Original Article: Mifepristone and Misoprostol for Early Pregnancy Loss and Medication Abortion
Issue Date: April 15, 2021
See additional reader comments at: https://www.aafp.org/afp/2021/0415/p473.html
To the Editor: We believe more information should be offered about the risks and indications for mifepristone (Mifeprex) for medication abortion. Tables 1 and 2 in the article emphasize the need for a careful history, physical examination, and important laboratory studies to determine eligibility. However, the authors do not emphasize in-person visits, stating, “Telehealth has been shown to be a safe and effective model for providing medication abortion....” This statement oversimplifies the referenced study,1 which says that “...each participant had ... pre-treatment laboratory tests and ultrasound....” The American College of Obstetricians and Gynecologists reports that approximately one-half of women inaccurately recall the date of their most recent menstrual period; therefore, the estimated gestational age in the first trimester is adjusted in 40% of pregnancies after ultrasonography.2 Without ultrasound visualization to determine an intrauterine pregnancy, it is difficult to diagnose or rule out an early ectopic pregnancy. Telehealth evaluation should not replace an adequate physical examination with vital signs, a speculum, bimanual examination, ultrasonography (for location, dating, and viability), and appropriate laboratory studies, including beta human chorionic gonadotropin, hemoglobin, and Rh status.
The overall complication rate of medication abortion after an appropriate in-person evaluation is 5.2%, based on a large study,3 and the risks of adverse events increase with advancing gestational age. These risks and concerns for diversion and misuse were why the U.S. Food and Drug Administration (FDA) implemented an in-person dispensing requirement. Of the 2,660 unique U.S.-only codable adverse event reports submitted for mifepristone between 2000 and 2016, 73% were classified as severe, 20% were life-threatening, and 0.75% resulted in death. Morbidity was primarily attributed to retained products of conception and hemorrhage, for which women with a gestational age greater than 49 days are at the highest risk. There were 1,639 bleeding events, including 466 life-threatening events, 642 severe events, and 106 moderate events; an additional 424 reports of bleeding were uncodable because of insufficient information. A total of 75 patients had ectopic pregnancies, with 25 presenting with ruptured ectopic pregnancies.4 We would encourage a more detailed review of the risks of mifepristone. Physicians must anticipate and be prepared to manage complications and adverse events that patients experience with mifepristone, especially if there are increasing numbers of medication abortions without an office visit, ultrasonography, and appropriate ancillary studies.
In Reply: Several important studies have been published on this topic recently. We appreciate the opportunity to share more information on the safety and effectiveness of providing mifepristone without in-person testing or ultrasonography. In a cohort study of 54,142 women in Great Britain, the rate of serious adverse events in 18,435 women who had a no-test telemedicine abortion between April and June 2020 (0.04%) was no different than in patients who received traditional in-person care (P = .56).1 In another study, family physicians in the United States successfully provided medication abortion to more than 500 women using an asynchronous telehealth platform, with 90% meeting criteria for no-test abortion care.2
On April 12, 2021, the FDA announced its intention “...to exercise enforcement discretion with respect to the in-person dispensing requirement of the Mifepristone REMS Program, ...during the COVID-19 public health emergency” as a “...result of a thorough scientific review by experts within FDA's Center for Drug Evaluation and Research (CDER), who evaluated relevant information, including available clinical outcomes data and adverse event reports.”3
Mifepristone is one of the most carefully studied medications that has been brought to market. Although the article by Aultman, et al., describes the breakdown of the types of reported adverse events, it does not include the denominator of mifepristone use since FDA approval in 2000.4 Over the past 20 years, mifepristone has been used for medication abortion by more than 2.75 million people, and there have been only 24 deaths, meaning that the risk of death is less than one in 100,000.4 Similarly, in considering the overall 5.2% complication rate after medication abortion reported by Upadhyay, et al., it is important to note that 94% of the documented complications were minor issues; the rate of major complications was 0.31 per 100 abortions. These rates of complications are far lower than rates associated with term delivery and indicate that mifepristone is safer than over-the-counter acetaminophen, which causes 500 deaths per year in the United States.5,6