Preimplantation Genetics Diagnosis (PGD)

Preimplantation Genetics is the genetic testing of the embryos before they are implanted into the uterus during in Vitro Fertilization (IVF) process. 

Preimplantation Genetics Diagnosis and Screening (PGD/PGS) method is used in In Vitro Fertilization (IVF), to detect the genetic anomalies in the egg cell before the zygote is formed, or to detect genetic anomalies in the embryo after the zygote is formed. 

There are several methods in preimplantation genetic diagnosis and screening; 

Embryo Biopsy Methods

There are basically 3 biopsy methods, and these methods can be used alone or together to confirm the diagnosis.

Polar body diagnosis (PBD) : Polar body diagnosis (PBD) is a diagnostic method for the indirect genetic analysis of oocytes. Polar cells (bodies) are the by-products of egg cell  during the meiosis. There are two types of polar cells, primary and secondary polar cells. Today, there are very few PGT laboratories that routinely use this method. Besides the advantages of this method, it has more disadvantages, for example, it cannot detect aneuploidies of paternal and mitotic origin.

Blastomer biopsy: Blastomer Biopsy is a method applied to embryos that have reached the 6-8 cell stage approximately 72 hours after the fertilization. On the 3rd day of embryonic development, the procedure is performed by removing one of the cells called blastomere.

Blastocyst trophectoderm biopsy: It is another biopsy method which performed on the 5th day after the fertilization. It is the most preferred method in recent years, and it is superior to the other two methods in many ways. It has advantages such as the possibility of taking several cells at once and it is an easier biopsy technique.

Indications for PGD/PGS

Numerical Chromosomal Anomalies (Aneuploidies): There are many reasons for recurrent pregnancy losses and IVF failures, the most important of which is numerical chromosomal abnormalities. 

Structural Chromosomal Anomalies: Structural chromosomal anomalies are balanced translocations, insertions, inversions, deletions and duplications. Especially balanced translocations are important causes of recurrent pregnancy loss. The risk of having a miscarriage is approximately doubled. In 3-5% of couples with recurrent miscarriage, one partner has a balanced translocation.

Single Gene Disorders:  In parallel with the development of molecular genetics and biopsy techniques, there have been significant developments in PGD/PGS methods, especially in single gene diseases. Today, more than 4000 single gene diseases have been identified. If both parents are sick or carriers for autosomal recessive diseases, and one of them is sick for autosomal dominant diseases, PGD/PGS techniques is indicated. Today, PGD can be applied for all single gene disorders with known genes like; Thalassemia, SMA etc. 

HLA (Human Leukocyte Antigen): Many genes related to the immune system have been identified in humans. The most important factor in organ transplants is the presence of HLA compatible tissue or organ in the recipient and donor. PGD method is a diagnostic method when applied for single gene diseases or structural chromosomal abnormalities. However, when HLA compatible embryos are selected in addition to single gene disease, it appears as a treatment method. The most effective treatment method for many severe blood diseases such as beta thalassemia, fanconi aplastic anemia, sickle cell anemia and acute leukemias is allogeneic stem cell transplantation. The best results in treatments performed with this method are obtained as a result of transplantation from a completely HLA compatible sibling donor.

Testing Methods in PGD

There are many methods used for PGD, they are used alone or together for the same disease. The most commonly used methods are; 

• FISH
• Single Nucleotide Polymorphism (SNP)
• Short Tandem Repeats (STR)
• Microarray
• Sequence analysis
• Next Generation Sequencing

Today, many couples resort to assisted reproductive techniques to have children. Parallel to the spread of IVF centers and the developments in genetics, PGD procedure is both gaining importance and becoming widespread, especially with the latest developments in aCGH and new generation sequencing in the last few years.