What is reproduction. Male infertility

The population of many developed countries is facing an acute problem of male and female infertility... 15% of married couples in our country have a violation reproductive function... Some statistics say that the percentage of such families is even higher. In 60% of cases, the reason for this is female infertility, and in 40% of cases - male.

Causes of violations of male reproductive function

Secretory (parenchymal) disorder, in which the production of spermatozoa is disrupted in the seminiferous tubules of the testicles, which manifests itself in aspermia (there are no spermatozoa cells in the ejaculate, as well as spermatozoa directly), azoospermia (there are no spermatozoa, but there are spermatogenesis cells), oligozoospermia (the structure and mobility of spermatozoa are changed).

1. Testicular dysfunctions.
2. Hormonal disturbance. Hypogonadotropic hypogonadism is a deficiency of pituitary hormones, namely luteinizing and follicle-stimulating hormones involved in the formation of sperm and testosterone.
3. Autoimmune disorder. Your own immune cells produce antibodies to sperm cells, thereby destroying them.

Excretory violation. Violation of patency (obstruction, obstruction) of the vas deferens, as a result of which the release of the constituent elements of sperm into the urethra through the genital tract is disrupted. It can be permanent or temporary, one- and two-sided. The semen contains sperm, a secret prostate and the secret of the seminal vesicles.

Mixed violation. Excretory-inflammatory or excretory-toxic. It occurs as a result of the mediated damage to the spermatogenic epithelium by toxins, a violation of metabolism and synthesis of sex hormones, as well as the direct damaging effect of bacterial toxins and pus on sperm, leading to a deterioration in its biochemical characteristics.

Other reasons:

• Sexy. Erectile dysfunction, ejaculation disorders.
• Psychological. Anejaculation (no sperm ejection).
• Neurological (consequence of damage spinal cord).

Causes of violations of female reproductive function

• Hormonal
• Testicular tumors (cystomas)
• The consequences of inflammatory processes in the small pelvis. These include the formation of adhesions, tubo-peritoneal factor, or, in other words, obstruction fallopian tubes.
• Endometriosis
• Tumors of the uterus (fibroids)

Treatment of female infertility

Based on the results of the tests, the doctor prescribes certain methods of infertility treatment. Usually the main forces are directed to correct diagnosis causes of infertility.

In the case of endocrine pathology, treatment consists in normalizing hormonal background, as well as in the use of drugs stimulating the ovaries.

In case of obstruction of the tubes, laporoscopy is included in the treatment.

Endometriosis is also treated with laparoscopy.

Defects in the development of the uterus are eliminated using the capabilities of reconstructive surgery.

The immunological cause of infertility is eliminated artificial insemination husband's sperm.

Fertility treatment is most difficult if the underlying cause cannot be identified. As a rule, in this version, IVF technologies are used - artificial insemination.

Male infertility treatment

If a man has infertility of a secretory nature, that is, having a connection with a violation of spermatogenesis, the beginning of treatment is to eliminate the causes. Are being treated infectious diseases are eliminated inflammatory processes, apply hormonal agents to normalize spermatogenesis.

If a man has diseases such as an inguinal hernia, cryptorchidism, varicocele and others, it is prescribed surgery... Surgical intervention is also indicated in cases where infertility in a man is due to obstruction of the vas deferens. The greatest difficulty is caused by the treatment of male infertility in the case of exposure to autoimmune factors, when sperm motility is impaired, antisperm bodies are affected. In this version, appoint hormonal drugs, use laser therapy, as well as plasmapheresis and more.

What could become more pleasant event, how happy marriage? Thinking logically, most come to an answer. The best thing is just the opportunity to become happy parents. Most often, every married couple sooner or later thinks about this important step like giving birth to a child. However, to our great regret, not everyone succeeds in implementing their plans on the first try, and for 15% of couples such efforts are doomed to failure. What could be the cause of this situation?

When faced with a similar problem, don't panic. If the desire to have a child did not come true within 2-7 months, this is not a problem. You need to calm down and not get hung up on this. There are many reasons for not getting pregnant: from simple psychological factor before serious problems develop.

Such problems include:

infertility of a man;

infertility of a woman;

immunological incompatibility (a woman is allergic to components of male sperm) - while none of the spouses suffers from pathologies that can provoke infertility, but such a couple cannot have common children;

psychological aspects.

However, if a completely healthy woman does not become pregnant with regular sexual intercourse without the use of contraception for a year, then it’s time to think about the fact that it might be a man. It is worth talking about this situation in more detail - what is it? How is it diagnosed? How to treat?

Male infertility- despite regular sexual intercourse, this is the inability of a man's sperm to fertilize female ovum... Ideally, in the spermogram of a healthy man, 1 ml of sperm should contain about 20 million sperm, which move rapidly forward and are capable of fertilization. Also, about 50% of the sperm must have the correct structure.

Causes

The reasons that can provoke infertility in men may be:

complication after mumps;

inflammation of the urogenital organs;

diabetes mellitus (ejaculation disorders);

a small number and sluggish activity of sperm in the semen (the complete absence of "tadpoles" is also not excluded);

psychological infertility (when a man, on a subconscious level, is subject to fear of future responsibility that will arise with the birth of a baby or in the presence of other obsessive fears and arguments);

immunological infertility (the formation of antibodies that prevent sperm from performing their normal functions).

Well, the simplest and most common reason that comes to mind last is the presence of bad habits. Smoking and alcohol abuse also have a detrimental effect on the body of a man in general and on reproductive function in particular.

Diagnostics

Male infertility is subdivided into:

primary - in which a man could not fertilize a single representative of the opposite sex;

secondary - when at least one woman becomes pregnant from a particular man.

A urologist-andrologist and an endocrinologist-andrologist will help identify this pathology in a man and determine the cause of this condition. The beginning of the research is the delivery of a semen analysis. Such an analysis is usually called a spermogram. It determines the activity and viability of sperm, in addition, an assessment of other pathological changes is carried out.

Also, doctors may advise other studies to determine exact reason or pathology:

Ultrasound of the prostate;

hormone analysis;

diagnosis of immune infertility - MAR test;

bacteriological culture to identify infectious pathologies of the genitourinary sphere.

Depending on the test results, the specialist will prescribe treatment. Therapy is divided into three methods, which will be discussed below.

Treatment methods

Conservative therapy

It consists in the use of drugs in the presence of genital infections of various origins... Also, a similar type of treatment is often prescribed in the presence of infertility against the background of hormonal disruption.

Surgery

Appointed in the presence of anomalies urethra, in the presence of inguinal hernia and other anatomical abnormalities that cannot be corrected without surgery.

Alternative therapy

TO this method resort in the presence of serious reproductive disorders in the stronger sex. It consists in the artificial introduction of sperm into the genital tract of a woman to achieve fertilization.

Fertility treatment should be comprehensive and adequate. In addition, the representatives of the stronger sex (not only when making a diagnosis, but also when planning a pregnancy) must reconsider their own rhythm of life and adjust it if necessary. It is worth giving up bad habits, starting to eat right and not forgetting about good rest. The solution to problems of an intimate nature in men can be achieved through the use of herbal remedies for the treatment and prevention of pathologies of the male reproductive system. Quite often, after the normalization of their own diet and rest and following simple rules reproductive function is normalized without additional intervention.

Comprehensive research that identifies leading genetic causes male infertility and choose the appropriate tactics for managing the patient.

The study included the most common genetic causes of male infertility: identification of deletions in the region of the locus AZF affecting spermatogenesis, determining the number of CAG repeats in a gene AR associated with changes in sensitivity to androgens and the search for mutations in the gene CFTR, which is responsible for the development of the disease, the clinical manifestation of which is obstructive azoospermia.

What biomaterial can be used for research?

Buccal (buccal) epithelium, venous blood.

How to properly prepare for the study?

No preparation required.

General information about the study

Male infertility (MB) is a serious pathological condition, requiring a comprehensive comprehensive diagnosis, urgent correction, and in some cases, prevention.

Infertility affects 15-20% of couples of reproductive age. In half of the cases, it is associated with the "male factor", manifested by deviations in the parameters of the ejaculate.

The complexity of MB diagnostics lies in the large number of reasons that cause it. These include anomalies genitourinary system, tumors, infections of the genitourinary tract, endocrine disorders, immunological factors, genetic mutations, etc. In contrast to the above reasons, genetic ones do not always have clinical manifestations, but are extremely important for the diagnosis of MB in the subject.

It is important to understand that the diagnosis of "MB" and its forms can be made only specialist doctor based on anamnestic data, examination data, results of instrumental and laboratory research... The reason for going to the doctor may be the following reasons:

• the impossibility of conceiving a child within a year, provided that there are no signs of female infertility in the partner;
• violations of erectile and ejaculatory functions;
• concomitant diseases of the urogenital sphere (inflammatory, tumor, autoimmune, congenital, etc.);
• taking hormonal and cytostatic drugs;
• discomfort in the urogenital area.

Frequent causes of male infertility are disorders in the structure and number of sperm, which affect their mobility and ability to fertilize.

The main genetic causes of MB development are:

1) deletion (removal of genetic fragments) of the locus AZF;

2) polymorphism (increased repeats of the genetic fragment - CAG) of the gene AR;

3)m mutation (discontinuity) of a gene CFTR .

Currently, these markers are an integral part of the standard criteria for complex diagnostics genetic manifestations of MB, occurring in a group of patients in 10-15% of cases.

Deletions of the AZF locus and the SRY gene

An important role in the development of pathologies such as oligozoospermia and azoospermia is played by deviations in a specific region of the Y chromosome - AZF- locus (azoospermia factor). Included in him determine the normal course of spermatogenesis, and in case of violation of the genetic structure AZF-locus, the formation of male germ cells can be seriously impaired.

AZF- the locus is in the long arm of the Y chromosome (q11). Genes located at this locus play an important role in the process of spermatogenesis.

Microdeletion of the Y chromosome is the loss of certain areas, is found on average in 10-15% of cases of azoospermia and in 5-10% of cases of severe oligozoospermia and causes impaired spermatogenesis and infertility in men.

Locus AZF divided into 3 sections: AZFa, AZFb and AZF c. In each of them, genes involved in the control of spermatogenesis have been identified. Deletions at the AZF locus can be complete, i.e. deleting one of the AZF-regions or more, and partial when they do not completely capture any of its three regions.

With full AZF-deletions, there is a fairly clear dependence of the degree of impairment of spermatogenesis on the size and location of deletions, which may have a prognostic value in obtaining spermatozoa suitable for in vitro fertilization programs.

• The absence of the entire locus AZF, as well as deletions covering the entire regions AZFa and / or AZFb indicate the impossibility of obtaining sperm.
• In almost all patients with deletions AZFb or AZFb + c note azoospermia due to severe disorders of spermatogenesis (syndrome "only Sertoli cells").
• With complete deletions of the region AZFc manifestations range from azoospermia to oligozoospermia. On average, 50-70% of patients with an entirely exciting deletion AZF c-region, it is possible to obtain spermatozoa suitable for artificial insemination.
• With partial AZF with deletions, manifestations range from azoospermia to normozoospermia.

Condition research AZF- locus of the Y chromosome in patients with azoospermia and severe oligozoospermia allows to establish the genetic cause of spermatogenesis disorders, to conduct differential diagnosis infertility in men and adjust treatment, check the possibility of obtaining sperm with testicular biopsy and the possibility of obtaining sperm for ICSI (intracytoplasmic sperm injection).

It should be borne in mind that in the case of successful use of assisted reproductive technologies, the deletion of the Y chromosome is transmitted through the male line. This shows the need dispensary observation for boys born after the use of ICSI in fathers with microdeletions in the Y chromosome to assess their fertile status.

Screening indications AZF-deletions are based on sperm count and include azoospermia and severe oligozoospermia (

In the genetic control of male development, the gene is especially important Sry(Sex-determining Region Y). It was in it that the largest number mutations associated with gonadal dysgenesis and / or sex reversal. In the absence of a chromosome section containing the gene Sry, the phenotype will be female with a male karyotype of 46XY.

This genetic study includes analysis AZF-locus chromosome - 13 clinically significant deletions: sY86, sY84, sY615, sY127, sY134, sY142, sY1197, sY254, sY255, sY1291, sY1125, sY1206, sY242, as well as determination of the gene deletion Sry.

AR androgen receptor gene

Another determining factor in male infertility is a violation of the hormonal regulation of spermatogenesis, in which the male sex hormones androgens play a key role. They interact with specific androgen receptors, determining the development of male sexual characteristics and activating spermatogenesis. Receptors are found in the cells of the testes, prostate, skin, cells nervous system and other fabrics. The androgen receptor gene is characterized by the presence of a sequence of CAG (cytosine-adenine-guanine) repeats, the number of which can vary significantly (from 8 to 25). The CAG triplet encodes the amino acid glutamine, and when the number of CAG repeats of nucleotides changes, the amount of the amino acid glutamine in the protein also changes. From the number of repetitions in a gene AR the sensitivity of the receptor to depends, and the relationship is inversely proportional: the more repeats, the less sensitive the receptor. An increase in the number of CAG repeats in receptors reduces their activity, they become less sensitive to testosterone, which can lead to impaired spermatogenesis, and the risk of developing oligozoospermia and azoospermia increases. There is also evidence that with a reduced number of CAG repeats (AR, there is an increased sensitivity to androgens and an increased risk in men. An increase in the number of CAG repeats to 38-62 leads to spinbulbar muscle atrophy, Kennedy type.

The test result makes it possible to assess the activity of spermatogenesis and take, if necessary, appropriate measures to compensate for the pathology.

Male infertility with cystic fibrosis

Luteinizing hormone (LH)

Follicle-stimulating hormone (FSH)

Prostate specific antigen total (PSA total)

Karyotype research

Important notes

Throughout life, these genetic markers do not change, the study is carried out once.

Literature

1. Naina Kumar and Amit Kant Singh Trends of male factor infertility, an important cause of infertility: A review of literature J Hum Reprod Sci. 2015 Oct-Dec; 8 (4): 191-196.

Violations and their causes in alphabetical order:

reproductive dysfunction -

Reproductive dysfunction(infertility) - the inability of a married couple to conceive during regular unprotected intercourse for 1 year (WHO).

In 75-80% of cases, pregnancy occurs during the first 3 months of regular sexual activity of young, healthy spouses, that is, when the husband's age is up to 30, and the wife's age is up to 20 years. In the older age group (30-35 years old) this period is increased to 1 year, and after 35 years - more than 1 year.

In about 35-40% of infertile couples, it is caused by a man, in 50% - by a woman, and in 15-20% there is a mixed factor of reproductive dysfunction.

What diseases there is a violation of reproductive function:

Causes of impaired reproductive function in men

I. Parenchymal (secretory) violation of reproductive function - violation of spermatogenesis (production of spermatozoa in the convoluted seminiferous tubules of the testicles), which manifests itself in the form of aspermia (absence of spermatogenesis cells and spermatozoa in the ejaculate), azoospermia (absence of spermatozoa in the ejaculate when spermatozoa cells are detected) , decreased motility, disturbances in the structure of spermatozoa:

1. Testicular dysfunction:
- cryptorchidism, monorchism and testicular hypoplasia
- orchitis (viral etiology)
- testicular torsion
- primary and secondary congenital hypogonadism
- elevated temperature- violation of thermoregulation in the scrotum (varicocele, hydrocele, tight clothing)
- Sertoli-cell-only syndrome
- diabetes
- excessive physical stress, psychological stress, severe chronic diseases, vibration, overheating of the body (work in hot workshops, abuse of the sauna, fever), hypoxia, physical inactivity
- endogenous and exogenous toxic substances (nicotine, alcohol, drugs, chemotherapy, occupational health)
- radiation therapy
- mutations: mutation of the muscoviscidosis gene (congenital absence of the vas deferens - obstructive azoospermia, determined by the polymerase chain reaction method; microdeletion of the Y chromosome (disorders of spermatogenesis of various degrees of severity of karyotype disorders - structural chromosomal aberrations - chromosomal aberrations - Klinefelter's syndrome, autosomal translocation) fluorescent hybridization (FISH) method using fluorochrome-labeled probes to different chromosomes

2. Hormonal (endocrine) impairment of reproductive function - hypogonadotropic hypogonadism - deficiency of luteinizing (LH) and follicle-stimulating (FSH) hormones of the pituitary gland, which play a role in the formation of testosterone and sperm:
- Pathology of the hypothalamus region
o Isolated gonadotropin deficiency (Kalman syndrome)
o Isolated luteinizing hormone deficiency ("fertile eunuch")
o Isolated FSH deficiency
o Congenital hypogonadotropic syndrome
- Pathology of the pituitary gland
o Pituitary insufficiency (tumors, infiltrative processes, operations, radiation)
o Hyperprolactinemia
o Hemochromatosis
o Influence of exogenous hormones (excess of estrogens and androgens, excess of glucocorticoids, hyper- and hypothyroidism)

3.autoimmune processes - destruction of sperm by own immune cells, production of antibodies to sperm
o parotitis- "pig"
o testicular injury
o cryptorchidism (undescended testes)
o operations on the organs of the scrotum
o passive homosexuals

II. Obstructive (excretory) violation of reproductive function is associated, as a rule, with bilateral, temporary or permanent impairment of patency (obstruction, obstruction) of the vas deferens and impaired output of the constituent elements of sperm (sperm, prostate secretion, secretion of seminal vesicles) through the genital tract into the urethra :
- congenital underdevelopment or absence of the vas deferens, violation of its patency, lack of communication between the tubule of the epididymis of the vas deferens and the ejaculatory duct
- cysts of the Müllerian ducts of the prostate
- inflammatory process in the genitals, complicated by obliteration of the vas deferens - chronic epididymitis, deferentitis, spermatocele
retrograde ejaculation - aspermatism (absence of ejaculate during intercourse) with congenital or cicatricial changes in the urethra at the level of the seminal tubercle, stricture of its membranous part of the urethra, damage to the nerve centers that regulate ejaculation.
- genital trauma, including during surgical interventions(for example, with hernia repair),
- the consequences of vasoresection

III. Mixed impairment of reproductive function (excretory-toxic, or excretory-inflammatory) is the result of indirect toxic damage to the spermatogenic epithelium, impaired synthesis and metabolism of sex hormones and the direct damaging effect of pus and bacterial toxins on sperm; biochemical characteristics of sperm:
- vulnerability of spermatozoa to the immune system due to impaired maturation, enveloping with protection from proteins in the ovarian epididymis (epididymitis)
- changes in the composition of the secretion of the prostate gland, seminal vesicles (prostatitis, vesiculitis), STIs
- other inflammatory diseases male reproductive system (urethritis)

IV. Other causes of reproductive disorders
- sexual problems - erectile dysfunction, ejaculation disorders
- anejaculation, aspermia - psychological, neurological (spinal cord injury)

V. Idiopathic reproductive disorder
The cause cannot be determined.

Causes of reproductive dysfunction in women
- inflammatory processes and their consequences ( adhesive process in the small pelvis and obstruction of the fallopian tubes - "tubo-peritoneal factor)
- endometriosis
- hormonal disorders
- tumors of the uterus (fibroids)
- ovarian tumors (cystomas)

Which doctor should i contact if there is a violation of reproductive function:

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If you have previously performed any research, be sure to take their results for a consultation with your doctor. If the research has not been performed, we will do everything necessary in our clinic or with our colleagues in other clinics.

Is your reproductive function impaired? You need to be very careful about your overall health. People don't pay enough attention symptoms of diseases and do not realize that these diseases can be life-threatening. There are many diseases that at first do not manifest themselves in our body, but in the end it turns out that, unfortunately, it is too late to treat them. Each disease has its own specific signs, characteristic external manifestations - the so-called disease symptoms... Identifying symptoms is the first step in diagnosing diseases in general. To do this, you just need to several times a year. be examined by a doctor, in order not only to prevent a terrible disease, but also to maintain a healthy mind in the body and the body as a whole.

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Infertility existed for thousands of years ago and will occur in the future. The leading researcher of the laboratory of genetics of reproductive disorders of the Federal State Budgetary Scientific Institution "Medical Genetic Research Center", doctor medical sciences Vyacheslav Borisovich Chernykh.

Vyacheslav Borisovich, what are the main causes of reproductive disorders?

- There are a lot of reasons and factors for reproductive dysfunctions. These can be genetically determined disorders (various chromosomal and gene mutations), negative environmental factors, as well as their combination - multifactorial (multifactorial) pathology. Many cases of infertility and miscarriage are caused by a combination of various genetic and non-genetic (environmental) factors. But most severe forms violations reproductive system associated with genetic factors.

With the development of civilization and the deterioration of the environment, the reproductive health person. In addition to genetic reasons, many different non-genetic factors can affect fertility (the ability to have their own offspring): past infections, tumors, injuries, operations, radiation, intoxication, hormonal and autoimmune disorders, smoking, alcohol, drugs, stress, etc. mental disorders, wrong lifestyle, occupational hazards and others.

Various infections, primarily sexually transmitted infections, can lead to decreased fertility or infertility, fetal malformations and / or miscarriage. Complications from infection (eg, orchitis and epididymitis orchitis with mumps in boys) and treatment drugs(antibiotics, chemotherapy) in a child, and even in a fetus during his intrauterine development(when taking medication by the mother during pregnancy) can lead to impaired gametogenesis and cause reproductive problems that he will face as an adult.

Over the past decades, the indicators of the quality of seminal fluid in men have changed significantly, therefore, the standards for its analysis - spermograms, have been revised several times. If in the middle of the last century the concentration of 100-60-40 million sperm in one milliliter was considered the norm, at the end of the twentieth century - 20 million, but now the lower limit of the norm "went down" to 15 million in 1 milliliter, with a volume of at least 1.5 ml and the total not less than 39 million. Indicators of motility and morphology of spermatozoa were also revised. Now they account for at least 32% of progressively motile and at least 4% of normal sperm.

But, be that as it may, sterility existed thousands and millions of years ago, and will occur in the future. And they register it not only in the human world, but also in different living things, including infertility or miscarriage may be associated with genetic disorders that block or reduce the ability to bear children.

What are these violations?

There are many genetic disorders reproduction, which can affect different levels of the hereditary apparatus - genome (chromosomal, gene and epigenetic). They can negatively affect different stages development or function of the reproductive system, stages of the reproductive process.

Some of the genetic disorders are associated with anomalies in the formation of sex and malformations of the genital organs. For example, when a girl does not form or develop any organs of the reproductive system in utero, she may be born with underdevelopment or even with the absence of ovaries or uterus and fallopian tubes. The boy may have defects associated with anomalies of the male genital organs, for example, underdevelopment of one or both testicles, epididymis or vas deferens, cryptorchidism, hypospadias. In especially severe cases, there are violations of the formation of sex, to the point that at the birth of a child it is even impossible to determine its gender. In general, malformations of the reproductive system are in third place among all congenital anomalies - after malformations of the cardiovascular and nervous systems.

Another group of genetic disorders does not affect the formation of genital organs, but leads to a delay in puberty and / or to a violation of gametogenesis (the process of formation of germ cells), hormonal regulation of the functioning of the hypothalamic-pituitary-gonadal axis. This is often observed with damage to the brain, with dysfunction of the gonads (hypogonadism) or other organs endocrine system, and can ultimately lead to infertility. Chromosomal and gene mutations can affect only gametogenesis - completely or partially disrupt the production of a sufficient number and quality of germ cells, their ability to participate in fertilization and the development of a normal embryo / fetus.

Genetic disorders are often the cause or factors of miscarriage. In general, most pregnancy losses occur due to newly emerged chromosomal mutations that are formed during the division of immature germ cells. The fact is that "heavy" chromosomal mutations (for example, tetraploidy, triploidy, monosomy and most trisomy by autosomes) are incompatible with the continued development of the embryo and fetus, so in such situations, most conceptions do not end with childbirth.

How many married couples have this problem?

In general, 15-18% of married couples face the problem of infertility, and every seventh (about 15%) of clinically recorded pregnancies ends in miscarriage. Most pregnancies are terminated spontaneously at the most early dates... Often this happens so early that the woman did not even know that she had a pregnancy - these are the so-called preclinical losses (unrecorded pregnancies). About two thirds of all pregnancies are lost in the first trimester - up to 12 weeks. There are biological reasons for this: the amount chromosomal mutations in abortive material is about 50-60%, the highest in anembryonic disease. In the first days - weeks, this percentage is even higher - it reaches 70%, and mosaicism in the set of chromosomes occurs in 30-50% of embryos. Not very connected with this high efficiency(approximately 30-40%) pregnancy in IVF / ICSI programs without preimplantation genetic diagnosis (PGD).

Who is more often the carrier of the “defective” gene - a man or a woman? And how to understand how genetically "compatible" spouses are?

- "Male" and "female" factors of infertility occur with approximately the same frequency. Moreover, a third of infertile married couples have reproductive system disorders on the part of both spouses. They are all, of course, very different. Some genetic disorders are more common in women, while others are more common or predominantly in men. There are also couples with severe or severe disorders of the reproductive system of one of the partners, as well as a decrease in fertility in both spouses, while they have a reduced ability to conceive and / or an increased risk of carrying a pregnancy. When changing partners (when meeting a partner with a normal or high reproductive potential) pregnancy may occur. Accordingly, all this gives rise to idle fictions about the "incompatibility of spouses." But as such, there is no genetic incompatibility in any married couples. In nature, there are barriers to interspecific crossing - in different types there is a different set of chromosomes. But all people belong to the same species - Homo sapiens.

How then can a couple be sure that they are not infertile and, most importantly, can have healthy offspring?

It is impossible to say in advance for sure whether or not a given couple will have childbirth problems. For this, it is necessary to carry out comprehensive survey... And even after that, it is impossible to guarantee the success of the onset of pregnancy. This is due to the fact that the ability of fertility (to have viable offspring) is a very complex phenotypic trait.

It is assumed that the reproductive system of a person, his ability to have children is influenced by at least every 10th gene - about 2-3 thousand genes in total. In addition to mutations in the human genome, there is a large number (millions) of DNA variants (polymorphisms), the combination of which forms the basis of a genetic predisposition to a particular disease. The combination of different genetic variants that affect the ability to have offspring is enormous. Many genetic causes of infertility do not have clinical manifestations from the reproductive system. Many genetically determined disorders of the reproductive system clinically look the same when completely different reasons, including with various chromosomal and gene mutations, many so-called non-syndromic disorders do not have specific clinical picture, according to which a specific genetic effect could be assumed. All this greatly complicates the search for genetic disorders and the diagnosis of hereditary diseases. Unfortunately, there is a huge gap between the knowledge of human genetics and their practical use in medicine. In addition, in Russia there is a significant shortage of geneticists, cytogeneticists and other specialists qualified in medical genetics.

Nevertheless, with many hereditary diseases and reproductive disorders, including those associated with genetic factors, it is possible to have healthy children. But, of course, it is necessary to plan treatment and prevention in such a way as to minimize the risks of hereditary diseases and malformations in offspring.

Ideally, any married couple before planning a pregnancy should undergo a comprehensive, including medical and genetic examination and counseling. A geneticist will study the history, pedigree and, if necessary, conduct specific tests to identify genetic diseases / disorders or their carriage. Clinical examination, cytogenetic study, chromosome analysis are carried out. If necessary, they are supplemented by a more detailed molecular genetic or molecular cytogenetic study, that is, the study of the genome for some specific gene mutations or microstructural rearrangements of chromosomes. At the same time, genetic diagnostics is exploratory, confirming, but cannot completely exclude the presence of a genetic factor. It can be aimed at finding mutations, and if found, then this is a great success. But if mutations were not found, this does not mean that they are not.

If the diagnosis of genetic disorders itself is so difficult, then what can we say about treatment?

- Genetic changes by themselves, indeed, cannot be corrected. At least to date, gene therapy has been developed for only a small number of hereditary diseases, and these diseases are predominantly unrelated to the reproductive system. But this does not mean that influencing reproduction genetic diseases do not respond to treatment. The fact is that the treatment can be different. If we talk about eliminating the cause of the disease, then so far this is really impossible. But there is still another level of treatment - the fight against the mechanisms of the development of the disease. For example, in diseases associated with impaired production of gonadotropic or sex hormones, replacement therapy or hormone-stimulating therapy is effective. But with a defect in the receptor for the hormone (for example, for the male - androgens), treatment may be ineffective.

Many problems of childbirth can be successfully solved with the help of assisted reproductive technologies (ART), among which IVF methods - in vitro fertilization - occupy a special place. IVF gives a chance to have their own offspring for many married couples with severe forms of infertility and recurrent miscarriage, including those caused by genetic reasons.

With the help of methods of assisted reproduction, it became possible to overcome infertility, even with such severe violations of fertility in men as azoospermia, oligozoospermia and severe astheno- / teratozoospermia, with obstruction or absence of fallopian tubes, pronounced disorders of egg maturation in women. In the absence or defectiveness of one's own gametes (mature germ cells), it is possible to achieve conception and give birth to a child using donor germ cells, and if it is impossible to bear it, by resorting to a surrogacy program.

Additional methods of selection of germ cells make it possible to use better quality male germ cells for fertilization. And preimplantation genetic diagnosis (PGD) of embryos, which is aimed at identifying chromosomal and gene mutations, helps to give birth to genetically healthy offspring that do not have those mutations that the parents carried.

Assisted reproductive technologies can also help couples with an increased risk of miscarriage or having a baby with an imbalanced karyotype and severe malformations. In such cases, an IVF procedure with pre-implantation genetic diagnosis is performed, in which embryos with a normal set of chromosomes that do not have mutations are selected. New methods of assisted reproduction are also emerging. For example, for women with poor quality oocytes (female reproductive cells during their growth in the ovary), oocyte reconstruction technology is used, in which donor cells are used, from which nuclei have been removed. The nuclei of the recipients are inserted into these cells, after which they are fertilized with the husband's sperm.

Are there any disadvantages to assisted reproductive technologies?

- Yes, it can negatively affect the demographic picture in the future. Among couples who have problems with childbirth and go to IVF, the frequency of genetic changes, especially those related to reproductive system disorders, is increased. Including those that are not diagnosed and can be passed on to future generations. This means that future generations will increasingly carry the burden of gene mutations and polymorphisms associated with infertility and miscarriage. To reduce the likelihood of this, it is necessary to carry out a widespread medical and genetic examination and counseling of married couples with childbirth problems, including before IVF, as well as the development and widespread use of prenatal (preimplantation and prenatal) diagnostics.