{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T11:38:54Z","timestamp":1793533134841,"version":"4.5.0"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,10,9]],"date-time":"2016-10-09T00:00:00Z","timestamp":1475971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Research Foundation Flanders","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Flanders' Agency for Innovation by Science and Technology (IWT-Vlaanderen)"},{"name":"NIHR Biomedical Research Centre (Imperial College Healthcare NHS Trust and Imperial College London)"},{"name":"NIHR CLAHRC NWL (Collaboration for Leadership in Applied Health Research & Care, NorthWest London)"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp; Gyne"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>A uniform rationalized management protocol for pregnancies of unknown location (PUL) is lacking. We developed a two\u2010step triage protocol to select PUL at high risk of ectopic pregnancy (EP), based on serum progesterone level at presentation (step 1) and the serum human chorionic gonadotropin (hCG) ratio, defined as the ratio of hCG at 48\u2009h to hCG at presentation (step 2).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was a cohort study of 2753 PUL (301 EP), involving a secondary analysis of prospectively and consecutively collected PUL data from two London\u2010based university teaching hospitals. Using a chronological split we used 1449 PUL for development and 1304 for validation. We aimed to assign PUL as low risk with high confidence (high negative predictive value (NPV)) while classifying most EP as high risk (high sensitivity). The first triage step assigned PUL as low risk using a threshold of serum progesterone at presentation. The remaining PUL were triaged using a novel logistic regression risk model based on hCG ratio and initial serum progesterone (second step), defining low risk as an estimated EP risk of\u2009&lt;\u20095%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>On validation, initial serum progesterone \u2264\u20092\u2009nmol\/L (step 1) classified 16.1% PUL as low risk. Second\u2010step classification with the risk model selected an additional 46.0% of all PUL as low risk. Overall, the two\u2010step protocol classified 62.1% of PUL as low risk, with an NPV of 98.6% and a sensitivity of 92.0%. When the risk model was used in isolation (i.e. without the first step), 60.5% of PUL were classified as low risk with 99.1% NPV and 94.9% sensitivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PUL can be classified efficiently into being either high or low risk for complications using a two\u2010step protocol involving initial progesterone and hCG levels and the hCG ratio. Copyright \u00a9 2016 ISUOG. Published by John Wiley &amp; Sons Ltd.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/uog.15864","type":"journal-article","created":{"date-parts":[[2016,1,18]],"date-time":"2016-01-18T08:16:42Z","timestamp":1453105002000},"page":"642-649","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Managing pregnancy of unknown location based on initial serum progesterone and serial serum hCG levels: development and validation of a two\u2010step triage protocol"],"prefix":"10.1002","volume":"48","author":[{"given":"B.","family":"Van Calster","sequence":"first","affiliation":[{"name":"KU Leuven Department of Development and Regeneration  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Bobdiwala","sequence":"additional","affiliation":[{"name":"Tommy's National Centre for Miscarriage Research Queen Charlotte's &amp; Chelsea Hospital, Imperial College  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Guha","sequence":"additional","affiliation":[{"name":"West Middlesex Hospital  Isleworth, Middlesex UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Van Hoorde","sequence":"additional","affiliation":[{"name":"Open Analytics  Antwerp Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Al\u2010Memar","sequence":"additional","affiliation":[{"name":"Tommy's National Centre for Miscarriage Research Queen Charlotte's &amp; Chelsea Hospital, Imperial College  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Harvey","sequence":"additional","affiliation":[{"name":"Charing Cross Oncology Laboratory and Trophoblastic Disease Center Charing Cross Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Farren","sequence":"additional","affiliation":[{"name":"Tommy's National Centre for Miscarriage Research Queen Charlotte's &amp; Chelsea Hospital, Imperial College  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Kirk","sequence":"additional","affiliation":[{"name":"North Middlesex Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Condous","sequence":"additional","affiliation":[{"name":"Acute Gynaecology, Early Pregnancy and Advanced Endosurgery Unit Nepean Medical School, Nepean Hospital, University of Sydney  Kingswood NSW Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Sur","sequence":"additional","affiliation":[{"name":"Tommy's National Centre for Miscarriage Research Queen Charlotte's &amp; 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