The effect of mifepristone pretreatment on bleeding and pain during medical management of early pregnancy loss

Contraception. 2021 Oct;104(4):432-436. doi: 10.1016/j.contraception.2021.04.023. Epub 2021 Apr 28.


Objectives: To compare participant-reported bleeding and pain with two medication regimens for early pregnancy loss (EPL).

Study design: We performed a secondary analysis of a randomized trial in which participants took either mifepristone 200 mg orally followed by misoprostol 800 mcg vaginally 24 hours later or misoprostol alone for medical management of EPL. Participants reported bleeding and pain (Numeric Pain Rating Scale, NPRS, 0-10) with daily paper diaries and at study visits on trial days 3, 8, and 30. We used, Fisher's exact, Pearson chi-square, Wilcoxon rank sum, and Student's t-tests to compare onset, duration, and severity of bleeding and pain symptoms between trial arms after misoprostol administration.

Results: Among 291 participants who submitted diary data, 143 received mifepristone pretreatment. A larger proportion of this group reported moderate or heavy bleeding on trial day 2, the day of misoprostol administration, compared with those who did not receive pretreatment (73% vs 47%, p < 0.01). Between days 4 and 8, more mifepristone-pretreatment participants reported mild or no bleeding, compared with the misoprostol-only arm (78% vs 61%, p < 0.01). Average pain score for trial days 2-4 was higher for the pretreatment group compared with the misoprostol-only group (6.9 vs 6.0, p = 0.01), and there was a trend toward shorter total duration of pain (15 vs 19 hours, p = 0.08). These differences remained after controlling for treatment success across arms.

Conclusions: Mifepristone pretreatment increased the severity of pain but not bleeding and resulted in a shorter trajectory of symptoms during medical management of EPL.

Implications: Mifepristone pretreatment decreases the duration of heavy bleeding and there was a trend toward decreased duration of pain during medical management of miscarriage, indicating that this medication improves the efficiency, in addition to the efficacy, of this treatment.

Trial registration: NCT02012491.

Keywords: Bleeding; Early pregnancy loss; Mifepristone; Miscarriage; Misoprostol; Pain.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Abortifacient Agents, Nonsteroidal*
  • Abortifacient Agents, Steroidal*
  • Abortion, Induced*
  • Abortion, Spontaneous*
  • Female
  • Humans
  • Mifepristone
  • Misoprostol*
  • Pain / drug therapy
  • Pregnancy


  • Abortifacient Agents, Nonsteroidal
  • Abortifacient Agents, Steroidal
  • Misoprostol
  • Mifepristone

Associated data