PGS/PGD - Preimplementation genetic screening/diagnosis
The complete "human genetic code", i.e. information about all of his characteristics and signs, is stored in deoxyribonucleic acid (DNA). It is an enormous molecule, macromolecule, twisted into the shape of a double spiral, which together with proteins and other substances forms chromosomes. Individual segments of DNA represent specific genes; a set of genes is called the genome. In humans, the vast majority of genetic material determining inheritance is stored in the nuclei of cells. All cells in the body that have the nucleus contain identical nuclear DNA, i.e. identical genetic information.
A normal healthy individual has 46 chromosomes in the nuclei of all cells, except for reproductive cells. Of these 22 pairs, i.e. 44 chromosomes are called autosomes and 2 chromosomes represent sex chromosomes - gonosomes. While women have two XX sex chromosomes, men have X and Y sex chromosomes. This means that the physiological female karyotype is 46, XX and the physiological male karyotype is 46, XY.
Female chromosomes after analysis in the genetic laboratory: (46, XX).
Male chromosomes after analysis in the genetic laboratory: (46, XY).
Unlike somatic cells, sex cells only contain half the number of chromosomes. It means that there is only a half set, i.e. 23 chromosomes in mature sex cells. All normal mature female eggs carry 22 autosomes and one sex chromosome X, while mature male sperms, in addition to 22 autosomes, contain either an X chromosome or a Y chromosome. The sex of future child is therefore determined by genetic makeup of a sperm fertilizing an egg.
If an error occurs in the number or arrangement of chromosomes during the formation of sex cells or during their merging, the born individual may be is seriously disabled or may have a problem with subsequent reproduction.
Medical science offers many methods that are being constantly improved, minimizing the risk of birth of a disabled child (ultrasound diagnostics, biochemical and genetic analysis).
Benefits and procedure of preimplantation genetic screening
Preimplantation genetic screening and genetic diagnosis allow a shift in diagnosis to the earliest stage of embryo development (3-5 day old embryo). Although there are certain correlations between the dynamics of development, the morphology of embryos and the prognosis in terms of pregnancy, this type of assessment is not fully sufficient for some couples with increased genetic risk. Provided that more than one embryo is produced after the fertilization of oocytes by in vitro fertilisation method, then the embryos not carrying a particular genetic disorder can be selected by using this method. This increases a probability of pregnancy and birth of a healthy child. It simultaneously reduces the risk of miscarriage or the need to terminate the pregnancy for genetic reasons.
Part of examination is a biopsy of the embryo cells where some cells (blastomeres) are removed from the best developing embryo by using the micromanipulation technique. The number and place of their removal depends on the stage of development and required examination. In view of the fact that the cells of the embryo in its early stage of development are not yet specialised, this intervention does not pose a burden to the vital embryo and the embryo continues to develop normally.
After genetic analysis, only the embryos with a normal genetic test result (i.e. without a genetic disorder) are selected for transfer to the uterus. Thanks to this, the probability of pregnancy and subsequent safe delivery increases.
PGS method – for whom it is intended
This method is not specifically focused on a particular genetic disorder, but on pathological changes in chromosomal makeup during the fusion of egg and sperm and subsequent early embryo development. These errors are primarily accompanied by an abnormal number of chromosomes (e.g. the Down's syndrome). Using the PGS method either only particular, the most affected chromosomes, or all embryo chromosomes can be screened.
Upon consultation with a clinical geneticist, this method is particularly recommended for the following couples:
- the age of the female partner is over 35 years, and thus there is an increased probability that a child will be born with an abnormal number of chromosomes;
- there has been repeated failure of IVF treatment or recurrent miscarriage in the early stage of gravidity;
- 1 partner has undergone or is undergoing some form of chemo- or radiotherapy;
- the eggs were fertilized in IVF cycle with sperm of the male partner suffering from azoospermia in its non-obstructive form and the sperm was obtained by the MESA or TESE methods;
- the sex selection needs to be performed for medical reasons (the disease is determined by sex of the child)
PGD method – for whom it is intended
This method is focused directly on a specific diagnosis of genetic diseases that might be transmitted from parents.
Upon consultation with a clinical geneticist, this method is particularly recommended for couples where the parents were diagnosed with a genetic disorder.
Genetic testing techniques are constantly developing and getting more accurate and faster. The possibilities of testing and their accuracy may in some cases allow targeted genetic diagnosis and genetic screening within a single test.
Examples of PGD results
- The picture shows a PGD analysis carried out on 1 cell of a three-day embryo. The presence of chromosomes 13, 18, 21, X and Y is being monitored. These chromosomes most frequently occur as numerous abnormalities in children born with birth defects.
The X and Y sex chromosomes each occur in one copy here, while all other coloured signals indicating individual chromosomes 13, 18, and 21 are present in the cell in pairs. This is therefore a normal finding and a normal healthy boy may be born from this embryo.
- The picture shows the result of a PGD analysis of the cell of a three-day embryo. The X and Y sex chromosomes each occur in one copy here, the chromosomes 13 and 21 are present in pairs, but chromosome 18 occurs in three copies in the cell. There is one extra copy of this chromosome. This means that the male foetus would be born with a very serious handicap (the Edward’s syndrome).
What does/does not genetic testing allow
Preimplantation genetic analysis enables us to reveal a series of abnormalities in a number of chromosomes, preventing the embryo from proper developing. In the genetic makeup of the embryo we can also reveal some specific hereditary diseases or abnormalities in the structure of the chromosomes. Despite the fact that there is a continuous progress enabling us to detect more defects, we cannot fully guarantee the selection of the embryo that has no defects at all.
We are increasing the chances for the success of IVF programme by not transferring the embryos detected as defective in the performed tests. Without PGD we would not be able to gain this information and would often transfer the embryos that cannot give rise to a normal pregnancy. However, even the transfer of healthy embryos cannot automatically guarantee the success of IVF programme, i.e. the implantation of the embryo after transfer to the uterus and occurrence of pregnancy. Likewise, we cannot guarantee the birth of a healthy child. All this is affected by a great number of other factors.