Ms. Reilly, a 31-year-old primigravida woman at 10 weeks of gestation, sits anxiously in front of you awaiting her diagnosis. She presented to the emergency department reporting 3 hours of severe uterine cramping and was promptly evaluated. Vaginal exam demonstrated a closed cervical os, but ultrasound and serum β-hCG test confirmed a nonviable fetus. After counselling Ms. Reilly about her diagnosis, you discuss management options for first-trimester miscarriages, including expectant management, medical management with misoprostol, and surgical evacuation of the gestational sac. Ms. Reilly wants to pursue quick treatment but would prefer to avoid surgery. She would like to consider medical management, but is concerned about misoprostol because her friends have warned her about its low efficacy. She wonders if another option is available for successful medical management.
Misoprostol, a synthetic prostaglandin analogue, and mifepristone, a prostaglandin and glucocorticoid receptor antagonist that primes the uterus and cervix for prostaglandin activity, have been studied in the medical management of early pregnancy loss. Misoprostol alone has a substantial failure rate in women with a closed cervical os, requiring a second dose in 15%–40% of women or uterine aspiration of the gestational sac. It is not known whether treatment with mifepristone before misoprostol administration improves the success rate.
In this week’s issue of NEJM, Schreiber et al. report the findings of a randomized clinical trial of 300 women with nonviable intrauterine pregnancy by 12 weeks of gestation. Patients received pretreatment with 200 mg of mifepristone, administered orally, followed by 800 μg of misoprostol, administered vaginally approximately 24 hours later, or standard therapy with 800 μg of misoprostol alone, administered vaginally. Patients with a persistent gestational sac at initial follow-up (24 hours to 4 days after misoprostol use) could receive additional treatment. The primary outcome of treatment success was defined as gestational sac expulsion at initial follow-up and no additional interventions within 30 days.
The rate of treatment success was 83.8% among women who received mifepristone pretreatment at a median follow-up of 2 days and 67.1% among women who received misoprostol alone at a median follow-up of 2.6 days. At 30 days, the rate of uterine aspiration was 8.8% following mifepristone pretreatment versus 23.5% following misoprostol alone. The rate of bleeding requiring blood transfusion did not differ significantly between the two groups (2.0% and 0.7%, respectively).
In an accompanying editorial, Carolyn L. Westhoff applauds the addition of mifepristone to treatment for early pregnancy loss, stating that the new regimen “aligns with patient preferences for quicker treatment success.” She also notes the need to improve patient access to mifepristone, which is currently limited by Risk Evaluation and Mitigation Strategy restrictions enforced by the Food and Drug Administration that prevent prescription sales of mifepristone in retail pharmacies and restrict use to hospitals and clinicians with stocks available in their office.
Given the results of the present trial, I would inform Ms. Reilly of the higher success rates in managing early pregnancy loss with mifepristone pretreatment as compared with misoprostol alone, and would recommend the combined regimen where available. Further efforts are needed to ensure that access to clinically effective medications are readily available to health care providers and patients.
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Lisa is a 2017-2018 NEJM Editorial Fellow. An otolaryngologist-head and neck surgeon by training, she graduated from the University of Toronto Medical School and completed her residency training at the University of Ottawa. She has a Master's in Public Health from the Harvard T. H. Chan School of Public Health.