At the Controversies in Rheumatology session at the 2015 CRA Meeting, Dr. Carl Laskin presented a very informative and entertaining talk on whether there is reasonable evidence for an adverse effect on conception or pregnancy when the male is on MTX.
Based on a general poll prior to the presentation, 50% of the audience said that they would advise a patient to stop MTX for 3 months prior to conception, whereas the other 50% would not, indicating a true controversy.
The percentage of anomalies (usually craniofacial) found in women on MTX during pregnancy varies between 9-17%. Weber-Schoendorfer found that women stopping MTX prior to conception had anomaly rates decrease from 6.6% to 3.5% and spontaneous abortion rates decreased from 42.5% to 14.4%. This was independent of how long they stopped it before conception. This begs the question of whether women need to hold MTX for an entire 3 months prior to conception or even at all. From a legal perspective, as this is not clear, we should probably continue to recommend holding MTX for 3 months prior to conception. The big controversy is how to approach accidental pregnancies on MTX which remains to be seen.
With regards to MTX use in men, issues include fertility and pregnancy outcomes. Data from one study showed that MTX in men can cause reversible oligoathenospermia. Based on this, we may consider holding MTX to help with conception in couples having fertility difficulty.
What about teratogenicity? According to Mother Risk, there are no adverse pregnancy outcomes in men exposed to MTX around the time of conception. This is supported by data from two studies. Beghin et al (2011) followed 42 pregnancies in 40 men on MTX and found 36/42 had live births with no anomalies reported. There were 3 miscarriages and 3 elective terminations. Wallenius et al (2015) reported on 29 pregnancies involving men who were exposed to MTX (up to 30 mg/wk) within 12 weeks of conception and found no adverse pregnancy outcomes or anomalies. Despite these recent case series, the product monograph for methotrexate still warns on potential teratogenicity with methotrexate in men at the time of exposure.
Bottom line: You would not be wrong if you either advised for or against holding MTX prior to conception. Semen analysis is not needed or helpful, as there is no abnormality noted on sperm analysis that can predict an anomaly or birth defect. If the female partner of a man on MTX gets pregnant accidentally, you likely do not need to recommend termination. If you are worried, you could do Level II U/S (after 18w) to determine embryonopathy. When asked what he does, Dr. Laskin stated that he counsels on the data presented but ultimately does not recommend holding MTX in men. prior to conception.
Dr. Jamal is a Clinical Associate Professor at the University of British Columbia and an active staff physician at Vancouver Coastal Health. Her interests include diagnosis and prognosis of early inflammatory arthritis, and timely assessment and access to care for patients with rheumatoid arthritis.View Full Bio