What is the effect of Methotrexate (MTX) on spermatogenesis and oogenesis, and how long before conception should a male or female patient discontinue Methotrexate (MTX) to minimize its impact on fertility?

From the Guidelines

Methotrexate should be discontinued for at least 3 months in men and 6 months in women prior to conception due to its potential effects on sperm and egg cells, as well as its teratogenic and embryotoxic effects. The medication can cause temporary oligospermia (reduced sperm count) and chromosomal abnormalities in sperm, and its effects on female fertility and fetal development are also a concern 1. Some studies suggest that men may not need to discontinue methotrexate prior to conception 1, but the evidence is not strong, and a 3-month washout period is generally recommended 1. Women, on the other hand, should discontinue methotrexate at least 6 months before attempting pregnancy, as the medication can deplete folate stores needed for proper fetal development and can potentially remain in tissues 1. During this pre-conception period, both men and women should begin taking folic acid supplements (typically 1mg daily) to replenish folate levels 1. Patients should not stop methotrexate without consulting their healthcare provider, as alternative medications may be needed to control their underlying condition 1. The washout period allows the body to clear the medication and restore normal reproductive cell function, reducing the risk of birth defects or pregnancy complications 1. Reliable contraception should be used until the recommended washout period is complete 1. Key points to consider include:

• Methotrexate's potential effects on sperm and egg cells
• The recommended washout periods for men and women
• The importance of folic acid supplements during the pre-conception period
• The need for reliable contraception until the washout period is complete
• The potential risks of birth defects or pregnancy complications if methotrexate is not discontinued prior to conception 1.

From the FDA Drug Label

Methotrexate can cause fetal death or teratogenic effects when administered to a pregnant woman. Pregnancy should be avoided if either partner is receiving methotrexate; during and for a minimum of three months after therapy for male patients, and during and for at least one ovulatory cycle after therapy for female patients.

Methotrexate affects spermatogenesis and ova by causing fetal death or teratogenic effects. To get pregnant,

• male patients must stop methotrexate for at least three months before attempting pregnancy.
• female patients must stop methotrexate for at least one ovulatory cycle before attempting pregnancy 2.

From the Research

Methotrexate and Affection on Spermatogenesis or Ova

• Methotrexate is a folic acid antagonist that can affect fertility and pregnancy outcomes 3, 4, 5.
• The effect of methotrexate on male fertility is not well understood, but it is recommended to stop methotrexate three months prior to conception as a precautionary measure 3.
• A study found that paternal periconceptional methotrexate use does not increase the risk of congenital anomalies, preterm birth, or small for gestational age in offspring, but may temporarily reduce fertility 6.

Recommendations for Stopping Methotrexate

• For males, it is recommended to stop methotrexate at least three months prior to conception 3.
• For females, methotrexate should be stopped before conception, as it can cause teratogenic effects if taken during pregnancy 4, 5.
• One study suggests that stopping methotrexate at least two years before conception may be sufficient to minimize the risk of adverse effects on fertility and pregnancy outcomes 6.

Teratogenic Effects of Methotrexate

• Methotrexate can cause teratogenic effects if taken during pregnancy, particularly between 6-8 weeks post-conception 4, 5.
• The teratogenic effects of methotrexate can include growth deficiency, microcephaly, hypoplasia of skull bones, and limb abnormalities 4, 5.
• A distinct syndrome may occur with early exposure to methotrexate, characterized by tetralogy of Fallot and other neural crest cell-related abnormalities 5.

Fertility and Methotrexate

• Methotrexate may temporarily reduce fertility in males, but the effect is not well understood 6.
• A study found that methotrexate had no unfavorable effect on male fertility, but a long follow-up is needed to exclude possible teratogenic effects 7.
• The use of intracytoplasmic sperm injection (ICSI) may be increased in couples where the male partner is taking methotrexate 6.