WHAT IS PRE-IMPLANTATION GENETIC DIAGNOSIS (PGD)?

Recent developments in genetics allow genetic studies to be performed on embryos developed by in vitro fertilization methods. This method is called 'genetic diagnosis in embryo' or 'preimplantation genetic diagnosis'. These processes are carried out by removing 1 or more cells from the embryos that develop as a result of fertilization of egg cells with sperm cells in the laboratory.

By using special methods in the cells taken, the diagnosis of numerical and structural chromosomal disorders and single gene diseases (such as thalassemia, sickle cell anemia, cystic fibrosis) of the future babies that these embryos will develop can be made.

What is the purpose of PGD?

Individuals have the risk of transmitting the hereditary disease they carry to their children at different rates. For this reason, it is important to determine genetic diseases in couples and embryos in order to have healthy children. PGD ​​performed using different techniques can detect many hereditary diseases while they are still at the embryo level.

What are the indications for preimplantation genetic diagnosis?

In cases with genetic disease carriers;

• Chromosome Numerical disorders (Karyotype anomalies; Down Syndrome, Turner Syndrome, Klineferter Syndrome etc.)

• Structural anomalies (Reciprocal and Robertsonian Translocations)

• Single gene diseases (Thalassemia, cystic fibrosis and Duchenne Muscular Dystrophy etc.)

• X-linked diseases (linked to the sex chromosome)

In infertile patient groups;

• Repeated IVF attempts ( > 3)

• Advanced female age (> 37 years)

• Severe male factor

• Recurrent pregnancy losses ( > 3)

What are the advantages of preimplantation genetic diagnosis?

• "Healthy embryos" can be detected as a result of genetic screening performed on embryos before embryo transfer.

• It ensures that the embryo attaches to the endometrium and increases the chance of pregnancy.

• It reduces the risk of miscarriage by allowing the transfer of a chromosomally normal embryo.

• The family is protected from medical and psychological traumas due to termination of pregnancy.

• Tissue typing in hereditary diseases such as thalassemia, cystic fibrosis and DMD (Duchenne Muscular Dystrophy) provides treatment for the couple's previously born sick child.

• It is a much more useful and inexpensive diagnostic method when compared with the health problems that sick people face throughout their lives, the difficulties in the treatment of diseases and high treatment costs.

What are the diseases that can be detected by preimplantation genetic diagnosis?

Chromosomal diseases are divided into two main groups numerically and structurally. In couples with numerical chromosomal abnormalities such as Klinefelter (46,XXY) and Turner (45,X0) syndromes or structural chromosomal disorders such as translocation and inversion, specific PGD is applied during IVF to detect the chromosomal abnormality present at the embryo development stage. PGD ​​can be recommended for couples with normal chromosome analysis. In cases such as recurrent pregnancy losses and repeated unsuccessful IVF attempts, PGD panels are used to detect chromosomal disorders originating from reproductive cells, which allow the screening of chromosomes with the most common abnormality (13, 18, 21, X and Y). In recent years, PGS techniques have become preferred over PGD techniques in chromosomal scans, as they provide much more comprehensive and reliable results with the developing technology.

Single gene diseases are more difficult to identify at the embryo stage than chromosomal diseases. For PGD, blood is taken from the couples and the DNA change that causes the disease, called mutation, must be determined beforehand.
For this reason, a preparation stage, called the set-up stage, which usually lasts for 1-2 months, is required in order to be able to examine the embryo stage in the aforementioned patient groups. Single gene diseases nowadays; With methods such as DNA sequence analysis and fragment analysis, Mediterranean anemia (thalassemia), cystic fibrosis, spinal muscular atrophy (SMA), hemophilia, duchenne muscular dystrophy (DMD) etc. Many genetic diseases can be identified at the embryo level.
The set-up phase is completed after the aforementioned mutations are approved, the 'informative (information) markers' specific to the disease to be used in the PGD process in embryos are determined, produced and tested. The use of family-specific informative markers provides the control mechanism. Embryos determined to be healthy after the evaluation are transferred to the expectant mother.

WHAT IS PRE-IMPLANTATION GENETIC SCREENING (PGS)?

PGS techniques are a form of holistic screening used to determine whether an embryo has a normal number of chromosomes. This screening is limited to specific chromosomes only for PGD methods. Therefore, much higher success rates have been achieved with PGS techniques in chromosomal anomalies, both in terms of clinical pregnancy and increasing birth rates.

a-CGH (Comparative Chromosome Screening)
It is a current method that detects changes in the amount of DNA. While a limited number of chromosomes can be scanned with PGD (FISH method), which is a genetic screening method that has been used for a long time in IVF applications, 24 chromosomes can be scanned with the a-CGH method. This method is based on scanning the whole gene with Oligonucleotide \ BAC array.

With the a-CGH method, possible abnormalities in chromosomes can be detected due to duplications (increase), deletions (loss) and translocation (replacement) carriers on chromosomes. While it allows the detection of both maternal and paternal abnormalities, it also enables the screening of single gene diseases.

a-CGH advantages;
• Patients' repeated unsuccessful IVF attempts are prevented.
• Since this technique allows scanning of all chromosomes (22 XY), its reliability is higher than the FISH method.
• It is less risky in terms of monosomy and other complicated numerical chromosomal disorders (aneuploidy), and since more cells can be examined, it provides a healthier analysis opportunity compared to third-day embryo biopsy.
• The rate of mosaicism in the blastocyst is lower than that of the third day embryo, providing a more reliable analysis.

NGS (Next Generation Sequencing)

With this method, structural and numerical anomalies on chromosomes can be detected with a computerized system by comparing with a second DNA known to be normal after DNA amplification. The sequences of DNA fragments that have undergone various processes are read separately for each embryo and evaluated with a special algorithm.

The advantages of the NGS method over the a-CGH method are as follows;

• Since it is a direct analysis method, it is a technique that works with a higher sensitivity.

• While the detection rate of mosaic embryos with a-CGH is 5%, this rate is between 15-30% with NGS (12% mosaicism can be observed even in embryos reaching the blastocyst).

• 'Normal' embryos defined by NGS have a lower abortion rate than other PGS methods.

• Higher implantation (clinical pregnancy) rates are obtained compared to the a-CGH method.

As a result, with the use of the aforementioned genetic screening methods, selective embryo transfer is provided and pregnancy rates are significantly increased.
Finally, do not forget that the determination of which of these methods is right for you will be done by the IVF team.