title: Managing pregnancy of unknown location based on initial serum progesterone and serial serum hCG levels: development and validation of a two-step triage protocol.
abstract: OBJECTIVE
  A uniform rationalized management protocol for pregnancies of unknown location (PUL) is lacking. We developed a two-step 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 h to hCG at presentation (step 2).
  
  
  METHODS
  This was a cohort study of 2753 PUL (301 EP), involving a secondary analysis of prospectively and consecutively collected PUL data from two London-based 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 < 5%.
  
  
  RESULTS
  On validation, initial serum progesterone ≤ 2 nmol/L (step 1) classified 16.1% PUL as low risk. Second-step classification with the risk model selected an additional 46.0% of all PUL as low risk. Overall, the two-step 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.
  
  
  CONCLUSIONS
  PUL can be classified efficiently into being either high or low risk for complications using a two-step protocol involving initial progesterone and hCG levels and the hCG ratio. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
authors.affiliation: KU Leuven, Department of Development and Regeneration, Leuven, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Van Calster
authors.affiliation: Tommy's National Centre for Miscarriage Research, Queen Charlotte's & Chelsea Hospital, Imperial College, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bobdiwala
authors.affiliation: West Middlesex Hospital, Isleworth, Middlesex, UK.
authors.forename: S
authors.initials: S
authors.lastname: Guha
authors.affiliation: Open Analytics, Antwerp, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Van Hoorde
authors.affiliation: Tommy's National Centre for Miscarriage Research, Queen Charlotte's & Chelsea Hospital, Imperial College, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Al-Memar
authors.affiliation: Charing Cross Oncology Laboratory and Trophoblastic Disease Center, Charing Cross Hospital, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Harvey
authors.affiliation: Tommy's National Centre for Miscarriage Research, Queen Charlotte's & Chelsea Hospital, Imperial College, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Farren
authors.affiliation: North Middlesex Hospital, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Kirk
authors.affiliation: Acute Gynaecology, Early Pregnancy and Advanced Endosurgery Unit, Nepean Medical School, Nepean Hospital, University of Sydney, Kingswood, NSW, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Condous
authors.affiliation: Tommy's National Centre for Miscarriage Research, Queen Charlotte's & Chelsea Hospital, Imperial College, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Sur
authors.affiliation: Tommy's National Centre for Miscarriage Research, Queen Charlotte's & Chelsea Hospital, Imperial College, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Stalder
authors.affiliation: KU Leuven, Department of Development and Regeneration, Leuven, Belgium.|Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Timmerman
authors.affiliation: KU Leuven, Department of Development and Regeneration, Leuven, Belgium.|Tommy's National Centre for Miscarriage Research, Queen Charlotte's & Chelsea Hospital, Imperial College, London, UK.|Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Bourne
mesh_terms: D000328:Adult; D006063:Chorionic Gonadotropin / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D011247:Pregnancy; D011256:Pregnancy Outcome; D011271:Pregnancy, Ectopic / Q000097:blood / Q000175:diagnosis*; D011374:Progesterone / Q000097:blood*; D014218:Triage
chemical_list: D006063:Chorionic Gonadotropin; D011374:Progesterone
keywords: decision-support techniques; ectopic pregnancy; human chorionic gonadotropin; pregnancy of unknown location; progesterone