New Genetic Sequencing Methods Means Accurate Embryo Screening

The clinical application of next generation DNA sequencing (NGS), a high throughput sequencing method, has the potential to revolutionize pre-implantation genetic screening (PGS).

The use of NGS in screening embryos for genetic disease prior to implantation in patients undergoing in vitro fertilization treatments shows that it is an effective reliable method of selecting the best embryos to transfer.


Molecular geneticists at the GENOMA Laboratory (Rome, Italy) enrolled 55 patients with a mean age of 40 years. In 45 cases they were undertaking in vitro fertilization (IVF) because of advanced age and in 10 because of repeated IVF failures. They carried out biopsies and analyzed the genetic make-up of the embryos at between five and six/seven days, depending on the speed of growth, and then measured the consistency of the diagnosis by comparing results from the two sequencing methods.

They performed a prospective, double blind trial using two methods of embryo screening, NGS, and the older method array-comparative genomic hybridization (Array-CGH) of 192 blastocysts, or early embryos, obtained from 55 consecutive clinical pre-implantation genetic screening (PGS) cycles. Array-CGH was the first technology to be widely available for the accurate analysis of chromosomal abnormalities in the embryo and is used extensively across the world for this purpose.

This comparison showed concordant results for 191 of the 192 embryos analyzed. One embryo showed a false positive for three copies of chromosome 22 (trisomy 22) using the NGS technique. But analysis of this embryo also showed concordance between the two methods in detecting several other chromosomal abnormalities, and it would therefore have been ruled out for transfer in any event. There were no other false negative diagnoses for chromosome abnormalities, and no inaccurate predictions of gender. NGS also showed itself to be as capable of identifying small, difficult to detect abnormalities.

Francesco Fiorentino, PhD, the lead author of the study and founder of GENOMA, said, “We found that results from the NGS and array-CGH diagnostic tests were highly concordant. NGS allowed us to detect a number of different abnormalities in 4,608 chromosomes with a very high degree of accuracy, and following the transfer of 50 healthy embryos in 46 women, with 30 pregnancies continued. A further advantage of the technique is that it is quicker and cheaper, while remaining just as sensitive as other methods of screening.” The study was presented at the annual conference of the European Society of Human Genetics held May 31–June 3, 2014, in Milan (Italy).

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