How Long Should I Wait to Conceive After an Ectopic Pregnancy?

I recently was treated with methotrexate for an ectopic pregnancy and was told I will need to wait three months to try to conceive again. However, I am seeing things online that this recommendation is overly cautious and outdated. Can you help me look for research studies that back this up?

—Anonymous

You are correct that the standard recommendation is to wait three months after receiving methotrexate before trying to conceive, and you are also correct that this recommendation is not based on perfect evidence, but that does not mean it is necessarily overly cautious or outdated.

First, some background. Methotrexate is a folic acid antagonist; meaning, it blocks the action of folic acid in our bodies. Since folic acid is critical in DNA synthesis and cell reproduction, methotrexate therefore blocks cell reproduction. As such, it is used to treat certain cancers and autoimmune conditions that have actively reproducing cells. Methotrexate is also an effective treatment for an ectopic pregnancy, as it inhibits growth of the pregnancy by blocking embryonic cell division and growth. This is desirable if your pregnancy is in the fallopian tube, as this is not a viable pregnancy (and it is also a dangerous one). However, if one had a viable pregnancy in the uterus, methotrexate has a very high chance of causing a miscarriage or fetal anomalies. So there is legitimate concern about conceiving after methotrexate exposure, and what should be the minimal time one should wait between receiving methotrexate and waiting to conceive. Hence your question.

The issue is that we don’t have terrific data to answer your question. The recommendation of three months came mostly from toxicology data that methotrexate stays in the human body for some time, so the effects can continue for months. We do know that getting methotrexate during the first trimester of pregnancy, specifically a few weeks after conception, has a high chance of adverse effects on the pregnancy. But it would be very hard to design a study that could test exactly how long one must wait from methotrexate to conception, given people’s hesitation to conceive within three months of methotrexate, as well as the overall rarity of birth defects. There have been studies looking at people who accidentally conceived after methotrexate, and they do seem to be reassuring. One study looked at women who conceived within six months of methotrexate for ectopic pregnancy (average time was 3.6 months), and no adverse effects were found. But that study is limited and doesn’t specifically answer your question either.

So we are unfortunately left with uncertainty. The typical recommendation is to wait three months, but we do not know exactly the best amount of time to wait, nor do we know what the magnitude of risk would be (if any) if someone conceived at one month or two months after receiving methotrexate. Some limited data suggests it seems to be safe, but that’s the best we have right now.