title: A pilot proof-of-principle study to compare fresh and vitrified cycle preimplantation genetic screening by chromosome microarray and next generation sequencing.
abstract: BACKGROUND
  Single embryo transfer (SET) has been utilized as a strategy to reduce the chance of multifetal gestations in in vitro fertilization (IVF) but lower pregnancy rate remains a concern. Recent studies showed that favorable outcome regarding SET can be achieved by selecting embryos with "more normal" genetic components. We explored the use of rapid array comparative genomic hybridization (aCGH) to select blastocysts for fresh SET and compared with the protocols adopting vitrified (ultrarapidly frozen) embryo transfer cycle. Validation of the rapid protocol of aCGH and comparison of the result with the regular protocol of aCGH and next generation sequencing (NGS) are also performed.
  
  
  RESULTS
  First-time IVF patients with normal karyotype (n = 21) were enrolled for elective fresh SET cycle (n = 8; designated as fresh SET group) or vitrified embryo transfer cycle (n = 13; designated as vitrified ET group) coupling with comprehensive chromosomal screening by a 9-h rapid aCGH from Day 5 trophectoderm (TE) biopsy. In fresh SET group, 86 blastocysts (10.8 blastocysts/patient) were biopsied and analyzed. Aneuploidy was detected in 53.5 % (46/86) of the biopsied blastocysts. All patients had a single embryo transferred on the following day. The clinical pregnancy rate was 87.5 % (7/8) and the ongoing pregnancy rate was 62.5 % (5/8). In vitrified ET group, 58 blastocysts (4.5 blastocysts/patient) were biopsied and 56 blastocysts were analyzed. Aneuploidy was detected in 39.3 % (22/56) of biopsies. The patients accepted for SET or double embryos transfer (DET) in non-stimulated cycles. The clinical pregnancy rate and the ongoing pregnancy rate was 76.9 % (10/13) and 53.8 % (7/13) respectively. Spontaneous abortions occurred in both of the two patient groups. In the series of fresh SET group, no twin pregnancy was noted and at least one healthy baby had been born at gestational age (GA) 37(+6) weeks when submission. The results of PGS by rapid aCGH, regular aCGH and NGS were comparable in most occasions.
  
  
  CONCLUSIONS
  This study evaluates the use of rapid aCGH to select blastocysts for fresh SET and demonstrates its feasibility in a real clinical IVF program. A successful livebirth is achieved and the favorable outcome is superior to the protocol adopting vitrified ET cycle in our own setting. Additional studies are needed to verify this pilot data and validate its application in large randomized trials.
authors.affiliation: Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan.|Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua, Taiwan.|Institute of Biochemistry, Microbiology and Immunology, Chung-Shan Medical University, Taichung, Taiwan.|Department of Medical Laboratory Science and Biotechnology, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: Gwo-Chin
authors.initials: GC
authors.lastname: Ma
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan.|Graduate Institute of Medical Genomics and Proteomics, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsin-Fu
authors.initials: HF
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Yu-Shih
authors.initials: YS
authors.lastname: Yang
authors.affiliation: Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan.|Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua, Taiwan.
authors.forename: Wen-Hsiang
authors.initials: WH
authors.lastname: Lin
authors.affiliation: Poyuan Women Clinic, Changhua, Taiwan.
authors.forename: Feng-Po
authors.initials: FP
authors.lastname: Tsai
authors.affiliation: Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan.
authors.forename: Chi-Fang
authors.initials: CF
authors.lastname: Lin
authors.affiliation: Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chi
authors.initials: C
authors.lastname: Chiu
authors.affiliation: Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua, Taiwan.|Department of Genomic Science and Technology, Changhua Christian Hospital Healthcare System, Changhua, Taiwan.|Department of Obstetrics and Gynecology, College of Medicine and Hospital, National Taiwan University, Taipei, Taiwan.|Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua, Taiwan.|Department of Life Science, Tunghai University, Taichung, Taiwan.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
keywords: Aneuploidy; Chromosomal microarray; Fresh embryo transfer; PGS; SET