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.

SUMMARY STATEMENTS

• 1.
  Progesterone therapy reduces the risk of spontaneous preterm birth in women with a short cervix (transvaginal length ≤25 mm) during the current pregnancy, when initiated between 16 and 24 weeks of gestation. However, it does not reduce the risk in women with a history of preterm birth who have a normal cervical length in their current singleton or twin pregnancy. (moderate)
• 2.
  Current evidence does not support the use of aspirin for prevention of spontaneous preterm birth. (low)
• 3.
  Universal cervical length screening by transvaginal ultrasound for identification of women who would benefit from vaginal progesterone followed by progesterone therapy as indicated reduces the risk of spontaneous preterm birth and is also cost effective. (moderate)

RECOMMENDED CHANGES IN PRACTICE

• 1.
  Progesterone should not be used for prevention of spontaneous preterm birth in women with prior spontaneous preterm birth and a normal transvaginal cervical length in the current pregnancy. (strong, moderate)
• 2.
  All pregnant women should undergo universal cervical length screening via transvaginal ultrasound between 18 and 24 weeks of gestation to identify those at increased risk of spontaneous preterm birth. (strong, moderate)

RECOMMENDATIONS

• 1.
  Prenatal care providers should not prescribe vaginal progesterone therapy for prevention of spontaneous preterm birth in women with previous preterm birth without concurrent cervical shortening in singleton or twin pregnancies (transvaginal length ≤25 mm). (strong, moderate)
• 2.
  Health authorities, institutions, and physicians in Canada (and internationally) should consider implementing universal cervical length screening using transvaginal ultrasound during the routine fetal anatomy scan, where feasible. (strong, moderate)