BACKGROUND AND PURPOSE:

• Chu et al. (The Lancet, 2020) examined whether treatment with mifepristone plus misoprostol resulted in a higher rate of completion of missed miscarriage vs misoprostol alone

METHODS:

• Multicenter, double-blind, placebo-controlled, randomized trial
  • Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso) Trial
• Participants
  • ≥16 years
  • Missed miscarriage | Diagnosed by pelvic ultrasound up to 14 weeks GA
  • Patient opts for medical management of miscarriage
• Interventions
  • Mifepristone group
    • Single 200 mg dose of oral mifepristone
    • Followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later
  • Control group
    • Oral placebo
    • Followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later
• Study design
  • 1:1 randomization | Study group balancing performed for the following
    • Maternal age (<30 years vs ≥30 years)
    • Body-mass index (<35 kg/m2 vs ≥35 kg/m2)
    • Previous parity (nulliparous women vs parous women)
    • Gestational age (<70 days vs ≥70 days)
    • Amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3)
    • Randomizing center
• Masking: Participants, clinicians, pharmacists, trial nurses, and midwives masked to study group assignment throughout the trial
• Power analysis: 335 women in each trial group required to provide 90% power to detect a difference of ten percentage points for primary outcome
  • Analyses based on intention-to-treat
• Primary outcome
  • Failure to spontaneously pass the gestational sac within 7 days after assignment

RESULTS:

• 711 women were randomized
  • Mifepristone and misoprostol group (mifepristone): 357 women
  • Placebo and misoprostol group (control): 354 women
• Fewer women in the mifespristone group did not pass the gestational sac spontaneously within 7 days
  • Mifepristone: 17%
  • Control: 24%
  • Risk ratio (RR) 0.73 (95% CI, 0.54 to 0.99; p=0.043)
• Fewer women in the mifepristone group required surgical intervention to complete the miscarriage
  • Mifepristone: 17%
  • Control: 25%
  • RR 0.71 (95% CI, 0.53 to 0.95; p = 0.021)
• No subgroup effect was noted based on GA
• Adverse events: There was no difference between groups

CONCLUSION:

• The combination of mifepristone and misoprostol was more effective for the treatment of missed miscarriage than misoprostol alone
  • Benefits include reduced need for surgical intervention
• The authors recommend

…women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery

Learn More – Primary Sources:

Mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage (MifeMiso): a randomised, double-blind, placebo-controlled trial

Related ObG Topics:

Managing Early Pregnancy Loss

Expectant Management vs Misoprostol for the Treatment of Miscarriage

Does Adding Mifepristone Prior to Misoprostol Improve Medical Management of Pregnancy Loss?

Is Surgical Evacuation Needed Following Incomplete Miscarriage?