Treatments

5/24 Chromosomes Advanced PGS

Preimplantation genetic screening (PGS) with Next Generation Sequencing (NGS) is the newest technique used to detect abnormal number of chromosomes from a single cell.
Next Generation Sequencing (NGS) is a new, cutting-edge technology which can analyse small quantities of DNA harnessed from cells biopsied from early developing embryos and generate the full 23 pairs of chromosomes of a sample with remarkable resolution and sensitivity.
Initially, the sample undergoes Whole Genome Amplification (WGA), a process that essentially turns the original quantity of a sample DNA into a significantly higher amount which is suitable for testing.
The DNA sequencer can run 24 samples at the same time. The samples are processed in a rigorous, hands-on protocol through which the DNA is added on the sequencer for processing. As new DNA is synthesized, fluorescent signals are emitted. The software uses these signals to identify the specific DNA sequence formed and its location. Finally, all sequences created are separated based on the specific markers added on each. During data analysis, results are imported on a specialized software which generates the chromosomal profile of each sample.
As NGS is highly sensitive, it allows the detection of whole copy numbers as well as small segmental changes (deletions/duplications) to be clearly and accurately seen, a significant advantage over FISH or aCGH technologies. Additionally, NGS as a method of analysis is superior in the context of its capacity to detect mosaicism and its level in an embryo. Due to the sequencer having a minimum capacity of running 21 samples at a time, and the required time it takes to run, process and read the results, a Fresh Embryo Transfer is not currently possible. The embryos are frozen after biopsy for implantation at a later stage. The implantation potential of embryos which have been found healthy for all chromosomes after NGS testing is as high as 80% following successful thawing. This rate further increases with a confirmation of a foetal heart pulse or ultrasound at 6 ½ weeks.
The only disadvantage of NGS technology is its inability to diagnose ploidy status in female embryos, a rare phenomenon which is minimized even more by good IVF practices.

Initially, the sample undergoes Whole Genome Amplification (WGA), a process that essentially turns the original quantity of a sample DNA into a significantly higher amount which is suitable for testing.
The DNA sequencer can run 24 samples at the same time. The samples are processed in a rigorous, hands-on protocol through which the DNA is added on the sequencer for processing. As new DNA is synthesized, fluorescent signals are emitted. The software uses these signals to identify the specific DNA sequence formed and its location. Finally, all sequences created are separated based on the specific markers added on each. During data analysis, results are imported on a specialized software which generates the chromosomal profile of each sample.

Embryo biopsies are conventionally performed on day 3 of in vitro development (6-8 cell stage) or on day 5 when the embryo is expected to have reached the blastocyst stage (several dozen cells). The blastocyst is structurally formed by an inner cell mass which subsequently integrates into the new organism. The outer layer of the blastocyst consists of cells collectively called the trophectoderm programmed to form the placenta. This layer surrounds the inner cell mass forming a fluid-filled cavity namely the blastocoele. By contrast today 3 biopsies where only one or two cells are removed from the embryo, the number is considerably higher when blastocyst biopsies are implemented.

The value of day 3 biopsies has received criticism pending the large volume of cellular material which is removed from the embryo (1/8 or 12.5%). Furthermore, the diagnosis derived from a single cell may be falsely positive or negative due to the risk of chromosomal mosaicism, a phenomenon which increases with age.