17-Alpha Hydroxyprogesterone Caproate
Intramuscular synthetic progestogen (C21 steroid) historically used for prevention of recurrent spontaneous preterm birth (sPTB) in singleton gestations with a prior sPTB. The landmark MFMU Network PREIS trial (Meis et al., NEJM 2003) demonstrated a 34% relative risk reduction in PTB <37 weeks, forming the basis of FDA accelerated approval of Makena (AMAG Pharmaceuticals) in 2011. However, the adequately powered PROLONG trial (Blackwell et al., 2019), conducted in a broader international population, failed to replicate efficacy on either primary or secondary outcomes. The 2021 EPPPIC individual patient data meta-analysis (Lancet) further confirmed no significant benefit on neonatal composite outcomes for 17-OHPC IM. Following an FDA advisory committee vote in 2019 and a formal benefit-risk reassessment, the FDA withdrew approval of Makena in April 2023 — the first withdrawal of an obstetric drug under the accelerated approval pathway. Current ACOG guidance (Practice Bulletin 234, reaffirmed 2023) and SMFM no longer recommend 17-OHPC IM as a standard strategy for sPTB prevention. Vaginal progesterone (90 mg gel or 200 mg micronized capsule) remains the preferred option for asymptomatic patients with a singleton pregnancy and sonographic short cervix (≤25 mm) at 16–24 weeks, supported by individual patient data meta-analyses (IPDMA, Romero et al., 2018).
