{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:16:01Z","timestamp":1777356961301,"version":"3.51.4"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013842","name":"Imperial Health Charity","doi-asserted-by":"publisher","award":["RFPrD1920\/116"],"award-info":[{"award-number":["RFPrD1920\/116"]}],"id":[{"id":"10.13039\/100013842","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013342","name":"NIHR Imperial Biomedical Research Centre","doi-asserted-by":"publisher","award":["IS\u2010BRC\u20101215\u201020013"],"award-info":[{"award-number":["IS\u2010BRC\u20101215\u201020013"]}],"id":[{"id":"10.13039\/501100013342","id-type":"DOI","asserted-by":"publisher"}]},{"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":["Acta Obstet Gynecol Scand"],"published-print":{"date-parts":[[2022,1]]},"abstract":"Abstract<\/jats:title>Introduction<\/jats:title>There is no global agreement on how to best determine pregnancy of unknown location viability and location using biomarkers. Measurements of progesterone and \u03b2 human chorionic gonadotropin (\u03b2hCG) are still used in clinical practice to exclude the possibility of a viable intrauterine pregnancy (VIUP). We evaluate the predictive value of progesterone, \u03b2hCG, and \u03b2hCG ratio cut\u2010off levels to exclude a VIUP in women with a pregnancy of unknown location.<\/jats:p><\/jats:sec>Material and methods<\/jats:title>This was a secondary analysis of prospective multicenter study data of consecutive women with a pregnancy of unknown location between January 2015 and 2017 collected from dedicated early pregnancy assessment units of eight hospitals. Single progesterone and serial \u03b2hCG measurements were taken. Women were followed up until final pregnancy outcome between 11 and 14\u00a0weeks of gestation was confirmed using transvaginal ultrasonography: (1) VIUP, (2) non\u2010viable intrauterine pregnancy or failed pregnancy of unknown location, and (3) ectopic pregnancy or persisting pregnancy of unknown location. The predictive value of cut\u2010off levels for ruling out VIUP were evaluated across a range of values likely to be encountered clinically for progesterone, \u03b2hCG, and \u03b2hCG ratio.<\/jats:p><\/jats:sec>Results<\/jats:title>Data from 2507 of 3272 (76.6%) women were suitable for analysis. All had data for \u03b2hCG levels, 2248 (89.7%) had progesterone levels, and 1809 (72.2%) had \u03b2hCG ratio. The likelihood of viability falls with the progesterone level. Although the median progesterone level associated with viability was 59\u00a0nmol\/L, VIUP were identified with levels as low as 5\u00a0nmol\/L. No single \u03b2hCG cut\u2010off reliably ruled out the presence of viability with certainty, even when the level was more than 3000\u00a0IU\/L, there were 39\/358 (11%) women who had a VIUP. The probability of viability decreases with the \u03b2hCG ratio. Although the median \u03b2hCG ratio associated with viability was 2.26, VIUP were identified with ratios as low as 1.02. A progesterone level below 2\u00a0nmol\/L and \u03b2hCG ratio below 0.87 were unlikely to be associated with viability but were not definitive when considering multiple imputation.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Cut\u2010off levels for \u03b2hCG, \u03b2hCG ratio, and progesterone are not safe to be used clinically to exclude viability in early pregnancy. Although \u03b2hCG ratio and progesterone have slightly better performance in comparison, single \u03b2hCG used in this manner is highly unreliable.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aogs.14295","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T10:16:46Z","timestamp":1637749006000},"page":"46-55","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Evaluating cut\u2010off levels for progesterone, \u03b2 human chorionic gonadotropin and \u03b2 human chorionic gonadotropin ratio to exclude pregnancy viability in women with a pregnancy of unknown location: A prospective multicenter cohort study"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0540-2191","authenticated-orcid":false,"given":"Shabnam","family":"Bobdiwala","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology Tommy\u2019s National Centre for Miscarriage Research Queen Charlotte\u2019s & Chelsea Hospital Imperial College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9001-5545","authenticated-orcid":false,"given":"Christopher","family":"Kyriacou","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Tommy\u2019s National Centre for Miscarriage Research Queen Charlotte\u2019s & Chelsea Hospital Imperial College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7900-5952","authenticated-orcid":false,"given":"Evangelia","family":"Christodoulou","sequence":"additional","affiliation":[{"name":"Department of Development & Regeneration KU Leuven Leuven Belgium"},{"name":"Department of Cancer Epidemiology DKFZ Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8082-6499","authenticated-orcid":false,"given":"Jessica","family":"Farren","sequence":"additional","affiliation":[{"name":"Department of Gynaecology St Mary\u2019s Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0299-9586","authenticated-orcid":false,"given":"Nicola","family":"Mitchell\u2010Jones","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Chelsea and Westminster NHS Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maya","family":"Al\u2010Memar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Tommy\u2019s National Centre for Miscarriage Research Queen Charlotte\u2019s & Chelsea Hospital Imperial College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis","family":"Ayim","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Hillingdon Hospital NHS Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baljinder","family":"Chohan","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Wexham Park Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Kirk","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Royal Free NHS Foundation Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osama","family":"Abughazza","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Royal Surrey County Hospital Guildford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bramara","family":"Guruwadahyarhalli","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Chelsea and Westminster NHS Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharmistha","family":"Guha","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Chelsea and Westminster NHS Trust London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veluppillai","family":"Vathanan","sequence":"additional","affiliation":[{"name":"Department of Gynaecology Wexham Park Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debbie","family":"Gould","sequence":"additional","affiliation":[{"name":"Department of Gynaecology St Mary\u2019s Hospital London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catriona","family":"Stalder","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Tommy\u2019s National Centre for Miscarriage Research Queen Charlotte\u2019s & Chelsea Hospital Imperial College London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3707-6645","authenticated-orcid":false,"given":"Dirk","family":"Timmerman","sequence":"additional","affiliation":[{"name":"Department of Development & Regeneration KU Leuven Leuven Belgium"},{"name":"Department of Gynecology University Hospital Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1613-7450","authenticated-orcid":false,"given":"Ben","family":"Van Calster","sequence":"additional","affiliation":[{"name":"Department of Development & Regeneration KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1421-6059","authenticated-orcid":false,"given":"Tom","family":"Bourne","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Tommy\u2019s National Centre for Miscarriage Research Queen Charlotte\u2019s & Chelsea Hospital Imperial College London London UK"},{"name":"Department of Development & Regeneration KU Leuven Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/1745505717709677"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmt047"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.15442"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijgo.2004.04.004"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dms035"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.6380"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2011.02893.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2006.00924.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.2636"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1553-2712.1997.tb03660.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu045"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000198635.25135.e7"},{"key":"e_1_2_10_14_1","first-page":"258","article-title":"Suspected ectopic pregnancy: expectant management in patients with negative sonographic findings and low serum hCG concentrations","volume":"1","author":"Hajenius PJ","year":"1995","journal-title":"Early Pregnancy"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(98)00278-7"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.e6077"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000002560"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.6061\/clinics\/2019\/e1111"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.06.013"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2016.02.015"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den221"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2014.05.033"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l6283"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.20420"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/1471-0528.16497"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/uog.15864"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.h5527"},{"key":"e_1_2_10_28_1","unstructured":"NEQAS U.UK NEQAS.2021."},{"key":"e_1_2_10_29_1","unstructured":"Pathologists TRCo.National Quality Assurance Advisory Panel (NQAAP).2021."},{"key":"e_1_2_10_30_1","unstructured":"UKAS.UKAS: United Kingdom Accreditation Service.2021."},{"key":"e_1_2_10_31_1","unstructured":"(ISO) IOfS.International Organization for Standardization (ISO) 15189:2012(en) Medical Laboratories \u2010 requirements for quality and competence.2021."},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des440"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew105"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1995.10476521"},{"key":"e_1_2_10_35_1","doi-asserted-by":"crossref","unstructured":"HarrellF.Regression Modelling Strategies 2e: Springer;2015.","DOI":"10.1007\/978-3-319-19425-7"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2393"},{"key":"e_1_2_10_37_1","first-page":"171","article-title":"Spontaneous pregnancy reaches viability after low first trimester serum progesterone: a case report","volume":"57","author":"Crochet JR","year":"2012","journal-title":"J Reprod Med"},{"key":"e_1_2_10_38_1","first-page":"831","article-title":"First\u2010trimester bleeding with falling HCG: don't assume miscarriage","volume":"53","author":"Konrad G","year":"2007","journal-title":"Can Fam Physician"}],"container-title":["Acta Obstetricia et Gynecologica Scandinavica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aogs.14295","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/aogs.14295","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aogs.14295","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T18:35:52Z","timestamp":1744310152000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1111\/aogs.14295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,24]]},"references-count":37,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1111\/aogs.14295"],"URL":"https:\/\/doi.org\/10.1111\/aogs.14295","archive":["Portico"],"relation":{},"ISSN":["0001-6349","1600-0412"],"issn-type":[{"value":"0001-6349","type":"print"},{"value":"1600-0412","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,24]]},"assertion":[{"value":"2021-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}