{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T14:16:27Z","timestamp":1765808187654,"version":"3.40.5"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J Gynecology &amp; Obste"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Misoprostol is widely used for cervical ripening and labour induction as it is heat\u2010stable and inexpensive. Oral misoprostol 25\u2009\u03bcg given 2\u2010hourly is recommended over vaginal misoprostol 25\u2009\u03bcg given 6\u2010hourly, but the need for 2\u2010hourly fetal monitoring makes oral misoprostol impractical for routine use in high\u2010volume obstetric units in resource\u2010constrained settings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To compare the efficacy and safety of oral misoprostol initiated at 25 or 50\u2009\u03bcg versus 25\u2009\u03bcg vaginal misoprostol given at 4\u2010 to 6\u2010hourly intervals for labor induction in women at or beyond term (\u2265\u200937\u2009weeks) with a single viable fetus and an unscarred uterus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Search Strategy<\/jats:title><jats:p>We identified eligible randomized, parallel\u2010group, labor\u2010induction trials from recent systematic reviews. We additionally searched PubMed, Cochrane CENTRAL, Epistemonikos, and clinical trials registries from February 1, 2020 to December 31, 2022 without language restrictions. Database\u2010specific keywords for cervical priming, labor induction, and misoprostol were used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Selection Criteria<\/jats:title><jats:p>We excluded labor\u2010induction trials exclusively in women with ruptured membranes, in the third trimester, and those that initiated misoprostol at doses not specified in the review's objectives. The primary outcomes were vaginal birth within 24\u2009h, cesarean section, perinatal mortality, neonatal morbidity, and maternal morbidity. The secondary outcomes were uterine hyperstimulation with fetal heart rate changes, and oxytocin augmentation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Data Collection and Analysis<\/jats:title><jats:p>Two or more authors selected studies independently, assessed risk of bias, and extracted data. We derived pooled weighted risk ratios with 95% confidence intervals (CIs) for each outcome, subgrouping trials by the dose and frequency of misoprostol regimens. We used the <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> statistic to quantify heterogeneity and the random\u2010effects model for meta\u2010analysis when appropriate. We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach to assess certainty (confidence) in the effect estimates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Results<\/jats:title><jats:p>Thirteen trials, from Canada, India, Iran, and the US, randomizing 2941 women at \u226537\u2009weeks of gestation with an unfavorable cervix (Bishop score\u2009&lt;6), met the eligibility criteria. Five misoprostol regimens were compared: 25\u2009\u03bcg oral versus 25\u2009\u03bcg vaginal, 4\u2010hourly (three trials); 50\u2009\u03bcg oral versus 25\u2009\u03bcg vaginal, 4\u2010hourly (five trials); 50\u2009\u03bcg followed by 100\u2009\u03bcg oral versus 25\u2009\u03bcg vaginal, 4\u2010hourly (two trials); 50\u2009\u03bcg oral, 4\u2010hourly versus 25\u2009\u03bcg vaginal, 6\u2010hourly (one trial); and 50\u2009\u03bcg oral versus 25\u2009\u03bcg vaginal, 6\u2010hourly (two trials).<\/jats:p><jats:p>The overall certainty in the evidence ranged from moderate to very low, due to high risk of bias in 11\/13 trials (affecting all outcomes), unexplained heterogeneity (1\/7 outcomes), indirectness (1\/7 outcomes), and imprecision (4\/7 outcomes).<\/jats:p><jats:p>Vaginal misoprostol probably increased vaginal deliveries within 24\u2009h compared with oral misoprostol (risk ratio [RR] 0.82, 95% CI 0.70\u20130.96; 11 trials, 2721 mothers; moderate\u2010certainty evidence); this was more likely with 4\u2010hourly than with 6\u2010hourly vaginal regimens. The risk of cesarean sections did not appreciably differ (RR 1.00, 95% CI 0.80\u20131.26; 13 trials, 2941 mothers; very low\u2010certainty evidence), although oral misoprostol 25\u2009\u03bcg 4\u2010hourly probably increased this risk compared with 25\u2009\u03bcg vaginal misoprostol 4\u2010hourly (RR 1.69, 95% CI 1.21\u20132.36; three trials, 515 mothers). The risk of perinatal mortality (RR 0.67, 95% CI 0.11\u20133.90; one trial, 196 participants; very low\u2010certainty evidence), neonatal morbidity (RR 0.84, 95% CI 0.67\u20131.06; 13 trials, 2941 mothers; low\u2010certainty evidence), and maternal morbidity (RR 0.83, 95% CI 0.48\u20131.44; 6 trials; 1945 mothers; moderate\u2010certainty evidence) did not differ appreciably. The risk of uterine hyperstimulation with fetal heart rate changes may be lower with oral misoprostol (RR 0.70, 95% CI 0.52\u20130.95; 10 trials, 2565 mothers; low\u2010certainty evidence). Oxytocin augmentation was probably more frequent with oral compared with vaginal misoprostol (RR 1.29, 95% CI 1.10\u20131.51; 13 trials, 2941 mothers; moderate\u2010certainty evidence).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Low\u2010dose, 4\u2010 to 6\u2010hourly vaginal misoprostol regimens probably result in more vaginal births within 24\u2009h and less frequent oxytocin use compared with low\u2010dose, 4\u2010 to 6\u2010hourly, oral misoprostol regimens. Vaginal misoprostol may increase the risk of uterine hyperstimulation with fetal heart changes compared with oral misoprostol, without increasing the risk of perinatal mortality, neonatal morbidity, or maternal morbidity. Indirect evidence indicates that 25\u2009\u03bcg vaginal misoprostol 4\u2010hourly may be more effective and as safe as the recommended 6\u2010hourly vaginal regimen. This evidence could inform clinical decisions in high\u2010volume obstetric units in resource\u2010constrained settings.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ijgo.14970","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T06:17:26Z","timestamp":1688451446000},"page":"482-498","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The efficacy and safety of 25\u2009\u03bcg or 50\u2009\u03bcg oral misoprostol versus 25\u2009\u03bcg vaginal misoprostol given at 4\u2010 or 6\u2010hourly intervals for induction of labour in women at or beyond term with live singleton pregnancies: A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2895-1663","authenticated-orcid":false,"given":"Hilda","family":"Yenuberi","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Christian Medical College  Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9366-9090","authenticated-orcid":false,"given":"Jiji","family":"Mathews","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Christian Medical College  Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0751-3709","authenticated-orcid":false,"given":"Anne","family":"George","sequence":"additional","affiliation":[{"name":"Department of Community Health Christian Medical College  Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1999-8387","authenticated-orcid":false,"given":"Santosh","family":"Benjamin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Christian Medical College  Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3660-7296","authenticated-orcid":false,"given":"Swati","family":"Rathore","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Christian Medical College  Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4956-9631","authenticated-orcid":false,"given":"Richa","family":"Tirkey","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Christian Medical College  Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prathap","family":"Tharyan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Christian Medical College  Vellore India"},{"name":"Clinical Epidemiology Unit Christian Medical College  Vellore India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,7,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000003372"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002838"},{"volume-title":"WHO recommendations: induction of labour at or beyond term","year":"2018","author":"World Health Organization","key":"e_1_2_9_4_1"},{"key":"e_1_2_9_5_1","unstructured":"National Institute for Health and Care Excellence.Inducing labour. 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