PGD-PGS (Genetic Diagnosis - Genetic Screening)

What is Preimplantation Genetic Diagnosis (PGD)? Advances in genetic science in recent years have made it possible to perform genetic examinations on embryos developed through assisted reproductive techniques like IVF. This method is referred to as “genetic diagnosis of embryos” or “preimplantation genetic diagnosis (PGD)”. These procedures are conducted by obtaining one or more cells from embryos developed through the laboratory fertilization of egg cells with sperm cells.

Using specific methods on the collected cells, we can diagnose numerical and structural chromosome abnormalities and single-gene disorders (such as thalassemia, sickle cell anemia, cystic fibrosis) in the future babies that these embryos will develop into.

What is the Purpose of PGD (Genetic Diagnosis)?

Individuals may carry a hereditary disease and have varying degrees of risk of passing it on to their children. Therefore, determining genetic diseases in couples and embryos is essential for achieving a healthy child. PGD, performed using different techniques, enables the detection of numerous hereditary diseases at the embryo stage.

In cases of genetic disease carriers:
• Numerical Chromosome Abnormalities (Karyotype Anomalies; Down Syndrome, Turner Syndrome, Klinefelter Syndrome, etc.)
• Structural Anomalies (Reciprocal and Robertsonian Translocations)
• Single-Gene Disorders (Thalassemia, Cystic Fibrosis, Duchenne Muscular Dystrophy, etc.)
• X-Linked Disorders (Sex chromosome-related) PGD is recommended.

What are the Advantages of Preimplantation Genetic Diagnosis?

Through genetic screening of embryos before transfer, “healthy embryos” can be identified.
• It allows for the transfer of a chromosomally normal embryo, reducing the risk of miscarriage.
• It protects the family from medical and psychological traumas associated with pregnancy termination.
In cases of hereditary diseases like thalassemia, cystic fibrosis, and DMD (Duchenne Muscular Dystrophy), tissue typing offers the opportunity for treatment for a previously affected child.

What is Preimplantation Genetic Screening (PGS)?

PGS techniques are comprehensive screening methods used to determine whether an embryo has a normal number of chromosomes. This screening is limited to specific chromosomes in PGD methods. Consequently, in terms of chromosomal anomalies, both from a clinical pregnancy and birth rate perspective, PGS techniques have achieved significantly higher success rates.

a-CGH (Comparative Genomic Hybridization)

This is a contemporary method that detects changes in DNA quantity. While the genetic screening method PGD (FISH method) used in IVF applications can only screen a limited number of chromosomes, the a-CGH method can screen 24 chromosomes. This method is based on scanning the entire genome using Oligonucleotide BAC arrays.

The a-CGH method can detect abnormalities in chromosomes due to carrier status for duplications (increase), deletions (loss), and translocations (rearrangement). It allows for the detection of abnormalities in both the mother and the father, while also enabling screening for single-gene disorders.

Advantages of a-CGH:
• Prevents repeated unsuccessful IVF attempts in patients.
• Since this technique scans all chromosomes (22 XY), it is more reliable than the FISH method.
• It provides a healthier analysis opportunity compared to third-day embryo biopsy, as it is less risky for monosomies and other complex numerical chromosomal disorders (aneuploidy), and a larger number of cells can be examined.
• The mosaic rate in blastocysts is lower than in third-day embryos, making it a more reliable analysis.

Next-Generation Sequencing (NGS)

With this method, after DNA amplification, a comparison is made between the known normal DNA and a second DNA on the chromosomes to detect structural and numerical anomalies on the chromosomes using a computerized system. The sequences of the DNA fragments subjected to various processes are read separately for each embryo and evaluated with a special algorithm.

Advantages of NGS over the a-CGH method are as follows:

It operates with higher sensitivity due to being a direct analysis method.
• While the mosaic embryo detection rate is 5% with a-CGH, it ranges from 15% to 30% with NGS (even embryos reaching the blastocyst stage may exhibit 12% mosaicism).
• In embryos defined as ‘normal’ by NGS, the miscarriage (miscarriage) rate is lower compared to other PGS methods.
• Higher implantation (clinical pregnancy) rates are achieved compared to the a-CGH method.

PGS is mainly used for:
• Repeated IVF trials (> 3)
• Advanced maternal age (> 37 years)
• Severe male factor
• Patients with repeated pregnancy losses (> 3).

In conclusion, using the mentioned genetic screening methods allows for selective embryo transfer, significantly increasing pregnancy rates.