QHow much time after stopping methotrexate can men father children?

A
Cynthia Lazzaro, DO

Cynthia Lazzaro, DO

Pacific Dermatology Specialists
Western University of Health Sciences
Los Angeles, CA

Methotrexate is a medication used in dermatology for psoriasis vulgaris and cutaneous lymphomas and used off-label for bullous disorders, sarcoidosis, autoimmune connective tissue diseases, and other dermatoses.

The teratogenic effects of methotrexate are well-known and females are advised to avoid pregnancy while on this medication. The effect of methotrexate on male fertility, pregnancy, and fetal outcomes will be discussed. According to the full prescribing insert for methotrexate, recommendations suggest stopping methotrexate 3 months before trying to impregnant a female partner.[1] This rationale is based on the timeframe of spermatogenesis.

There are reports of possible reversible oligospermia while on methotrexate.[2] A study out of Denmark identified all registered pregnancies in that nation from 1997 to 2015 and found no association between paternal exposure to methotrexate before and during early pregnancy and miscarriage. [3] Another study out of France revealed no congenital malformations on increase in spontaneous abortions in 40 men treated with methotrexate at the time of conception.[4] A 2017 study involving a very large cohort concluded that paternal exposure to methotrexate within 90 days before pregnancy was not associated with congenital malformations, stillbirths and preterm births.[5]

Given the unclear evidence, the recommendation for male patients to stop methotrexate three months prior to conception is safe, but the overall risk of adverse pregnancy outcomes with exposure remains low.

References:

  1. Methotrexate Tablets Package Insert. DAVA Pharmaceuticals, Inc. Reference ID: 387929.
  2. Pandhi D, Gupta R, Singal A. Gynaecomastia with oligospermia: an unusual complication of low-dose methotrexate for pustular psoriasis. Clin Exp Dermatol. 2006 Jan;31(1):138-40.
  3. Andersen J, Askaa B, Jensen T, et alP06 Paternal exposure to methotrexate and the risk of miscarriage – a register based nationwide cohort study. Archives of Disease in Childhood. 2019;104:e19-e20.
  4. Beghin D, Cournot MP, Vauzelle C, Elefant E. Paternal exposure to methotrexate and pregnancy outcomes. J Rheumatol. 2011 Apr;38(4):628-32. doi: 10.3899/jrheum.100600. Epub 2011 Jan 15.
  5. Eck, L.K.; Jensen, T.B.; Mastrogiannis, D.; Torp-Pedersen, A.; Askaa, B.; Nielsen, T.K.; Poulsen, H.E.; Jimenez-Solem, E.; Andersen, J.T. Risk of Adverse Pregnancy Outcome After Paternal Exposure to Methotrexate Within 90 Days Before Pregnancy. Obstet. Gynecol. 2017, 129, 707–714.