Is caffeine intake a risk factor leading to infertility? -An epidemiological systematic review of controlled clinical studies

Abstract Background: Previous studies showed that high dose of caffeine intake may induce some specific human reproductive system diseases, even lead to infertility. This review is aimed to systematically review the evidence from all controlled clinical studies of caffeine intake for infertility. Methods: Relevant randomized/quasi-randomized controlled trials, non-randomized clinical studies, cohort studies, and case-control studies were included. Participants were either those without a history of infertility who are willing to have a baby (for prospective studies) or infertile patients with confirmed diagnosis (for retrospective studies). Caffeine or caffeine-containing beverage was observed as the exposure factor. The key outcome was the diagnosis of infertility. Results: Four studies (one cohort study and three case-control studies) involving 12912 participants were included. According NOS, the average score of case-control studies was 6, and the cohort study achieved 9. Meta-analysis and subgroup analysis were conducted. The results showed that low (OR 0.95, 95%CI 0.78-1.16), medium (OR 1.14, 95%CI 0.69-1.86) and high doses (OR 1.86, 95%CI 0.28-12.22) of caffeine intake may not increase the risk of infertility. The GRADE method was used to assess the certainty of the evidence and the results showed that the quality of the three evidence bodies were all low. Conclusion: Our study provides low quality evidence that regardless of low, medium and high doses of caffeine intake do not appear increase the risk of infertility. But the conclusion should be treated with caution. We suggest high-risk population of infertility may consider to control the dose of caffeine intake (less than 200mg/d). Systematic review registration: PROSPERO CRD42015015714