title: Pregnancies conceived using assisted reproductive technologies (ART) have low levels of pregnancy-associated plasma protein-A (PAPP-A) leading to a high rate of false-positive results in first trimester screening for Down syndrome.
abstract: BACKGROUND
  First trimester screening (FTS) for Down syndrome combines measurement of nuchal translucency, free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein-A (PAPP-A). The aim of this study was to undertake a detailed analysis of FTS results in singleton pregnancies conceived using assisted reproductive technologies (ART) and non-ART pregnancies.
  
  
  METHODS
  A record linkage study compared outcomes in 1739 ART-conceived and 50 253 naturally conceived pregnancies.
  
  
  RESULTS
  Overall, significantly lower PAPP-A levels were detected in ART pregnancies (0.83 multiples of median, MoM) than in controls (1.00 MoM) (t-test P < 0.001). This difference remained after excluding complicated pregnancies. Analysis of factors affecting PAPP-A levels suggested fresh compared with frozen embryo transfers and use of artificial cycles compared with natural cycles for frozen transfers were associated with lower values. The adjusted odds ratio (AdjOR) for receiving a false-positive result was 1.71 (95% CI 1.44-2.04; P < 0.001) for ART pregnancies compared with non-ART pregnancies, and this leads to a higher AdjOR (1.24, 95% CI 1.03-1.49; P = 0.02) for having a chorionic villous sampling (CVS) or amniocentesis.
  
  
  CONCLUSIONS
  ART pregnancies have reduced FTS PAPP-A levels leading to an increased likelihood of receiving a false-positive result and having a CVS/amniocentesis. Lower PAPP-A may reflect impairment of early implantation with some forms of ART.
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia. david.amor@mcri.edu.au
authors.forename: D J
authors.initials: DJ
authors.lastname: Amor
authors.forename: J X
authors.initials: JX
authors.lastname: Xu
authors.forename: J L
authors.initials: JL
authors.lastname: Halliday
authors.forename: I
authors.initials: I
authors.lastname: Francis
authors.forename: D L
authors.initials: DL
authors.lastname: Healy
authors.forename: S
authors.initials: S
authors.lastname: Breheny
authors.forename: H W G
authors.initials: HW
authors.lastname: Baker
authors.forename: A M
authors.initials: AM
authors.lastname: Jaques
mesh_terms: D000293:Adolescent; D000328:Adult; D000649:Amniocentesis; D015415:Biomarkers / Q000097:blood*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000378:metabolism; D015193:Chorionic Villi Sampling; D004314:Down Syndrome / Q000175:diagnosis* / Q000453:epidemiology; D005189:False Positive Reactions; D005260:Female; D006321:Heart / Q000196:embryology; D006801:Humans; D008875:Middle Aged; D048208:Nuchal Translucency Measurement; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000097:blood; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011296:Prenatal Diagnosis / Q000592:standards*; D027724:Reproductive Techniques, Assisted; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A