
Am Fam Physician. 2021;103(8):473-480
Related letter to the Editor: Risks of and Indications for Mifepristone for Medication Abortion
Related letter to the Editor: 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.2–4 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

Determining Eligibility
Before prescribing mifepristone and misoprostol, clinicians should determine gestational age, evaluate for contraindications, provide patient-centered counseling on management options, and assess the need for laboratory testing.
Regimens using mifepristone and misoprostol are effective up to 84 days' gestation for early pregnancy loss,2,3 and up to 77 days' gestation for medication abortion.5–8 Ultrasonography is indicated to establish the diagnosis and confirm gestational dating before using medications for early pregnancy loss. Ultrasonography, if needed, or menstrual dating can establish that gestational age is less than 77 days before a medication abortion is provided.9–11 Ultrasonography should be performed in patients at risk of ectopic pregnancy or if gestational age cannot be confirmed using clinical data alone (Table 1).9–11

Increased risk of ectopic pregnancy |
Adnexal mass or tenderness on examination |
History of ectopic pregnancy |
History of treatment for pelvic inflammatory disease |
History of tubal surgery, including sterilization |
Pregnancy with intrauterine device in place |
Vaginal bleeding or unilateral pelvic pain |
Unable to confirm gestational age less than 11 weeks |
Hormonal contraceptive use within the past two months |
Last menstrual period more than 10 weeks ago |
Unsure date of last menstrual period |
Uterine size/date discrepancy on bimanual examination |
There are few contraindications to using mifepristone and misoprostol12 (Table 24,12,13). Medication management research has excluded patients with severe hepatic, renal, respiratory, or cardiovascular disease, or with hemoglobin levels of less than 10 g per dL (100 g per L). Laboratory testing should be considered for patients with symptoms of or at risk of anemia or sexually transmitted infections. An initial quantitative beta human chorionic gonadotropin (β-hCG) level is needed if serial β-hCG will be used to confirm completed abortion. The standard of care has been to administer RhO(D) immune globulin (Rhogam) to all patients who are Rh-negative and who are undergoing early pregnancy loss or abortion.14 However, according to preliminary research findings, the risk of alloimmunization in early gestation may be negligible.15 If future research confirms this finding, testing for Rh status may not be indicated when prescribing mifepristone and misoprostol in the first trimester.16

Absolute contraindications |
Adrenal insufficiency |
Allergy to mifepristone or misoprostol |
Chronic systemic glucocorticoid use |
Confirmed or suspected ectopic pregnancy |
Hemodynamic instability |
Hemorrhagic disorder or current anticoagulant use (excluding aspirin) |
Inherited porphyrias |
Intrauterine device in place (remove, then proceed with medications) |
Septic abortion |
Relative contraindications |
Hemoglobin less than 10 g per dL (100 g per L) |
Inability to access emergency or follow-up services |
Providing Counseling and Consent
Patients with early pregnancy loss or unintended pregnancy should receive patient-centered counseling on all management options because patients who are included in the decision-making process and whose treatment preferences are honored have better mental health outcomes.17,18 The risks and benefits of treatment options for early pregnancy loss (i.e., expectant management, medication management, and uterine aspiration) are reviewed at https://www.aafp.org/afp/2019/0201/p166.html. For an in-depth discussion of the options for unintended pregnancy, including parenting, adoption, and medication or aspiration abortion, see https://www.aafp.org/afp/2015/0415/p544.html. All patients should be interviewed alone to ensure they are not being coerced by a partner or anyone else to decide against their will.19 The FDA requires patients who use mifepristone to sign a patient agreement that is available on the drug manufacturers' websites.20,21
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