Navigating the path of fatherhood can be complex for men undergoing treatment for rheumatic diseases.

The concern about how these medications might impact male fertility and potential pregnancy outcomes is a critical aspect that needs more light.

This article aims to provide clarity on the paternal safety of commonly used anti-rheumatic drugs, focusing on their effects on fertility and potential risks during conception.

The Impact of Rheumatic Medications on Male Fertility

Cyclophosphamide and Irreversible Infertility

  • Significant Risk: Cyclophosphamide, an alkylating agent used in managing rheumatic diseases, poses a substantial risk of causing irreversible or prolonged oligospermia.
  • Fertility Preservation: It is imperative to counsel patients about fertility preservation options, including sperm banking, before commencing cyclophosphamide therapy.

Sulfasalazine and Reversible Effects

  • Reversible Azospermia: Sulfasalazine can lead to reversible azoospermia and reduced sperm motility.
  • Pre-Conception Planning: In cases where conception is delayed, discontinuing sulfasalazine for three months and performing a semen analysis is recommended.

Other Medications and Fertility Considerations

  • Aspirin and NSAIDs: While high doses of aspirin may impact spermatogenesis, low-dose aspirin and NSAIDs are generally safe.
  • Methotrexate: Contrary to package recommendations, existing data suggest that methotrexate does not significantly impact male fertility.
  • Immunosuppressants and Biologics: Current evidence does not indicate a reduction in male fertility with drugs like azathioprine, TNF-alpha blockers, or other biologics.

Paternal Exposure and Teratogenic Risk

Direct Impact on Sperm and Seminal Fluid

  • Mechanisms of Teratogenicity: The risk of male-mediated teratogenicity can arise from direct drug effects on sperm development or seminal fluid transfer during intercourse.
  • Challenges in Assessment: Evaluating the risk is complex due to the lack of extensive studies focusing on paternal drug exposure and teratogenic outcomes.

Medications with Known Teratogenic Risks

  • Cyclophosphamide: Known to cause direct DNA damage in germ cells, it should be avoided for three months before conception.
  • Thalidomide: Despite low seminal fluid levels, its high teratogenic risk warrants avoidance in men planning to conceive.

Navigating Treatment Decisions for Prospective Fathers

Navigating Treatment Decisions for Prospective Fathers - Safe Therapeutics

  • Counseling and Decision-Making: Men undergoing treatment for rheumatic conditions should engage in thorough discussions with their healthcare providers about the implications of their medication on fertility and potential pregnancy outcomes.
  • Individualized Approaches: Treatment plans should be tailored, considering the patient’s desire for fatherhood, the severity of the rheumatic condition, and the risks associated with medication.


For men with rheumatic diseases planning to embark on the journey of fatherhood, understanding the impact of their medication on fertility and potential pregnancy outcomes is crucial.

While medicines like cyclophosphamide and sulfasalazine have known effects on male fertility, others like methotrexate and various biologics have shown compatibility with paternal exposure.

However, the landscape of paternal drug safety in rheumatology is still evolving, underscoring the need for ongoing research and individualized patient care.

Prospective fathers should engage in open dialogues with their healthcare providers to navigate the complexities of treatment while considering their reproductive goals. By staying informed and proactive, men can make empowered health decisions and family planning decisions.