What is the role of progesterone (P4) in managing threatened abortion?

Progesterone for Threatened Abortion

Progesterone should NOT be routinely used for threatened abortion, as current guidelines from the Society for Maternal-Fetal Medicine (SMFM) explicitly state there is "no evidence of effectiveness" for symptomatic threatened miscarriage. 1

Guideline-Based Recommendations

The evidence against progesterone use in threatened abortion is clear from professional society guidelines:

• SMFM guidelines specifically list symptomatic populations, including threatened miscarriage, as conditions where progesterone has no evidence of effectiveness 1
• Threatened miscarriage is notably absent from the SMFM recommendations table listing approved indications for progesterone therapy 1
• The American College of Obstetricians and Gynecologists does not recommend progesterone supplementation based solely on symptoms of threatened abortion 1, 2

Conflicting Research Evidence

While guidelines are clear, some research studies suggest potential benefit, creating a disconnect between evidence and recommendations:

• A 2018 Cochrane systematic review of 7 trials (696 participants) found that progesterone treatment probably reduces miscarriage risk compared to placebo (RR 0.64,95% CI 0.47-0.87), though the quality of evidence was only moderate 3
• When analyzed by route, oral progesterone showed benefit (RR 0.57,95% CI 0.38-0.85), but vaginal progesterone showed little or no effect (RR 0.75,95% CI 0.47-1.21) 3
• Individual trials have shown mixed results, with some demonstrating reduced abortion rates but without statistical significance 4

The critical issue is that these research findings have not translated into guideline recommendations, likely due to methodological limitations, small sample sizes, and inconsistent results across studies. 3

Where Progesterone IS Indicated

Progesterone has proven efficacy in distinctly different clinical scenarios that should not be confused with threatened abortion:

For Prior Spontaneous Preterm Birth

• 17-hydroxyprogesterone caproate (17P) 250 mg IM weekly from 16-20 weeks until 36 weeks for singleton pregnancies with prior spontaneous preterm birth 5, 1, 2
• This represents the strongest evidence for progesterone use, based on large randomized trials showing reduced preterm birth rates and neonatal complications 5

For Short Cervical Length Without Prior Preterm Birth

• Vaginal progesterone 90-mg gel or 200-mg suppository daily for singleton pregnancies with cervical length ≤20 mm at 18-24 weeks, continued until 36 weeks 1, 2
• This indication is based on screening findings, not symptoms 5

Critical Clinical Distinctions

Do not conflate threatened abortion (first trimester bleeding) with preterm labor prevention (second/third trimester). These are entirely different clinical entities:

• Threatened abortion occurs before 20 weeks and involves vaginal bleeding with a closed cervix 3, 4
• Preterm birth prevention targets women at 16-24 weeks based on risk factors, not acute symptoms 5, 1
• Progesterone is ineffective as rescue therapy once active symptoms begin, whether for threatened abortion or active preterm labor 5, 1

Important Caveats

• Progesterone has no role in multiple gestations for preterm birth prevention, with multiple trials showing no benefit in twins or triplets 5
• Evidence on congenital abnormalities is very limited and uncertain (RR 0.70,95% CI 0.10-4.82), based on only two small trials 3
• Many oral micronized progesterone formulations contain peanut oil and should be avoided in patients with severe peanut allergies; vaginal gel formulations are peanut-free alternatives 6
• Long-term effects of progesterone therapy on child development remain poorly established 1

Clinical Bottom Line

Despite some positive research signals, the absence of guideline support for progesterone in threatened abortion reflects the overall weak and inconsistent evidence base. In clinical practice, prioritize expectant management for threatened abortion, reserving progesterone exclusively for the evidence-based indications of prior preterm birth or documented short cervix in the second trimester. 1, 3