Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization

Author:

Xu Juanjuan,Fang Rui,Chen Li,Chen Daozhen,Xiao Jian-Ping,Yang Weimin,Wang Honghua,Song Xiaoqing,Ma Ting,Bo Shiping,Shi Chong,Ren Jun,Huang Lei,Cai Li-Yi,Yao Bing,Xie X. Sunney,Lu Sijia

Abstract

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.

Funder

National Natural Science Foundation of Jiangsu Province

National Natural Science Foundation of China

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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