What are the recommended dosing and treatment guidelines for progesterone (P4) supplementation in patients with threatened miscarriage?

Progesterone for Threatened Miscarriage: Recommendations and Dosing

Vaginal progesterone 400 mg daily (200 mg twice daily) is recommended for women with threatened miscarriage who have a history of one or more previous miscarriages until 12 weeks of gestation. This recommendation is based on the most recent high-quality evidence showing significant benefit in this specific population 1, 2.

Patient Selection and Evidence Base

Who Benefits from Progesterone Therapy:

• Women with threatened miscarriage AND prior miscarriage history:

  • Vaginal progesterone increases live birth rates by approximately 5% in women with bleeding in early pregnancy who have had one or more previous miscarriages 1
  • The benefit is greater (15% increase in live birth rate) for women with 3+ previous miscarriages and current pregnancy bleeding 1

• Women with threatened miscarriage but NO prior miscarriage:

  • Limited evidence of benefit (RR 0.99,95% CI 0.95 to 1.04) 3
  • Progesterone likely makes little to no difference in this population

Recommended Dosing and Administration

1. Formulation and Dose:

   • Vaginal micronized progesterone 400 mg daily (typically 200 mg twice daily) 1
   • Alternative: Oral dydrogesterone (though less evidence supports this route)

2. Duration of Treatment:

   • Start as soon as threatened miscarriage is diagnosed
   • Continue until 12 weeks of gestation 4
   • Note: While some guidelines suggest continuing until 16 weeks, evidence indicates the beneficial effect of progesterone is complete by 12 weeks when placental production takes over 4

3. Administration Route:

   • Vaginal administration is preferred based on strongest evidence
   • Vaginal gel formulations can be used for patients with peanut allergies (as some capsule formulations contain peanut oil) 5

Important Clinical Considerations

Contraindications:

• Severe peanut allergies (for micronized progesterone capsules containing peanut oil)
• Hormone receptor-positive breast cancer
• Known hypersensitivity to progesterone

Monitoring:

• Follow-up ultrasound to confirm ongoing pregnancy
• Monitor for adverse effects (though progesterone has a favorable safety profile)

Potential Adverse Effects:

• No significant increase in congenital abnormalities (RR 1.06,95% CI: 0.76-1.48) 2
• No significant increase in other serious adverse pregnancy events (RR 1.07,95% CI: 0.83-1.40) 2

Common Pitfalls to Avoid

1. Extending treatment unnecessarily: While some guidelines recommend continuing until 16 weeks, evidence suggests benefits are complete by 12 weeks when placental production of progesterone is established 4

2. Using progesterone for all threatened miscarriages: The strongest evidence supports use only in women with both threatened miscarriage AND prior miscarriage history

3. Incorrect dosing: Ensure proper dosing (400 mg daily) as lower doses may be ineffective

4. Delayed initiation: Treatment should begin as soon as threatened miscarriage is diagnosed for maximum benefit

Special Populations

• Multiple gestations: Insufficient evidence to recommend progesterone for threatened miscarriage in twin or higher-order pregnancies 5

• Preterm premature rupture of membranes (PPROM): Insufficient evidence to support progesterone use 5

The evidence clearly supports using vaginal progesterone for women with threatened miscarriage who have a history of previous miscarriage(s), with treatment continuing until 12 weeks gestation.