Progesterone Administration at 12 Weeks for Threatened Miscarriage
For threatened miscarriage at 12 weeks gestation with confirmed fetal heartbeat, you should NOT combine oral and vaginal progesterone, and treatment should be discontinued by 12 weeks as the beneficial effects are complete by this gestational age.
Evidence-Based Treatment Duration
The critical finding from the PRISM trial demonstrates that progesterone's beneficial effects are complete by 12 weeks of gestation, with no benefit observed when treatment is started after 9 weeks 1, 2. At 12 weeks, the placenta—not the maternal ovary—becomes the primary source of progesterone production, making exogenous supplementation unnecessary 1.
Treatment should be stopped at 12 weeks, not continued to 16 weeks, despite some guidelines suggesting longer duration 1. The evidence shows:
- Full therapeutic effect achieved by 12 weeks gestation 1
- No additional benefit from continuing beyond this point 1
- Theoretical concerns about long-term offspring health effects with prolonged exposure 1
Route Selection: Single Agent Only
Use vaginal micronized progesterone 400 mg twice daily as monotherapy 2, 3. There is no evidence supporting combination therapy with both oral and vaginal routes simultaneously.
For women with threatened miscarriage AND one or more previous miscarriages, vaginal micronized progesterone increases live birth rate (RR 1.08,95% CI 1.02-1.15) compared to placebo 2, 3. However, for women with no previous miscarriages, there is probably little or no improvement in live birth rate (RR 0.99,95% CI 0.95-1.04) 3.
Alternative Oral Option
If vaginal administration is not feasible, oral dydrogesterone (40 mg stat, then 10 mg three times daily) is superior to oral micronized progesterone for threatened miscarriage, reducing miscarriage risk compared to both placebo (OR 0.5,95% CI 0.32-0.76) and vaginal progesterone (OR 0.57,95% CI 0.36-0.89) 4.
Safety Profile
Vaginal micronized progesterone shows no difference in congenital abnormalities (RR 1.00,95% CI 0.68-1.46) or adverse drug events (RR 1.07,95% CI 0.81-1.39) compared to placebo in threatened miscarriage 3.
Critical Caveats
- Never use progesterone as primary tocolysis in active preterm labor—insufficient evidence of benefit 5
- Avoid in multiple gestations—multiple RCTs show no effect on preterm birth rates or perinatal outcomes, exposing patients to risk without benefit 5
- Contraindicated with severe peanut allergy if using capsules containing peanut oil; use progesterone gel instead 6
- Starting treatment after 9 weeks provides no benefit 1, 2