Low-dose Methotrexate Therapy Does Not Affect Semen Parameters and Sperm DNA

Area of Science:

• Reproductive medicine
• Immunology
• Pharmacology

Background:

• Methotrexate is a common treatment for inflammatory diseases during reproductive years.
• Its impact on male fertility and sperm DNA integrity remains largely unexamined.
• This study addresses the unknown effects of methotrexate on male reproductive health.

Purpose of the Study:

• To evaluate sperm DNA integrity and semen parameters in men with inflammatory diseases undergoing methotrexate therapy.
• To compare these parameters with healthy volunteers and assess changes during and after methotrexate treatment.

Main Methods:

• Compared semen samples from 14 methotrexate-treated patients with 40 healthy volunteers.
• Analyzed sperm DNA fragmentation index (DFI), concentration, motility, and morphology.
• Measured blood sex hormones and methotrexate levels, including paired comparisons from 5 patients on and off therapy.

Main Results:

• Sperm DNA fragmentation index (DFI) was comparable between methotrexate-treated patients and healthy controls (11.5% vs 15.0%, P = .06).
• No significant changes in DFI were observed when patients went on or off methotrexate therapy (12.0% vs 14.0%, P = .35).
• Sperm concentration, motility, and morphology were similar; progressive motility showed minor fluctuations within WHO limits.

Conclusions:

• Low-dose methotrexate therapy does not adversely affect sperm quality or increase DNA fragmentation in men.
• The findings do not support the need for semen cryopreservation before methotrexate initiation.
• A methotrexate-free interval prior to conception is not indicated based on this study's results.