The method of preimplantation genetic diagnosis is used to assess the health status of the embryo obtained by in vitro fertilization before implantation in the uterine cavity. The method allows not only to choose a healthy future baby, but also to increase the chance of pregnancy. The technique is widely used in all world clinics involved in in vitro fertilization.
General concepts
Preimplantation genetic diagnostics allows a comprehensive examination and to exclude the presence of chromosomal abnormalities as a whole or any one specific deviation. Recently, in parallel with early malformations, genes are screened that can provoke the emergence of tumors in adulthood (ovaries, intestines, breasts).
In the case of maternal genomic diseases, a biopsy of several polar egg cells is carried out before fertilization. The described methods are an alternative to early prenatal diagnosis, which allows to prevent pregnancy termination if the fetus suddenly has genetic pathologies.
Preimplantation genetic diagnosis allows you to determine the sex of the future baby already in the process of screening. This is used to prevent the development of anomalies linked to gender.
How genetic diseases are inherited
There are hereditary pathologies that have arisen in the dominant, recessive and x-linked type.
| Inheritance type | Features | The risk of having a sick child |
| Dominant | One of the partners has one defective gene that dominates its pair. | 50% inherit the gene |
| Recessive | Both partners are carriers of the same defective gene, but at the same time have a normal pair | 50% become a carrier, 25% get a disease |
| X-linked | Women are protected from pathology by their set of chromosomes and are exclusively carriers. Men are characterized by the development of anomalies | a man has the opportunity to inherit a gene and a disease - 50%, a woman has a 50% chance to become a carrier, like her mother |
Who should be screened?
Preimplantation genetic diagnosis (PGD) is performed in the following cases:
- The presence of hereditary diseases or changes in the karyotype in one or both of the couples. Often, partners themselves are aware of their problems, less often, they will find out during the screening process.
- Habitual miscarriage. The problem is not anomalies on the part of the parents (they may not exist at all), but genetic mutations of the fetus that cause miscarriages.
- The age of people undergoing IVF is more than 38 years.
- More than 3 unsuccessful attempts at in vitro fertilization.
- Male infertility
- The inclusion of ICSI (intracytoplasmic sperm injection) in the fertilization program. The process is fraught with the development of genetic abnormalities in the embryo.
- History of cystic drift .
PGD Features
Research in the field of preimplantation genetic diagnostics suggests that the method has the right to exist, helps to diagnose and prevent chromosomal abnormalities, however, it requires further improvement.
Features of PGD are as follows:
- the rate of miscarriage during screening is lower than without it;
- there is currently no evidence that the possibility of pregnancy is increasing;
- there is the possibility of a false result: the embryo is healthy, and the result shows deviations, the embryo is sick, and the study suggests the opposite (5-10% of cases).
Preimplantation genetic diagnostics (examination of blastomeres)
After agreeing on in vitro fertilization, the reproductologist assesses the need for PGD for the married couple. If there is evidence, partners can agree or refuse the procedure. Next, a document is signed confirming permission to conduct a survey.
On the third day after the fertilization of the embryo, the geneticist takes one of the formed blastomere cells for analysis. It is believed that this has no consequences for the fetus, since all cells are interchangeable.
The specialist conducts research in one of the previously selected areas: studying the cell structure under a special fluorescence microscope, DNA testing using the polymerase chain reaction method to determine the presence of a mutation.
Based on the result, embryos with abnormalities will not be used in the implantation process. Healthy and high quality are chosen. Further, one of them or several is transferred into the uterine cavity of the mother.
With a biopsy of the polar body, the mother's chromosome set is examined. It is carried out if the presence of a genetically determined pathology is revealed on the female line. The procedure allows you to determine whether the egg is healthy, which will be used for fertilization, without violating its structure. If anomalies are not detected, then it can be used for fertilization and transfer to the uterine cavity.
There are cases when polar bodies, and then blastomeres, are screened. This allows you to get a more reliable result. The scheme by which the examination will be carried out is chosen by a geneticist.
Methods used
Numerical and structural chromosome abnormalities are determined by fluorescence hybridization. This method allows you to refine the DNA sequence of the cell. Special DNA probes are used, which in their structure are complementary sites for blastomere DNA zones.
The probe contains a nucleotide and a fluorophore (a molecule capable of fluorescence). After the target DNA interacts with the DNA probe, illuminated areas are formed that are viewed under a fluorescence microscope.
Also use the PCR method (polymerase chain reaction). It consists in copying a portion of DNA using enzymes in certain laboratory conditions.
Diagnosis of aneuploidy
This is one of the methods of preimplantation genetic diagnostics, which allows to detect the presence of numerical chromosomal abnormalities (to determine extra or missing chromosomes).
Genetic material consists of 46 chromosomes, half of which is given by the father, and the second half by the mother. If the embryo receives an extra chromosome, this is called trisomy, and the loss of any is called monosomy. These defects can lead to consequences:
- lack of implantation of the embryo;
- spontaneous abortion;
- hereditary pathologies (Down syndrome, Klinefelter, Shereshevsky-Turner).
Male infertility and the age of a couple are frequent factors in the development of such anomalies.
PGD of monogenic pathologies
Preimplantation genetic diagnosis of embryos in order to determine the presence of monogenic diseases is carried out in families where the presence of hereditary abnormalities is established. If a couple already has a baby with a homogeneous disease, then the ability to give birth to another sick child increases several times.
The reason is a violation of the sequence of chromosomes in a certain section of DNA. Similar diseases include:
- cystic fibrosis;
- adrenogenital syndrome;
- phenylketonuria;
- hemophilia;
- sickle cell anemia;
- Wernig-Hoffman syndrome.
Advantages and risk of the method
Preimplantation genetic diagnosis, reviews of which are considered ambiguous, has certain advantages in the field of prenatal screening:
- only high-quality and healthy embryos are transferred to the uterus;
- the risk of having a baby with genetic abnormalities is reduced;
- the risk of miscarriage is halved;
- the risk of multiple pregnancy is halved;
- 10% increased chance of implantation of the embryo;
- the chance of a safe birth of a baby increases by 20%.
The risk of accidental damage to the embryo during PGD is 1%. The probability of an erroneous result is 1:10, in addition, there is a 3% chance that an embryo with any anomaly will be rated as healthy.
The likelihood that a healthy embryo will result in deviations is 1:10. The chance is 1: 5 that the transfer of embryos into the uterine cavity will be canceled due to abnormalities found in each of them.
Contraindications
Preimplantation genetic diagnostics (PGD), the consequences of which for the embryo are not exactly identified, has a number of contraindications for conducting:
- embryo fragmentation of more than 30% (the formation of fragments up to 25% is considered normal);
- the presence of multinucleated blastomeres in the embryo;
- the embryo has less than 6 blastomeres on the third day of its development.
Method Security
Diagnosis is carried out at an early stage in the creation of a future organism, when all its cells are pluripotent, that is, a full-fledged healthy organism can be formed from each one.
All ongoing stages of PGD do not apply time to the embryo, fetus and unborn baby. After the sample for research is received, it is prepared in a special way. Cells are placed on a glass slide on which they are fixed, or in a buffer solution.
Procedure cost
Preimplantation genetic diagnostics, the cost of which varies from 50 to 120 thousand rubles, at first glance, seems an expensive manipulation. However, the health and treatment of a child with genetically determined pathologies will cost much more.
The procedure gives all the advantages over women who were able to conceive a child in a natural way, since such a diagnostic method is not available to them. Preimplantation genetic diagnosis, the price of which is negligible compared to in vitro fertilization itself, serves only as an addition to the general program, which allows not only to bear and give birth, but also to raise a healthy baby.