Vaginal progesterone, oral progesterone, 17-OHPC, cerclage, and pessary for preventing preterm birth in at-risk singleton pregnancies: an updated systematic review and network meta-analysis

BJOG. 2019 Apr;126(5):556-567. doi: 10.1111/1471-0528.15566. Epub 2018 Dec 29.


Background: Recent progesterone trials call for an update of previous syntheses of interventions to prevent preterm birth.

Objectives: To compare the relative effects of different types and routes of administration of progesterone, cerclage, and pessary at preventing preterm birth in at-risk women overall and in specific populations.

Search strategy: We searched Medline, EMBASE, CINAHL, Cochrane CENTRAL, and Web of Science up to 1 January 2018.

Selection criteria: We included randomised trials of progesterone, cerclage or pessary for preventing preterm birth in at-risk singleton pregnancies.

Data collection and analysis: We used a piloted data extraction form and performed Bayesian random-effects network meta-analyses with 95% credibility intervals (CrI), as well as pairwise meta-analyses, rating the quality of the evidence using GRADE.

Main results: We included 40 trials (11 311 women). In at-risk women overall, vaginal progesterone reduced preterm birth <34 (OR 0.43, 95% CrI 0.20-0.81) and <37 weeks (OR 0.51, 95% CrI 0.34-0.74), and neonatal death (OR 0.41, 95% CrI 0.20-0.83). In women with a previous preterm birth, vaginal progesterone reduced preterm birth <34 (OR 0.29, 95% CI 0.12-0.68) and <37 weeks (OR 0.43, 95% CrI 0.23-0.74), and 17α-hydroxyprogesterone caproate reduced preterm birth <37 weeks (OR 0.53, 95% CrI 0.27-0.95) and neonatal death (OR 0.39, 95% CI 0.16-0.95). In women with a short cervix (≤25 mm), vaginal progesterone reduced preterm birth <34 weeks (OR 0.45, 95% CI 0.24-0.84).

Conclusions: Vaginal progesterone was the only intervention with consistent effectiveness for preventing preterm birth in singleton at-risk pregnancies overall and in those with a previous preterm birth.

Tweetable abstract: In updated NMA, vaginal progesterone consistently reduced PTB in overall at-risk pregnancies and in women with previous PTB.

Keywords: Cervical cerclage; cervical pessary; network meta-analysis; preterm birth; progesterone; systematic review.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • 17 alpha-Hydroxyprogesterone Caproate / administration & dosage*
  • Administration, Intravaginal
  • Administration, Oral
  • Cerclage, Cervical / statistics & numerical data*
  • Cervical Length Measurement
  • Cervix Uteri / pathology
  • Female
  • Humans
  • Infant, Newborn
  • Network Meta-Analysis
  • Perinatal Death / prevention & control
  • Pessaries / statistics & numerical data*
  • Pregnancy
  • Pregnancy, High-Risk
  • Premature Birth / pathology
  • Premature Birth / prevention & control*
  • Progesterone / administration & dosage*
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • 17 alpha-Hydroxyprogesterone Caproate
  • Progesterone

Associated data

  • GENBANK/CRD42015016166
  • GENBANK/ed2015