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

Planning a baby when you're on immunosuppressants isn't something you can wing. These drugs keep your immune system from attacking your organs or your own body, but they also interfere with reproduction in ways most people don’t expect. If you're on medication for lupus, rheumatoid arthritis, a kidney transplant, or another autoimmune condition, your fertility and future child’s health depend on more than just stopping birth control. The right drug, the right timing, and the right advice can make the difference between a healthy pregnancy and serious complications.

Not All Immunosuppressants Are Created Equal

Some immunosuppressants are relatively safe during pregnancy. Others are dangerous-even deadly-to a developing baby. It’s not just about whether you’re male or female. It’s about which drug you’re taking, how long you’ve been on it, and how much you’ve taken. Take azathioprine. It’s one of the few immunosuppressants with solid, long-term safety data. Over 1,200 pregnancies in women taking azathioprine showed no increase in birth defects, miscarriages, or stillbirths. It’s the go-to choice for many doctors when a patient wants to conceive. For men, it doesn’t seem to affect sperm quality either. If you’re on this drug and thinking about kids, you’re in a much better position than most. Now look at cyclophosphamide. This one is a different story. It’s a chemotherapy drug used for severe autoimmune diseases. In women, it can permanently destroy ovarian function-up to 70% of women who take more than 7 grams per square meter of body surface area lose their ability to have biological children. In men, it causes irreversible infertility in about 40% of cases. If you’re on this, fertility preservation-like freezing eggs or sperm-should be discussed before you even start the drug. Methotrexate is another big red flag. It’s commonly used for rheumatoid arthritis and psoriasis, but it’s a known teratogen. That means it causes birth defects. Even small doses can lead to severe abnormalities in the skull, face, heart, and limbs. You need to stop it at least three months before trying to conceive. And no, waiting two months isn’t enough. The drug sticks around in your system longer than people think. For men, sulfasalazine can cut sperm counts in half. That’s not permanent, but it’s enough to make conception harder. The good news? Sperm counts bounce back within three months after stopping the drug. If you’re on this and trying to get your partner pregnant, plan ahead. Get a semen analysis before and after switching meds.

What About Steroids? Prednisone Isn’t Harmless

Many people assume steroids like prednisone are safe because they’re used all the time. But they’re not harmless when it comes to fertility or pregnancy. Prednisone messes with your hormone signals. In women, it can disrupt ovulation. In men, it can lower testosterone and reduce sperm production. It’s not as bad as cyclophosphamide, but it’s not nothing. During pregnancy, prednisone increases the risk of premature rupture of membranes by 15-20%. That means your water breaks too early, which can lead to preterm labor. It’s still often continued during pregnancy because the risk of your autoimmune disease flaring is worse than the steroid risk. But you need to be monitored closely. Your doctor should check your blood pressure, blood sugar, and fetal growth regularly.

Transplant Patients Face a Tightrope Walk

If you’ve had a kidney, liver, or heart transplant, your life depends on immunosuppressants. Stopping them isn’t an option. But pregnancy adds another layer of risk. Your body is already under stress. Adding a baby on top of that can strain your transplanted organ. Ciclosporine and tacrolimus are common in transplant patients. Both are considered safer than older drugs, but they’re not risk-free. Ciclosporine raises your chance of preterm birth by about 25%. Tacrolimus increases the risk of gestational diabetes by 30-40%. That means you’ll need more frequent glucose tests and possibly insulin during pregnancy. Babies born to mothers on these drugs also have lower B-cell and T-cell counts-the cells that fight infection. That means they’re more likely to get sick in their first year. Doctors now recommend close monitoring of newborns, especially for infections like pneumonia or sepsis.

The New Kids on the Block: Belatacept and Sirolimus

Newer drugs are being used more often, but we don’t know enough about them yet. Sirolimus is a big concern. There are only a handful of human pregnancy cases, but they’re alarming. Of the seven reported pregnancies, three ended in miscarriage. One baby had a major birth defect. Animal studies didn’t show harm, but humans aren’t rats. Right now, sirolimus is strictly contraindicated in pregnancy. If you’re on it and want a baby, you need to switch to something safer-like azathioprine or mycophenolate (which is also risky, but less so than sirolimus). Belatacept is the opposite. Only three pregnancies have been documented in women taking it. All three babies were born healthy, with no birth defects. That’s promising, but it’s not enough data to call it safe. It’s being used cautiously in transplant patients who want to conceive, but only after careful discussion with a specialist.

Men Matter Too

Too often, fertility advice focuses only on women. But men on immunosuppressants need counseling too. Many of these drugs were approved decades ago, before anyone thought to test them for effects on sperm. The FDA didn’t require male fertility studies until recently. So we’re playing catch-up. Drugs like cyclophosphamide and chlorambucil can cause permanent damage to sperm production. Others, like sulfasalazine, cause temporary drops in sperm count. The key is timing. The FDA recommends semen analysis at three key points: before starting the drug, after one full sperm cycle (about 74 days), and 13 weeks after stopping it. That’s because sperm takes about three months to fully renew. If you’re switching meds, don’t try to conceive until you’ve waited at least that long.

Preconception Counseling Isn’t Optional

You can’t just read a pamphlet and hope for the best. You need a plan. And it needs to start at least 3-6 months before you try to get pregnant. Here’s what a good preconception plan looks like:

• Meet with your rheumatologist, transplant specialist, and a fertility expert together.
• Get a full fertility evaluation-hormone levels, ovarian reserve, semen analysis.
• Switch to safer drugs if possible. Azathioprine is the gold standard. Avoid methotrexate, cyclophosphamide, and sirolimus.
• For women: Consider egg freezing if you’re on cyclophosphamide or high-dose steroids.
• For men: Get a baseline semen analysis and retest after switching meds.
• Check your kidney and liver function. High creatinine levels (above 13 mg/L) before pregnancy raise your risk of preeclampsia.
• Make sure your disease is stable. Flares during pregnancy are dangerous for both you and the baby.

What About Breastfeeding?

Some drugs pass into breast milk. Others don’t. Azathioprine is generally considered safe during breastfeeding. Only tiny amounts get into milk, and studies show no harm to babies. Chlorambucil is a hard no. It’s linked to bone marrow suppression in infants. You must avoid breastfeeding if you’re on it. Tacrolimus and ciclosporine are used by some nursing mothers, but only under close supervision. Your baby’s blood levels may need to be checked. Always talk to your doctor before nursing. Don’t assume it’s safe just because it’s natural.

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. Now, most transplant centers have formal protocols. But big gaps remain. We don’t know the long-term effects on children exposed to newer drugs like belatacept or voclosporin. Do they have higher rates of asthma? Learning delays? Autoimmune disorders later in life? We don’t have answers. We also don’t have good data on paternal exposure. Most studies focus on the mother. But if the father is on sulfasalazine or methotrexate, does that affect the baby? We’re still figuring that out. That’s why registries are being created-to track outcomes over time. If you’ve had a baby while on immunosuppressants, consider joining one. Your data helps others.

Bottom Line: You Can Have a Baby. But You Need a Plan.

Yes, pregnancy is possible even if you’re on immunosuppressants. But it’s not automatic. It’s not luck. It’s strategy. Don’t wait until you miss a period to talk to your doctor. Don’t assume your rheumatologist knows everything about fertility. Don’t skip the semen test just because you’re the man. The right team-transplant specialist, rheumatologist, OB-GYN, and fertility expert-can help you navigate this. The right drugs, taken at the right time, give you the best shot at a healthy baby. Your health matters. Your future child’s health matters. And with the right planning, you don’t have to choose between them.