Fertility and Immunosuppressants: What You Need to Know About Medication Risks and Planning for Pregnancy

Planning a pregnancy while taking immunosuppressants isn’t something most people expect to navigate. But for those managing autoimmune diseases like lupus, rheumatoid arthritis, or who’ve had organ transplants, it’s a reality. These medications keep the body from attacking itself or a transplanted organ-but they can also interfere with fertility, pregnancy, and the health of the baby. The good news? With the right planning, many people can have safe, healthy pregnancies. The bad news? Not all immunosuppressants are created equal. Some are risky. Others are surprisingly safe. And knowing the difference can make all the difference.

Which Immunosuppressants Are Safe During Pregnancy?

Not every drug in this category is dangerous. In fact, one of the most commonly used immunosuppressants, azathioprine, has been studied in over 1,200 pregnancies with no increased risk of birth defects or miscarriage. It’s considered one of the safest options for both men and women who need to stay on medication while trying to conceive. Many transplant centers now recommend azathioprine as the go-to drug for pregnant patients because it crosses the placenta minimally and doesn’t harm developing cells.

Corticosteroids like prednisone are also generally safe during pregnancy, though they can slightly increase the risk of premature rupture of membranes by 15-20%. They’re often continued throughout pregnancy because stopping them can trigger a flare-up of the underlying disease-which is far riskier than the medication itself. The key is using the lowest effective dose and monitoring closely.

Belatacept, a newer drug used mainly in kidney transplant patients, has shown early promise. Only three documented pregnancies have occurred while on belatacept, and all resulted in healthy babies without abnormalities. While the sample size is small, it’s encouraging. Still, azathioprine remains the gold standard due to decades of reliable data.

The High-Risk Drugs You Need to Stop Before Conception

Some immunosuppressants are outright dangerous during pregnancy-and not just for the baby, but for your own fertility too.

Methotrexate, often used for rheumatoid arthritis and psoriasis, is a known embryotoxin. It can cause severe birth defects, including missing limbs, facial abnormalities, and brain malformations. You must stop taking it at least three months before trying to conceive. Even small doses can linger in the body and harm a developing embryo.

Cyclophosphamide is even more serious. It doesn’t just risk birth defects-it can permanently destroy ovarian function. Up to 70% of women who receive cumulative doses over 7g/m² experience premature menopause. For men, it can cause irreversible infertility in 40% of cases. If you’re on this drug and want to have children, fertility preservation-like egg or sperm freezing-should be discussed before starting treatment.

Chlorambucil, another chemotherapy-grade drug, carries a high risk of congenital abnormalities. Studies show 8% of exposed fetuses develop renal agenesis (missing kidneys), 12% have ureteral malformations, and 15% suffer heart defects. It’s classified as FDA Risk Category D, meaning there’s clear evidence of harm. Breastfeeding is also prohibited while taking it.

Sirolimus has been linked to a 43% miscarriage rate in early case reports-more than double the normal rate. Although animal studies haven’t shown birth defects, human data is too concerning to ignore. It’s currently contraindicated during pregnancy.

How Immunosuppressants Affect Male Fertility

Most people focus on women when talking about fertility and pregnancy-but men matter too. Several immunosuppressants impact sperm production, and the effects aren’t always obvious.

Sulfasalazine, often prescribed for Crohn’s disease and ulcerative colitis, reduces sperm count by 50-60%. The good news? It’s reversible. Once you stop taking it, sperm levels usually return to normal within three months. If you’re planning a pregnancy, your doctor may switch you to mesalamine, which doesn’t affect sperm.

Like in women, cyclophosphamide can cause permanent azoospermia (no sperm) in men. Even short-term use can damage sperm DNA, which might lead to miscarriage or developmental issues. Semen analysis should be done before starting treatment, again after one full spermatogenic cycle (about 74 days), and finally 13 weeks after stopping the drug.

What’s worrying is that many older immunosuppressants were approved before regulators required testing for male reproductive toxicity. So we’re still catching up on how drugs like mycophenolate or tacrolimus affect sperm quality. The FDA now requires new drugs to be tested in controlled trials with at least 200 men-but that doesn’t help those already on older meds.

Why Preconception Counseling Isn’t Optional

Trying to get pregnant while on immunosuppressants isn’t something you can wing. You need a plan-and it needs to start months before you even try.

Most experts recommend beginning preconception counseling at least 3-6 months before attempting pregnancy. This gives time to switch medications safely, monitor disease stability, and address any fertility concerns. For example, switching from methotrexate to azathioprine takes time to ensure the old drug is fully cleared and the new one is working.

Transplant recipients face an extra layer of complexity. Stopping or changing immunosuppressants increases the risk of organ rejection. But staying on the wrong drug risks the baby’s health. That’s why a team approach is essential: your transplant doctor, rheumatologist, and a reproductive endocrinologist should all be involved. In fact, 85% of transplant centers now have formal protocols for managing pregnancy in these patients.

For women, blood tests like creatinine levels are critical. A creatinine level above 13 mg/L before pregnancy significantly raises the risk of pre-eclampsia. For men, sperm analysis is just as important. If your sperm count is low or abnormal, you may need to freeze samples before starting treatment.

What About Breastfeeding?

Many people wonder if they can breastfeed while on immunosuppressants. The answer varies by drug.

Azathioprine is generally considered safe during breastfeeding. Only tiny amounts pass into breast milk, and studies haven’t shown harm to infants. Prednisone is also low-risk, especially if taken right after nursing to minimize exposure.

But chlorambucil? Absolutely not. It’s excreted in breast milk and can suppress the baby’s immune system. Cyclophosphamide and methotrexate are also contraindicated. Sirolimus and mycophenolate are too risky to use while nursing. Always check with your doctor before starting breastfeeding-don’t assume it’s safe just because the drug is used during pregnancy.

What’s Still Unknown-and Why More Research Matters

Even with all we know, big gaps remain. Most of the data on newer drugs like belatacept or voclosporin comes from just a handful of cases. We don’t yet know how exposure to these drugs affects children’s long-term immune development. One study found that babies born to mothers on immunosuppressants had significantly lower B- and T-cell counts in their first year, putting them at 2.3 times higher risk of infections.

There’s also no long-term data on cognitive development, growth patterns, or cancer risk in children exposed in utero. And for men? We still don’t have good data on whether sperm DNA damage from these drugs leads to higher rates of childhood illness or developmental delays.

Regulators are catching up. New drugs now undergo strict reproductive toxicity testing. But for the millions already on older medications, the burden falls on patients and doctors to make informed choices with incomplete information.

What to Do Next

If you’re on immunosuppressants and thinking about having a baby:

1. Don’t stop your medication on your own. Flares can be dangerous.
2. Schedule a preconception visit with your specialist. Bring a list of all your meds.
3. Ask about switching to safer alternatives like azathioprine or corticosteroids.
4. If you’re on cyclophosphamide or chlorambucil, talk about fertility preservation immediately.
5. For men: get a semen analysis before starting or changing treatment.
6. Track your disease activity. Stable disease = safer pregnancy.
7. Work with a team: transplant doctor, rheumatologist, OB-GYN, and fertility specialist.

Having a child while managing a chronic condition isn’t easy-but it’s possible. The key is planning, not panic. With the right team and the right drugs, you can reduce risks and increase your chances of a healthy pregnancy-and a healthy baby.