The use of vaginal natural progesterone for prevention of preterm birth in IVF/ICSI pregnancies

Stock

Rode

et al. 2014

BJOG

198

123

Background In twin pregnancies, the rates of adverse perinatal outcome and subsequent long-term morbidity are substantial, and mainly result from preterm birth (PTB). Objectives To assess the effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta-analysis (IPDMA). Search strategy We searched international scientific databases, trial registration websites, and references of identified articles. Selection criteria Randomised clinical trials (RCTs) of 17-hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment. Data collection and analysis Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB. Main results Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97–1.4, vaginal progesterone RR 0.97; 95% CI 0.77–1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47–0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42–0.75). Author’s conclusions In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.

“…There was one study in which participants were not blinded to the treatment . Exclusion of the participants of this study did not lead to different results (data not shown).…”

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Effectiveness of progestogens to improve perinatal outcome in twin pregnancies: an individual participant data meta‐analysis

Stock

Rode

et al. 2014

BJOG

198

123

“…28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 Eighteen studies provided data on both monochorionic and dichorionic,16 30 32 34 36 38 40 42 43 44 45 48 49 50 51 54 56 57 seven on only monochorionic,29 31 37 39 41 47 53 and seven on only dichorionic twin pregnancies 2833 35 46 52 55 58 Twenty three authors provided relevant unpublished data 16…”

Section: Resultsmentioning

confidence: 99%

Prospective risk of stillbirth and neonatal complications in twin pregnancies: systematic review and meta-analysis

Cheong-See

Arroyo-Manzano

et al. 2016

BMJ

188

150

Objective To determine the risks of stillbirth and neonatal complications by gestational age in uncomplicated monochorionic and dichorionic twin pregnancies.Design Systematic review and meta-analysis.Data sources Medline, Embase, and Cochrane databases (until December 2015). Review methods Databases were searched without language restrictions for studies of women with uncomplicated twin pregnancies that reported rates of stillbirth and neonatal outcomes at various gestational ages. Pregnancies with unclear chorionicity, monoamnionicity, and twin to twin transfusion syndrome were excluded. Meta-analyses of observational studies and cohorts nested within randomised studies were undertaken. Prospective risk of stillbirth was computed for each study at a given week of gestation and compared with the risk of neonatal death among deliveries in the same week. Gestational age specific differences in risk were estimated for stillbirths and neonatal deaths in monochorionic and dichorionic twin pregnancies after 34 weeks’ gestation.Results 32 studies (29 685 dichorionic, 5486 monochorionic pregnancies) were included. In dichorionic twin pregnancies beyond 34 weeks (15 studies, 17 830 pregnancies), the prospective weekly risk of stillbirths from expectant management and the risk of neonatal death from delivery were balanced at 37 weeks’ gestation (risk difference 1.2/1000, 95% confidence interval −1.3 to 3.6; I2=0%). Delay in delivery by a week (to 38 weeks) led to an additional 8.8 perinatal deaths per 1000 pregnancies (95% confidence interval 3.6 to 14.0/1000; I2=0%) compared with the previous week. In monochorionic pregnancies beyond 34 weeks (13 studies, 2149 pregnancies), there was a trend towards an increase in stillbirths compared with neonatal deaths after 36 weeks, with an additional 2.5 per 1000 perinatal deaths, which was not significant (−12.4 to 17.4/1000; I2=0%). The rates of neonatal morbidity showed a consistent reduction with increasing gestational age in monochorionic and dichorionic pregnancies, and admission to the neonatal intensive care unit was the commonest neonatal complication. The actual risk of stillbirth near term might be higher than reported estimates because of the policy of planned delivery in twin pregnancies.Conclusions To minimise perinatal deaths, in uncomplicated dichorionic twin pregnancies delivery should be considered at 37 weeks’ gestation; in monochorionic pregnancies delivery should be considered at 36 weeks.Systematic review registration PROSPERO CRD42014007538.

“…Thirteen trials met the inclusion criteria and contributed individual participant data to the meta-analysis; however, only the 11 trials that included a minimum of 40 women with a twin pregnancy were included in this study. [4][5][6][7][8][9][17][18][19][20][21] Inclusion/exclusion criteria and treatment regimens varied between these trials (Table S1). The study size ranged from 67 to 677 twin pairs, with trials either including both monochorionic and dichorionic twin pregnancies, 4,5,7,17,18,21 dichorionic twin pregnancies only 6,8,19 or not recording chorionicity 9,20 (Table S2).…”

Section: Data Setsmentioning

confidence: 99%

Correlation between neonatal outcomes of twins depends on the outcome: secondary analysis of twelve randomised controlled trials

Yelland

Zamora

et al. 2018

BJOG