{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T20:38:43Z","timestamp":1791837523191,"version":"4.3.4"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high\u2010risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Search strategy<\/jats:title><jats:p>We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023.<\/jats:p><\/jats:sec><jats:sec><jats:title>Selection criteria<\/jats:title><jats:p>We included placebo\u2010controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Data collection and analysis<\/jats:title><jats:p>We extracted absolute event numbers for HDP and pre\u2010eclampsia in women receiving vaginal progesterone or placebo, and meta\u2010analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main results<\/jats:title><jats:p>The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53\u20130.93, 2 RCTs, <jats:italic>n<\/jats:italic>\u2009=\u20094431 women, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090%; moderate\u2010certainty evidence) and pre\u2010eclampsia (RR 0.61, 95% CI 0.41\u20130.92, 3 RCTs, <jats:italic>n<\/jats:italic>\u2009=\u20095267 women, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090%; moderate\u2010certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67\u20132.12, 3 RCTs, <jats:italic>n<\/jats:italic>\u2009=\u20091602 women, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20099%; low\u2010certainty evidence) or pre\u2010eclampsia (RR 0.97, 95% CI 0.71\u20131.31, 5 RCTs, <jats:italic>n<\/jats:italic>\u2009=\u20094274 women, <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090%; low\u2010certainty evidence).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our systematic review found first\u2010trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre\u2010eclampsia.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1471-0528.17705","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T08:23:22Z","timestamp":1699518202000},"page":"727-739","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Vaginal micronised progesterone for the prevention of hypertensive disorders of pregnancy: A systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6809-6107","authenticated-orcid":false,"given":"Pedro","family":"Melo","sequence":"first","affiliation":[{"name":"Nuffield Department of Women's and Reproductive Health University of Oxford  Oxford UK"},{"name":"Tommy's National Centre for Miscarriage Research, College of Medical and Dental Sciences, Institute of Metabolism and Systems Research University of Birmingham  Edgbaston 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UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Granne","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women's and Reproductive Health University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aris T.","family":"Papageorghiou","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women's and Reproductive Health University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8337-550X","authenticated-orcid":false,"given":"Ben W.","family":"Mol","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Monash University  Clayton Victoria Australia"},{"name":"Aberdeen Centre for Women's Health Research, School of Medicine, Medical Sciences and Nutrition University of Aberdeen  Aberdeen 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