What is the recommended progesterone regimen (dose, route, and duration) for a pregnant woman with cervical insufficiency (short cervix ≤25 mm before 24 weeks)?

Role of Progesterone in Management of Cervical Insufficiency

For pregnant women with a short cervix (≤25 mm) diagnosed before 24 weeks of gestation, vaginal progesterone is the recommended first-line treatment, administered as either 90-mg gel or 200-mg micronized capsules daily, starting at diagnosis and continuing until 34-36 weeks of gestation. 1

Evidence-Based Treatment Algorithm

For Cervical Length ≤20 mm

• Vaginal progesterone is strongly recommended (GRADE 1A evidence) for all asymptomatic women with singleton gestations and transvaginal cervical length ≤20 mm diagnosed before 24 weeks 1
• This reduces preterm birth at <33 weeks by 45% (RR 0.55), at <28 weeks by 50% (RR 0.50), and respiratory distress syndrome by 61% (RR 0.39) 1
• Treatment reduces composite neonatal morbidity and mortality by 43% 1

For Cervical Length 21-25 mm

• Vaginal progesterone should be offered based on shared decision-making (GRADE 1B evidence) 1
• While evidence is slightly less robust than for ≤20 mm, meta-analyses demonstrate significant reductions in preterm birth at <32 weeks (RR 0.64) and composite neonatal morbidity 1

Specific Dosing Regimens

The two most extensively studied formulations are equally acceptable 1:

• 90-mg progesterone gel (8%) administered vaginally once daily, OR
• 200-mg micronized progesterone capsules administered vaginally once daily

Duration of treatment: Start at diagnosis (typically 18-24 weeks) and continue until 34-36 weeks of gestation 1

What NOT to Use

17-Alpha Hydroxyprogesterone Caproate (17-OHPC)

• Do NOT prescribe 17-OHPC for short cervix management (GRADE 1B) 1
• The FDA withdrew approval in 2023 due to lack of efficacy 1
• Large multicenter trials showed no reduction in preterm birth rates (25.1% vs 24.2%; RR 1.03) in women with short cervix and no prior preterm birth 1
• This applies to both branded and compounded formulations 1

Important Distinction for Prior Preterm Birth

• If a woman has BOTH a history of prior spontaneous preterm birth AND develops a short cervix, the evidence is conflicting 1, 2
• In this specific scenario, some older guidelines suggested continuing 17-OHPC (which would have been started at 16 weeks for history alone) rather than switching to vaginal progesterone 1, 2
• However, given the 2023 FDA withdrawal of 17-OHPC, vaginal progesterone is now the preferred agent even in this population 1

Alternative Interventions NOT Recommended

Cerclage

• Do NOT place cerclage in women with short cervix (10-25 mm) without prior preterm birth, in the absence of cervical dilation (GRADE 1B) 1
• Cerclage has not demonstrated consistent benefit in this population and carries procedural risks 1

Cervical Pessary

• Do NOT place cervical pessary for short cervix management (GRADE 1B) 1
• Recent large trials showed no benefit and one trial was stopped early due to increased perinatal mortality (13.1% vs 6.8%; RR 1.93) 1

Clinical Implementation Pearls

Measurement Technique

• All cervical length measurements must be performed via transvaginal ultrasound using standardized techniques (Perinatal Quality Foundation or Fetal Medicine Foundation protocols) 1
• Optimal screening window is 18-24 weeks of gestation 1, 3

Safety Considerations

• Contraindication: Severe peanut allergy is a contraindication to micronized progesterone capsules (contain peanut oil); use vaginal gel formulation instead 1
• No increase in infection, bleeding, or premature rupture of membranes has been documented 1
• Long-term safety data beyond the neonatal period remain limited 4

Number Needed to Treat

• For every 10-19 women with short cervix treated with vaginal progesterone, one case of preterm birth is prevented 3
• Number needed to screen is 125 women to prevent one preterm birth <34 weeks 3

Common Pitfalls to Avoid

1. Do not use 17-OHPC instead of vaginal progesterone for short cervix—the evidence base is completely different and 17-OHPC is ineffective for this indication 1

2. Do not assume formulations are interchangeable—17-OHPC is a synthetic progestin with different pharmacology than natural progesterone 5, 6

3. Do not delay treatment while considering cerclage or pessary—vaginal progesterone should be initiated promptly upon diagnosis 1

4. Do not apply these recommendations to multiple gestations—progesterone has not shown benefit in twin or triplet pregnancies with short cervix 1

Cost-Effectiveness and Public Health Impact

Universal cervical length screening combined with vaginal progesterone treatment is cost-effective and could prevent approximately 30,000 preterm births annually in the United States 3. Implementation of universal screening programs has demonstrated real-world reductions in preterm birth rates at <37, <34, and <32 weeks 1.