One of the questions I often get is from patients who want to know if there is a supplement they can take to restore their fertility. Some of the supplements are little more than a tweaked daily vitamin with a “fertility optimized” mix of vitamins. They probably won’t hurt you but hard scientific evidence is weak at best to enthusiastically recommend that everyone get on the supplement bus.
All of us would like if science could issue a unequivocable result for every question we are struggling with. How can we find the best health care practices when there are so many studies with conflicting results? Which studies should we believe? How can we better understand what the science is telling us? One method is through the Cochrane Collaboration which is an organization and a methodology to look at multiple studies that are asking the same question and identifying studies that were well done (appropriate controls used, good statistics, reproducibility of results) and looking for a common, evidence-based message. The purpose of doing an Cochran review is to find the truths in studies so that patients can benefit from evidence based health care instead of anecdotal stories and a physician’s own limited experience. The methodology that is used for a Cochrane review is explained here. Briefly, a Cochran systemic review “is a high-level overview of primary research on a particular research question that tries to identify, select, synthesize and appraise all high quality research evidence relevant to that question in order to answer it.“
- Systematic reviews seek to collate all evidence that fits pre-specified eligibility criteria in order to address a specific research question
- Systematic reviews aim to minimise bias by using explicit, systematic methods
- The Cochrane Collaboration prepares, maintains and promotes systematic reviews to inform healthcare decisions: Cochrane Reviews
A patient wanted to know which supplements are best to treat DNA fragmentation in the sperm head, which degrades fertility.
In a published Cochran review in 2013, Dr. Marian G. Showell and colleagues published “Antioxidants for Male Subfertility”. The abstract of their study can be found here and the full article with a “plain language summary” here, and copied below:
Review question: do supplementary oral antioxidants improve fertility outcomes for subfertile men when compared with placebo, no treatment or another antioxidant?
Background: many subfertile men who are part of a couple undergoing fertility treatment are also taking dietary supplements in the hope of improving their fertility. It is important that these men have access to high quality evidence that informs them on the benefits and risks of taking an antioxidant. This review aimed to assess whether oral antioxidants would increase the chances of a couple with a subfertile male partner achieving a clinical pregnancy and ultimately a live birth. This review did not examine the use of antioxidants in men with normal sperm.
Study characteristics: the Cochrane review authors included in this updated review 48 randomised controlled trials that compared single and combined antioxidants with placebo, no treatment or another antioxidant in a population of 4179 subfertile men. The duration of the trials ranged from 3 to 26 weeks with follow up ranging from 3 weeks to 2 years. The men were aged from 20 to 52 years. Most of the men enrolled in these trials had low total sperm motility and sperm concentration. One study enrolled men after varicocelectomy (surgical removal of an engorged vein in the scrotum), one enrolled men with a varicocoele (an engorged vein in the scrotum) and one recruited men with chronic prostatitis (infection of the prostate gland). Three trials enrolled men who, as a couple, were undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) and one trial enrolled men who were part of a couple undergoing intrauterine insemination (IUI). The data were current to 31 January 2014.
Funding sources were stated by 15 trials. Four of these trials stated that funding was from a commercial source and the remaining 11 obtained funding through non-commercial sources or university grants. Thirty-three trials did not report any funding sources.
Key results: antioxidants may have been effective in treating subfertile men but the reporting of studies was too inconsistent to be confident in these findings. The live birth results suggest that we would expect a live birth of a baby for 5 out of 100 subfertile men who did not take any antioxidants, compared to between 10 and 31 out of 100 men who were taking antioxidants. The results for the clinical pregnancy rate showed an expected clinical pregnancy for 6 out of 100 subfertile men who did not take any antioxidants, compared to between 11 and 28 out of 100 men who were taking antioxidants. Adverse events were poorly reported and we could not make conclusions on any harmful effects. More high quality, larger placebo-controlled trials reporting on these outcomes and adverse events are needed to draw definite conclusions.
Quality of the evidence: the quality of the evidence for live birth and clinical pregnancy was deemed ‘low’ while adverse events was assessed as ‘very low’. These ‘low’ and ‘very low’ assessments were due to the lack of a clear description of trial methods and inconsistent, inadequate reporting of live births and clinical pregnancies. Not enough trials compared the same interventions to make any conclusions about whether one intervention worked better than the other.
Bottom line: We need better studies to determine whether oxidants are beneficial. In the absence of these studies, it is prudent to have a discussion with your doctor about the risks/benefits of any supplement you may be considering.