ArticleAnnals of the rheumatic diseases2023
Is methotrexate safe for men with an immune-mediated inflammatory disease and an active desire to become a father? Results of a prospective cohort study (iFAME-MTX).
Article in Annals of the rheumatic diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- The protective role of curcumin in mitigating drug-induced toxicity in male reproductive system.Frontiers in pharmacology · 2025Pooled it
- Urate-lowering agents do not have clinically relevant negative effects on sperm quality and reproductive hormones in men with gout: a prospective open-label cohort study.Rheumatology international · 2024Trial
- Fertility and Birth Outcomes in Rheumatoid Arthritis: A Narrative Review.Rheumatology and therapy · 2026Review
- Risk-benefit considerations for antirheumatic drug use in pregnancy, breastfeeding, and male preconception: expert perspectives.EULAR rheumatology open · 2026Article
- Methotrexate Maintenance After Initiation of Biological or Targeted Synthetic DMARDs in Rheumatoid Arthritis: Results from the 2-Year Longitudinal Prospective Non-interventional STRATEGE2 Study.Rheumatology and therapy · 2026Article
- Reproductive Health in Rheumatology: Making 'Early and Regular' Work in Practice.EULAR rheumatology open · 2025Review
- Article
- Male Fertility in Spondyloarthritis: from Clinical Issues to Cytokines Milieu. A Narrative Review.Current rheumatology reports · 2024Review
- Male patients with inflammatory joint diseases are less likely than controls to be childless: results from a Norwegian population-based cohort study of 10 865 patients.Annals of the rheumatic diseases · 2024Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCurrent scientific evidence guiding the decision whether men with an active desire to become a father should be treated with methotrexate (MTX) remains controversial. We aimed to prospectively evaluate the testicular toxicity profile of MTX focusing on several markers of male fertility, including semen parameters and sperm DNA fragmentation index (sDFI). As a secondary outcome, we aimed to evaluate whether MTX-polyglutamates can be detected in spermatozoa and seminal plasma and to evaluate the enzymatic activity in spermatozoa of folylpolyglutamate synthetase (FPGS).
methodsIn a prospective cohort study, men ≥18 years who started therapy with MTX were invited to participate (MTX-starters). Participants were instructed to produce two semen samples (a pre-exposure and a post-exposure sample after 13 weeks). Healthy men ≥18 years were invited to participate as controls. Conventional semen analyses, male reproductive endocrine axis and sDFI were compared between groups. FPGS enzymatic activity and MTX-PG1-5 concentrations were determined by mass spectrometry analytical methods.
resultsIn total, 20 MTX-starters and 25 controls were included. The pre-exposure and postexposure semen parameters of MTX-starters were not statistically significant different. Compared with healthy controls, the conventional semen parameters and the sDFI of MTX-starters were not statistically significant different. These data were corroborated by the marginal accumulation of MTX-PGs in spermatozoa, consistent with the very low FPGS enzymatic activity associated with the expression of an alternative FPGS splice-variant. DISCUSSION: Treatment with MTX is not associated with testicular toxicity, consistent with the very low concentration of intracellular MTX-PG. Therefore, therapy with MTX can be safely started or continued in men and with a wish to become a father.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.