of a live birth from around 20% for women not taking additional antioxidant supplementation, to between 26 and 43% when they took them.
It was much more common for the trials to investigate other outcomes and we also wanted to examine the impact on clinical pregnancy and adverse effects. However, although 35 trials reported some adverse events, there was insufficient evidence to draw conclusions about these and to determine if there were any differences in miscarriage rate, multiple pregnancies or gastrointestinal disturbances in women taking antioxidants.
Clinical pregnancy showed a small improvement for women taking antioxidants. Using data on nearly 4300 women in 26 trials, we found a significant difference, with the chances of a clinical pregnancy increasing from around 22% to between 27 and 33%.
The next obvious question is which antioxidant is better, but it’s difficult to draw conclusions from the trials that directly compared one antioxidant with another, because there are too few that directly tested the same pairs of antioxidants. From the trials against no treatment or placebo, live births were statistically significant increased when women took either combined antioxidants or N-acetyl-cystine; while Co enzyme Q10, L-carnitine and combined antioxidants all showed an improvement in clinical pregnancy outcomes.
In summary, our updated review now suggests that antioxidants may be associated with an increase in live births and clinical pregnancies. We still need to see more rigorous high quality trials to allow firmer recommendations regarding the use of these drugs, but subfertile women should consider taking those combination antioxidants that are designed specifically for antenatal and pregnancy care, including folic acid, while any other antioxidants should only be taken on medical advice.

John: If you’d like to learn more about the overall findings of this updated review and those for the specific antioxidants in the included studies, you can find the review online at Cochrane Library dot com. Just go to the website and search 'antioxidants for female subfertility' to see it at the top of the list.