When will the child's health stop depending on the genetic roulette?

Legacy Life

Natalia Kirillova, "Results" No. 32-2013

Hereditary diseases and related family dramas are usually talked about sparingly. The exception that only confirms this rule is Angelina Jolie's recent admission that she received a defective BRCA1 gene from her mother, and with it a predisposition to breast cancer. The press noisily discussed the difficult choice of an actress who had made a preventive operation for herself. However, in the future, such sacrifices may not be required – thanks to the development of personalized medicine.

Mark Kurtzer, a well-known obstetrician-gynecologist, professor, corresponding member of the Russian Academy of Medical Sciences, chairman of the Board of Directors of the Mother and Child Group of companies, told the Results about whether it is possible to give birth to a healthy child despite the family fate.

– Mark Arkadyevich, what do you say to those in whose family there are hereditary diseases? Is there a chance to give birth to a healthy baby?

– The current decade has become a key one in the development of various genetic research methods. Devices and technologies are being improved. For example, noninvasive genetic diagnostics has been used in the USA since 2011. It is possible to take blood from a vein in the first trimester of pregnancy, extract fetal DNA from it and, based on this, determine during pregnancy whether the child will be a carrier of a chromosomal pathology or mutation. It is absolutely safe for the mother and fetus.

– Suppose the analysis showed a genetic anomaly. Do I need to terminate my pregnancy?

– There are cases when it is possible to cope with the problem. For example, we can identify the genes of congenital phenylketonuria and prescribe treatment from the first days of a child's life to reduce his risk of an early heart attack. It is possible to recognize the development of other genetically determined diseases. Every year their list grows.

– And if the hereditary disease is incurable?

– Today it is possible to carry out a genetic analysis of the embryo even before pregnancy. We were one of the first in Russia, since 2007, to conduct preimplantation genetic diagnostics, or PGD – preimplantation genetic diagnosis. What is it? A married couple is taken into the IVF cycle. A woman is stimulated to ovulate in order to take several eggs from her at once. They are fertilized with her husband's sperm. The resulting embryos are cultured. Then they take the material for genetic diagnosis. Previously, this was done on the third day of embryo development, when it consists of six, seven or eight blastomeres. Its shell is dissected, one cell is taken away, diagnostics is carried out during the day. On the fifth day, we have several embryos and the result of genetic testing. As a result of a complex analysis, it is possible to determine not only a chromosomal anomaly, but also genomic rearrangements. Next, a healthy embryo is transferred to the uterine cavity on the fifth day. Now technology has gone a little further. The current trend is to do a biopsy not on the third day of embryo development, but on the fifth. In this case, the embryo is at the most advanced stage. There are more cells in it – already about a hundred, you can take a little more material for research. Now we are rebuilding our programs for such work. But these are details. The main thing is that we can look at the genetic abnormalities in the embryo even before it enters the uterine cavity. Preimplantation diagnostics always serves as an addition to the IVF cycle and is done only for medical reasons. That is, if we suspect that the embryo may be a carrier of monogenic diseases or chromosomal abnormalities.

– What diseases can be prevented in this way today?

– Recessive hereditary diseases are the greatest danger. Imagine a situation: there are two healthy people. They are fine, but they are both carriers of the mutant gene. If a child receives two copies of this gene from them at once, then he will get sick. Thus, cystic fibrosis, spinal amyotrophy, Huntington's chorea, phenylketonuria and other diseases can be transmitted. As a rule, both parents are healthy and do not know that they are carriers of a dangerous mutation. Most often they come to us after having already given birth to a sick child. And in the future, this risk will not disappear anywhere. There are two paths in front of them. You can do a chorion biopsy during pregnancy, and then decide whether to give birth or not. Agree, this is not acceptable for everyone. It is possible to go a more modern way – to do preimplantation genetic diagnostics in order to select a healthy embryo. For example, we were the first clinic in Russia where, after preimplantation diagnosis, a healthy child was born in a family with cystic fibrosis.

– Does this mean that the born child will not then pass on the hereditary disease to his children?

– The child will be a carrier of one copy of the recessive gene. That is, the disease will not leave the family at all. But he himself will be healthy. By the way, in the same way we can select a suitable embryo for a Rh-negative mother. After all, if she has a Rh-positive child, then there will be a Rh-conflict, fraught with many complications. Today, this situation can be avoided. Another problem: there is a child with leukemia, and he needs a bone marrow transplant. They begin to look for a donor compatible with the main histocompatibility complex. Sometimes parents give birth to his brother or sister, hoping that they will become donors – because in this case there is a high probability that they will be compatible with the patient. Most parents in this case do not turn to reproductologists: they hope for good luck. But in the IVF program, with the help of preimplantation diagnostics, it is possible to choose an embryo suitable for the main histocompatibility complex. Thus, we are able to grow an ideal donor.

Another area of application of preimplantation diagnostics is chromosomal abnormalities. There are chromosomal translocations when chromosomes exchange their sites: this also leads to a high frequency of offspring with anomalies. So far, we are practically the only ones dealing with this problem. It so happens that a couple of healthy people, who seem to have everything normal, can not deliver a single pregnancy. And it turns out that they form embryos with mutations, which is why constant miscarriages occur.

– That is, nature acts wisely, rejecting defective embryos and terminating pregnancy?

– It is true. But here we can simply increase the chances of the mother. After all, she only gets one egg every month. Only one embryo can be formed. And we get a dozen embryos at once and choose from them the one that nature will not reject. Another factor is the age of the mother. It is known that over the years the risk of having a child with an "extra" chromosome increases. With the help of preimplantation diagnostics, it is now possible to avoid the situation with Down syndrome. And you can go even further. Today we learned how to freeze eggs. This technique has been actively implemented in the world since 2005. We have been doing this in Russia since 2009. Previously, in IVF programs, we could only save embryos – they tolerated freezing well, but eggs did not survive this procedure. Now there are new approaches in this area. Today, a woman can freeze eggs at the age of 26 and thus get a chance to give birth to a healthy child later. By the way, this procedure is increasingly used by patients with cancer, freezing eggs before chemotherapy. Now we are working with the Federal Center for Pediatric Hematology, Oncology and Immunology – we are dealing with teenage girls there who will undergo bone marrow transplantation. However, unfortunately, patients often simply do not know that there is such a possibility.

– In the case of Angelina Jolie, there was a different situation. There is a spoiled dominant gene in the family that does its terrible job in every generation of women...

– Even in this case, parents have a 50 percent chance of getting healthy offspring, because the child may not inherit the mutation. But we are able to make this possibility almost one hundred percent by selecting an embryo that is not a carrier of an abnormal gene. We are developing these programs not only at our perinatal center. There are different approaches to diagnosis. There is a FISH method, there is a PCR (polymerase chain reaction) method. FISH – rougher: we know that anomalies can be at certain points. It is for these points that the so-called probes exist. This technique is widely used. The PCR method is more detailed. When we do a full study of the problem area, we can find a mutation that we didn't know about before. Now we are promoting this technique to the regions.

When people talk about IVF, many have the impression that this is a terrible method in which twins, triplets are born... In fact, the achievements of modern technology allow us to approach a woman more delicately and select a healthier embryo. It is not only the fact of pregnancy that is important to us. The most important thing is that a healthy full-term baby is born. All the achievements of modern technologies are aimed at making the approach to each person more accurate, more detailed. In fact, this is genetic engineering in human reproduction.

– Some people may reproach you with the fact that this is an improvement of human nature...

– Any medical initiative can be considered as an improvement of a person. All medicine is essentially a struggle with nature. On the one hand, we are really trying to do something better. But let's not overestimate our capabilities. Nature will take its course anyway. Of course, certain ethical regulators are needed in this area. There is a law in our country that defines the procedure for the use of assisted reproductive technologies. And it states that only sex selection is prohibited in Russia. In some countries, such norms are more stringent, in some less strict. Therefore, by the way, there is medical tourism in the field of IVF. I will tell the story of one of my patients. She is Italian and did IVF for the first time ten years ago in Italy. This is a Catholic country, and there are restrictions: only three eggs can be fertilized. Thirty eggs were taken from her, three were fertilized, the rest were thrown out. She didn't get pregnant. Then she decided to go to Sweden, where all the eggs can be fertilized. But there is socially oriented medicine. And she was transferred only one embryo, which, unfortunately, did not take root. She has visited both Eastern Europe and us. She never managed to give birth to a child. Nature said no, and there was nothing we could do.

– There are cases when the disease is transmitted only to girls or only to boys. For example, hemophilia...

– The law does not prohibit us from rejecting a male embryo in this case. After all, if a girl is born, she will not suffer from hemophilia. There are many other sexually transmitted anomalies. And we can inform the parents about it. But their choice should not be based solely on the desire to give birth to a boy or a girl.

– I remember those times when sex selection was not prohibited in our country. In the reception rooms of IVF laboratories, there were a lot of patients who came with a specific purpose: to give birth only to a boy, less often to a girl...

– This ban has been in place in Russia since 2012. Previously, such people came to us. I remember a woman came who had three sons. She dreamed of having a daughter. But no matter how many eggs we took from her, only male embryos turned out to be good, strong. Apparently, there were some qualities linked to the X-chromosome that did not allow her to give birth to a healthy girl. So all our efforts are futile if they go against nature. You can't fool her. But we are able to increase the chance of having a healthy baby. So, to give happiness to a particular family.

Portal "Eternal youth" http://vechnayamolodost.ru12.08.2013