PGD and PGS

dish and syringesIntroduction to PGS and PGD

Clinics around the world offer a range of genetic testing options that can be very helpful in having a successful IVF treatment with the end result of a new born healthy child without a genetic disease and sometimes it is used for sex selection. The array of terms concerning the preimplantation genetic diagnosis and other embryo genetic tests however can be a wide and confusing subject. What are the differences between PGD, GGS, CCS? With this guide the genetic testing will have no secrets before you.

Preimplantation Genetic Testing

Preimplantation genetic testing is a broad concept of the genetic testing on embryos.
This is a procedure that involves removing one or more of the nuclei from the eggs or embryos in order to test the gene sequence or aneuploidy for mutations before they will be transferred into the uterus.

PGD – Preimplantation Genetic Diagnosis

The most common of the genetic testing terms is the Preimplantation genetic diagnosis (PGD). It is the most widely used as the whole broad concept that refers to any of the embryo genetic testing kinds.
PGD was developed in the end of the 1980s to be the alternative for couples which were at risk of passing genetic diseases on their offspring. Using this testing and IVF the couple is able to conceive using the embryos that were tested for genetic disorders before they are transferred into the uterus for implantation. This was and still is a great alternative to the prenatal diagnosis of the genetic disorder and a possible termination of the fetus.
Currently the term PGD is used for describing the testing for a particular genetic disease. Patients who have a high risk for transmitting a single-gene defect to their offspring are offered to do this specific test to avoid for example such diseases like haemophilia, cystic fibrosis or Tay-Sachs disease.
To put it simply those single gene disorders are genetic conditions which occur in the affected person’s DNA – because of the alteration or mutation of the specific gene in it. According to the Practice Committee of the Society for Assisted Reproductive Technology (SART) and the Practice Committee of the American Society for Reproductive Medicine (ASRM) this term is put in use if one or both of the parents carry the mutated gene or a balanced chromosomal rearrangement, then testing is being performed to determine whether this particular mutation or the unbalanced chromosomal complement was transmitted to the oocyte or embryo.

PGS – Preimplantation Genetic Screening

The newer term used to describe the embryo screening process to check if the number of chromosomes is correct and to check the chromosomes for structural abnormalities is the Preimplantation Genetic Screening (PGS) (also called aneuploidy screening). According to the SART and ASRM this term is used if it is known or presumed that the genetic parents are chromosomally normal and they are screened for aneuploidy.

It is said that women over 35, also women which had failed IVF procedures in the past or recurrent miscarriages have a higher success rate for IVF if they use PGS.
In the older technique of PGS, fluorescence in situ hybridization (FISH) was used (a method used to detect and localize the presence or absence specific DNA sequences on chromosomes) which was only able to analyse from 5 to 10 pairs of chromosomes out of the 23 pairs in a single cell. More current methods like single nucleotide polymorphism (SNP) or comparative genomic hybridization (CGH) allow to analyse all 23 pairs of chromosomes.

CCS – Comprehensive Chromosomal Screening

The term Comprehensive Chromosomal Screening (CCS) is used to describe a type of PGS – aneuploidy screening. 23 pairs of human chromosomes in a single cell can be evaluated with this method by using the quantitative polymerase chain reaction (qPCR), Single Nucleotide Polymorphism (SNP) or Comparative genomic hybridization (CGH).
Using CCS you can retrieve from 5 to 10 cells from a 5 or 6 day embryo. While waiting for the end result the embryo is frozen. Afterwards the embryo is thawed and transferred in a separate cycle. Followed by the day 5 embryo biopsy which has better accuracy and it significantly lowers the chances for potential damage which a biopsy could cause to the embryo which by then has couple hundreds of cells.
Conducting the biopsy on a 5 day embryo gives the advantage over the 3 day embryo because it already has not a single cell but a few more cells which gives you more material to work with. In theory the 5 day embryo might be more resistant to the test than a 3 day embryo.

PGD METHODS

There are several methods of genetic analysis that are used to perform PGD. Those methods are FISH, PCR, CGH, SNP and also P-STR and the most recent method Karyomapping.

FISH – Fluorescent In Situ Hybridization

This method is used to determine the sex for X-linked diseases (recessive inheritance), abnormalities in the chromosomes and aneuploidy screening. The downside to this method is that it allows to accurately estimate only 10 to 12 chromosomes pairs in each biopsied cell out of the whole 23 pairs of chromosomes.
So in the end the chromosomes are only partly screened for disorders. Furthermore in this method the chromosomes do not undergo screening for translocations and inversions which makes it a less effective test.

PCR – Polymerase Chain Reaction

This method is sometimes referred to as DNA amplification. In most of the cases it is used to diagnose a single gene defect which includes the dominant and recessive disorders.

CGH – Comparative Genomic Hybridization

The CGH method is more effective than FISH because it allows the examination of all 23 chromosomes an in this way provides a significantly more detailed view of the whole length of the chromosome. It is able to detect imbalances in the segments of the chromosomes.
There is also a new technique in the field of CGH called array CGH or microarray CGH. This is an enhanced CGH test which can provide the results for all chromosomes in just 24 hours.

SNP – Single Nucleotide Polymorphism Analysis

This testing technique also provides you with the ability to examine all 23 pairs of chromosomes. Furthermore it allows you to register and copy all the number changes, translocations and inversions in the entire length of the chromosome.

P-STR – polymorphic short tandem repeats

The STR method is a simple alternative to FISH used to detect unbalanced chromosomal states in preimplantation embryos. It helps in discriminating between the normal and the unbalanced chromosome states in each of the embryos.

Next generation sequencing

NGS method allows to sequence whole genomes, zoom into target regions and utilize RNA sequencing. It also allows to analysing the genome-wide methylation. It does a full chromosome screening and translocations and for monogenic diseases.

Karyomapping

It is the newest method in PGD testing. The father, mother and another relative which is carries or is affected with the disorder give their blood samples. What Karyomapping does is that it examines the chromosomes of the mother, father and the relative from 300.000 different points. This way it is searching for the characteristic features of the defective chromosome. Eventually the karyomapping finds the “mark” which is unique for the specific chromosome that carries the gene with the defect. Afterwards it is possible to check the embryos for the presence of the “mark” and any embryo carrying it means it has inherited the chromosome that carries the gene with the defect. If the mark isn’t detected it means that the embryo is free of the genetic disorder and that it is a proper embryo to be transferred to the uterus.
Karyomapping’s advantage is that waiting time before the treatment is just a couple of weeks and with other methods it can be sometimes even months because they have to be prepared individually for each patient. Karyomapping is a universal test for PGD that can find almost all gene defects.

If this amount of PGD and PGS methods and all the different tests give you a headache and you don’t know which one to choose ask about it at your clinic.

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