What is the role of 17α-hydroxyprogesterone caproate (17-OHPC) in preventing preterm labor in pregnant women with a history of spontaneous preterm birth?

Role of 17α-hydroxyprogesterone caproate (17-OHPC) in Preventing Preterm Labor

17α-hydroxyprogesterone caproate (17-OHPC) is recommended for all women with a singleton pregnancy and history of spontaneous preterm birth (PTB), administered as weekly 250 mg intramuscular injections from 16-20 weeks until 36 weeks of gestation. 1

Evidence Supporting 17-OHPC Use

• 17-OHPC reduces the risk of recurrent preterm birth by approximately 34% (from 54.9% to 36.3%) in women with a history of spontaneous preterm birth 1
• Treatment with 17-OHPC significantly reduces preterm delivery at:
  • Less than 37 weeks gestation (36.3% vs 54.9%) 2
  • Less than 35 weeks gestation (20.6% vs 30.7%) 2
  • Less than 32 weeks gestation (11.4% vs 19.6%) 2
• 17-OHPC treatment is associated with significant reductions in infant complications including intraventricular hemorrhage, necrotizing enterocolitis, and need for supplemental oxygen 1, 2
• A meta-analysis showed 17-OHPC reduced neonatal death by 68% compared to placebo (RR 0.32; 95% CI, 0.15-0.66) 3

Administration Protocol

• Dosage: 250 mg intramuscularly once weekly 4
• Initiation: Begin treatment between 16 weeks, 0 days and 20 weeks, 6 days of gestation 4, 1
• Duration: Continue weekly injections until 36 weeks, 6 days of gestation or delivery, whichever occurs first 4
• Administration technique:
  • Use 21 gauge 1½ inch needle for injection
  • Inject slowly (over one minute) into the upper outer quadrant of the gluteus maximus
  • Apply pressure to minimize bruising and swelling 4

Patient Selection Criteria

• 17-OHPC is specifically indicated for women with:
  • Singleton pregnancy
  • History of spontaneous preterm birth between 20 and 36 6/7 weeks 1, 4
• 17-OHPC is NOT indicated for:
  • Multiple gestations
  • Other risk factors for preterm birth without history of spontaneous preterm birth 4
  • Preterm labor or preterm premature rupture of membranes in current pregnancy 1

Clinical Considerations and Caveats

• Plasma concentrations of 17-OHPC vary substantially between patients; women with concentrations in the lowest quartile have significantly higher risk of spontaneous preterm birth 5
• Factors associated with poor response to 17-OHPC include:
  • Earlier gestational age of previous spontaneous preterm birth
  • Vaginal bleeding/abruption in current pregnancy
  • First-degree family history of spontaneous preterm birth 6
• Contraindications include:
  • Current or history of thrombosis or thromboembolic disorders
  • Known or suspected breast cancer or hormone-sensitive cancer
  • Undiagnosed abnormal vaginal bleeding
  • Cholestatic jaundice of pregnancy
  • Liver tumors or active liver disease
  • Uncontrolled hypertension 4

Monitoring and Special Considerations

• Monitor prediabetic and diabetic women closely as progestins may decrease glucose tolerance 4
• Watch for signs of fluid retention in women with conditions that may be affected by fluid retention (preeclampsia, epilepsy, cardiac or renal dysfunction) 4
• Monitor women with history of depression; discontinue if depression recurs 4
• Common adverse reactions include injection site reactions (pain 35%, swelling 17%, pruritus 6%, nodule 5%), urticaria (12%), pruritus (8%), nausea (6%), and diarrhea (2%) 4

Vaginal Progesterone vs. 17-OHPC

• The Society for Maternal-Fetal Medicine (SMFM) specifically recommends 17-OHPC over vaginal progesterone for women with a history of spontaneous preterm birth 1
• Vaginal progesterone should not be considered a substitute for 17-OHPC in women with prior spontaneous preterm birth 1
• In women with a history of preterm birth who develop cervical shortening while on 17-OHPC, continuation of 17-OHPC is recommended rather than switching to vaginal progesterone 1

Despite strong recommendations from SMFM, some recent evidence has questioned the efficacy of 17-OHPC in clinical practice, with one retrospective cohort study finding no association between 17-OHPC use and pregnancy prolongation 7. However, current guidelines still support its use based on the preponderance of evidence showing benefit in reducing preterm birth and associated neonatal complications.