| Indication | Progesterone supplementation indicated? | Management |
| Singleton pregnancy, prior spontaneous singleton preterm birth, normal cervical length | Yes | Hydroxyprogesterone caproate 250 mg intramuscularly weekly beginning between 16 and 20 weeks of gestation and continuing through 36 weeks of gestation or until delivery and monitor cervical length. Natural progesterone administered vaginally is a reasonable alternative. Short (≤25 mm) cervix → consider performing cerclage |
| Singleton pregnancy, prior spontaneous twin preterm birth, normal cervical length | Possibly | Hydroxyprogesterone caproate 250 mg intramuscularly weekly beginning between 16 and 20 weeks of gestation and continuing through 36 weeks of gestation or until delivery and monitor cervical length. Natural progesterone administered vaginally is a reasonable alternative. Short (≤25 mm) cervix → consider performing cerclage |
| Singleton pregnancy, no prior spontaneous preterm birth, short cervix (≤20 mm) | Yes | Progesterone suppository 90 to 200 mg vaginally each night from time of diagnosis through 36 weeks of gestation. A vaginal suppository can be prepared by a compounding pharmacy utilizing a commercially available standardized kit. Other options include a 100 mg micronized progesterone vaginal tablet or an 8% vaginal gel containing 90 mg micronized progesterone per dose. Both preparations are commercially available in United States but not approved for prevention of preterm birth in cervical shortening. |
| Multiple pregnancy (twins or triplets) without prior preterm birth, normal cervical length | No | No progesterone, no cerclage. |
| Twins, prior preterm birth | Possibly | Hydroxyprogesterone caproate 250 mg intramuscularly weekly beginning between 16 and 20 weeks of gestation and continuing through 36 weeks of gestation or until delivery. Natural progesterone administered vaginally is a reasonable alternative. |
| Twins, short cervix | Possibly | Vaginal progesterone, no cerclage. |
| Preterm premature rupture of membranes | No | – |
| Positive fetal fibronectin test | No | – |
| Undelivered after an episode of preterm labor | No | – |
