Fertility and Immunosuppressants: What You Need to Know About Medication Risks and Counseling

When you’re on immunosuppressants for an autoimmune disease or after an organ transplant, planning a baby isn’t just about timing-it’s about survival. Not just your own, but your future child’s too. These drugs keep your body from attacking itself or a new kidney, liver, or heart. But they also mess with the very systems that make babies possible. The good news? You can have a healthy pregnancy. The catch? It takes planning, patience, and the right team.

Which Immunosuppressants Are Safe During Pregnancy?

Not all immunosuppressants are created equal when it comes to fertility and pregnancy. Some are outright dangerous. Others? They’ve been used in hundreds of pregnancies with no major red flags.

Azathioprine is the gold standard. Over 1,200 pregnancies in studies dating back to 2000 show no increase in birth defects or miscarriages. It’s the go-to for women with lupus or kidney transplants who want to conceive. Doctors often switch patients to azathioprine months before trying to get pregnant because it’s predictable and safe.

Contrast that with cyclophosphamide. This drug, often used for severe rheumatoid arthritis or vasculitis, can permanently destroy ovarian tissue. In women who take more than 7 grams per square meter of body surface, 60-70% lose their fertility. For men, it causes irreversible sperm loss in about 40% of cases. If you’re on this drug and thinking about kids, talk to your doctor about freezing eggs or sperm before starting treatment.

Methotrexate is another no-go during pregnancy. It’s a powerful drug that causes severe birth defects-even at low doses. You need to stop it at least three months before trying to conceive. And even then, some doctors recommend waiting longer. It doesn’t just affect the baby-it can linger in your system long after you stop taking it.

For men, sulfasalazine is a sneaky one. It cuts sperm count by 50-60%, making conception harder. The good part? It’s reversible. Once you stop the drug, sperm numbers bounce back in about three months. But you can’t just stop cold. You need to plan the switch with your doctor.

Then there’s sirolimus. It’s been linked to a 43% miscarriage rate in early case reports-more than double the normal rate. Even though animal studies didn’t show birth defects, human data is too scary to ignore. It’s still contraindicated in pregnancy. Belatacept is newer and looks promising-only three pregnancies reported so far, all with healthy babies-but there’s not enough data yet to call it safe. Stick with what’s proven.

Steroids and Fertility: The Hidden Impact

Prednisone and other corticosteroids are often seen as harmless because they’re used for so many things-from asthma to eczema. But when you’re trying to get pregnant, they’re not as innocent as they seem.

These drugs interfere with the hormones that control ovulation in women and sperm production in men. Studies show that women on long-term steroids have a 15-20% higher chance of premature rupture of membranes. That means your water breaks too early, increasing the risk of early delivery and complications for the baby.

For men, steroids can lower testosterone levels, which reduces sperm quality and quantity. It’s not always permanent, but it can last months after stopping. If you’re on daily steroids and your partner hasn’t conceived after six months, get your sperm checked. It might not be her issue.

Here’s the upside: unlike methotrexate or cyclophosphamide, steroids can often be continued during pregnancy-with close monitoring. Your doctor might lower the dose once you’re pregnant, but stopping cold could trigger a disease flare. The goal isn’t to stop them-it’s to use the lowest effective dose.

Male Fertility: The Overlooked Side of the Story

Most fertility conversations focus on women. But men on immunosuppressants face real risks too-and they’re rarely discussed.

Chlorambucil, used for some types of lymphoma and autoimmune diseases, is classified as FDA Risk Category D. That means there’s clear evidence of harm. In 43 reported cases, 8% of babies had missing kidneys, 12% had malformed ureters, and 15% had heart defects. If you’re on this drug, fathering a child isn’t just risky-it’s potentially dangerous.

Sulfasalazine? It lowers sperm count. But as mentioned, it’s reversible. The FDA recommends semen analysis at three key points: at the start of treatment, after one full sperm cycle (about 74 days), and 13 weeks after stopping. That’s not something your rheumatologist will usually bring up. You have to ask.

And here’s the kicker: many of these drugs were approved decades ago-before regulators required testing for male fertility effects. That means we’re still playing catch-up. A 2020 study found that most immunosuppressants used today were never properly tested for how they affect sperm. The FDA now requires new drugs to include male fertility studies, but older ones? They’re still in the dark.

Preconception Counseling: Why Timing Matters

You can’t wing this. Waiting until you’re pregnant to ask about your meds is too late.

Experts recommend starting the conversation at least six months before you want to conceive. That gives you time to switch drugs, monitor recovery, and stabilize your condition. For example, if you’re on methotrexate, you need to stop three months before trying. If you’re on cyclophosphamide, you might need to freeze eggs or sperm first.

For transplant patients, the stakes are even higher. A flare-up of rejection or disease activity during pregnancy can be life-threatening-for both you and your baby. Your transplant team needs to work with your rheumatologist or OB-GYN to make sure your drug levels are just right. Too much? You risk infection. Too little? Your body might attack the transplant.

Monitoring is key. Before pregnancy, your creatinine levels should be under 13 mg/L. Higher than that? Your risk of preeclampsia shoots up. Monthly blood tests are standard. For men, sperm counts should be tracked before, during, and after treatment changes. Don’t assume your fertility is fine because you’ve been sexually active. Sperm quality can drop without you noticing.

What About Breastfeeding?

Once the baby’s born, the question shifts: can I breastfeed?

Chlorambucil? No. It passes into breast milk and can suppress the baby’s immune system. Azathioprine? Yes, with caution. Studies show only tiny amounts pass into milk, and no adverse effects have been reported in over 100 breastfed infants. Still, your pediatrician should monitor the baby for signs of infection.

For other drugs like mycophenolate or sirolimus, breastfeeding isn’t recommended. The data is too thin. If you’re on one of these, you’ll need to decide: formula or risk. There’s no perfect answer, but you’re not alone. Many mothers on immunosuppressants choose to pump and dump or switch to formula for the first few months.

The Bigger Picture: Progress and Gaps

Twenty years ago, doctors told women with lupus or kidney transplants not to get pregnant. Now, 85% of transplant centers have formal protocols for managing pregnancy. That’s progress.

But gaps remain. We still don’t know how newer drugs like belatacept affect children long-term. We don’t have data on whether kids exposed in utero have weaker immune systems later in life. We don’t know if boys exposed to sulfasalazine in the womb will have fertility issues as adults.

And while the FDA now requires male fertility testing for new drugs, most of the immunosuppressants in use today were approved before those rules existed. That means your doctor might not know the full risk-because the data doesn’t exist yet.

The field is moving toward personalized care. Instead of one-size-fits-all advice, doctors now look at your disease, your drug, your age, your fertility history, and your goals. It’s not about avoiding pregnancy. It’s about making it safe.

What to Do Next

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

1. Don’t stop your meds without talking to your doctor.
2. Ask for a referral to a reproductive specialist who understands autoimmune disease and transplants.
3. Get a full fertility check: sperm analysis for men, ovarian reserve testing for women.
4. Map out your drug plan: which meds to stop, which to switch, when to start.
5. Set up a team: transplant doctor, rheumatologist, OB-GYN, fertility specialist.
6. Track your health: blood tests, hormone levels, sperm counts.

This isn’t a one-time conversation. It’s an ongoing dialogue. Your needs change as your body changes. What’s safe at 25 might not be at 35. What works for one person might not work for you. The goal isn’t to be perfect. It’s to be informed.