What is the recommended dosing schedule of oral mifepristone followed by buccal, sublingual, or vaginal misoprostol for medical management of a confirmed intra‑uterine embryonic demise ≤10 weeks gestation in a patient without contraindications?

Medical Management of Embryonic Demise ≤10 Weeks: Mifepristone and Misoprostol Dosing

For confirmed intrauterine embryonic demise ≤10 weeks gestation, administer mifepristone 200 mg orally followed 24–48 hours later by misoprostol 800 mcg administered vaginally or buccally, with a second dose of misoprostol 400 mcg available 3 hours later if needed. 1

Recommended Dosing Protocol

Initial Dose

• Mifepristone 200 mg orally as the first medication 1, 2
• This primes the uterus by blocking progesterone receptors and sensitizing the myometrium to prostaglandins 1

Prostaglandin Administration (24–48 hours after mifepristone)

• Misoprostol 800 mcg administered either:
  • Vaginally (preferred route for embryonic demise) 1, 2
  • Buccally (alternative route with similar efficacy) 1
  • Sublingual administration is also effective but associated with more side effects 3

Repeat Dosing if Needed

• Second dose: Misoprostol 400 mcg administered 3 hours after the first dose if expulsion has not occurred 2
• Third dose: Misoprostol 400 mcg may be given 3 hours after the second dose for gestations approaching 10 weeks 2
• The median total misoprostol dose required is 1600 mcg 2

Timing Flexibility

The interval between mifepristone and misoprostol can range from 24–72 hours without compromising efficacy, though 36–48 hours is most commonly studied 2, 4. Research demonstrates that misoprostol administered 1,2, or 3 days after mifepristone achieves complete medical abortion rates of 96–98% 4. This flexibility allows for more convenient scheduling while maintaining safety and effectiveness 4.

Expected Efficacy and Timeline

• Overall success rate: 84–98% for complete uterine evacuation without surgical intervention 1, 2
• Median time to expulsion: 8 hours after first misoprostol dose (range 0.6–50.5 hours) 2
• Approximately 18% of women will expel after mifepristone alone before taking misoprostol 2
• Asymptomatic women at presentation have higher success rates (93.6%) compared to symptomatic women (78.9%) 2

Route Comparison: Vaginal vs. Buccal vs. Sublingual

Vaginal administration is preferred for embryonic demise because it results in fewer prostaglandin-related side effects while maintaining equivalent efficacy 1, 3. Sublingual misoprostol, while effective, causes significantly more diarrhea, shivering, and unpleasant mouth taste compared to vaginal administration 3. Buccal administration offers a middle ground with good efficacy and tolerability 1.

Critical Contraindications and Safety Considerations

Absolute Contraindications

• Previous cesarean delivery: Misoprostol carries a risk of uterine rupture in women with uterine scars 5, 6
• Confirmed or suspected ectopic pregnancy 1

High-Risk Patients Requiring Specialized Management

• Cardiac disease, end-stage renal disease, or other severe comorbidities should be managed in experienced centers with emergency support services 5, 6
• For high-risk patients, dilatation and evacuation may be safer than medical management 5

Expected Side Effects and Management

Common Expected Effects

• Cramping and bleeding are therapeutic effects, not complications 1
• Bleeding duration: 9–16 days on average 1
• Gastrointestinal symptoms (nausea, vomiting, diarrhea) are common with misoprostol 5
• Low-grade fever may occur 1

Side Effect Management

• NSAIDs (ibuprofen, naproxen) for cramping and pain 1
• Antiemetics for nausea if needed 1
• Reassure patients that these symptoms are expected and manageable 1

Follow-Up and Confirmation of Complete Expulsion

Confirm complete passage of pregnancy tissue using:

• Clinical history combined with resolution of symptoms 1
• Serial quantitative β-hCG levels (should decline appropriately) 1
• Urine pregnancy testing (should become negative over time) 1
• Ultrasonography if clinical assessment is inconclusive 1, 2

Follow-up should occur 3 days and 14 days after mifepristone administration to assess completion 7.

Rare Complications Requiring Intervention

• Ongoing pregnancy: Occurs in <2% of cases 1, 2
• Hemorrhage requiring emergency curettage: Approximately 3–4% of cases 2
• Infection: Rare complication 1
• Undiagnosed ectopic pregnancy: Emphasizes importance of proper screening 1
• Overall surgical intervention rate: 1.7–2.6% for incomplete expulsion 2, 3

Common Pitfalls to Avoid

1. Do not use this regimen in women with prior cesarean delivery due to rupture risk 5, 6
2. Do not skip ectopic pregnancy screening when gestational dating is uncertain or risk factors are present 1
3. Do not use oral misoprostol as first-line—vaginal or buccal routes are more effective 1
4. Do not delay surgical intervention if heavy bleeding occurs (>2 pads per hour for 2 consecutive hours) 2
5. Do not assume failure too early—expulsion can take up to 50 hours after first misoprostol dose 2