title: Validation of multiple annealing and looping-based amplification cycle sequencing for 24-chromosome aneuploidy screening of cleavage-stage embryos.
abstract: OBJECTIVE
  To validate multiple annealing and looping-based amplification cycle (MALBAC) sequencing for 24-chromosome aneuploidy screening of cleavage embryos and to explore the chromosomal characteristics of embryos at the cleavage stage.
  
  
  METHODS
  The 24-chromosome aneuploidy analyses of the blastomeres included comparative genomic hybridization (CGH), single nucleotide polymorphism (SNP), and MALBAC sequencing.
  
  
  METHODS
  University-affiliated IVF center.
  
  
  METHODS
  Three couples who delivered babies from the same IVF cycle, which included 23 donated, frozen cleavage embryos.
  
  
  METHODS
  None.
  
  
  METHODS
  Three blastomeres were selected from each single embryo and subject to CGH, SNP, and MALBAC sequencing for 24-chromosome aneuploidy, respectively. The results of MALBAC sequencing were compared with the results of CGH and SNP. The chromosomal status and occurrence of the abnormal chromosomes were investigated. The relationship between the embryos' morphology and the euploid state was analyzed.
  
  
  RESULTS
  Among the 23 donated embryos, the MALBAC sequencing results of 18 (78.26%) embryos were identical to those of CGH or SNP, including 8 embryos that had identical results by all three techniques. In terms of euploidy, only 6 of these 23 embryos (26.09%) were diploid. Blastomere abnormality was observed in all autosomes and sex chromosomes. In addition, the frequency of abnormality was different for certain chromosomes.
  
  
  CONCLUSIONS
  With sequencing at 0.04× genome depth, MALBAC sequencing has been validated as a satisfactory method for 24-chromosome aneuploidy screening. The proportion of abnormal chromosomes was high in cleavage-stage embryos, and any chromosome could be abnormal.
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medical Centre, Peking University Third Hospital, Beijing, People's Republic of China; Key Laboratory of Assisted Reproduction, Ministry of Education and Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medical Centre, Peking University Third Hospital, Beijing, People's Republic of China; Key Laboratory of Assisted Reproduction, Ministry of Education and Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, People's Republic of China.
authors.forename: Liying
authors.initials: L
authors.lastname: Yan
authors.affiliation: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medical Centre, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medical Centre, Peking University Third Hospital, Beijing, People's Republic of China; Key Laboratory of Assisted Reproduction, Ministry of Education and Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Fuchou
authors.initials: F
authors.lastname: Tang
authors.affiliation: Biodynamic Optical Imaging Center, College of Life Sciences, Peking University, Beijing, People's Republic of China; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts.
authors.forename: X Sunney
authors.initials: XS
authors.lastname: Xie
authors.affiliation: Department of Obstetrics and Gynecology, Reproductive Medical Centre, Peking University Third Hospital, Beijing, People's Republic of China; Key Laboratory of Assisted Reproduction, Ministry of Education and Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, People's Republic of China. Electronic address: jie.qiao@263.net.
authors.forename: Jie
authors.initials: J
authors.lastname: Qiao
mesh_terms: D000328:Adult; D000782:Aneuploidy; D001757:Blastomeres; D002869:Chromosome Aberrations; D002970:Cleavage Stage, Ovum; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods*
keywords: 24-chromosome aneuploidy screening; Cleavage embryo; comparative genomic hybridization (CGH); multiple annealing and looping-based amplification cycles (MALBAC); single nucleotide polymorphism (SNP)