title: Clinically recognizable error rate after the transfer of comprehensive chromosomal screened euploid embryos is low.
abstract: OBJECTIVE
  To determine the clinically recognizable error rate with the use of quantitative polymerase chain reaction (qPCR)-based comprehensive chromosomal screening (CCS).
  
  
  METHODS
  Retrospective study.
  
  
  METHODS
  Multiple fertility centers.
  
  
  METHODS
  All patients receiving euploid designated embryos.
  
  
  METHODS
  Trophectoderm biopsy for CCS.
  
  
  METHODS
  Evaluation of the pregnancy outcomes following the transfer of qPCR-designated euploid embryos. Calculation of the clinically recognizable error rate.
  
  
  RESULTS
  A total of 3,168 transfers led to 2,354 pregnancies (74.3%). Of 4,794 CCS euploid embryos transferred, 2,976 gestational sacs developed, reflecting a clinical implantation rate of 62.1%. In the cases where a miscarriage occurred and products of conception were available for analysis, ten were ultimately found to be aneuploid. Seven were identified in the products of conception following clinical losses and three in ongoing pregnancies. The clinically recognizable error rate per embryo designated as euploid was 0.21% (95% confidence interval [CI] 0.10-0.37). The clinically recognizable error rate per transfer was 0.32% (95% CI 0.16-0.56). The clinically recognizable error rate per ongoing pregnancy was 0.13% (95% CI 0.03-0.37). Three products of conception from aneuploid losses were available to the molecular laboratory for detailed examination, and all of them demonstrated fetal mosaicism.
  
  
  CONCLUSIONS
  The clinically recognizable error rate with qPCR-based CCS is real but quite low. Although evaluated in only a limited number of specimens, mosaicism appears to play a prominent role in misdiagnoses. Mosaic errors present a genuine limit to the effectiveness of aneuploidy screening, because they are not attributable to technical issues in the embryology or analytic laboratories.
authors.affiliation: Robert Wood Johnson Medical School of Rutgers University, New Brunswick, New Jersey. Electronic address: mwerner@rmanj.com.
authors.forename: Marie D
authors.initials: MD
authors.lastname: Werner
authors.affiliation: Reproductive Medicine Associates of Connecticut, Norwalk, Connecticut.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Leondires
authors.affiliation: Colorado Center for Reproductive Medicine, Lone Tree, Colorado.
authors.forename: William B
authors.initials: WB
authors.lastname: Schoolcraft
authors.affiliation: Reproductive Medicine Associates of Michigan, Troy, Michigan.
authors.forename: Brad T
authors.initials: BT
authors.lastname: Miller
authors.affiliation: Reproductive Medicine Associates of New York, New York, New York.
authors.forename: Alan B
authors.initials: AB
authors.lastname: Copperman
authors.affiliation: Center for Reproductive Health, Spokane, Washington.
authors.forename: Edwin D
authors.initials: ED
authors.lastname: Robins
authors.affiliation: Reproductive Medicine Associates of Texas, San Antonio, Texas.
authors.forename: Francisco
authors.initials: F
authors.lastname: Arredondo
authors.affiliation: Houston IVF, Houston, Texas.
authors.forename: Timothy N
authors.initials: TN
authors.lastname: Hickman
authors.affiliation: Reproductive Medicine Associates of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Gutmann
authors.affiliation: Reproductive Medicine Associates of Pennsylvania, Allentown, Pennsylvania.
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Schillings
authors.affiliation: Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey.
authors.forename: Brynn
authors.initials: B
authors.lastname: Levy
authors.affiliation: Robert Wood Johnson Medical School of Rutgers University, New Brunswick, New Jersey; Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey.
authors.forename: Deanne
authors.initials: D
authors.lastname: Taylor
authors.affiliation: Robert Wood Johnson Medical School of Rutgers University, New Brunswick, New Jersey; Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Treff
authors.affiliation: Robert Wood Johnson Medical School of Rutgers University, New Brunswick, New Jersey; Reproductive Medicine Associates of New Jersey, Basking Ridge, New Jersey.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Scott
mesh_terms: D000328:Adult; D000782:Aneuploidy; D003951:Diagnostic Errors; D010064:Embryo Implantation; D004624:Embryo Transfer; D005260:Female; D006801:Humans; D009030:Mosaicism; D011247:Pregnancy; D011256:Pregnancy Outcome; D019836:Preimplantation Diagnosis / Q000592:standards*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies
keywords: Aneuploidy; misdiagnosis; preimplantation genetic screening; quantitative PCR; trophectoderm biopsy