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: The mifepristone (Mifeprex) package insert states that it is “...indicated, in a regimen with misoprostol, for the medical termination of intrauterine pregnancy through 70 days gestation.”¹ The article by MacNaughton and colleagues states, “Evidence-based regimens, however, demonstrate safety and effectiveness [of medication abortion] up to 77 days' gestation.” However, in the article cited for that sentence, it states that “Although the success rate at 71–77 days of gestation was within the non-inferiority margin, we cannot rule out that it is statistically worse than in the previous gestational week. Significantly more ongoing pregnancies in the later group raise concerns about using the regimen at 71–77 days.”² An additional citation states, “Regimen effectiveness was high at 64–70 and 71–77 days among clients who attended follow up. However, with 25% attrition, it is difficult to draw definitive conclusions about effectiveness and associated safety,” and “Mifepristone 200 mg followed by two doses of misoprostol 800 mcg four hours apart is a promising medical abortion regimen to improve efficacy in pregnancies from 64–77 days of gestation as compared to regimens with an initial single misoprostol dose. Prospective research is recommended to achieve more robust efficacy estimates.”³

At least two of the articles MacNaughton and colleagues referenced do not support the article's statement that the use of mifepristone for up to 77 days is evidence based. Although the difference is only seven days' gestation (70 vs. 77 days), at least one study showed a statistically significant increase in the percentage of patients who required a surgical evacuation of the uterus between days 70 and 84, with an upward trend between days 70 and 77.⁴ These data suggest that seven days' additional gestation may pose a significantly increased risk that a patient undergoing medication abortion will ultimately require surgical evacuation.

In Reply: Although we agree that medication abortion using mifepristone, 200 mg, followed by a single dose of misoprostol (Cytotec), 800 mcg, between 71 and 77 days' gestation may be less effective than at earlier gestations, medication abortion at this gestational age is still a safe and effective option for people who prefer a nonprocedural abortion or are unable to access procedural abortion care.^1,2 Based on these studies, guidelines suggest using a second dose of misoprostol after 70 days. For this reason, we assigned an evidence rating of C to the SORT key recommendations for practice.^1–3 The limitations of these studies should be shared with patients in the context of their values and preferences. Effectiveness, although important to many, may not be the most important factor in all patients' decisions. Notably, in the noninferiority study by Dzuba, et al., there was no difference in acceptability of medication abortion between 64 and 70 days' gestation and 71 and 77 days' gestation.¹ We agree that more study of preferred regimens for medication abortion is needed beyond 70 days.