Paternal methotrexate use confers no teratogenic effects but may temporarily reduce fertility

The periconceptional use of methotrexate among men does not contribute to an increase in the risk of congenital anomalies, preterm birth (PTB), and being small for gestational age (SGA), but it may lead to a temporary decrease in fertility, according to a study.

The study included all children born alive in Sweden between 2006 and 2014 and their fathers. The participants were grouped into three, as follows: children born to fathers with periconceptional methotrexate exposure (exposed cohort), children whose fathers stopped methotrexate intake ≥2 years before conception (previously exposed cohort), and children of fathers with no methotrexate exposure (control cohort).

Periconceptional exposure was defined as having at least one dispensed methotrexate prescription from pharmacies 0–3 months before conception, along with at least one more dispensed methotrexate prescription 0–12 months before conception (periconceptional exposure). Previous exposure on the other hand was defined as having no dispensed methotrexate prescriptions in the 2 years before conception but having at least two dispensed prescriptions before that.

The primary outcome was congenital anomalies. Secondary outcomes included PTB, SGA, and need of intracytoplasmic sperm injection (ICSI) to achieve pregnancy. The analysis included 223 father-child pairs in the exposed cohort, 356 pairs in the previously exposed cohort, and 809,706 pairs in the control cohort.

Compared with the control cohort, the exposed cohort had similar odds of major congenital anomalies (adjusted odds ratio, [aOR], 1.1, 95 percent confidence interval [CI], 0.4–2.6), any congenital anomalies (aOR, 1.3, 95 percent CI, 0.7–2.4), and SGA (aOR, 1.1, 95 percent CI, 0.4–2.6). However, the exposed cohort had higher odds of conception by use of ICSI (aOR, 3.9, 95 percent CI, 2.2–7.1).

Meanwhile, the use of ICSI was not increased among fathers who stopped methotrexate intake ≥2 years before conception (aOR, 0.9, 95 percent CI, 0.4–1.9).