Effects of antioxidant use in fertility parameters on animal models using methotrexate and implications: a systematic review

Introduction: Methotrexate (MTX) is a widely used drug against diseases like cancer and rheumatoid arthritis. The genotoxic nature of MTX affects male fertility, causing an increase in oxidative stress in semen and testicular tissue, and affecting spermatic parameters like motility, count, etc. Antioxidant use is documented to help mediate oxidative stress in patients with infertility. Objective: To review the literature to analyze the effects antioxidants have on animal models taking methotrexate on fertility and oxidative stress parameters. Materials and Methods: A systematic review encompassing two databases: PubMed and Web of Science, terms used in the search were: “male”, “methotrexate”, “antioxidants” and “infertility” as well as synonyms for the two latter terms. The PICO portal tool joined both searches and presented review titles and abstracts for selection. Exclusion criteria included animal models with underlying pathologies, subjects without MTX exposure, or studies that didn’t measure fertility outcomes. The review protocol was published in PROSPERO. Two blinded researchers conducted title & abstract screening, and an additional reviewer participated in case of discrepancy. Data extracted were: name of the author, year of publication, article title, animal model, sample size, and fertility outcomes before and after intervention (sperm motility, count and abnormal percentage; oxidative stress; sperm DNA fragmentation and testicular weight). Results: The joined search yielded 279 articles, 22 were duplicates. The first reviewer selected 35 articles for a full-length review. As a pilot, 10% of the articles were analyzed. This sample will help determine the deleterious or protective role antioxidants have. Conclusion: There is evidence of antioxidant use to mediate methotrexate-induced genotoxicity in male fertility parameters.