Women who go to IVF do not always have a good idea of the main stages of this technique. And when the doctor asks if the patients would like to make preimplantation diagnostics, the questions become even more. Some refuse, having learned that PGD leads to an increase in the cost of the protocol, others simply do not know for what purpose such a genetic study is prescribed and whether it is necessary at all. In this article we will tell you what PGD in IVF is and what it can tell you.
PGD - what is it?
From the moment of the fusion of a woman's egg cell with a man's sperm, everything has been predetermined at the genetic level - the hair color of the unborn child and its height, intellectual abilities and gender, as well as possible genetic anomalies and diseases that the child inherited from parents, grandparents or other relatives ...
Preimplantation diagnostics is a complex of genomic studies that allows you to identify in an embryo that is only a few days old, various developmental abnormalities, diseases, syndromes and other troubles. PGD is able to identify about 150 hereditary genetic ailments, among which are quite common - Down syndrome, Turner, and quite rare - cystic fibrosis, hemophilia, butterfly wing syndrome, etc.
With the help of special techniques and high-precision equipment, diseased embryos are identified and screened out. For transplantation into the uterine cavity, women use only high-quality, healthy and viable embryos.
Standard IVF does not include the mandatory stage of preimplantation diagnosis. After fertilization and cultivation of the embryos for several days, only the growth rate, cleavage rate, and embryo viability are assessed. After that, they are transferred to the woman's uterine cavity. Which of them will take root and whether they will take root at all is a big question. The efficiency of standard IVF is about 35%.
If pre-implantation diagnostics is carried out, then future parents may not worry about the baby's health, even if they themselves have certain genetic problems. In addition, the effectiveness of IVF with PGD is slightly higher - about 40-45%. This is due to the fact that a large embryo, even when implanted into the uterus, has very little chance of development and survival. A healthy and examined embryo is more likely to successfully establish itself and begin to grow and develop.
The purpose of the survey
PGD is highly recommended for parents who have genetic diseases that can be inherited by a baby. Also, such a preliminary genetic examination of embryos will not hurt if there were hereditary ailments in the ranks of close relatives of future parents.
Diagnostics before implantation is important and necessary for couples in which one of the parents is a carrier of the disease linked to the sex chromosome. For example, a woman carries the hemophilia gene, but the child will be sick only if it is a male baby. PGD in this case determines the sex of embryos that are only a few days old, and doctors select for replanting only those embryos that are not threatened by hemophilia, that is, girls.
For a woman with a negative Rh factor and several pregnancies in the past (it does not matter how they ended), PGD is recommended if the husband's sperm with a positive Rh factor was used for in vitro fertilization. In this case, doctors will select from all the resulting embryos only those who have inherited the maternal Rh identity. In this case, pregnancy after IVF will proceed with lower risks, and the baby will not be threatened by a dangerous hemolytic disease.
PGD is recommended for a couple in the event that a woman has had two or more miscarriages before, if there have been cases of miscarriage, and also if any of the spouses in their first marriage or have already had a child with chromosomal abnormalities together, or genetic pathologies. Diagnosis before transfer allows excluding those who are sick or have abnormalities of non-genetic origin from the number of embryos considered for transplantation.
Preimplantation diagnostics in the second or third IVF protocol allows to establish with high accuracy the reasons for unsuccessful previous attempts.
And a completely non-standard, but, alas, a real situation - parents go to IVF in order to give birth to a baby who can become a donor, for example, of bone marrow, for their own older brother or sister. In this case, relying on natural conception is too risky. The born child may not be suitable as a donor for a sick relative.
Preimplantation diagnostics will help to select individuals from the resulting embryos with a certain combination of genetic information that guarantees genomic matching between children. This study is called HLA typing.
What does the survey show?
Preimplantation genetic diagnostics allows you to identify in advance various diseases and conditions in which a child may be unviable or disabled. It all depends on what recommendations the geneticist gives. If necessary, embryos are examined only for certain criteria and gene mutations; in general, it is possible to assess all the parameters determined by research.
So, PGD with an accuracy of 97-99% determines blindness and deafness, congenital deafness, retinoblastoma, Fanconi anemia, neurofibromatosis, phenylketonuria, myopathy, torsion dystonia, Duchenne muscular dystrophy and several dozen dangerous and incurable diseases and syndromes.
Also, PGD determines the karyotype of the embryo, its blood group and Rh factor, gender, the presence of mutations at the gene level, unusual for parents and manifested for the first time.
Who is appointed?
Because pre-implantation diagnostics in itself is not cheap. Not every woman who dares to undergo in vitro fertilization is recommended this additional stage. It is offered to everyone, but there are categories of patients for whom it is highly undesirable to abandon the preliminary genetic assessment of embryos before transfer to the uterus.
These patients include:
- "Age" women and couples. With age, the sex cells of men and women age and lose health. Under the influence of drugs, bad habits, unfavorable ecology and just past years, their DNA set can mutate. Therefore, “older” women and men have higher risks of fetal chromosomal abnormalities. PGD is strongly recommended for women over 35 years old, as well as for couples in whom a man is over 40 years old.
- Rh negative womenwho had abortions, miscarriages, childbirth, children with hemolytic disease were born. Diagnostics is relevant only if the spouse has a positive blood Rh factor. If donor sperm is used, then the biomaterial of a man with a negative Rh factor is initially selected, then the probability of obtaining Rh-positive embryos is zero.
- Women who already have 1-2 unsuccessful IVF attempts in the absence of objective reasons (the protocols were carried out correctly and without complications, there are no endometriosis and other obstacles to implantation).
- If the sperm of a man with low quality indicators of spermogram is used for fertilization (teratozoospermia, azoospermia, asthenozoospermia). With natural conception, low quality sperm die, have no chance of fertilization, with IVF they may well fertilize the egg, because natural selection is disturbed, which can lead to the development of various pathologies in the fetus.
Types of diagnostics
There are several types of genetic diagnosis of embryos. They differ in terms of research, technical nuances, equipment and research methods. Let's list the main ones, without going into laboratory and genetic details:
- FISH Is a fluorescent hybridization method. This is a fairly standard study, the cost of which is low compared to other methods of preimplantation diagnosis. But its accuracy is somewhat lower than that of other methods. This method is widely used in clinics in Russia, Ukraine and Belarus. Foreign clinics practically abandoned it due to the fact that more accurate studies appeared. The plus is that the research is fast - within a few hours. The downside is that many chromosomes are not even examined.
- CGH - a method of comparative genomic hybridization. A very expensive way. Moreover, both financially and temporarily. But the list of defined pathologies is larger than that of the above-described method, and the accuracy is immeasurably higher. Among other things, this method of diagnosis before replanting allows you to determine which embryos have a higher chance of implantation.
- PCR - method of polymerase chain reaction. Identifies the Rh-belonging of the embryo, its blood group, as well as a fairly large list of genetic problems. The study requires a mandatory preliminary examination of biological parents for genetic mutations. If a woman is implanted with a donor embryo or donor oocytes were taken for fertilization, the PCR method cannot be used.
- NGS - sequencing method. This is a modern way of conducting pre-implantation diagnostics, which combines the best from all of the above. It gives the most complete picture of the health of embryos, however, and its cost is higher than that of other methods.
How is the research going?
In order for embryologists and geneticists to have the opportunity to do PGD, a sufficient number of eggs must be obtained through preliminary hormonal stimulation. If it is less than 3-4, then preimplantation diagnosis is usually not performed. After the doctors "organize" the meeting of the eggs with the purified sperm, the development of the embryos is monitored for 2-5 days. Then the embryologist can select the most viable ones. On the fifth day, blastocysts already have about 200 cells. It becomes possible to take about 5-7 cells from each embryo for genetic research without prejudice to the embryo.
For the collection of cells, modern high-precision lasers are used, a biopsy of cell membranes is performed, and other methods are used. The examination of the DNA strand provides comprehensive information about whether the embryo is healthy. Then it is recommended for transfer.
The embryo transfer itself, if the couple consents to preliminary genetic diagnosis of the embryos, may be postponed. If, with the standard IVF protocol, it is carried out on the 2nd, 3rd or 5th day from the moment of fertilization, then the results of PGD can be expected from several hours to 5-6 days. Thus, the IVF cycle is extended by at least a week. The cost of the protocol may increase in the case of consent to the preliminary diagnosis of embryos by 40-240 thousand rubles.
It all depends on how many embryos are planned to be examined, which method from the above will be examined.
To reduce costs, a couple can use the means of a quota, diagnostics is included in the list of services that can be provided under compulsory medical insurance, but each clinic should clarify this issue separately. Some do PGD at the expense of the budget, others do not.
Possible complications
As already mentioned, material for the study of genetics is obtained by a biopsy method. Despite the state-of-the-art precision equipment, the possibility of injury to the fetus during this procedure remains. Most often, "three days" are subject to injury. It should be noted that the probability of injury is quite low - about 3%, and the benefit from the study will be much greater. Otherwise, the complications with such IVF can be the same as with IVF in the standard protocol.
Any of the stages of in vitro fertilization can be associated with certain risks, and this cannot be avoided. It is important that all risks are low.
The couple needs to be well aware that even modern and accurate devices, with which doctors of the highest qualification category work, do not guarantee 100% that the baby will be healthy. So, with extensive mosaicism, biological errors can occur, and a sick embryo can be implanted in a woman. There is such a probability, but it is very small - no more than 0.05%.
Reviews
According to official information from the World Health Organization, IVF with PGD increases the success rate of the protocol by about 7-10% relative to the base 35%. However, there are not so many positive reviews in the Russian segment of the Internet about preimplantation diagnostics.
Some women note that the survival rate of embryos from which cells were taken for analysis is somewhat worse, and therefore there are quite a few reviews about unsuccessful IVF protocols with preliminary genetic diagnosis of the fetus. Medicine does not confirm this popular opinion, and official statistics do not indicate a reduced percentage of successful implantation after examination of the embryos.
Often women ask the question whether it is possible to do PGD in order to choose the gender of the baby, because besides the fact that you really want children, you also want either a son or a daughter. There is a technical ability to determine the sex, but no doctor will weed out the embryos of the "unnecessary" sex, unless there is a specific indication of the geneticist (for diseases linked to the sex chromosome). Discrimination of embryos on the basis of gender is prohibited by law in Russia.
According to reviews, the diagnostic process itself, which can last several days, gives a woman a lot of worries, because she does not know until the last how many high-quality embryos have turned out and whether they have turned out at all. In addition, she needs to maintain the state of the endometrium in the desired form - take prescribed medications, donate blood for progesterone, do several ultrasounds to determine the thickness of the functional layer of the uterus. It is important that the transfer is as successful as possible and the ovum can be implanted.
It happens that while the diagnostics are in progress, the "good" time for the transfer passes. In this case, the protocol can be interrupted, and the embryos that have passed the test are frozen and sent to the cryobank. They will be transferred in the next protocol.
For the intricacies of preimplantation genetic diagnostics, see the next video.
