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Progestogens for preventing miscarriage: a network meta-analysis.

ABSTRACT:

SUBMITTER: Devall AJ

PROVIDER: S-EPMC8406671 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Progestogens for preventing miscarriage: a network meta-analysis.

Devall Adam J AJ Papadopoulou Argyro A Podesek Marcelina M Haas David M DM Price Malcolm J MJ Coomarasamy Arri A Gallos Ioannis D ID

The Cochrane database of systematic reviews 20210419

<h4>Background</h4>Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime, and 15% to 20% of pregnancies ending in a miscarriage. Progesterone has an important role in maintaining a pregnancy, and supplementation with different progestogens in early pregnancy has been attempted to rescue a pregnancy in women with early pregnancy bleeding (threatened miscarriage), and to prevent ...[more]

PMID: 33872382

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Project description:IntroductionClinical practice guidelines provide inconsistent recommendations regarding progestogen supplementation for threatened and recurrent miscarriage. We conducted a systematic review and meta-analysis to assess the effectiveness and safety of progestogens for these patients.Material and methodsWe searched Medline, Embase, and Cochrane Central Registry of Controlled Trials up to October 6, 2023 for randomized control trials (RCTs) comparing progestogen supplementation to placebo or no treatment for pregnant women with threatened or recurrent miscarriage. We assessed the risk of bias using a modified version of the Cochrane risk-of-bias tool and the certainty of evidence using the GRADE approach.ResultsOf 15 RCTs (6616 pregnancies) reporting on threatened or recurrent miscarriage, 12 (5610 pregnancies) reported on threatened miscarriage with or without a prior history of miscarriage. Results indicated that progesterone probably increases live births (relative risk (RR) 1.04, 95% confidence interval (CI) 0.99-1.10, absolute increase 3.1%, moderate certainty). Of these RCTs, three (1973 pregnancies) reporting on threatened miscarriage with a prior history of miscarriage indicated that progesterone possibly increases live births (RR 1.06, 95% CI: 0.97-1.16, absolute increase 4.4%; low certainty), while four (2540 pregnancies) reporting on threatened miscarriage and no prior miscarriage left the effect very uncertain (RR 1.02, 95% CI: 0.96-1.10, absolute increase 1.7%; very low certainty). Three trials reporting on 1006 patients with a history of two or more prior miscarriages indicated progesterone probably increases live births (RR 1.08, 95% CI: 0.98-1.19, absolute increase 5.7%, moderate certainty). Six RCTs that reported on 2979 patients with at least one prior miscarriage indicated that progesterone probably increases live births (RR 1.07, 95% CI: 1.01-1.13, absolute increase 5.0%; moderate certainty). Progesterone probably has little or no effect on congenital anomalies (RR 1.06, 95% CI: 0.76-1.48, absolute increase 0.1%; moderate certainty), and other serious adverse pregnancy events (RR 1.07, 95% CI: 0.83-1.40, absolute increase 0.2%, moderate certainty).ConclusionsIn women at increased risk of pregnancy loss, progestogens probably increase live births without increasing adverse maternal and neonatal events. It remains possible that the benefit is restricted to those with prior miscarriages.

Project description:ObjectivePrevention of preterm birth (PTB) with progestogens after an episode of threatened preterm labour is still controversial. As different progestogens have distinct molecular structures and biological effects, we conducted a systematic review and pairwise meta-analysis to investigate the individual role played by 17-alpha-hydroxyprogesterone caproate (17-HP), vaginal progesterone (Vaginal P) and oral progesterone (Oral P).MethodsThe search was performed in MEDLINE, ClinicalTrials.gov and the Cochrane Central Register of Controlled Trials (CENTRAL) up to 31 October 2021. Published RCTs comparing progestogens to placebo or no treatment for maintenance tocolysis were considered. We included women with singleton gestations, excluding quasi-randomized trials, studies on women with preterm premature rupture of membrane, or receiving maintenance tocolysis with other drugs. Primary outcomes were preterm birth (PTB) < 37 weeks' and < 34 weeks'. We assessed risk of bias and evaluated certainty of evidence with the GRADE approach.ResultsSeventeen RCTs including 2152 women with singleton gestations were included. Twelve studies tested vaginal P, five 17-HP, and only 1 oral P. PTB < 34 weeks' did not differ among women receiving vaginal P (RR 1.21, 95%CI 0.91 to 1.61, 1077 participants, moderate certainty of evidence), or oral P (RR 0.89, 95%CI 0.38 to 2.10, 90 participants, low certainty of evidence) as opposed to placebo. Instead, 17-HP significantly reduced the outcome (RR 0.72, 95% CI 0.54 to 0.95, 450 participants, moderate certainty of evidence). PTB < 37 weeks' did not differ among women receiving vaginal P (RR 0.95, 95%CI 0.72 to 1.26, 8 studies, 1231 participants, moderate certainty of evidence) or 17-HP (RR 0.86, 95%CI 0.60 to 1.21, 450 participants, low certainty of evidence) when compared to placebo/no treatment. Instead, oral P significantly reduced the outcome (RR 0.58, 95% CI 0.36 to 0.93, 90 participants, low certainty of evidence).ConclusionsWith a moderate certainty of evidence, 17-HP prevents PTB < 34 weeks' gestation among women that remained undelivered after an episode of threatened preterm labour. However, data are insufficient to generate recommendations in clinical practice. In the same women, both 17-HP and vaginal P are ineffective in the prevention of PTB < 37 weeks'.

Dataset Information

Progestogens for preventing miscarriage: a network meta-analysis.

Publications

Progestogens for preventing miscarriage: a network meta-analysis.

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