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

Planning a baby while on immunosuppressants isn’t something most people expect to think about. But for those managing autoimmune diseases or organ transplants, it’s a real and urgent question. Can you get pregnant safely? Will your meds harm the baby? Can your partner’s meds affect sperm? The answers aren’t simple, but they’re not impossible either. The truth is, many people on these drugs have healthy babies - but only if they plan ahead and work with the right team.

Not All Immunosuppressants Are Created Equal

If you’re taking immunosuppressants and thinking about starting a family, the first thing you need to know is that not all these drugs are the same. Some are relatively safe. Others can cause permanent damage. The difference isn’t subtle - it’s life-changing.

Azathioprine stands out as one of the safest options. Over 1,200 documented pregnancies in women taking this drug showed no increase in birth defects or miscarriage rates. That’s not luck. It’s data. For men, azathioprine doesn’t appear to harm sperm quality either. If you’re on this drug, your doctor might recommend staying on it through conception and pregnancy, with monitoring.

On the other end of the spectrum is cyclophosphamide. This drug, often used for severe lupus or vasculitis, can permanently destroy ovarian reserve. Up to 70% of women who take cumulative doses over 7 grams per square meter of body surface area lose the ability to have biological children. For men, it can cause irreversible infertility in 40% of cases. If you’re prescribed this, fertility preservation - like egg or sperm freezing - should be discussed before you even start treatment.

Methotrexate is another big red flag. It’s a known embryotoxin. Even small amounts can cause severe birth defects. The rule is simple: stop it at least three months before trying to conceive. And don’t assume it’s safe after you miss a few doses. It lingers in your system. Blood tests to confirm clearance are often needed.

For men, sulfasalazine is a common culprit for reduced fertility. It can cut sperm counts by 50-60%. The good news? It’s reversible. Sperm counts usually bounce back within three months after stopping the drug. But if you’re trying to conceive, you need to plan that gap. Don’t wait until you’ve been trying for six months to realize your meds might be the issue.

Steroids, Ciclosporine, and Tacrolimus: The Hidden Risks

Corticosteroids like prednisone are often seen as harmless because they’re so common. But they’re not harmless when it comes to reproduction. They can interfere with ovulation in women and reduce testosterone production in men. Even if you’re still getting periods or producing sperm, the quality may be off. And during pregnancy, steroid use increases the risk of premature rupture of membranes by 15-20%.

Ciclosporine and tacrolimus are staples for transplant patients. They’re effective at preventing rejection. But they come with trade-offs. Babies born to mothers on ciclosporine have a 25% higher chance of being born prematurely. Tacrolimus raises the risk of gestational diabetes by 30-40%. That means more ultrasounds, more glucose tests, and possibly more interventions during labor.

And here’s something rarely talked about: newborns exposed to these drugs in the womb often have lower B-cell and T-cell counts. That’s not just a lab number. It means their immune systems are weaker in the first year of life. One study found these babies had a 2.3 times higher risk of serious infections. That’s why pediatricians need to know about prenatal exposure - and why vaccinations need to be timed carefully.

Sirolimus and Chlorambucil: Avoid Pregnancy Altogether

Some drugs are simply too risky to use if you’re trying to conceive. Sirolimus is one of them. In early case reports, seven pregnancies involving sirolimus included three first-trimester miscarriages and one baby born with serious structural defects. Even though animal studies didn’t show birth defects, the human data is too alarming to ignore. Current guidelines say: don’t use it during pregnancy.

Chlorambucil is even worse. Classified as FDA Risk Category D, it’s linked to specific, severe birth defects: renal agenesis (missing kidneys) in 8% of cases, ureteral malformations in 12%, and heart defects in 15%. These aren’t rare anomalies - they’re patterns. And if you’re on chlorambucil, breastfeeding is off the table too. The drug passes into breast milk and can suppress the baby’s bone marrow.

If you’re on either of these drugs and want children, your options are limited. You may need to switch to a safer alternative - if your disease allows it. Or you may need to consider donor eggs, sperm, or surrogacy. This isn’t a conversation you have once. It’s one you revisit with your rheumatologist, transplant team, and fertility specialist every few months.

Preconception Counseling Isn’t Optional - It’s Essential

You wouldn’t drive across the country without checking your oil, tires, and fuel. So why would you try to get pregnant without checking your meds?

Preconception counseling for people on immunosuppressants should start at least 3-6 months before you plan to conceive. That’s not a suggestion. It’s a requirement. Why? Because some drugs take months to clear. Others need to be replaced with safer ones, and your body needs time to adjust.

For women: This means checking ovarian reserve with an AMH blood test and an antral follicle count via ultrasound - especially if you’re on cyclophosphamide or other gonadotoxic drugs. It means stopping methotrexate, switching from sirolimus to azathioprine, and confirming your disease is stable. A flare during pregnancy is dangerous for both you and the baby.

For men: Semen analysis should be done before starting any immunosuppressant, then again after one full spermatogenic cycle (about 74 days) and again 13 weeks after stopping. The FDA recommends this. Most doctors don’t. But if you care about having biological children, you need to push for it.

And don’t forget your partner. If your partner is on immunosuppressants, their meds matter too. Sulfasalazine, cyclophosphamide, and even azathioprine can affect sperm DNA. While most studies show no increase in birth defects, the long-term effects on child health aren’t fully known. That’s why both partners should be evaluated.

Transplant Recipients: A Special Challenge

If you’ve had a kidney, liver, or heart transplant, pregnancy is possible - but it’s high-risk. Your immune system is already fighting to keep the organ alive. Pregnancy adds stress. Blood pressure rises. Kidneys work harder. The risk of rejection spikes.

Studies show that 85% of transplant centers now have formal protocols for managing pregnancy in transplant patients. That’s progress. But not all centers are equal. Some still rely on outdated guidelines. You need a team: a transplant nephrologist, a maternal-fetal medicine specialist, a rheumatologist (if you have lupus), and a fertility expert.

One key rule: your creatinine level should be below 13 mg/L before you get pregnant. Higher levels mean a much greater risk of preeclampsia, preterm birth, and fetal growth restriction. If your kidney function is poor, pregnancy may not be safe - no matter how much you want it.

Belatacept, a newer drug, shows promise. Only three pregnancies have been reported so far, but all resulted in healthy babies with no birth defects. It’s not yet the standard of care, but it’s a hopeful sign for the future.

What About Breastfeeding?

Many women worry: Can I breastfeed if I’m on immunosuppressants? The answer depends on the drug.

Azathioprine is considered compatible. Only tiny amounts pass into breast milk, and studies show no adverse effects in infants. The same is true for prednisone - as long as you wait 4 hours after taking your dose before nursing.

But chlorambucil? No. It concentrates in breast milk and can suppress the baby’s immune system. Cyclophosphamide? Avoid. Tacrolimus? Use with caution - levels in milk are low, but long-term effects are unknown. Always check with your pharmacist or neonatologist before nursing.

What’s Changing in 2025?

The rules are getting stricter - and better. New drugs now have to go through mandatory male fertility testing before approval. The FDA requires randomized trials with at least 200 men to check sperm count and DNA integrity. That didn’t exist 20 years ago. Back then, drugs like methotrexate and cyclophosphamide were approved without any male reproductive data.

Today, we’re building registries to track outcomes for children exposed to newer drugs like belatacept and voclosporin. We’re learning that paternal exposure matters. We’re learning that timing matters. We’re learning that fertility isn’t just a women’s issue.

But gaps remain. We still don’t know how these drugs affect children’s immune systems long-term. We don’t have enough data on autism, learning delays, or cancer risk in offspring. That’s why research continues - and why your participation in a registry might help others.

What Should You Do Right Now?

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

1. Don’t stop your meds on your own. A flare can be more dangerous than the drugs.
2. Call your rheumatologist or transplant team and ask for a preconception consult.
3. Ask for a referral to a fertility specialist - even if you’re not sure yet.
4. If you’re male, request a semen analysis. Don’t wait.
5. If you’re female and on cyclophosphamide or high-dose steroids, ask about egg freezing.
6. Get your disease under control. Stable disease = safer pregnancy.
7. Track your meds. Know exactly what you’re taking and why.

This isn’t about giving up your dreams. It’s about protecting them. With the right planning, many people on immunosuppressants go on to have healthy children. But you can’t wing it. You need a plan - and you need it now.