Do the advances in preimplantation genetic diagnosis bring us closer to the dream, increasing the success rate?

Preimplantation genetic diagnosis (PGD) is a technique that was first applied in humans in 1990. Because only unaffected embryos are transferred to the uterus for implantation, preimplantation genetic testing provides an alternative to current postconception diagnostic procedures (amniocentesis or chorionic villus sampling), which are frequently followed by the difficult decision of pregnancy termination if results are unfavorable. PGD and PGS are currently the only options available for avoiding the high risk of having a child affected with a genetic disease prior to implantation.

Preimplantation genetic diagnosis (PGD) is a procedure used by fertile or infertile couples at high risk of transmitting a genetic condition and allows diagnosis of single gene disorders such as Mediterranean anemia, cystic fibrosis, muscular dystrophy, Duchenne disease and other rare genetic diseases, chromosomal abnormalities or HLA typing in embryos prior to transfer and implantation.
Preimplantation genetic screening for aneuploidy (PGS) is a procedure that is offered to infertile couples with advanced age of the female partner, previously failed in vitro fertilization (IVF) treatment or unexplained recurrent miscarriage or in couples that the male has severely reduced sperm quality, with the aim of improving the success rate of IVF. It allows the enumeration of chosen chromosome pairs and can be considered as an early form of prenatal aneuploidy screening.

After biopsy, PGD/PGS can be performed at either DNA or chromosomal level. PCR have been developed to detect many genetic abnormalities (single-gene mutation, chromosomal imbalances and mitochondrial mutation). Likewise, fluorescence in situ hybridization (FISH) method has been performed to screen aneuploidy and chromosomal translocations for many years. However, these two methods become obsolete due to their limitation (such as sensitivity issues that lead to the false positive or false negative).
Until recently, the preimplantation diagnosis was performed on embryos that were on the 3rd day of their development (at the stage of 8 cells), with the removal of a blastomere (a cell) followed by genetic testing for 10 chromosomes. The disadvantage was that, on the one hand, the 10 chromosomes were not representative of the whole, and on the other hand that the embryos in these early stages, at a rate of 20%, are mosaic, meaning they can have smooth and abnormal cells and are in the reprogramming phase. In this way, there was a risk of biopsy and analysis of a cell that was abnormal, although the rest was normal, and was thus classified as an abnormal fetus and discarded while it was genetically normal.
Over the past several decades the world has witnessed incredible advances in many medical fields in a similar, technology surrounding preimplantation genetic diagnosis or screening has advanced greatly in recent years. New diagnosis methods, such as array-comparative genomic hybridixation (aCGH), Next Generation Sequencing, single nucleotide polymorphism (SNP) microarray, multiplex quantitative PCR (qPCR) are developed to improve clinical efficiency and outcome.

At Assisting Nature IVF unit, we have a team of specialist scientists and the latest technology, which means we are able to offer our patients the very best quality standards in the results obtained whilst decreasing the time taken and auditing the entire process.
Recently, in Assisting Nature IVF unit, preimplantation diagnosis takes place at the blastocyst stage (5 day embryos), and genetic analysis is carried out with the new methods CGH and NGS.
We also have a collaborating unit that specializes in Genetics and provide a personalized analysis of each case.
The advantages are that the day 5 embryos ensure higher implantation / decreased miscarriage rate, it is possible to analyze all 23 chromosomes inherited by the embryo from the parents and, furthermore, the result is known within 24 hours.
Thus, embryo transfer can be done the next morning, while pregnancy rates rise to 70%, as only healthy genetic embryos are transferred. The new method, of course, also has drawbacks, such as the additional financial cost of the procedure (biopsy and genetic analysis), and the fact that many embryos do not manage to reach the blastocyst stage. In this factor, however, the quality of the laboratory plays an important role. In recent years, the contribution of Assisting Nature researchers to the improvement of blastocyst culture conditions is great.

Eleni Katsiani
Biologist MSc, PhD