Vaginal progesterone is as effective as cervical cerclage to prevent preterm birth in women with a singleton gestation, previous spontaneous preterm birth, and a short cervix: updated indirect comparison meta-analysis

Am J Obstet Gynecol. 2018 Jul;219(1):10-25. doi: 10.1016/j.ajog.2018.03.028. Epub 2018 Apr 7.

Abstract

Background: An indirect comparison meta-analysis published in 2013 reported that both vaginal progesterone and cerclage are equally efficacious for preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic short cervix. The efficacy of vaginal progesterone has been challenged after publication of the OPPTIMUM study. However, this has been resolved by an individual patient-data meta-analysis (Am J Obstet Gynecol. 2018;218:161-180).

Objective: To compare the efficacy of vaginal progesterone and cerclage in preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix.

Data sources: MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to March 2018); Cochrane databases, bibliographies, and conference proceedings.

Study eligibility criteria: Randomized controlled trials comparing vaginal progesterone to placebo/no treatment or cerclage to no cerclage in women with a singleton gestation, previous spontaneous preterm birth, and a sonographic cervical length <25 mm.

Study appraisal and synthesis methods: Updated systematic review and adjusted indirect comparison meta-analysis of vaginal progesterone vs cerclage using placebo/no cerclage as the common comparator. The primary outcomes were preterm birth <35 weeks of gestation and perinatal mortality. Pooled relative risks (RRs) with 95% confidence intervals were calculated.

Results: Five trials comparing vaginal progesterone vs placebo (265 women) and 5 comparing cerclage vs no cerclage (504 women) were included. Vaginal progesterone, compared to placebo, significantly reduced the risk of preterm birth <35 and <32 weeks of gestation, composite perinatal morbidity/mortality, neonatal sepsis, composite neonatal morbidity, and admission to the neonatal intensive care unit (RRs from 0.29 to 0.68). Cerclage, compared to no cerclage, significantly decreased the risk of preterm birth <37, <35, <32, and <28 weeks of gestation, composite perinatal morbidity/mortality, and birthweight <1500 g (RRs from 0.64 to 0.70). Adjusted indirect comparison meta-analyses did not show statistically significant differences between vaginal progesterone and cerclage in the reduction of preterm birth or adverse perinatal outcomes.

Conclusion: Vaginal progesterone and cerclage are equally effective for preventing preterm birth and improving perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix. The choice of treatment will depend on adverse events and cost-effectiveness of interventions and patient/physician's preferences.

Keywords: admission to neonatal intensive care unit; birthweight <1500 g; cervical length; cervical stitch; perinatal mortality; prematurity; progestin; progestogens; recurrent preterm birth; transvaginal ultrasound; uterine cervix.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Intramural
  • Systematic Review

MeSH terms

  • Administration, Intravaginal
  • Cerclage, Cervical*
  • Cervical Length Measurement
  • Female
  • Humans
  • Infant, Extremely Premature
  • Infant, Newborn
  • Infant, Premature
  • Infant, Very Low Birth Weight
  • Intensive Care Units, Neonatal / statistics & numerical data
  • Neonatal Sepsis / epidemiology
  • Perinatal Mortality
  • Pregnancy
  • Pregnancy Trimester, Second
  • Pregnancy Trimester, Third
  • Premature Birth / prevention & control*
  • Progesterone / administration & dosage*
  • Progestins / administration & dosage*
  • Secondary Prevention

Substances

  • Progestins
  • Progesterone