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How does methotrexate work for ectopic pregnancy?

Medically reviewed by Sally Chao, MD. Last updated on May 2, 2023.

Official answer


Methotrexate, a drug commonly used in cancer chemotherapy treatment, works by preventing the growth of rapidly dividing cells in the body. Cancer cells rapidly divide, but so do the cells in a human embryo. So, methotrexate is used to treat an ectopic pregnancy because it stops the embryo's cells from growing and dividing, which eventually ends the pregnancy.

Methotrexate injection is the favored medicine for treating ectopic pregnancies when surgery is not necessary. Methotrexate is a type of medicine called a folic acid antagonist. It works by blocking an enzyme, dihydrofolate reductase, which is involved in making cellular proteins. By blocking this process, methotrexate keeps cells from copying themselves and dividing into more cells.

In terms of an ectopic pregnancy, methotrexate stops the pregnancy from continuing to develop.

  • The use of methotrexate for treating ectopic pregnancies is considered an "off-label" use of this medication. Providers have deemed it medically appropriate to treat ectopic pregnancy, although it’s not yet approved by the Food and Drug Administration for this use.
  • According to the American Society for Reproductive Medicine, nearly 90% of ectopic pregnancies can be successfully treated with methotrexate when found early.

Methotrexate is given as one intramuscular shot. Then, blood levels of the pregnancy hormone human chorionic gonadotropin (hCG) need to be measured every few days to make sure they’re decreasing enough. If the hCG levels aren't falling sufficiently, a second shot of methotrexate may be given.

The ectopic pregnancy is slowly absorbed in the body and ends when the level of hCG in the blood is zero. This usually takes about 4 to 6 weeks to complete.

Cautions and side effects

Because of the way methotrexate works, taking in large amounts of folic acid (a type of B vitamin) can decrease the drug's effectiveness. Women given methotrexate for an ectopic pregnancy should avoid taking vitamins containing folic acid or eating foods high in folic acid (such as broccoli, leafy greens and some beans) until the ectopic pregnancy has ended.

Other drugs taken in combination with methotrexate may cause adverse reactions. It’s important to tell your care team about all of the medications and supplements you’re taking.

Common side effects of methotrexate are:

  • Nausea
  • Stomach distress
  • Sores in the mouth

Lower white blood cell count may also be found on blood tests.

Because methotrexate can cause birth defects, the manufacturer recommends using effective birth control for at least 3 months after receiving methotrexate.

Ectopic pregnancy

A woman's egg is usually fertilized by a man's sperm within the fallopian tube. Under ideal circumstances, this fertilized egg then travels along the fallopian tube to the uterus, where it implants into the lining and develops into a full-term pregnancy. The term ectopic pregnancy is used for any pregnancy where the fertilized egg implants somewhere other than the uterine lining.

The most common location for ectopic pregnancies to occur is the fallopian tube.

It is estimated that 1.5% to 2% of pregnancies are ectopic. Complications of an ectopic pregnancy include possible rupture of the fallopian tube and severe internal bleeding. Ectopic pregnancies can be life-threatening.

Because an ectopic pregnancy can be life-threatening, it’s important to diagnose and treat it promptly. Symptoms of an ectopic pregnancy include abdominal pain and vaginal bleeding. Diagnosis involves obtaining an ultrasound and measuring the level of hCG in a woman's blood.
The choice of treatment depends on where in the reproductive system the ectopic pregnancy is located and how far along the pregnancy is. Surgery may be required, especially if the fallopian tube has already ripped open. Otherwise, treating the ectopic pregnancy with methotrexate is often effective.

  1. U.S. Food and Drug Administration (FDA). Highlights of Prescribing Information: Methotrexate Injection. March 2021. Available at: [Accessed March 30, 2021].
  2. American Society for Reproductive Medicine (ASRM). Ectopic Pregnancy Fact Sheet. 2014. Available at: [Accessed March 25, 2021].
  3. Weant KA, Bailey AM, Baum RA, Justice SB, Calhoun CD. Chemotherapy in the emergency department? There is a role for that: Methotrexate for ectopic pregnancy. Advanced Emergency Nursing Journal. 2017;39(1):18-25. doi: 10.1097/TME.0000000000000137
  4. National Health Service (NHS). Use of methotrexate to treat pregnancy of unknown location and ectopic pregnancy. February 2020. Available at: [Accessed April 9, 2021].
  5. American College of Obstetricians and Gynecologists (ACOG). Ectopic Pregnancy. February 2018. Available at: [Accessed April 9, 2021].
  6. U.S. Food and Drug Administration (FDA). Understanding unapproved use of approved drugs "off-label." February 5, 2018. Available at: [Accessed April 3, 2021].

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