title: Evaluation of ADAM-12 as a diagnostic biomarker of ectopic pregnancy in women with a pregnancy of unknown location.
abstract: BACKGROUND
  Ectopic pregnancy (EP) remains the most life-threatening acute condition in modern gynaecology. It remains difficult to diagnose early and accurately. Women often present at emergency departments in early pregnancy with a 'pregnancy of unknown location' (PUL) and diagnosis/exclusion of EP is challenging due to a lack of reliable biomarkers. Recent studies suggest that serum levels of a disintegrin and metalloprotease protein-12 (ADAM-12) can be used differentiate EP from viable intrauterine pregnancy (VIUP). Here we describe a prospective study evaluating the performance of ADAM-12 in differentiating EP from the full spectrum of alternative PUL outcomes in an independent patient cohort.
  
  
  RESULTS
  Sera were collected from 120 patients at their first clinical presentation with a PUL and assayed for ADAM-12 by ELISA. Patients were categorized according to final pregnancy outcomes. Serum ADAM-12 concentrations were increased in women with histologically-confirmed EP (median 442 pg/mL; 25%-75% percentile 232-783 pg/mL) compared to women with VIUP (256 pg/mL; 168-442 pg/mL) or miscarriage (192 pg/mL; 133-476 pg/mL). Serum ADAM-12 did not differentiate histologically-confirmed EP from spontaneously resolving PUL (srPUL) (416 pg/mL; 154-608 pg/mL). The diagnostic potential of ADAM-12 was only significant when 'ambiguous' PUL outcomes were excluded from the analysis (AROC = 0.6633; P = 0.03901).
  
  
  CONCLUSIONS
  When measured in isolation, ADAM-12 levels had limited value as a diagnostic biomarker for EP in our patient cohort. The development of a reliable serum biomarker-based test for EP remains an ongoing challenge.
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom. andrew.horne@ed.ac.uk
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Horne
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Brown
authors.forename: Stephen
authors.initials: S
authors.lastname: Tong
authors.forename: Tu'uhevaha
authors.initials: T
authors.lastname: Kaitu'u-Lino
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000072199:ADAM12 Protein; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D011247:Pregnancy; D011271:Pregnancy, Ectopic / Q000097:blood* / Q000175:diagnosis*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human