Technical Update No. 467: Progesterone for Previous Spontaneous Preterm Birth

ABSTRACT Objective To assess the benefits and risks of progesterone therapy for women at increased risk of spontaneous preterm birth and to make recommendations for the use of progesterone to reduce the risk of spontaneous preterm birth and improve postnatal outcomes. Target Population Pregnant women at increased risk of spontaneous preterm birth (SPB) solely because of prior spontaneous preterm birth. Options To administer or withhold progesterone therapy for women deemed to be at high risk of SPB. Outcomes Preterm birth, neonatal morbidity and mortality, and postnatal outcomes including neurodevelopmental outcomes. Benefits, Harms, and Costs Therapy with progesterone significantly reduces the risk of spontaneous preterm birth only in some subpopulations of women at increased risk. Although this therapy entails a cost to the woman in addition to the discomfort associated with its use, no other significant adverse effects to the mother or the newborn have been identified. Evidence Medline, PubMed, EMBASE, and the Cochrane Library were searched from November 2018 to November 2025 for medical subject heading (MeSH) terms and keywords related to pregnancy, preterm birth, previous preterm birth, neonatal morbidity and mortality, and postnatal outcomes. This document represents an abstraction of the evidence rather than a methodological review. Validation Methods The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations). Intended Audience Obstetric care providers, including obstetricians, family physicians, nurses, midwives and maternal-fetal medicine specialists Social Media Abstract Progesterone therapy should be used in women with a short cervix on transvaginal imaging (≤25 mm) in the current pregnancy (between 16-24 weeks) but not in those with a history of spontaneous preterm birth and a normal cervical length.