What is the recommended progesterone regimen for a pregnant woman with a short cervix (≤25 mm) or a history of cervical insufficiency?

Progesterone for Cervical Insufficiency and Short Cervix

For Women WITHOUT Prior Spontaneous Preterm Birth

Vaginal progesterone (90-mg gel or 200-mg suppository daily) is the definitive treatment for singleton pregnancies with a short cervix ≤25 mm detected before 24 weeks, reducing preterm birth and neonatal morbidity. 1, 2

Specific Indications by Cervical Length

• Cervical length ≤20 mm: Vaginal progesterone is strongly recommended, reducing preterm birth before 33 weeks by 45% (RR 0.55), before 28 weeks by 50% (RR 0.50), and respiratory distress syndrome by 61% (RR 0.39). 2

• Cervical length 21-25 mm: Vaginal progesterone should be offered after shared decision-making, with demonstrated reduction in preterm birth before 32 weeks (RR 0.64). 2

Dosing Protocol

• Start vaginal progesterone at diagnosis (typically 18-24 weeks) and continue until 34-36 weeks of gestation. 1, 2

• Either 90-mg progesterone gel (8% formulation) or 200-mg micronized progesterone capsules vaginally once daily are equally acceptable. 1, 2

• Critical contraindication: Severe peanut allergy prohibits micronized progesterone capsules (contain peanut oil); use gel formulation instead. 2

What NOT to Use

• 17-alpha-hydroxyprogesterone caproate (17-OHPC) must NOT be used for short cervix management in women without prior preterm birth—the FDA withdrew approval in 2023 due to lack of demonstrated efficacy (25.1% vs 24.2% preterm birth; RR 1.03). 2

• Cervical cerclage is not recommended for short cervix (10-25 mm) in women without prior preterm birth and without cervical dilation, as it has not shown consistent benefit and carries procedural risks. 2

• Cervical pessary is not recommended—recent large trials showed no benefit and one trial was halted early due to higher perinatal mortality (13.1% vs 6.8%; RR 1.93). 2

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For Women WITH Prior Spontaneous Preterm Birth (20-36 6/7 Weeks)

17-alpha-hydroxyprogesterone caproate (17-OHPC) 250 mg intramuscularly weekly is the recommended treatment, starting at 16-20 weeks and continuing until 36 weeks of gestation. 1, 3, 4

Surveillance Protocol

• Perform serial transvaginal ultrasound cervical length assessments every 2-4 weeks from 16-24 weeks of gestation to guide subsequent interventions. 3

• Approximately 69% of women with prior spontaneous preterm birth maintain cervical length >25 mm throughout pregnancy. 3

Management Algorithm Based on Cervical Length

If cervical length remains >25 mm:

• Continue 17-OHPC therapy alone with routine obstetric care. 1, 3

If cervical length shortens to ≤25 mm before 24 weeks:

• Offer cervical cerclage placement while continuing 17-OHPC therapy. 1, 3
• Women with cervical length <25 mm had a 34% risk of preterm birth <32 weeks with neither intervention, 25% with cerclage alone, 21% with 17-OHPC alone, and 17% with both. 1

If cervical length is ≤20 mm:

• Strongly consider cerclage placement, as this threshold represents significant cervical insufficiency. 3

If cervical length shortens to <10 mm despite vaginal progesterone:

• Consider adding cervical cerclage, which significantly decreases spontaneous preterm birth rates (44.1% vs 84.2% at <37 weeks), prolongs pregnancy latency by 2-fold (14 weeks average), and decreases neonatal intensive care unit admission (36.1% vs 65.7%). 5

Critical Management Pitfall

Do NOT substitute vaginal progesterone for 17-OHPC in women with prior spontaneous preterm birth. 1, 3, 4

• Multiple randomized controlled trials have failed to demonstrate efficacy of vaginal progesterone in reducing recurrent preterm birth in this population. 1, 4

• The OPPTIMUM study showed no significant differences in preterm birth rates at <34 weeks between vaginal progesterone and placebo in women with prior spontaneous preterm birth (15.9% vs 18.8%). 1, 4

• If cervical shortening develops despite 17-OHPC therapy, continue 17-OHPC rather than switching to vaginal progesterone, as there is no evidence that changing progestogen formulations provides additional benefit. 1, 3, 4

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Special Populations Where Progesterone Is NOT Effective

• Multiple gestations (twins or triplets): Progestogens have not been associated with prevention of preterm birth in multiple gestations, even with short cervix. 1, 2

• Preterm labor (symptomatic): Insufficient evidence to recommend progestogens for primary, adjunctive, or maintenance tocolysis. 1

• Preterm premature rupture of membranes (PPROM): Insufficient evidence to assess effect of progesterone, though it is reasonable to continue 17-OHPC if already initiated for prior spontaneous preterm birth. 1