Vaginal progesterone decreases preterm birth ≤ 34 weeks of gestation in women with a singleton pregnancy and a short cervix: an updated meta‐analysis including data from the OPPTIMUM study

Abstract

ObjectiveTo evaluate the efficacy of vaginal progesterone administration for preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton gestation and a mid‐trimester sonographic cervical length (CL) ≤ 25 mm.MethodsThis was an updated systematic review and meta‐analysis of randomized controlled trials comparing the use of vaginal progesterone to placebo/no treatment in women with a singleton gestation and a mid‐trimester sonographic CL ≤ 25 mm. Electronic databases, from their inception to May 2016, bibliographies and conference proceedings were searched. The primary outcome measure was preterm birth ≤ 34 weeks of gestation or fetal death. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated.ResultsFive trials involving 974 women were included. A meta‐analysis, including data from the OPPTIMUM study, showed that vaginal progesterone significantly decreased the risk of preterm birth ≤ 34 weeks of gestation or fetal death compared to placebo (18.1% vs 27.5%; RR, 0.66 (95% CI, 0.52–0.83); P = 0.0005; five studies; 974 women). Meta‐analyses of data from four trials (723 women) showed that vaginal progesterone administration was associated with a statistically significant reduction in the risk of preterm birth occurring at < 28 to < 36 gestational weeks (RRs from 0.51 to 0.79), respiratory distress syndrome (RR, 0.47 (95% CI, 0.27–0.81)), composite neonatal morbidity and mortality (RR, 0.59 (95% CI, 0.38–0.91)), birth weight < 1500 g (RR, 0.52 (95% CI, 0.34–0.81)) and admission to the neonatal intensive care unit (RR, 0.67 (95% CI, 0.50–0.91)). There were no significant differences in neurodevelopmental outcomes at 2 years of age between the vaginal progesterone and placebo groups.ConclusionThis updated systematic review and meta‐analysis reaffirms that vaginal progesterone reduces the risk of preterm birth and neonatal morbidity and mortality in women with a singleton gestation and a mid‐trimester CL ≤ 25 mm, without any deleterious effects on neurodevelopmental outcome. Clinicians should continue to perform universal transvaginal CL screening at 18–24 weeks of gestation in women with a singleton gestation and to offer vaginal progesterone to those with a CL ≤ 25 mm. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

The Role of PTB Clinics: A Review of the Screening Methods, Interventions and Evidence for Preterm Birth Surveillance Clinics for High-Risk Asymptomatic Women

“…Contrastingly, the OPPTIMUM study (n = 1228) found that prophylactic progesterone was not associated with reduced risk of PTB (adjusted OR 0.86, 95% CI 0.61 -1.22), and that childhood outcomes were not significantly different (mean difference in cognitive scores at 2 years old -0.48, 95% CI -2.77 -1.81) (65). A subsequent meta-analysis (n = 974) of five trials including the OPPTIMUM study found that progesterone decreased the risk of PTB ≤ 34 weeks (RR 0.66, 95% CI 0.52 -0.83) and had no adverse effects on neurodevelopmental outcomes (20). However, the study only included women with a short cervix (only 251 out of 1228 OPPTIMUM patients were included), and there remains uncertainty as to which populations benefit from progesterone.…”

“…A previous PTB or late miscarriage is a widely recognized risk factor for PTB, which could be linked to many mechanisms (3). Systemic maternal infections, urinary tract or intra-uterine infections, bacterial vaginosis, and douching may all disrupt the maternal vaginal microbiome and are linked with the release of pro-inflammatory factors, which are linked to increased rates of sPTB (3,8,20,21). Uterine and cervical weakness impair their ability to support mechanical stresses induced by full-term pregnancy.…”

Placental dysfunction as a predictor of miscarriage

“…Прогестерон по-зитивно впливає на процеси інвазії трофобласту шляхом стимуляції росту та ремоделювання спіральних артерій, а також посилення експресії VEGF, що покращує процеси ан-гіогенезу; забезпечує баланс ангіогенних факторів -VEGF та PEGF; збільшує синтез NO ендотеліальними клітинами, і як наслідок -сприяє оптимальному кровообігу в матці й адап-тації її ендотелію до оптимальної імплантації та розвитку ва-гітності [1,9].…”

“…У 2016 році в престижному міжнародному виданні Ultrasound Obstet Gynecology були опубліковані результа-ти оновленого мета-аналізу R. Romero та співавторів [9], доповнені індивідуальними даними пацієнток з короткою шийкою матки, які отримували Утрожестан в дозі 200 мг на добу з метою профілактики ПП. Було показано, що вагіналь-…”

Lactoginal for correction of abnormal vaginal microbiocenosis in pregnant woman with cervical cerclage: clinical case and literature review

“…Интравагинальное введе-ние прогестерона также рассматривается как эффективный подход к снижению показателя преждевременных родов при длине шейки мат-ки ≤ 25 мм, установленной при ультразвуковом исследовании в средних сроках беременно-сти [9]. Необходимо отметить, однако, что на-личие признаков преждевременных родов при короткой шейке матки может являться показа-нием для терапии прогестероном, но не церви-кального серкляжа, для которого должен также присутствовать критерий невынашивания бе-ременности в анамнезе [5].…”