Fertility and Immunosuppressants: What You Need to Know Before Trying to Conceive

Trying to get pregnant while taking immunosuppressants isn’t something most people plan for. But for those managing autoimmune diseases or organ transplants, it’s a reality. The good news? pregnancy is possible-but only if you plan ahead. The risks aren’t theoretical. Some drugs can permanently damage eggs or sperm. Others increase the chance of premature birth, gestational diabetes, or birth defects. And the worst part? Many people don’t know any of this until they’re already pregnant.

Not All Immunosuppressants Are Created Equal

If you’re on immunosuppressants and thinking about having a baby, the first thing you need to know is this: not all drugs carry the same risk. Some are relatively safe. Others should be avoided entirely.

Azathioprine is one of the safest options. Over 1,200 pregnancies have been studied, and there’s no evidence it causes birth defects. It’s often the go-to choice for women with lupus or kidney transplants who want to conceive. It doesn’t cross the placenta in large amounts, and babies born to mothers on azathioprine show no increased risk of developmental issues.

Then there’s methotrexate. This drug is a hard no during pregnancy. It’s known to cause severe birth defects-cleft palate, brain malformations, limb abnormalities. Even if you’re only taking it for rheumatoid arthritis, you need to stop at least three months before trying to conceive. The drug sticks around in your system longer than you think.

Cyclophosphamide is even more serious. For women, it can wipe out ovarian function permanently. If you’ve taken more than 7 grams per square meter of body surface area, your chances of natural conception drop by 60-70%. For men, it can cause irreversible infertility in up to 40% of cases. If you’re on this drug and want kids someday, fertility preservation-freezing eggs or sperm-should be discussed before you even start treatment.

For men, sulfasalazine is a sneaky one. It cuts sperm count by half or more. But here’s the relief: it’s reversible. Once you stop taking it, sperm counts bounce back within three months. No need to panic, but you do need to plan. Get a semen analysis before you try to conceive, and wait at least 74 days after stopping the drug to allow for a full sperm cycle to recover.

Steroids, Tacrolimus, and 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 fertility. They throw off your hormone balance. In women, that can mean irregular or absent ovulation. In men, it can lower testosterone and reduce sperm production. And during pregnancy, they’re linked to a 15-20% higher chance of your water breaking too early.

Tacrolimus, used mostly after organ transplants, increases your risk of gestational diabetes by 30-40%. That means more ultrasounds, more blood sugar checks, and possibly insulin therapy. It’s manageable, but not something you want to discover after you’re already pregnant.

Ciclosporine, another transplant drug, raises the risk of premature birth by about 25%. Babies born early face breathing problems, feeding difficulties, and longer hospital stays. If you’re on this drug and planning pregnancy, your care team needs to monitor you closely from the start.

And then there’s sirolimus. It’s banned during pregnancy. In the few documented cases, there were three miscarriages out of seven pregnancies-and one baby born with serious structural defects. Animal studies say it’s safe, but human data says otherwise. Don’t risk it.

What About the Dad? Male Fertility Is Often Overlooked

Most counseling focuses on the woman. But men matter too. A 2020 study showed that many immunosuppressants were approved by the FDA and EMA before anyone had to test them for male fertility effects. That means we’re playing catch-up.

Chlorambucil, used for severe autoimmune conditions, is especially dangerous. It’s classified as FDA Risk Category D-meaning there’s clear evidence of harm. Studies of 43 pregnancies exposed to this drug found 8% of babies had missing kidneys, 12% had malformed ureters, and 15% had heart defects. If you’re on this drug, you need to know: it’s not just about sperm count. It’s about genetic damage.

Even if you’re not on chlorambucil, other drugs can still affect sperm quality. Sperm takes about 74 days to fully renew. That’s why experts recommend a semen analysis after 74 days of exposure-and another one 13 weeks after stopping the drug. If your sperm count is low or motility is poor, you might need to delay conception or consider IVF.

Preconception Counseling Isn’t Optional-It’s Essential

You wouldn’t drive a car without checking the brakes. Yet, many people start trying to conceive while still on high-risk drugs. That’s not bravery. It’s dangerous.

Real preconception counseling means meeting with your rheumatologist, transplant team, and a fertility specialist-at least three to six months before you plan to get pregnant. This isn’t a one-time chat. It’s a plan.

For example: if you’re on methotrexate, you stop it three months before trying. If you’re on cyclophosphamide, you freeze your eggs or sperm first. If you’re on tacrolimus, your blood levels are monitored monthly to keep them in the safest range. If you’re on azathioprine, you keep taking it-it’s safer than stopping.

For transplant patients, the stakes are even higher. Stopping immunosuppressants can lead to organ rejection. That’s why coordination between your transplant team and your OB-GYN is non-negotiable. About 85% of transplant centers now have formal protocols for pregnancy. You need to be in one of those programs.

Breastfeeding and Newborn Risks

Even if you make it through pregnancy, the risks don’t end at birth. Some drugs pass into breast milk. Chlorambucil? Absolutely no breastfeeding. It’s too toxic.

Azathioprine is different. It’s considered safe for breastfeeding because very little passes into milk. But your baby’s immune system might still be slightly suppressed. Studies show newborns exposed in utero have lower B- and T-cell counts-and a 2.3 times higher risk of infections in their first year. That means keeping them away from crowds, staying up to date on vaccines, and watching closely for fevers.

Belatacept is new. Only three pregnancies have been documented so far, and all babies were healthy. But that’s not enough to call it safe. It’s promising, but still experimental.

What’s Changed Since 2000-and What Still Isn’t Known

Back in 2000, doctors had almost no data on children born to parents on immunosuppressants. Today, we have thousands of cases tracked. We know which drugs are safe. We know which ones aren’t. We know how to manage them.

But gaps remain. We don’t know the long-term effects on brain development for kids exposed to newer drugs like belatacept or voclosporin. We don’t have enough data on paternal exposure. We don’t have registries tracking outcomes for every new drug.

Regulations have improved. The FDA now requires new immunosuppressants to be tested in at least 200 men before approval. But older drugs? They slipped through. That’s why your doctor can’t just rely on the label. They need to know the latest research.

And that’s why you need to be your own advocate. Don’t assume your doctor knows everything. Bring the studies. Ask about alternatives. Push for a multidisciplinary plan. If your rheumatologist doesn’t talk about fertility, find one who does.

What to Do Next

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

1. Stop trying to conceive until you’ve talked to your care team.
2. Get a full fertility evaluation-sperm analysis for men, ovarian reserve testing for women.
3. Review every medication you’re taking. Don’t skip the ones you think are "minor."
4. Ask about switching to safer alternatives like azathioprine.
5. If you’re on cyclophosphamide or chlorambucil, ask about fertility preservation immediately.
6. Plan for at least 3-6 months of medication adjustment before trying.
7. Find a care team that includes a reproductive endocrinologist, a transplant specialist, and a high-risk OB-GYN.

Pregnancy on immunosuppressants isn’t easy. But it’s not impossible. Thousands of people have done it. The key isn’t luck. It’s preparation.