Mifepristone and Misoprostol for Early Pregnancy Loss and Medication Abortion


Am Fam Physician. 2021 Apr 15;103(8):473-480.

  Related letter: Risks of and Indications for Mifepristone for Medication Abortion

  Related letter: More Study Needed of Preferred Regimens for Medication Abortion Beyond 70 Days

Author disclosure: No relevant financial affiliations.

Medication regimens using mifepristone and misoprostol are safe and effective for outpatient treatment of early pregnancy loss for up to 84 days' gestation and for medication abortion up to 77 days' gestation. Gestational age is determined using ultrasonography or menstrual history. Ultrasonography is needed when gestational dating cannot be confirmed using clinical data alone or when there are risk factors for ectopic pregnancy. The most effective regimens for medication management of early pregnancy loss and medication abortion include 200 mg of oral mifepristone (a progesterone receptor antagonist) followed by 800 mcg of misoprostol (a prostaglandin E1analogue) administered buccally or vaginally. Cramping and bleeding are expected effects of the medications, with bleeding lasting an average of nine to 16 days. The adverse effects of misoprostol (e.g., low-grade fever, gastrointestinal symptoms) can be managed with nonsteroidal anti-inflammatory drugs or antiemetics. Ongoing pregnancy, infection, hemorrhage, undiagnosed ectopic pregnancy, and the need for unplanned uterine aspiration are rare complications. Clinical history, combined with serial quantitative beta human chorionic gonadotropin levels, urine pregnancy testing, or ultrasonography, is used to establish complete passage of the pregnancy tissue.

Medication management of early pregnancy loss and medication abortion has become increasingly common since the U.S. Food and Drug Administration (FDA) approval of mifepristone (Mifeprex) in 2000. Medication abortion now accounts for 60% of all abortions completed before 10 weeks' gestation.1 The most effective medication regimens combine mifepristone, a progesterone receptor antagonist that causes decidual necrosis and uterine contractions, and misoprostol (Cytotec), a prostaglandin E1 analogue that causes cervical ripening and uterine contractions. These regimens are safe and acceptable to patients and can be prescribed by primary care clinicians in the outpatient setting.24 Primary care clinicians are uniquely positioned to counsel patients and provide access to medications, with their wide geographic distribution, skills in shared decision-making, and longitudinal relationships with patients; however, only 1% of abortions currently occur in clinicians' offices.1


Early Pregnancy Loss and Medication Abortion

Based on a 2018 review, the National Academies of Sciences, Engineering, and Medicine concluded that medication abortion does not increase the risk of breast cancer, mental health problems, infertility, pregnancy loss, or preterm birth.

Medication abortion accounts for 60% of all abortions before 10 weeks' gestation.

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Clinical recommendationEvidence ratingComments

Mifepristone (Mifeprex) and misoprostol (Cytotec) can be safely prescribed by primary care clinicians in the outpatient setting.4


Consensus guideline on the safety and quality of abortion care by the National Academies of Sciences, Engineering, and Medicine

Menstrual dating or ultrasonography is required to confirm gestational age prior to medication abortion; ultrasonography should be performed in patients at risk of ectopic pregnancy or if gestational age cannot be confirmed using clinical data alone.911


Consistent results from two prospective case series and a retrospective review

The most effective regimen for medication management of early pregnancy loss is mifepristone, 200 mg orally, followed 24 to 48 hours later by misoprostol, 800 mcg vaginally; when available, the combination should be recommended over misoprostol alone.2,3


Consistent results of randomized controlled trials demonstrating that mifepristone and misoprostol are more effective than misoprostol alone for early pregnancy loss

The recommended regimen for medication abortion up to 70 days' gestation is mifepristone, 200 mg orally, followed by misoprostol, 800 mcg administered buccally 24 to 48 hours later or vaginally 0 to 72 hours later.6,13,2327


Systematic review of using mifepristone and misoprostol buccally and individual randomized controlled trials of using misoprostol vaginally

To increase effectiveness of medication abortion, a second dose of misoprostol four hours after the first is recommended at 71 to 77 days' gestation and should be considered at 64 to 70 days' gestation.8,28,29


Retrospective chart review and consensus guideline

Following medication management, completed early pregnancy loss or abortion is confirmed using clinical history and an 80% decline from pretreatment in serum beta human chorionic gonadotropin levels, ultrasonography documenting the absence of a previously seen gestational sac, or a negative urine pregnancy test result.11,35


Retrospective review and a systematic review of lower quality clinical trials

A = consistent, good-quality patient-oriented evidence; B = inconsistent

The Authors

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HONOR MACNAUGHTON, MD, is the associate program director of the Tufts University Family Medicine Residency at Cambridge Health Alliance, Malden, Mass., and an associate professor in the Department of Family Medicine at Tufts University School of Medicine, Boston, Mass....

MELISSA NOTHNAGLE, MD, MSc, is the program director of the Natividad Family Medicine Residency, Salinas, Calif., and clinical professor in the Department of Family and Community Medicine at the University of California San Francisco School of Medicine.

JESSICA EARLY, MD, is faculty at the Tufts University Family Medicine Residency at Cambridge Health Alliance, and an assistant professor in the Department of Family Medicine at Tufts University School of Medicine.

Author disclosure: No relevant financial affiliations.

Address correspondence to Honor MacNaughton, MD, 195 Canal St., Malden, MA 02148 (email: homacnaughton@challiance.org). Reprints are not available from the authors.


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