Long-term reproductive outcomes after exposure to different disease-modifying therapies (DMTs) in multiple sclerosis (MS) are a complex and evolving area of study, influenced by the type of DMT, timing of exposure relative to conception and pregnancy, and individual patient factors. MS primarily affects women of childbearing age, making understanding these outcomes critical for family planning and disease management.
DMTs for MS vary widely in their mechanisms, safety profiles, and recommendations regarding pregnancy. Some DMTs are considered relatively safe or have limited data suggesting minimal risk when discontinued before conception, while others carry known risks of teratogenicity or adverse pregnancy outcomes.
**Impact of DMTs on Fertility and Pregnancy**
Most first-line injectable therapies, such as interferon-beta and glatiramer acetate, have not been shown to significantly impair fertility or cause adverse long-term reproductive outcomes. These agents are often discontinued during pregnancy as a precaution, but emerging evidence suggests that inadvertent exposure early in pregnancy may not be associated with major congenital anomalies or pregnancy loss. However, their long-term effects on ovarian reserve or male fertility remain less well characterized.
Oral DMTs like fingolimod, dimethyl fumarate, and teriflunomide present more concerns. Teriflunomide, in particular, is known for its teratogenic potential and requires an accelerated elimination procedure before conception attempts. Fingolimod has been associated with fetal malformations in animal studies, and its use is generally contraindicated during pregnancy. Dimethyl fumarate’s data are more limited but suggest caution, with recommendations to discontinue before conception.
More potent immune-depleting therapies such as alemtuzumab, cladribine, and anti-CD20 monoclonal antibodies (ocrelizumab, rituximab) have complex implications. These agents can cause prolonged lymphocyte depletion, which may affect the immune environment critical for conception and fetal development. For example, cladribine requires a waiting period of several months post-treatment before attempting pregnancy to minimize risks. Alemtuzumab’s effects on fertility are less clear, but pregnancy is usually deferred for at least four months after treatment.
**Pregnancy Outcomes and Disease Activity**
Pregnancy itself often leads to a natural reduction in MS relapse rates, especially in the second and third trimesters, likely due to immunological changes. However, discontinuation or switching of DMTs before or during pregnancy can increase relapse risk, which may indirectly affect pregnancy outcomes and maternal health. Careful timing of DMT cessation and resumption postpartum is essential to balance disease control with fetal safety.
Long-term reproductive outcomes also include considerations of pregnancy complications, birth outcomes, and breastfeeding. Some DMTs may influence the risk of preterm birth, low birth weight, or other neonatal complications, though data are often limited and confounded by disease severity and other factors.
**Male Fertility and DMTs**
Less is known about the impact of DMTs on male fertility. Some therapies may affect sperm quality or quantity, but evidence is sparse. Men planning fatherhood are generally advised to discuss DMT use with their neurologist to weigh potential risks.
**Psychosocial and Sexual Health Considerations**
Beyond biological effects, MS and its treatments can influence sexual function, energy levels, and psychological well-being, which indirectly affect reproductive decisions and outcomes. Multidisciplinary care addressing physical, psychological, and relational aspects is important for optimizing reproductive health.
**Monitoring and Counseling**
Given the diversity of DMTs and individual patient circumstances, personalized counseling is critical. Women and men with MS should receive guidance on timing of pregnancy relative to DMT exposure, potential risks, and strategies to minimize disease activity during reproductive periods. This includes preconception screening, contraception counseling, and postpartum management plans.
In summary, long-term reproductive outcomes after different DMT exposures in MS depen
