Background/Purpose: In rheumatology, fertile men and women are commonly treated with methotrexate (MTX). Maternal preconceptional MTX exposure is teratogenic, but less is known about paternal MTX exposure. Due to possible teratogenic risk, current treatment recommendations advocate that men should discontinue MTX three months before conception. This may lead to impaired adherence to treatment, fear among the future parents and even unnecessary induced abortions.
Here we systematically review and meta-analyse the collective data on paternal MTX exposure and the risk of congenital malformations.

Methods: Systematic searches in the databases PubMed, Embase, Cochrane central, and cinahl were performed 1st March 2018. We included studies with an English abstract that assessed pregnancy outcome following paternal exposure to MTX. No time restriction was applied. Review Manager Version 5.3 was used for the meta-analysis.

Results: We identified twelve studies assessing congenital malformations following paternal exposure to MTX of which 3 were case reports. Three studies were included in the meta-analysis including in total 265 fathers exposed to MTX and 1,004,834 controls. Among the MTX-exposed 13 had malformations of which 7 was major, and among the non-exposed 50,576 had malformations, of which 33,816 was major. Odds ratio for major malformations was 1.02 (95% confidence interval [CI] 0.48-2.20). Odds ratio for all malformations was 0.86 (CI 0.48-1.54). Thus no association was found.

Conclusion: In a systematic review and meta-analysis we found no association between preconceptional paternal MTX use and major or all congenital malformations. Thus, there is no evidence supporting the current recommendations to avoid paternal MTX use before conception.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/paternal-use-of-methotrexate-mtx-and-congenital-malformations-a-systematic-review-and-meta-analysis/