How long before conception should methotrexate be held in both male and female patients?

• A. 1 month
• B. 6 weeks
• C. 3 months
• D. 6 months

Answer: (C)

Methotrexate is highly teratogenic, so stopping it before conception helps prevent fetal harm from drug exposure in both eggs and sperm. The roughly three-month interval matches the time needed for a full cycle of germ cell development—about three months for oocytes in females and the duration of spermatogenesis in males—so conception occurs with gametes that have not been exposed to methotrexate. This washout period gives the body time to clear the drug and for new, drug-free gametes to form, reducing the risk of birth defects or miscarriage. Shorter intervals could allow residual drug effects to impact the embryo, while three months is a practical, commonly recommended window for both sexes.