How does the combination of mifepristone and misoprostol (miso) work in medical abortion, with mifepristone blocking progesterone receptors and misoprostol inducing uterine contractions?

Mechanism of Action of Mifepristone and Misoprostol in Medical Abortion

Mifepristone blocks progesterone receptors to destabilize the pregnancy, while misoprostol induces uterine contractions to expel the pregnancy tissue. 1, 2

How the Combination Works

• Mifepristone (also known as RU-486) acts as an antiprogesterone by competitively binding to progesterone receptors, blocking the action of progesterone which is necessary to sustain pregnancy 1
• By blocking progesterone receptors, mifepristone causes:
  • Decidual degeneration
  • Cervical softening
  • Increased uterine sensitivity to prostaglandins
  • Detachment of the implanted embryo 2
• Misoprostol, a prostaglandin E1 analogue, completes the process by:
  • Causing strong uterine contractions
  • Inducing cervical ripening and dilation
  • Facilitating the expulsion of the detached pregnancy tissue 1, 2

Efficacy of the Combination

• The mifepristone-misoprostol regimen is highly effective for medical abortion up to 77 days' gestation 2
• The most effective regimen includes 200 mg of oral mifepristone followed by 800 mcg of misoprostol administered buccally or vaginally 2
• Complete abortion rates are approximately 95-97% when the medications are used in combination 3
• Mifepristone significantly enhances the effectiveness of misoprostol compared to using misoprostol alone 4

Clinical Considerations

• Expected effects include cramping and bleeding, with bleeding lasting an average of 9-16 days 2
• Common side effects of misoprostol include low-grade fever, nausea, vomiting, and diarrhea 2, 5
• The timing between medications can be flexible:
  • Studies show similar efficacy when misoprostol is administered simultaneously with mifepristone or 24 hours later 3
  • However, traditional protocols typically use a 24-48 hour interval between medications 1

Important Safety Considerations

• Rare complications include ongoing pregnancy, infection, hemorrhage, and the need for unplanned uterine aspiration 2
• Misoprostol should be avoided in women with previous cesarean delivery due to the risk of uterine rupture 5
• High-risk patients should be managed in experienced centers with appropriate emergency support services 5

The mechanism of action clearly demonstrates the complementary roles of these medications: mifepristone creates the conditions for pregnancy termination by blocking progesterone action, while misoprostol provides the mechanical force through uterine contractions to complete the expulsion process.