Reviewed research

Authors Showell MG, Brown J, Yazdani A, Stankiewicz MT, Hart RJ

Review Date Mar 2011

Citation Cochrane Database of Systematic Reviews 2011, Issue 1. Art No: CD007411



It has been estimated that between 30% and 80% of male subfertility cases could be due to the damaging effects of oxidative stress on sperm. Oxidative stress occurs when reactive oxygen species (ROS) overcome the semen’s natural antioxidant defences and cause cellular damage. Increased ROS levels in recent years are thought to be due to environmental factors such as electromagnetic radiation, lifestyle factors such as obesity and poor diet and other factors such as infection. It is thought that supplementation with antioxidants may improve sperm quality by reducing oxidative stress. 



This Cochrane review aimed to evaluate the effect of oral supplementation with antioxidants for male partners of couples undergoing assisted reproduction techniques (ART).



Search strategy: The authors searched the Cochrane Menstrual Disorders and Subfertility Group Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, CINAHL, PsycINFO and AMED databases (from their inception until Febuary 2010), trial registers, sources of unpublished literature, reference lists and they asked experts in the field.

Selection criteria; Randomised controlled trials comparing any type or dose of antioxidant supplement (single or combined) taken by the male partner of a couple seeking fertility assistance with placebo, no treatment or another antioxidant, were included. The outcomes were live birth, pregnancy, miscarriage, stillbirth, sperm DNA damage, sperm motility, sperm concentration and adverse effects.

Data collection and analysis: Two review authors independently assessed studies for inclusion and trial quality, and extracted data. 



Thirty-four trials with 2876 couples in total were included.
Live births: three trials reported live birth. Men taking oral antioxidants had an associated statistically significant increase in live birth rate (pooled odds ratio (OR) 4.85, 95% CI 1.92 to 12.24; P = 0.0008, I2 = 0%) when compared with the men taking the control. This result was based on 20 live births from a total of 214 couples in only three studies.
Pregnancy rate: there were 96 pregnancies in 15 trials including 964 couples. Antioxidant use was associated with a statistically significant increased pregnancy rate compared to control (pooled OR 4.18, 95% CI 2.65 to 6.59; P < 0.00001, I2 = 0%).



The evidence suggests that antioxidant supplementation in subfertile males may improve the outcomes of live birth and pregnancy rate for subfertile couples undergoing ART cycles. Further head to head comparisons are necessary to identify the superiority of one antioxidant over another and to determine appropriate dosing.


Points to Note
  1. There is limited evidence that antioxidant supplementation improves outcomes for subfertile couples. Some trials have suggested benefit, while others have failed to demonstrate benefit, hence this Cochrane review was done.
  2. A wide variety of antioxidants and comparisons were used in the included trials making it difficult to determine the potentially effective agent(s). Head to head comparisons are needed in future trials.
  3. The primary outcome for the review (live birth per couple) was only reported in 3 trials of the 34 included trials and there were some methodological issues in these trials.
  4. The authors reported a high potential for reporting bias in the trials suggesting caution in interpretation of results.
  5. Evidence regarding side effects of antioxidant use is scant and these need to be measured in future trials


Website: http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles/CD007411/frame.html

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