title: Randomized comparison of next-generation sequencing and array comparative genomic hybridization for preimplantation genetic screening: a pilot study.
abstract: BACKGROUND
  Recent advances in next-generation sequencing (NGS) have provided new methods for preimplantation genetic screening (PGS) of human embryos from in vitro fertilization (IVF) cycles. However, there is still limited information about clinical applications of NGS in IVF and PGS (IVF-PGS) treatments. The present study aimed to investigate the effects of NGS screening on clinical pregnancy and implantation outcomes for PGS patients in comparison to array comparative genomic hybridization (aCGH) screening.
  
  
  METHODS
  This study was performed in two phases. Phase I study evaluated the accuracy of NGS for aneuploidy screening in comparison to aCGH. Whole-genome amplification (WGA) products (n = 164) derived from previous IVF-PGS cycles (n = 38) were retrospectively analyzed with NGS. The NGS results were then compared with those of aCGH. Phase II study further compared clinical pregnancy and implantation outcomes between NGS and aCGH for IVF-PGS patients. A total of 172 patients at mean age 35.2 ± 3.5 years were randomized into two groups: 1) NGS (Group A): patients (n = 86) had embryos screened with NGS and 2) aCGH (Group B): patients (n = 86) had embryos screened with aCGH. For both groups, blastocysts were vitrified after trophectoderm biopsy. One to two euploid blastocysts were thawed and transferred to individual patients primarily based on the PGS results. Ongoing pregnancy and implantation rates were compared between the two study groups.
  
  
  RESULTS
  NGS detected all types of aneuploidies of human blastocysts accurately and provided a 100 % 24-chromosome diagnosis consistency with the highly validated aCGH method. Moreover, NGS screening identified euploid blastocysts for transfer and resulted in similarly high ongoing pregnancy rates for PGS patients compared to aCGH screening (74.7 % vs. 69.2 %, respectively, p >0.05). The observed implantation rates were also comparable between the NGS and aCGH groups (70.5 % vs. 66.2 %, respectively, p >0.05).
  
  
  CONCLUSIONS
  While NGS screening has been recently introduced to assist IVF patients, this is the first randomized clinical study on the efficiency of NGS for preimplantation genetic screening in comparison to aCGH. With the observed high accuracy of 24-chromosome diagnosis and the resulting high ongoing pregnancy and implantation rates, NGS has demonstrated an efficient, robust high-throughput technology for PGS.
authors.affiliation: ZytoGen Global Genetics Institute, Timonium, MD, USA. sunmiy31@hotmail.com.|Reproductive Fertility Center, Irvine, CA, USA. sunmiy31@hotmail.com.|Jia En De Yun Hospital, Beijing, P. R. China. sunmiy31@hotmail.com.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Reproductive Fertility Center, Irvine, CA, USA. drlin@reproductivefertilitycenter.com.
authors.forename: James
authors.initials: J
authors.lastname: Lin
authors.affiliation: New Hope Fertility Center, New York, NY, USA. johnzhang98@yahoo.com.
authors.forename: John
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Hospital Conde S. Januário, Macau, P. R. China. fongwi@hotmail.com.
authors.forename: Wai Ieng
authors.initials: WI
authors.lastname: Fong
authors.affiliation: Jia En De Yun Hospital, Beijing, P. R. China. yucenxlpxw@126.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: Jia En De Yun Hospital, Beijing, P. R. China. zz6667@vip.sina.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Jia En De Yun Hospital, Beijing, P. R. China. liujiaen@126.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Pacific Reproductive Center, Torrance, CA, USA. williampodevin@yahoo.com.
authors.forename: William
authors.initials: W
authors.lastname: Podevin
authors.affiliation: Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China. kuangyanp@126.com.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Jia En De Yun Hospital, Beijing, P. R. China. jiaenliu@hotmail.com.
authors.forename: Jiaen
authors.initials: J
authors.lastname: Liu
mesh_terms: D000328:Adult; D000782:Aneuploidy; D055028:Comparative Genomic Hybridization; D010064:Embryo Implantation; D005260:Female; D005307:Fertilization in Vitro; D005820:Genetic Testing / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000379:methods*; D012189:Retrospective Studies