Why is progesterone prescribed during pregnancy?

Why Progesterone is Prescribed During Pregnancy

Progesterone is prescribed during pregnancy primarily to prevent preterm birth in women at high risk, specifically those with a history of prior spontaneous preterm birth or those found to have a short cervix on ultrasound. 1, 2

Primary Indications for Progesterone Therapy

For Women with Prior Spontaneous Preterm Birth

17-alpha-hydroxyprogesterone caproate (17P) 250 mg intramuscularly weekly, starting at 16-20 weeks until 36 weeks, is the recommended first-line treatment for singleton pregnancies with a history of spontaneous preterm birth between 20-36 6/7 weeks. 1, 2, 3

• This therapy reduces recurrent preterm birth at <37 weeks by 34% (from 54.9% to 36.3%) 1
• It significantly reduces perinatal mortality by 50% 4
• It decreases preterm birth at <34 weeks by 69% 4
• It reduces neonatal complications including intraventricular hemorrhage, necrotizing enterocolitis, need for assisted ventilation, and neonatal death 1, 4

For Women with Short Cervical Length

Vaginal progesterone (either 90-mg gel or 200-mg suppository daily) is recommended for singleton pregnancies without prior preterm birth but with cervical length ≤20 mm detected at ≤24 weeks gestation. 1, 2, 3

• This reduces preterm birth and perinatal morbidity and mortality 1, 2
• Vaginal progesterone reduces preterm birth at <34 weeks by 36% and at <28 weeks by 41% in women with short cervix 3

Mechanism of Action

Progesterone prevents preterm birth through multiple pathways: 2, 5

• Anti-inflammatory effects that counteract inflammatory processes leading to preterm labor 2
• Myometrial relaxation by reducing prostaglandin synthesis and decreasing contraction frequency 5
• Maintenance of progesterone receptor expression that keeps the uterus in a non-contractile state 5
• Cervical effects including alteration of cervical stromal degradation and providing a barrier to ascending infection 2
• Local increase in progesterone in gestational tissues that counteracts functional progesterone withdrawal 2

Algorithm for Clinical Use

For singleton pregnancies with prior spontaneous preterm birth (20-36 6/7 weeks): 1, 3

• Start 17P 250 mg IM weekly at 16-20 weeks, continue until 36 weeks
• If cervical length shortens to <25 mm at ≤24 weeks, consider adding cervical cerclage 1

For singleton pregnancies without prior preterm birth: 1, 3

• Perform transvaginal ultrasound cervical length screening at 18-24 weeks (though universal screening remains debated) 1, 3
• If cervical length ≤20 mm: start vaginal progesterone 90-mg gel or 200-mg suppository daily 1, 3
• If cervical length >20 mm: routine obstetric care 1

Critical Caveats and Situations Where Progesterone Does NOT Work

Progesterone is NOT effective and should NOT be used in the following situations: 1, 2, 3

• Multiple gestations (twins, triplets) - no benefit demonstrated 1, 2, 3
• Active preterm labor in current pregnancy - not effective as rescue therapy 1, 2, 3
• Preterm premature rupture of membranes (PPROM) - no benefit 1, 2, 3
• Singleton pregnancies with no prior preterm birth and unknown cervical length - insufficient evidence 1

Common Pitfalls to Avoid

• Do not use progesterone once active preterm labor has begun - it only works as prevention, not treatment 2, 3
• Do not extrapolate cervical length cutoffs - the evidence specifically supports ≤20 mm, not measurements >20 mm 1
• Do not screen at incorrect gestational ages - screening should occur at 18-24 weeks for optimal evidence-based intervention 1
• Do not substitute formulations without evidence - 17P has stronger evidence for prior preterm birth than vaginal progesterone in this population 1
• Start therapy early (16-20 weeks) for maximum effectiveness, not later in pregnancy 1, 3

Safety Profile

No long-term adverse effects have been identified in children exposed to progesterone in utero, though long-term follow-up data remains limited. 2, 3