Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization.
Preimplantation genetic screening (PGS) is widely used to select in vitro-fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. Here, we present and validate a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. By using multiple annealing and looping-based amplification cycles (MALBAC) for whole-genome amplification (WGA), we performed next-generation sequencing (NGS) on the spent culture medium used to culture human blastocysts (n = 42) and obtained the ploidy information of all 24 chromosomes. We validated these results by comparing each with their corresponding whole donated embryo and obtained a high correlation for identification of chromosomal abnormalities (sensitivity, 0.882, and specificity, 0.840). With this validated NICS method, we performed chromosome screening on IVF embryos from seven couples with balanced translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved successful clinical pregnancies, and five have already achieved healthy live births thus far. The NICS method avoids the need for embryo biopsy and therefore substantially increases the safety of its use. The method has the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness.
Reproductive Medical Center of Nanjing Jinling Hospital and the Collaborative Innovation Platform for Reproductive Biology and Technology, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, China.
Juanjuan
J
Xu
Reproductive Medicine Center, Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China.
Rui
R
Fang
Reproductive Medical Center of Nanjing Jinling Hospital and the Collaborative Innovation Platform for Reproductive Biology and Technology, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, China.
Li
L
Chen
Reproductive Medicine Center, Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China.
Daozhen
D
Chen
Reproductive Medicine Center, Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China.
Jian-Ping
JP
Xiao
Reproductive Medicine Center, Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China.
Weimin
W
Yang
Reproductive Medicine Center, Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China.
Honghua
H
Wang
Reproductive Medicine Center, Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China.
Xiaoqing
X
Song
Department of Clinical Research, Yikon Genomics Company, Ltd., Shanghai 201499, China.
Ting
T
Ma
Department of Clinical Research, Yikon Genomics Company, Ltd., Shanghai 201499, China.
Shiping
S
Bo
Department of Clinical Research, Yikon Genomics Company, Ltd., Shanghai 201499, China.
Chong
C
Shi
Department of Clinical Research, Yikon Genomics Company, Ltd., Shanghai 201499, China.
Jun
J
Ren
Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China; Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115; Harvard Medical School, Boston, MA 02115; Beijing Advanced Innovation Center for Genomics, Peking University, Beijing 100871, China.
Lei
L
Huang
Reproductive Medicine Center, Wuxi Maternity and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, China; caili76@hotmail.co.jp yaobing@nju.edu.cn xie@chemistry.harvard.edu lusijia@yikongenomics.com.
Li-Yi
LY
Cai
Reproductive Medical Center of Nanjing Jinling Hospital and the Collaborative Innovation Platform for Reproductive Biology and Technology, Nanjing University School of Medicine, Nanjing, Jiangsu 210002, China; caili76@hotmail.co.jp yaobing@nju.edu.cn xie@chemistry.harvard.edu lusijia@yikongenomics.com.
Bing
B
Yao
Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, China; Beijing Advanced Innovation Center for Genomics, Peking University, Beijing 100871, China; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 01238 caili76@hotmail.co.jp yaobing@nju.edu.cn xie@chemistry.harvard.edu lusijia@yikongenomics.com.
X Sunney
XS
Xie
Department of Clinical Research, Yikon Genomics Company, Ltd., Shanghai 201499, China; caili76@hotmail.co.jp yaobing@nju.edu.cn xie@chemistry.harvard.edu lusijia@yikongenomics.com.
Sijia
S
Lu
D000328:Adult; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D002874:Chromosome Mapping; D017077:Culture Media, Conditioned; D046149:Embryo Culture Techniques; D004622:Embryo, Mammalian; D005260:Female; D005307:Fertilization in Vitro; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D011247:Pregnancy; D011256:Pregnancy Outcome; D019836:Preimplantation Diagnosis / Q000379:methods; D014178:Translocation, Genetic; D000073336:Whole Genome Sequencing
D017077:Culture Media, Conditioned
IVF; MALBAC; PGS; WGA; chromosomal abnormalities
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