Fertility and Immunosuppressants: Risks, Medications, and What You Need to Know

Planning a pregnancy while taking immunosuppressants isn’t something most people expect to face. But for those managing autoimmune diseases or who’ve had organ transplants, it’s a real and urgent question: Can I get pregnant safely? And more importantly, will my medication put my baby at risk?

The answer isn’t simple. Some drugs are safe. Others aren’t. And for many, the key isn’t stopping treatment-it’s switching to the right one, at the right time. This isn’t about fear. It’s about facts. And the facts have changed a lot since the early 2000s, when doctors barely had data to go on.

Which Immunosuppressants Are Safe for Pregnancy?

Not all immunosuppressants are created equal when it comes to fertility and pregnancy. Some have decades of safety data. Others are still a mystery.

Azathioprine stands out. It’s been used in over 1,200 documented pregnancies with no increase in birth defects or miscarriages. It’s the gold standard for women with lupus, Crohn’s, or kidney transplants who want to conceive. Doctors often keep patients on azathioprine throughout pregnancy because the risk of disease flare is higher than the risk from the drug itself.

Corticosteroids like prednisone are also generally safe during pregnancy. They don’t cause birth defects, but they can raise blood pressure and blood sugar. That means close monitoring for gestational diabetes and pre-eclampsia. A 15-20% higher chance of premature membrane rupture is a real concern, but manageable with regular check-ups.

Belatacept is newer. Only three pregnancies have been reported so far, and all resulted in healthy babies. That’s promising, but too few to call it definitive. Still, for transplant patients who can’t tolerate other drugs, it’s a viable option under careful supervision.

The Dangerous Ones: What to Avoid Before and During Pregnancy

Some medications are outright unsafe. These aren’t just "use with caution"-they’re stop-now-or-wait-3-months drugs.

Methotrexate is one of the most common culprits. Used for rheumatoid arthritis and psoriasis, it’s a powerful drug that can cause severe birth defects. The rule? Stop it at least three months before trying to conceive. And no, a single dose won’t ruin your chances-but lingering levels in your body might.

Cyclophosphamide is even more serious. It’s used for severe autoimmune diseases and some cancers. In women, it can destroy ovarian tissue permanently. Studies show 60-70% of women who take more than 7 grams per square meter of body surface area lose their fertility. In men, it can cause permanent azoospermia (zero sperm count) in 40% of cases. If you’re on this drug and want kids, talk to your doctor about freezing eggs or sperm before you start.

Chlorambucil is classified as FDA Category D-meaning there’s clear evidence of harm. It’s linked to kidney malformations (8% of cases), heart defects (15%), and urinary tract problems (12%). It also blocks breastfeeding. If you need this drug, pregnancy isn’t advised.

Sirolimus has a 43% miscarriage rate in early case reports-more than double the normal rate. It’s still considered contraindicated during pregnancy, even though animal studies show no direct toxicity. Human data is too risky to ignore.

Male Fertility: It’s Not Just a Woman’s Issue

Most people think fertility risks only apply to women. That’s outdated.

Sulfasalazine, often used for ulcerative colitis and ankylosing spondylitis, cuts sperm counts by 50-60%. The good news? It’s reversible. Sperm numbers bounce back within three months of stopping the drug. If you’re trying to conceive, a simple semen analysis can confirm if your count has improved.

But here’s the problem: many of these drugs were approved before regulators required testing for male fertility effects. That means we’re still playing catch-up. The FDA now requires men to undergo semen analysis before, during, and after treatment with new immunosuppressants. But for older drugs? There’s no mandatory data. So if you’re a man on immunosuppressants and want kids, don’t assume you’re fine-get tested.

When Should You Talk to Your Doctor?

Waiting until you’re pregnant to ask about your meds is too late. You need to plan ahead.

Start the conversation at least 3 to 6 months before you try to conceive. That gives time to switch drugs, monitor your body’s response, and adjust doses. For example:

• If you’re on methotrexate: stop 3 months before trying
• If you’re on cyclophosphamide: discuss egg or sperm freezing immediately
• If you’re on azathioprine: you may not need to change anything
• If you’re on sirolimus or chlorambucil: pregnancy should be delayed until you can switch

Transplant patients face an extra layer of complexity. Stopping immunosuppressants-even briefly-can trigger organ rejection. That’s why teams of specialists (transplant doctors, rheumatologists, fertility experts) now work together to manage these cases. Over 85% of transplant centers have formal protocols in place for pregnancy planning.

Monitoring During Pregnancy

Even if you’re on a safe drug, pregnancy with an immunosuppressed system needs extra care.

Women should have monthly kidney function tests (creatinine levels). A creatinine level above 13 mg/L before pregnancy raises the risk of pre-eclampsia dramatically. Blood pressure, glucose, and fetal growth scans should be done more frequently than in typical pregnancies.

For babies born to mothers on immunosuppressants, immune system development is a concern. Studies show newborns of transplant recipients have significantly lower B- and T-cell counts. That means a 2.3-fold higher risk of serious infections in the first year of life. Pediatricians need to be aware-vaccines may need to be delayed, and early signs of infection should be treated aggressively.

What About Breastfeeding?

Some drugs are okay. Others aren’t.

Azathioprine passes into breast milk in tiny amounts. Most experts agree it’s safe to breastfeed while on it, especially if the baby is healthy and full-term.

Chlorambucil and cyclophosphamide are absolute no-gos. They can poison a nursing infant.

For newer drugs like belatacept or sirolimus, data is too limited. Most doctors recommend avoiding breastfeeding until more is known.

If you’re unsure, ask for a drug-specific lactation consultation. Many hospitals have specialists who can check drug levels in breast milk and give clear guidance.

What’s Still Unknown?

We’ve come a long way since 2000, when doctors had almost no data on children born to parents on immunosuppressants. But big gaps remain.

Long-term studies on brain development, immune function, and cancer risk in children exposed in utero? Almost none. We don’t know if exposure to newer drugs like belatacept affects a child’s immune system 20 years later.

Also, there’s no national registry tracking pregnancy outcomes for immunosuppressant users. That means data is scattered, incomplete, and slow to grow. Researchers are pushing for this, but until it happens, decisions are still based on small studies and case reports.

And while the FDA now requires rigorous testing for male reproductive toxicity before approving new drugs, older medications are still flying blind. That’s why so many men are surprised to learn their fertility was affected.

Bottom Line: You Have Options

Having an autoimmune disease or a transplanted organ doesn’t mean you can’t have a child. But you can’t wing it.

Know your drug. Know your risks. Know your timeline. And don’t wait until you’re pregnant to ask questions.

Work with your care team-your rheumatologist, transplant specialist, and OB-GYN. Ask for a preconception fertility review. Get blood tests. Get sperm analyses. Get a second opinion if needed.

Pregnancy is possible where it was once forbidden. But only if you plan for it.