Vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in twin gestations: a systematic review and meta-analysis.

Autores de IIS La Fe

• Alfredo José Perales Marín

  Autor

Participantes ajenos a IIS La Fe

• Conde-Agudelo, Agustin
• Romero, Roberto
• Rehal, Anoop
• Brizot, Maria L
• Serra, Vicente
• Fonseca, Eduardo Da
• Cetingoz, Elcin
• Syngelaki, Argyro
• Hassan, Sonia S
• Nicolaides, Kypros H

Grupos

• Medicina Reproductiva

  

  Investigador Principal

  José Morales Roselló

Abstract

OBJECTIVE: To evaluate the efficacy of vaginal progesterone for the prevention of preterm birth and adverse perinatal outcomes in twin gestations. DATA SOURCES: MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to January 31, 2023), Cochrane databases, Google Scholar, bibliographies, and conference proceedings. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials that compared vaginal progesterone to placebo or no treatment in asymptomatic women with a twin gestation. STUDY APPRAISAL AND SYNTHESIS METHODS: The systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcome was preterm birth <34 weeks of gestation. Secondary outcomes included adverse perinatal outcomes. Pooled relative risks (RR) with 95% confidence intervals (CI) were calculated. We assessed the risk of bias in each included study, heterogeneity, publication bias, and quality of evidence, and performed subgroup and sensitivity analyses. RESULTS: Eleven studies (3401 women and 6802 fetuses/infants) fulfilled the inclusion criteria. Among all twin gestations, there were no significant differences between the vaginal progesterone and placebo or no treatment groups in the risk of preterm birth <34 weeks (RR, 0.99; 95% CI, 0.84-1.17; high-quality evidence), <37 weeks (RR, 0.99; 95% CI, 0.92-1.06; high-quality evidence), and <28 weeks (RR, 1.00; 95% CI, 0.64-1.55; moderate-quality evidence), and spontaneous preterm birth <34 weeks of gestation (RR, 0.97; 95% CI, 0.80-1.18; high-quality evidence). Vaginal progesterone had no significant effect on any of the perinatal outcomes evaluated. Subgroup analyses showed that there was no evidence of a different effect of vaginal progesterone on preterm birth <34 weeks of gestation related to chorionicity, type of conception, history of spontaneous preterm birth, daily dose of vaginal progesterone, and gestational age at initiation of treatment. The frequencies of preterm birth <37, <34, <32, <30, and <28 weeks of gestation and adverse perinatal outcomes did not significantly differ between the vaginal progesterone and placebo or no treatment groups in unselected twin gestations (8 studies; 3274 women and 6548 fetuses/infants). Among twin gestations with a transvaginal sonographic cervical length <30 mm (6 studies; 306 women and 612 fetuses/infants), vaginal progesterone was associated with a significant decrease in the risk of preterm birth occurring at <28 to <32 gestational weeks (RRs, 0.48-0.65; moderate- to high-quality evidence), neonatal death (RR, 0.32; 95% CI, 0.11-0.92; moderate-quality evidence), and birthweight<1500 g (RR, 0.60; 95% CI, 0.39-0.88; high-quality evidence). Vaginal progesterone significantly reduced the risk of preterm birth occurring at <28 to <34 gestational weeks (RRs, 0.41-0.68), composite neonatal morbidity and mortality (RR, 0.59; 95%, 0.33-0.98), and birthweight<1500 g (RR, 0.55; 95%, 0.33-0.94) in twin gestations with a transvaginal sonographic cervical length =25 mm (6 studies; 95 women and 190 fetuses/infants). The quality of evidence was moderate for all these outcomes. CONCLUSION: Vaginal progesterone does not prevent preterm birth, nor does it improve perinatal outcomes in unselected twin gestations, but it appears to reduce the risk of preterm birth occurring at early gestational ages and of neonatal morbidity and mortality in twin gestations with a sonographic short cervix. However, more evidence is needed before recommending this intervention to this subset of patients..

Copyright © 2023. Published by Elsevier Inc.

Keywords

• cervical length; multiple gestation; neonatal morbidity; neonatal mortality; prematurity; preterm delivery; progestins; progestogens; transvaginal ultrasound