Massive parallel sequencing (NGS) opens up new possibilities for mosaic embryos

Massive parallel sequencing (NGS) opens up new possibilities for mosaic embryos

The development of high sensitivity technologies for embryonic DNA analysis, such as next generation massive parallel sequencing techniques (Next Generation Sequencing, NGS) has provided greater diagnostic accuracy that has resulted in better embryonic selection and an increase in the number of embryos diagnosed as mosaic. "Mosaic embryos" are embryos in which genetically normal and abnormal cells coexist.

Until recently, the diagnostic techniques used were less sensitive than the current ones, so few mosaic embryos were detected. Using the techniques prior to NGS, in order to detect that an embryo was mosaic, a high proportion of the analysed cells was required to be abnormal, and these embryos were not considered suitable for reproductive use. However, the advantage of the new NGS technologies is that, being more sensitive, they have allowed to expand the number of embryos that present this type of alterations and make a better selection of the embryo to be transferred. In 2015, a group of researchers showed that the transfer of some mosaic embryos could lead to pregnancy and the birth of a healthy baby (Greco et al., 2015). This caused a paradigm shift when considering mosaic embryos as suitable for reproductive use, if they represented the only option available to patients.

Taking into account this new reality, a group of researchers from various centres, including Dr Mònica Parriego - expert in Preimplantation Genetic Diagnosis (PGD) of Dexeus Mujer - has conducted a study to observe and compare the ability to achieve pregnancy that three different types of embryos show in clinical practice: euploid embryos transferred after having performed an analysis and a prior selection by PGD; euploid embryos analysed using the new NGS technologies and mosaic embryos analysed through NSG technology as well.

The results show that transferred embryos classified as euploid with NGS showed a higher pregnancy rate than those that were selected through less advanced PGD techniques: 77% vs 63%. However, the pregnancy rate of mosaic embryos that were analysed using NSG technology is not negligible, since it reached 37%.

The final recommendations of the authors for the management of mosaic embryos, based on the data currently available, is to classify them by groups of higher or lower risk (those with more than 40% of chromosomal alterations are considered high risk), and in the event that only mosaic embryos are available, the patient should be informed of the possible risks of miscarriage and of the development of chromosomal alterations. These guidelines should also be adjusted to the profile of the patient and her chances of performing new cycles in which embryos with greater chances of achieving a pregnancy and the birth of a healthy baby can be obtained.

Clinical outcomes after the transfer of blastocysts characterized as mosaic by high resolution Next Generation Sequencing- further insights.

Munné S, Spinella F, Grifo J, Zhang J, Beltran MP, Fragouli E, Fiorentino F.

Eur J Hum Genet. 2020 Feb;63(2):103741. doi: 10.1016,j.ejmg.2019.103741