Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta‐analysis

Abstract Introduction Clinical 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. Materi...

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Main Authors: Yunli Zhao, Rohan D'Souza, Ya Gao, Qiukui Hao, Lucas Kallas‐Silva, Jeremy P. Steen, Gordon Guyatt
Format: Article
Language:English
Published: Wiley 2024-09-01
Series:Acta Obstetricia et Gynecologica Scandinavica
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Online Access:https://doi.org/10.1111/aogs.14829
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author Yunli Zhao
Rohan D'Souza
Ya Gao
Qiukui Hao
Lucas Kallas‐Silva
Jeremy P. Steen
Gordon Guyatt
author_facet Yunli Zhao
Rohan D'Souza
Ya Gao
Qiukui Hao
Lucas Kallas‐Silva
Jeremy P. Steen
Gordon Guyatt
author_sort Yunli Zhao
collection DOAJ
description Abstract Introduction Clinical 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 methods We 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. Results Of 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). Conclusions In 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.
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spelling doaj-art-268c4260f7284394902a541efdc8264b2025-08-20T02:09:35ZengWileyActa Obstetricia et Gynecologica Scandinavica0001-63491600-04122024-09-0110391689170110.1111/aogs.14829Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta‐analysisYunli Zhao0Rohan D'Souza1Ya Gao2Qiukui Hao3Lucas Kallas‐Silva4Jeremy P. Steen5Gordon Guyatt6Department of Geriatric Medicine The Second Affiliated Hospital of Chongqing Medical University Chongqing ChinaDepartment of Health Research Methods, Evidence, and Impact McMaster University Hamilton Ontario CanadaDepartment of Health Research Methods, Evidence, and Impact McMaster University Hamilton Ontario CanadaDepartment of Health Research Methods, Evidence, and Impact McMaster University Hamilton Ontario CanadaFaculdade Israelita de Ciȇncias da Saúde Albert Einstein São Paulo BrazilFaculty of Health Sciences McMaster University Hamilton Ontario CanadaDepartment of Health Research Methods, Evidence, and Impact McMaster University Hamilton Ontario CanadaAbstract Introduction Clinical 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 methods We 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. Results Of 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). Conclusions In 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.https://doi.org/10.1111/aogs.14829live birthmeta‐analysisprogestogensrecurrent miscarriagethreatened miscarriage
spellingShingle Yunli Zhao
Rohan D'Souza
Ya Gao
Qiukui Hao
Lucas Kallas‐Silva
Jeremy P. Steen
Gordon Guyatt
Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta‐analysis
Acta Obstetricia et Gynecologica Scandinavica
live birth
meta‐analysis
progestogens
recurrent miscarriage
threatened miscarriage
title Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta‐analysis
title_full Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta‐analysis
title_fullStr Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta‐analysis
title_full_unstemmed Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta‐analysis
title_short Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta‐analysis
title_sort progestogens in women with threatened miscarriage or recurrent miscarriage a meta analysis
topic live birth
meta‐analysis
progestogens
recurrent miscarriage
threatened miscarriage
url https://doi.org/10.1111/aogs.14829
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AT qiukuihao progestogensinwomenwiththreatenedmiscarriageorrecurrentmiscarriageametaanalysis
AT lucaskallassilva progestogensinwomenwiththreatenedmiscarriageorrecurrentmiscarriageametaanalysis
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