Safety of Taking Methotrexate While Pregnant

Methotrexate is a disease-modifying antirheumatic drug (DMARD) used to treat rheumatoid arthritis and certain other rheumatic diseases. The dose used for rheumatoid arthritis is considered low. Comparatively, methotrexate is also used as a high-dose cancer therapy and at high doses to terminate an ectopic pregnancy.

Pregnant woman watering orchids in kitchen
Hero Images / Getty Images

Technically-speaking, methotrexate is a dihydrofolate reductase inhibitor that impairs purine metabolism. That said, it can lead to abnormalities in ribonucleic acid and deoxyribonucleic acid synthesis. Methotrexate is contraindicated in pregnancy (category X) and is a known teratogen, which is defined as any substance, organism, or process that causes malformations in a fetus., which is defined as any substance, organism, or process that causes malformations in a fetus. Methotrexate can cause dysmorphic facial features, abnormalities of the skull and limbs, growth deficiency, developmental delays, and mental retardation.

The potential for fetal complications makes the drug a serious concern for those of childbearing age, those planning to become pregnant, and especially those who become pregnant while being treated with methotrexate.

Fetal Anomalies and Pregnancy Loss Associated With Methotrexate

Women must be made aware of the risk of fetal anomalies and pregnancy loss associated with methotrexate, even though the rate of fetal anomalies is considered low. In a French study, women with chronic inflammatory disorders who were treated with low-dose methotrexate during the first trimester were assessed. Of the 28 cases analyzed, methotrexate exposure ended prior to 8 weeks gestation in 26 women. Four women had miscarriages, while five opted for termination of the pregnancy. There were 19 live births, of which three were premature. Researchers concluded that their results support the idea that there is not a strong teratogenic risk with low-dose methotrexate, providing the drug is stopped as early in pregnancy as possible.

Another study looked at 8 methotrexate-exposed pregnancies. There was one case of typical methotrexate embryopathy identified. It is the first such case found among people taking the lower once-weekly dose of methotrexate (the usual dose for rheumatic diseases). Even though it was only one case, researchers concluded that the assumption of methotrexate safety at low doses is premature.

What About Men?

According to, a couple should not conceive during treatment if either the woman or the man is taking methotrexate. Men should wait at least three months after stopping treatment, and women for at least one ovulatory cycle after treatment.

There is a theoretical risk of sperm mutation in men taking methotrexate, but it has not been proven. Also, according to the Journal of Rheumatology, paternal methotrexate exposure at the time of conception does not seem to raise concerns or issues for the fetus.

Bottom Line

There is no 100% safe period of gestational exposure to methotrexate. The effect of methotrexate seems unpredictable, in part due to genetic differences in placental and fetal response to toxins. Following exposure to methotrexate during the first trimester, a mother choosing to continue with the pregnancy should know that there is about a 10/42 chance of abnormality in the fetus (QJM: An International Journal of Medicine).

According to Kelley's Textbook of Rheumatology, women are advised to discontinue methotrexate at least 3 months prior to conceiving. Folic acid supplementation should be continued through pregnancy. The American College of Rheumatology recommends the use of effective contraception while taking methotrexate and for 3 months after stopping methotrexate.

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  • Food and Drug Administration. Methotrexate prescribing information. Updated May 2020.

  • Low dose methotrexate in the first trimester of pregnancy: results of a French collaborative study. Lewden B et al. Journal of Rheumatology. December 2004.

  • Methotrexate (Rheumatrex, Trexall). American College of Rheumatology. Michael Cannon, M.D. May 2012.

  • Methotrexate Embryopathy After Exposure to Low Weekly Doses in Early Pregnancy. Martin MC, et al. Reproductive Toxicology. October 26, 2013.

  • Paternal Exposure to Methotrexate and Pregnancy Outcomes. Journal of Rheumatology. Beghin, et al. January 15, 2011.

  • The effects of methotrexate on pregnancy, fertility and lactation. QJM: An International Journal of Medicine. 1999.

  • Kelley's Textbook of Rheumatology. Elsevier Saunders. Volume I. Pregnancy in the Rheumatic Diseases. Chapter 39. Page 552.

By Carol Eustice
Carol Eustice is a writer covering arthritis and chronic illness, who herself has been diagnosed with both rheumatoid arthritis and osteoarthritis.