The implementation of the Preimplantation Genetic Diagnosis (PGD) at Embryogenesis.
What is PGD
PGD or Preimplantation Genetic Diagnosis is a dynamically developing technique in the field of assisted reproduction and molecular biology and includes the genetic testing of embryos before their transfer into the uterus.
The genetic testing applies to the embryos of couples predisposed to child birth with a hereditary disease such as thalassemia and cystic fibrosis. In this case, the couple does not have fertility problems but they are subjected to a conventional IVF cycle in order to generically control the embryos and transfer only the healthy ones in the uterus of the mother. The main objective of the preimplantation genetic diagnosis is to give birth to a healthy child and to avoid the termination of abnormal pregnancies that can result from physical conceptions due to a history of hereditary diseases.
Specifically, the genes are part of our genetic material (DNA) and they give information about the structure and the functioning of all the features of our organization. We inherit from our parents the same amount of DNA, so the genes that control every feature found in our cells twice (one from each parent, egg and sperm). Humans possess about 25,000 genes. Specific changes in the continuity of a gene are called mutations and they can affect its normal functioning and turn it into "abnormal".
The mutations can occur in an individual de novo or they may be inherited from generation to generation. Some examples of diseases, the manifestation of which is the result of mutations in the action of a single gene (called monogenic), are the cystic fibrosis, sthe pinal muscular atrophy (SMA) and the fragile X syndrome. PGD can be used for the detection of the above diseases in embryos generated during an IVF cycle. Embryos found healthy after the control are transferred to the uterus of the mother aiming at pregnancy.
In order to realize a PGD, the equipment and the know-how of a molecular genetics laboratory are required. All PGD protocols for monogenic diseases are based on the polymerase chain reaction (PCR). The problems arising during this genetic examination is that the DNA controlled comes from a single cell and this can lead to a DNA amplification failure, or to a non-equivalent amplification of DNA from both alleles of the gene ( allelic drop-out, ADO) and / or to an infection by foreign DNA. All this can lead to either a diagnosis failure or to a misdiagnosis.
To avoid the above, the right planning for the disease before a PGD cycle is required, for which the limited DNA available for genetic diagnosis, the implementation failure for more than one PCR reaction and the particularities of the disease itself, such as the size of the gene responsible for the disease, the number and the location of the mutations in the gene should be taken into account. Also, a specific unique detector is designed for each couple in order to use it in the embryos for PGD.
For the detector design blood from their parents and other members (affected or not) of the family can be requested. Where feasible made and control of polymorphic microsatellite sequences or point changes that are close or within the gene are being controlled, so as to realize an indirect genetic diagnosis through linkage analysis. The analysis of more informative polymorphic areas in the gene increases the security of the PGD result, because it reduces the chance of misdiagnosis due to non equivalent amplification of the DNA of the two alleles of the gene (allelic drop-out, ADO).This technique increases the reliability of the PGD to 98-99%. Also, the introduction of wide application protocols for each disease is being facilitated, reducing the need to design protocols for individual incidents cases.
The design time of the protocols for the implementation of the PGD can last from two weeks to three months and the couple can not start an IVF cycle before its completion.
Which patients can use PGD
PGD is recommended to couples with a high risk of having a child with a monogenic disease. Some diseases are transmitted by autosomal domimant way and are inherited from parent suffering, while others are transmitted by autosomal recessive way, which means that they are inherited from both parents that do not suffer, but they are carriers of the disease. Other diseases are transmitted by X-linked manner and are inherited from either a carrier or a father or mother that suffers from the disease. Nevertheless, there are genetic diseases that are not caused by mutations in genes and can not be controlled through PGD. Couples with fertility and history of a genetic disease transfer can proceed with PGD which aims to prevent the transmission of serious diseases that create health problems for future generations.
At EMBRYOGENESIS we can carry out a PGD for all common and rare hereditary diseases with known genetic disorder as shown in panel:
Panel of the most common monogenic diseases
• Mediterranean diseases (beta-thalassemia)
• Cystic fibrosis
• Autosomal dominant Polycystic Kidney Disease
• Autosomal recessive Polycystic Kidney Disease
• Becker Muscular Dystrophy
• Marfan Syndrome
• Fabry Syndrome
• Familial adrenal hyperplasia (gene CYP21A2)
• Flesh-Marie-Touth, type 1A
• Duchenne Muscular Dystrophy
• Familial amyloid polyneuropathy
• fragile X syndrome
• Aimorrofilia A (F8)
• Aimorrofilia B (F9)
• Chorea of Hundigton's
• Multiple endocrine neoplasia type 2A
• Myotonic dystrophy type I (DMI)
• Type I neurofibromatosis (NF I)
• X-X-linked adrenoleukodystrophy
Which are the advantages of choosing EMBRYOGENESIS for carrying out a PGD?
• Detection of diseased embryos before transferring them into the uterus
• Personalized protocol design for each disease and for each couple
• Fast protocol design
• Treatment of almost all known genetic diseases
• Embryogenesis was the first IVF unit in Greece that implemented the preimplantation genetic diagnosis for the treatment of beta-thalassemia. Its experience in dealing with such diagnostic genetic tests counts 17 years now.
• Ability to tackle rare genetic diseases
• Treatment of each couple as a special case
Frequently asked questions
1. To impement a PGD for a monogenic disease is it necessary to detect the particular mutation involved in disease;
In most cases, the molecular analysis which reveals the mutation is necessary. Nevertheless, in some cases the clinical diagnosis as well as the family history may be sufficient.
2. Can the implementation of the preimplantation genetic diagnosis be combined with the chromosomal genetic testing of the embryos?
The aneuploidies are the numerical chromosome abnormalities in embryos and they are responsible for 60-70% of the first trimester miscarriages in humans. A typical and common aneuploidy of up to birth is Down syndrome. The probability of having embryos with aneuploidies increases exponentially with the age of the candidate mother. Thus, the goal of the aneuploidies control (PGS) is to prevent the first trimester miscarriage due to chromosomal abnormalities or even a potential termination of a chromosomally abnormal fetus following prenatal screening. Embryogenesis proposes a simultaneous control of chromosomes as well as of monogenic diseases in cases, in which the candidate mother is of advanced age and / or in cases of first trimester miscarriages. The control can be carried out on the same sample of the biopsy material without risk.
3.After the completion of the PGD protocol design, how soon an IVF cycle can be carried out?
Following the completion of the PGD protocol design, the couple can undertake an IVF cycle soon.
4. If a previous cycle with PGD has been done, do I have to wait for a new design before the next IVF attempt?
No new design and waiting are required in cases, in which a previous cycle with PGD has been carried out and the protocol has been tested. The couple can start a new IVF attempt whenever they wish to.