{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T08:29:19Z","timestamp":1793780959003,"version":"4.6.1"},"reference-count":20,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["G0B4716N"],"award-info":[{"award-number":["G0B4716N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp;amp; Gyne"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The M6 risk\u2010prediction model was published as part of a two\u2010step protocol using an initial progesterone level of \u2264\u20092\u2009nmol\/L to identify probable failing pregnancies (Step 1) followed by the M6 model (Step\u00a02). The M6 model has been shown to have good triage performance for stratifying women with a pregnancy of unknown location (PUL) as being at low or high risk of harboring an ectopic pregnancy (EP). This study validated the triage performance of the two\u2010step protocol in clinical practice by evaluating the number of protocol\u2010related adverse events and how effectively patients were triaged.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a prospective multicenter interventional study of 3272 women with a PUL, carried out between January 2015 and January 2017 in four district general hospitals and four university teaching hospitals in the UK. The final pregnancy outcome was defined as: a failed PUL (FPUL), an intrauterine pregnancy (IUP) or an EP (including persistent PUL (PPUL)). FPUL and IUP were grouped as low\u2010risk and EP\/PPUL as high\u2010risk PUL. Serum progesterone and human chorionic gonadotropin (hCG) levels were measured at presentation in all patients. If the initial progesterone level was \u2264\u20092\u2009nmol\/L, patients were discharged and were asked to have a follow\u2010up urine pregnancy test in 2\u2009weeks to confirm a negative result. If the progesterone level was &gt;\u20092\u2009nmol\/L or a measurement had not been taken, hCG level was measured again at 48\u2009h and results were entered into the M6 model. Patients were managed according to the outcome predicted by the protocol. Those classified as \u2018low risk, probable FPUL\u2019 were advised to perform a urine pregnancy test in 2\u2009weeks and those classified as \u2018low risk, probable IUP\u2019 were invited for a scan a week later. When a woman with a PUL was classified as high risk (i.e. risk of EP \u2265\u20095%) she was reviewed clinically within 48\u2009h. One center used a progesterone cut\u2010off of \u2264\u200910\u2009nmol\/L and its data were analyzed separately. If the recommended management protocol was not adhered to, this was recorded as a protocol deviation and classified as: unscheduled visit for clinician reason, unscheduled visit for patient reason or incorrect timing of blood test or ultrasound scan. The classifications outlined in the UK Good Clinical Practice (GCP) guidelines were used to evaluate the incidence of adverse events. Data were analyzed using descriptive statistics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 3272 women with a PUL, 2625 were included in the final analysis (317 met the exclusion criteria or were lost to follow\u2010up, while 330 were evaluated using a progesterone cut\u2010off of \u2264\u200910\u2009nmol\/L). Initial progesterone results were available for 2392 (91.1%) patients. In Step 1, 407 (15.5%) patients were classified as low risk (progesterone \u2264\u20092\u2009nmol\/L), of whom seven (1.7%) were ultimately diagnosed with an EP. In 279 of the remaining 2218 women with a PUL, the M6 model was not applied owing to protocol deviation or because the outcome was already known (usually on the basis of an ultrasound scan) before a second hCG reading was taken; of these patients, 30 were diagnosed with an EP. In Step 2, 1038 women with a PUL were classified as low risk, of whom eight (0.8%) had a final outcome of EP. Of 901 women classified as high risk at Step 2, 275 (30.5%) had an EP. Therefore, 275\/320 (85.9%) EPs were correctly classified as high risk. Overall, 1445\/2625 PUL (55.0%) were classified as low risk, of which 15\u00a0(1.0%) were EP. None of these cases resulted in a ruptured EP or significant clinical harm. Sixty\u2010two women participating in the study had an adverse event, but no woman had a serious adverse event as defined in the UK GCP guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study has shown that the two\u2010step protocol incorporating the M6 model effectively triaged the majority of women with a PUL as being at low risk of an EP, minimizing the follow\u2010up required for these patients after just two visits. There were few misclassified EPs and none of these women came to significant clinical harm or suffered a serious adverse clinical event. The two\u2010step protocol incorporating the M6 model is an effective and clinically safe way of rationalizing the management of women with a PUL. Copyright \u00a9 2019 ISUOG. Published by John Wiley &amp; Sons Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/uog.20420","type":"journal-article","created":{"date-parts":[[2019,8,6]],"date-time":"2019-08-06T07:24:22Z","timestamp":1565076262000},"page":"105-114","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Triaging women with  pregnancy of unknown location using  two\u2010step  protocol including  M6 model:  clinical implementation study"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0540-2191","authenticated-orcid":false,"given":"S.","family":"Bobdiwala","sequence":"first","affiliation":[{"name":"Tommy's National Centre for Miscarriage Research, Queen Charlotte's &amp; Chelsea Hospital, Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Christodoulou","sequence":"additional","affiliation":[{"name":"KU Leuven, Department of Development &amp; 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