Mifepristone Use in Missed Miscarriages
Yes, mifepristone is used in conjunction with misoprostol for the medical management of missed miscarriages, and this combination is more effective than misoprostol alone. The combination regimen increases successful completion rates and reduces the need for surgical intervention compared to misoprostol monotherapy.
Evidence for Combination Therapy
The landmark MifeMiso trial demonstrated that mifepristone pretreatment followed by misoprostol resulted in significantly better outcomes than misoprostol alone:
- Only 17% of women failed to pass the gestational sac within 7 days with combination therapy versus 24% with misoprostol alone (risk ratio 0.73, p=0.043) 1
- Surgical intervention was required in 17% of the combination group versus 25% of the misoprostol-only group (risk ratio 0.71, p=0.021) 1
- The overall success rate with combination therapy ranges from 84-89% depending on gestational age 1, 2
Recommended Regimen
The standard protocol consists of:
- Mifepristone 200 mg orally as a single dose 1, 3, 4
- Followed 36-48 hours later by misoprostol 800 μg (vaginal, oral, or sublingual route) 1, 5
- Additional doses of misoprostol 400 μg may be given at 3-hour intervals if needed 5
The 200 mg dose of mifepristone is as effective as higher doses (600 mg) and better tolerated with fewer adverse effects 4.
Success Rates by Gestational Age
Efficacy varies with uterine size at treatment:
- Success rate of 88.9% for uterine size below 9 weeks gestation 2
- Success rate of 85.5% for uterine size below 12 weeks gestation 2
- Uterine size of 9 gestational weeks or larger is the only significant risk factor for treatment failure requiring surgical intervention 2
Clinical Advantages
The combination approach offers several benefits:
- Mifepristone alone induces natural expulsion in approximately 18% of women before misoprostol administration 5
- Median time to expulsion after misoprostol is approximately 8 hours 5
- The regimen is cost-effective despite using two medications 3
- Asymptomatic women at presentation have higher success rates (93.6%) compared to symptomatic women (78.9%) 5
Safety Considerations
Important contraindications and precautions:
- Misoprostol should be avoided in women with previous cesarean delivery due to uterine rupture risk 6, 7
- High-risk patients (cardiac disease, end-stage renal disease) should be managed in experienced centers with emergency support 8, 9
- For high-risk patients, dilatation and evacuation remains the safest procedure 8, 6
- Mifepristone can be used up to 7 weeks gestation as an alternative to surgery in select high-risk populations 8, 9
Common Side Effects
Expected adverse effects include:
- Heavy bleeding in 38-54% of women, typically stopping by 7-8 days 4
- Nausea in 7-25% of women 4
- Diarrhea in 7-16% of women 4
- Pain requiring intramuscular opiates in 18-25% of cases 4
Clinical Pitfall
The most common reason for treatment failure is attempting medical management in women with symptomatic bleeding at presentation - these women have a 21% failure rate compared to only 6.4% in asymptomatic women 5. Consider offering surgical management upfront to symptomatic women or counseling them about higher failure rates.