Is progesterone supplementation effective for treating threatened miscarriage?

Progesterone for Threatened Miscarriage

Progesterone supplementation is not routinely recommended for treating threatened miscarriage as there is insufficient evidence of effectiveness for this indication. 1

Evidence for Progesterone Use in Threatened Miscarriage

• Current Society for Maternal-Fetal Medicine (SMFM) guidelines do not recommend progesterone for symptomatic threatened miscarriage, stating there is "no evidence of effectiveness" 1
• The guidelines specifically list "symptomatic" populations including preterm labor (PTL) and preterm premature rupture of membranes (PPROM) as conditions where progesterone has no evidence of effectiveness 1
• In the SMFM recommendations table, threatened miscarriage is not listed as an indication for progesterone therapy 1

Specific Populations Where Progesterone IS Recommended

Progesterone is only recommended in the following specific scenarios:

• Singleton pregnancies with prior spontaneous preterm birth: 17P 250 mg IM weekly from 16-20 weeks until 36 weeks 1, 2
• Singleton pregnancies without prior preterm birth but with short cervical length ≤20 mm at ≤24 weeks: vaginal progesterone 90-mg gel or 200-mg suppository daily 1, 2

Recent Research on Progesterone for Threatened Miscarriage

While the guidelines don't recommend routine use, some recent research suggests potential benefit in specific subgroups:

• The PRISM trial found that vaginal micronized progesterone 400 mg twice daily may benefit women with both current pregnancy bleeding AND history of previous miscarriage(s) 3
• For women with ≥3 previous miscarriages and current pregnancy bleeding, live birth rate was 72% with progesterone vs 57% with placebo (15% difference; RR 1.28) 3
• However, a 2021 Cochrane network meta-analysis concluded that progestogens probably make little or no difference to live birth rate for women with threatened miscarriage in general 4

Prognostic Value of Serum Progesterone

• Some research suggests using serum progesterone levels to guide management decisions:
  • Women with threatened miscarriage and serum progesterone ≥35 nmol/L had a miscarriage rate of only 9.6% without treatment 5
  • Those with levels <35 nmol/L had a 70.8% miscarriage rate despite treatment with dydrogesterone 5

Important Clinical Considerations

• Progesterone therapy should be started early (16-20 weeks) for maximum effectiveness in preterm birth prevention, but this timing doesn't apply to threatened miscarriage 2
• Progesterone is not effective as rescue therapy once active preterm labor has begun 1, 2
• The long-term effects of progesterone therapy on child development are not well-established 2

Potential Benefits Beyond Miscarriage Prevention

• Some evidence suggests that early progesterone supplementation (before 20 weeks) may reduce the risk of preeclampsia later in pregnancy (OR 0.64,95% CI 0.42-0.98) 6
• Oral dydrogesterone before 20 weeks may reduce the risk of low birth weight (OR 0.57,95% CI 0.34-0.95) 6

In summary, while progesterone is an established therapy for preventing preterm birth in specific high-risk populations, current guidelines do not support its routine use for threatened miscarriage. However, women with both current bleeding AND a history of previous miscarriage(s) may potentially benefit from vaginal progesterone therapy based on recent research.