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The primary outcome was accurate risk prediction of women initially diagnosed with a <jats:styled-content style=\"fixed-case\">PUL<\/jats:styled-content> having an ectopic pregnancy (high risk) as opposed to either a failed <jats:styled-content style=\"fixed-case\">PUL<\/jats:styled-content> or intrauterine pregnancy (low risk).<\/jats:p><\/jats:sec><jats:sec><jats:title>Selection criteria<\/jats:title><jats:p>All studies written in the English language, which were not case reports or series that assessed women classified as having a <jats:styled-content style=\"fixed-case\">PUL<\/jats:styled-content> at initial ultrasound.<\/jats:p><\/jats:sec><jats:sec><jats:title>Data collection and analysis<\/jats:title><jats:p>Forty\u2010three studies were included. <jats:styled-content style=\"fixed-case\">QUADAS<\/jats:styled-content>\u20102 criteria were used to assess the risk of bias. We used a novel, linear mixed\u2010effects model and constructed summary receiver operating characteristic curves for the thresholds of interest.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main results<\/jats:title><jats:p>There was a high risk of differential verification bias in most studies. Meta\u2010analyses of accuracy were performed on (i) single human chorionic gonadotrophin (<jats:styled-content style=\"fixed-case\">hCG<\/jats:styled-content>) cut\u2010off levels, (ii) <jats:styled-content style=\"fixed-case\">hCG<\/jats:styled-content> ratio (<jats:styled-content style=\"fixed-case\">hCG<\/jats:styled-content> at 48 hours\/initial <jats:styled-content style=\"fixed-case\">hCG<\/jats:styled-content>), (iii) single progesterone cut\u2010off levels and (iv) the \u2018M4 model\u2019 (a logistic regression model based on the initial <jats:styled-content style=\"fixed-case\">hCG<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">hCG<\/jats:styled-content> ratio). For predicting an ectopic pregnancy, the areas under the curves (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>) for these four management protocols were as follows: (i) 0.42 (0.00\u20130.99), (ii) 0.69 (0.57\u20130.78), (iii) 0.69 (0.54\u20130.81) and (iv) 0.87 (0.83\u20130.91), respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The M4 model was the best available method for predicting a final outcome of ectopic pregnancy. Developing and validating risk prediction models may optimise the management of <jats:styled-content style=\"fixed-case\">PUL<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Tweetable abstract<\/jats:title><jats:p>Pregnancy of unknown location meta\u2010analysis: M4 model has best test performance to predict ectopic pregnancy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1471-0528.15442","type":"journal-article","created":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T15:52:23Z","timestamp":1534953143000},"page":"190-198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Diagnostic protocols for the management of pregnancy of unknown location: a systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"126","author":[{"given":"S","family":"Bobdiwala","sequence":"first","affiliation":[{"name":"Tommys' National Centre for Miscarriage Research Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Saso","sequence":"additional","affiliation":[{"name":"Tommys' National Centre for Miscarriage Research Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JY","family":"Verbakel","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care KU Leuven Leuven Belgium"},{"name":"Nuffield Department of Primary Care Health Sciences University of Oxford Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Al\u2010Memar","sequence":"additional","affiliation":[{"name":"Tommys' National Centre for Miscarriage Research Imperial College London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Van Calster","sequence":"additional","affiliation":[{"name":"Department of Development and Regeneration KU Leuven Leuven Belgium"},{"name":"Department of Biomedical Data Sciences Leiden University Medical Centre Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Timmerman","sequence":"additional","affiliation":[{"name":"Department of Development and Regeneration KU Leuven Leuven Belgium"},{"name":"Department of Obstetrics and Gynaecology University Hospitals Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Bourne","sequence":"additional","affiliation":[{"name":"Tommys' National Centre for Miscarriage Research Imperial College London UK"},{"name":"Department of Development and Regeneration KU Leuven Leuven Belgium"},{"name":"Department of Obstetrics and Gynaecology University Hospitals Leuven Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmt047"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2010.09.006"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/1745505717709677"},{"key":"e_1_2_6_5_1","first-page":"525","article-title":"Suspected ectopic pregnancy. 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