The Future of Genetic Testing of Embryos

Abstract

It is now over 30 years since the first pregnancies and live births following IVF, embryo biopsy and preimplantation genetic testing (PGT) were reported in 1990, in several couples at risk of having children affected by X-linked diseases (Handyside et al., 1990). Since then, methods for genetic analysis at the single-cell level have evolved alongside the rapid advances in human genetics and sequencing of the human genome. The range of applications has also expanded beyond monogenic diseases to chromosome aneuploidy, structural chromosome rearrangements and other genetic abnormalities. PGT is now practiced world-wide and remains a valuable alternative for at risk couples. With the development of methods for whole genome amplification, such as multiple displacement amplification (MDA), genome-wide analysis became possible. This has led to the development of microarray or next generation sequencing (NGS) based methods for genome-wide haplotyping of parental chromosomes in embryo samples and enabled universal linkage-based testing for monogenic diseases combined with molecular cytogenetic analysis of chromosome abnormalities. In the future, these methods will become increasingly informative and accurate, and it may be possible to use cell-free DNA in spent culture medium to avoid embryo biopsy. Handyside AH, Kontogianni EH, Hardy K and Winston RML (1990) Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 344, 768