Podcast: Antioxidants for male subfertility

The Cochrane Gynaecology and Fertility Group maintains a pair of reviews on the use of antioxidants in the treatment of subfertility. The review for males was updated in May 2022 and we asked Wiep de Ligny from the Radboud University Medical Center at Nijmegen in the Netherlands to tell us about the importance of the review and its latest findings in this podcast.

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Mike: Hello, I'm Mike Clarke, podcast editor for the Cochrane Library. The Cochrane Gynaecology and Fertility Group maintains a pair of reviews on the use of antioxidants in the treatment of subfertility. The review for males was updated in May 2022 and we asked Wiep de Ligny from the Radboud University Medical Center at Nijmegen in the Netherlands to tell us about the importance of the review and its latest findings in this podcast.

Wiep: Although male subfertility is a widespread problem, the underlying causes are unclear and treatment options are lacking. One possible cause, which is reportedly present in up to 4 in every 5 subfertile men, is oxidative stress. In this, an excessive amount of reactive oxygen species can damage the sperm cell. This may weaken the cell or decrease their number, leading to impaired fertility. Antioxidants, which are substances present in our food, could prevent or neutralize oxidative stress and have been tested as a treatment for subfertile men.
Our review, therefore, investigates whether oral supplementation of antioxidants could improve the clinical pregnancy rate and live birth rate in subfertile men and their partners, and we've found evidence that it seems to do so. 
In the previous update of this review, in 2019, we concluded that there was evidence that treatment of subfertile men with antioxidants could improve live births, but that this evidence was of low quality and based on small studies. Now, three years later, we've added another 29 studies, which brings us to 90 studies and more than 10,000 couples. These studies investigated 18 different types of antioxidant or combinations of them and compared them with placebo, no treatment, or another antioxidant supplement. Unfortunately, though, despite recommendations made in the last update, there are still very few studies reporting clinical outcome measures. 
Only 12 of the 90 studies reported on live birth but, when their results are combined, these show a statistically significant benefit of antioxidant use, based on 246 live births from 1283 couples. Clinical pregnancy rate was reported in 20 studies and, based on data from just over 1700 couples, we found significantly more pregnancies in the group using antioxidants than in the control group.
We also wanted to look at adverse events and side effects, but these were poorly reported. However, based on the studies in this update, there appeared to be no association between antioxidant use and miscarriage but there were more gastrointestinal symptoms such as nausea and abdominal pain in the group using antioxidants than in the control group. 
To conclude, antioxidant supplementation in subfertile men appears to improve clinical pregnancy rate and live births. But it's important to note that all the results I've mentioned are based on very low to low quality evidence and because of the large number of different antioxidants used in the studies, we could not tell if one antioxidant was better than the other. This means that we still need more high quality data from large clinical trials to provide the evidence needed to answer this important question.

Mike: If you'd like to learn more about what the current evidence shows, and to watch for the next update of this review, it's available at Cochrane Library dot com. If you go to the website and type 'antioxidants for male subfertility' you'll see the link to it.

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