Randomized comparison of next-generation sequencing and array comparative genomic hybridization for preimplantation genetic screening: a pilot study

BMC Medical Genomics

Jiaen Liu¹  Yanping Kuang⁴  William Podevin⁵  Xiaohong Liu¹  Rong Zhao¹  Pei Li¹  Wai Ieng Fong²  John Zhang³  James Lin⁶  Zhihong Yang¹ 

[1]Jia En De Yun Hospital, Beijing, P. R. China

[2]Hospital Conde S. Januário, Macau, P. R. China

[3]New Hope Fertility Center, New York, NY, USA

[4]Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China

[5]Pacific Reproductive Center, Torrance, CA, USA

[6]Reproductive Fertility Center, Irvine, CA, USA

关键词: Implantation;    Ongoing pregnancy;    Aneuploidy screening;    PGS;    aCGH;    NGS;   

Others  :  1217181
DOI  :  10.1186/s12920-015-0110-4

 received in 2015-01-21, accepted in 2015-06-16,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Yang et al.

【 图 表 】

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