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Risk of Paternal Exposure to Anti-Rheumatic Drugs

Seminars in Arthritis and Rheumatism features a review of the effects of paternal use of antirheumatic drugs on pregnancy, specifically addressing the effects of NSAIDs, steroids, DMARDs and biologics on spermatogenesis and the effect on pregnancy outcomes and offspring.

There is limited data regarding paternal exposure to arthritis medications, and less counseling of would-be fathers about the fetal effects of their medications.  This review discusses the approach and provides a compendium of data in text and table form on what is currently known, as digested by authorities in this area. 

There are several take-home messages from this report:

1. Many of our current limitations are due to a lack of robust data regarding paternal exposure with individual drugs.

2. Many antirheumatic medications can be continued in men who want to father a child.

3. Regular pre-conceptional counseling should be given to male patients of fertile age as an integral part of family planning.

4. It is erroneous to extrapolate from the female pregnancy experience when counseling their male partners.

Examples of drug effect on Spermatogenesis and Counseling Recommendations include:  

DrugSpermatogenesisMale Counseling
NSAIDSNot fully investigated no link between paternal drug exposure and adverse pregnancy outcomes
SteroidsLimited data; no correlation with infertility in menNo harmful effects have emerged for low (<10 mg prednisone/day) doses.
MTXStudies showed alterations in sperm DNA after MTX exposure Some believe it is ok to maintain MTX therapy in men throughout the disease course to avoid unnecessary flares, as controlled studies have not shown increased malformation rates with male exposure
SSZOligospermia, reduced mobility and increase of pathologic sperm morphology Stop SSZ 3 months before conception 
MMFLimited data; but no effect on sperm in rat studies MMF is a known, clear teratogen in women. But 3 studies in men have failed to show any increase risk of malformations with male use of MMF.
AZANo impairment No increased risk of congenital abnormalities in offspring of fathers treated with thiopurines and male fertility not affected
 TNF inhibitors No impairment TNFi do not influence male fertility or harm offspring. Risks are the same as female exposure and thus should be continued to avoid flare (if needed)
Disclosures: 
The author has no conflicts of interest to disclose related to this subject

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