The infertility reason - immunity of
Infertility is a serious problem which many families face. Its reasons can be various. In this article it will be a question of one of most “mysterious“ connected with “behavior“ of immunity.
Existence of difficult metaphytes, including the person, is impossible without normal work of immune system. It protects us and from the microorganisms parasitizing in our body and from own cages which ceased to carry out the functions and began to breed uncontrolledly (such cages call “cancer“).
to provide performance of these tasks, in immune system special cages exist. They are capable to distinguish “strangers“ and to kill them. Also immunoglobulins (antibodies) participate in fight against infections. They are formed after contact of immune cages with a microorganism - a parasite and are strictly specific: for example, antibodies against the causative agent of chicken pox are capable to fight only against this activator, but not against the causative agent of measles, rubella, etc.
to destroy “strangers“, immune cages have to be able to distinguish them from ““. Distinctions in structure of anti-genes - special biological molecules which can cause the immune answer of cages in an organism are the cornerstone of such recognition. The most important for such recognition are anti-genes of a so-called main complex of a gistosovmestimost (compatibility of fabrics) which at the person are called leykotsitarny, or HLA.
Each person has the unique HLA set - anti-genes. All types of cages of an organism which are available for the baby at the time of the birth are considered “as“: immune cages normal do not react to them. Everything that from them differs, becomes “stranger“. So, “strangers“ are the bacteria and worms which got into an organism;“ the cages become strangers“ also if the virus or a bacterium with an intracellular cycle of development got into them (for example, a hlamidiya), or there was their malignant transformation.“ Their own spermatozoa, for women - the spermatozoa which got into a genital tract, and even the fruit developing in a maternal organism are strangers“ for men sometimes.
Why does that happen?to
Immunity on guards of reproductive healthto
Not all cages of an organism are available to the immune cages circulating in blood. Some are separated by special barriers: for example, brain neurons - gemato - entsefalichesky; the spermatogenesis cages providing formation of spermatozoa in testicles - gemato - testikulyarny (in the first case barriers exist between blood and tissue of a brain, in the second - between blood and fabric of a small egg). It is connected with the fact that in development some cages have proteinaceous structures (anti-genes) which were absent at the time of the birth and in the first days of life. For example, spermatozoa appear at boys in 11 - 13 years and contain the elements necessary for fertilization and earlier not contacting to immune cages. Therefore on them the immune answer can develop, that is antibodies will begin to be developed. That to avoid it, spermatozoa develop in special tubules - spermatogenny tubules which walls pass oxygen, hormones, nutrients, but do not allow to contact to the immune cages circulating in blood. On the developing spermatogenny cages and mature spermatozoa there are no HLA anti-genes - a complex. Besides, special cages of a small egg produce special substance - Fas - which causes fast death of the lymphocytes which got into small egg fabrics. The small egg cages producing male sex hormone testosterone also participate in decrease of the activity of immune reactions (it is known that androgens - male sex hormones, as well as other steroid hormones, are capable to weaken the immune answer).Pregnancy at first sight reminds
in the immunological plan the situation arising at transplantation of body as the fruit contains both mother`s anti-genes, and “others“ anti-genes of the father. However immunological recognition of an alien fruit at normally proceeding pregnancy usually does not lead to its rejection.
B than reasons of immunological privileges of a fruit?
In - the first, the embryo and 1 which is formed after introduction in a uterus trofoblast has no high-immunogene anti-genes of HLA on the surface. Besides, the surface of a germ is covered with the special layer protecting it from immune recognition.
In - the second, during pregnancy in an organism of the woman difficult reorganizations as a result of which the immune system begins to develop less than that cages which are capable to kill “others“ cages, including fruit cages happen. Many of these antibodies not only do not damage the developing germ, but even protect it, preventing recognition by cages - killers of fabrics of a fruit.
of the Cage of a placenta carry out function of “the universal card of identity“, allowing a cage of a fruit to be distinguished as not alien and to avoid attack of the special Tax Code - lymphocytes which kill the cages deprived of HLA. At the same time trofoblast and a liver of a fruit make the substances which are also oppressing activity immunno - active cages. As well as cages of a small egg, a cage of a placenta develop the factor leading to death of leukocytes. Cages of maternal part of a trofoblast produce the substance suppressing work of the cages killing alien. These and some other mechanisms provide suppression of immunological reactivity of a maternal organism in relation to the developing fruit. The system of antibacterial immunity (protection against bacteria) during pregnancy, on the contrary, is activated: the quantity of cages - devourers (granulocytes and monocytes) in mother`s blood increases, signs of their activation are observed. It provides reliable protection against microorganisms - parasites in the conditions of decrease of the activity of specific cellular immunity.
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of 1 Trofoblast - the part of a germ contacting to a uterus and providing a metabolism with a maternal organism.
Why immunological infertility arises?
Despite reliable protection of the developing gametes, sometimes situations when they are exposed to immune attack arise.
At men the sharp and stupid injuries of testicles which are followed by a rupture of seed tubules and capillaries are the most frequent reason of it. At the same time anti-genes get to blood and cause the immune answer. If the trauma was strong, inflammatory process in a small egg - orkhit - all body, at the same time functional fabric which provides development of spermatozoa usually takes, it is replaced on connecting fabric. If damage was not followed by pronounced painful feelings, then due to natural recovery processes integrity of a gematotestikulyarny barrier is restored and production of sperm continues. But specific antispermalny antibodies (ASAT) which began to be formed after a trauma continue to circulate in sperm and blood and break formation of spermatozoa. At the same time all spermatozoa formed both in injured, and in a healthy small egg are object of immune attack. In the presence of ASAT mobility of spermatozoa decreases, there is their agglutination (pasting among themselves), there is almost impossible a passing via the tservikalny channel to a uterus, akrosomalny reaction 2 is broken without what fertilization of an ovum even “in a test tube“ is impossible. Such situation received the name “autoimmune man`s infertility“. According to various data, from 5 to 40% of men from fruitless couples have ASAT; by results of our researches, more than at 20% of men autoimmune reactions against spermatozoa are the reason of infertility. At the same time some congenital features of a structure of genitals, for example the varikotsel 3 , several times increase risk of development of immune infertility and an orkhit after a subclinical trauma of a scrotum.
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of 2 Akrosomalnaya reaction - emission of special enzymes at contact of a spermatozoon with an ovum.
urogenital infections are Other reason of development of antispermalny immunity . It is considered to be that one of the reasons of formation of ASAT against infections is ability of many bacterial, virus and fungal organisms to be attached to a membrane of spermatozoa and to cause cross reactions (in this case antibodies are developed not only to causative agents of an infection, but also to spermatozoa). Among the most significant the hlamidiya should call, mycoplasmas, viruses of herpes and a papillomavirus. It is necessary to emphasize that not all antibodies which are developed against anti-genes of spermatozoa pose threat for their functioning. From more than 40 anti-genes of spermatozoa and seed plasma are a little bit connected with violation of the impregnating ability.
of ASAT in the slime produced in the channel of a neck of a uterus (tservikalny slime) at women meet several times more often (30 - 40%), than at men. The women capable have quantities of ASAT and to conception. Perhaps, they participate in elimination of defective spermatozoa. When ASAT at women becomes too much, these antibodies prevent fertilization. In half of cases development at the woman of own ASAT is reaction to hit in a genital tract of the sperm of the partner containing antibodies that does sperm of more immunogene. Except presence of man`s ASAT, antibodies against spermatozoa can be developed at women under the influence of various factors, for example in the presence of urogenital infections, at the increased maintenance of leukocytes in sperm of men with nonspecific bacterial prostatitis (a prostate gland inflammation), at the increased quantity of spermatozoa in sperm etc. But in case of existence of ASAT in sperm at the constant partner, especially the class IgA, antispermalny antibodies in uterus neck slime at women are developed practically always, and it sharply reduces probability of pregnancy.
Manifestation of action of female ASAT is inability of spermatozoa to get into uterus neck slime. It can be found at the special laboratory tests estimating interaction of spermatozoa with tservikalny slime.
numerous data on decrease in success of EKO and PE 4 when ASAT are available not only in tservikalny slime, but also in serum of blood of women Are available. According to some information, ASAT at women can also exert an adverse effect on early development of an embryo, implantation and the course of pregnancy. In the presence of antispermalny antibodies pregnancy not incubation is often observed.Long presence at a uterus of viruses and is conditional
- pathogenic microorganisms can also lead to immunological infertility. Such microbes are an obstacle for creation during the predymplantatsionny period of local oppression of immunity in a uterus. This oppression is necessary for formation of a barrier which protects a germ from the antibodies capable to attack it. Therefore the infection is considered as one of major factors of development of a habitual abortion: the women suffering from pregnancy not incubation in 60 - 75% of cases suffer from a chronic inflammation an endometriya (an inside layer of a uterus).
the Anti-phospholipidic syndrome (AFS) is also one of the reasons of a habitual abortion. Often the only manifestation of an anti-phospholipidic syndrome is pregnancy not incubation. Phospholipids are an important component of all biological membranes (walls of cages belong to biological membranes) therefore emergence of anti-phospholipidic antibodies can become the inflammation reason, cause fibrillation violations, insufficiency of blood circulation in a placenta, the thromboses of blood vessels, heart attacks (which are not supplied with blood sites) in a placenta are a consequence of what. AFS find in 27 - 31% of women with a habitual abortion. Believe that at women with AFS formation of blood clots in a placenta causes loss of a fruit in the main ambassador of 10 weeks of pregnancy. Frequency of AFS increases by 15% with each following abortion. Thus, AFS is not only the reason, but also complication of habitual not incubation of pregnancy.
At detection of autoimmune infertility and the reasons of not incubation of pregnancy detection matters autoantitet to hormones, that is antibodies to the hormones (HGCh hormone is most studied), and also antibodies against DNA.
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of 4 EKO and PE - extracorporal fertilization and transfer of an embryo, a method of fertilization of an ovum “in a test tube“ with the subsequent transfer of a germ in a uterus.
Manifestation of the immunological conflict of mother and a fruit is the hemolytic illness a fruit. It arises when on erythrocytes of a fruit there is a specific anti-gene received from the father and the called Rhesus factor - a factor, and at mother such protein is absent (a Rhesus factor - negative blood). As a result at the woman antibodies against fruit erythrocytes which lead to destruction of its erythrocytes can begin to be developed. As normal the fruit is rather effectively isolated from immune cells of mother, such reaction usually develops already before the childbirth or at the time of delivery, and the fruit does not manage to suffer. But these antibodies will constitute danger to the following a Rhesus factor - a positive fruit.
One more immunological complication is thrombocytopenia - damage under the influence of maternal antibodies of platelets of a fruit. Usually at the same time the fruit weight, content in blood of leukocytes and lymphocytes are reduced. It is established that in 3 of 4 cases thrombocytopenia is followed by existence of antibodies against fatherly HLA - fruit anti-genes.
All described syndromes are reflection of hyperimmune states, that is such states at which the system of immunity works too actively. But in recent years there were data that also lack of immunological recognition by mother of a fruit can be the reason of pathology of pregnancy. It was shown that the women close to the husband on HLA - anti-genes, for example relatives, often suffer from a habitual abortion. The researches HLA - anti-genes of mother and a fruit at not incubation of pregnancy showed that coinciding with mother on HLA - to anti-genes of the II class fruits are torn away most often. It turned out that development of “tolerance“ of immune system of mother to a fruit at pregnancy is a kind of the active immune answer assuming recognition and active processing of alien anti-genes at the initial stage. Trofoblast, distinguished by mother`s organism, causes not reaction of rejection, but reaction of the most immunological favored treatment.
Diagnostics and treatment
Diagnosis of immunological infertility has to be complex, and both spouses have to address experts - the andrologist and the gynecologist - surely.
to Men . The first and obligatory stage of inspection is complex research of sperm. Detection of ASAT any of laboratory methods (MAR - the test, 1 W - the test, IFA / ELISA, etc.) allows to establish existence of autoimmune reactions against spermatozoa. If ASAT are covered more than 50% of mobile spermatozoa, the diagnosis “man`s immune infertility“ is made. As it is frequent are the reason of development of antispermalny immunity Ouro - genital infections, it is necessary to be examined on hlamidiya, mycoplasmas, herpes and other activators. At the same time it is necessary to remember that detectability of these microorganisms at men even when using modern methods of diagnostics, such as, polimerazny chain reaction (a method of detection of microorganisms on their specific DNA and RNA), not 100%.
Treatment of man`s immune infertility is based on data on the established reasons of formation of this state and can include the surgeries directed to elimination of impassability of a semyavynosyashchy path and violations of blood circulation, purpose of various hormonal and non-hormonal medicines, application of methods of an otmyvka of sperm for removal of antibodies from a surface of spermatozoa with preservation of their function. It is necessary to be ready to the fact that treatment can be long. In the absence of effect of treatment within a year it can be recommended to EKO and PE with application of an injection of spermatozoa directly in an ovum (IKSI).
to Women . Often lead chronic inflammatory diseases and genital infections to development of immunological violations, quite often endometriosis is found in the woman (growth an endometriya - cages of an inside layer of a uterus in atypical places).by
To detection of ASAT at women apply the postkoitalny test (PKT), the test of interaction of spermatozoa with TsS “on glass“ (Kurtsrok`s test - Muller) and direct definition of ASAT. The habitual abortion defined as two and more clinically found losses of pregnancy on term till 20 weeks demands a kariotipirovaniye - definition of number and integrity of chromosomes in cages of a trofobrast: 60 - 70% of early spontaneous abortions are the cornerstone exile of genetically defective embryo; also definition of dynamics a beta - HGCh and progesterone is useful.
At inspection of patients with pregnancy not incubation without fail conduct a blood test on an autoantitel.by
Usually carry out definition of antibodies to phospholipids, to DNA and to factors of a thyroid gland. Important diagnostic value for recognition of immune forms of not incubation of pregnancy has definition of a genotype of spouses on HLA - anti-genes of the II class. Carrying out definition of HLA - DR and - DQ of anti-genes is desirable.
Methods of medical influences at immunological violations of reproductive function at women depend on nature of violations, extent of violations and the general condition of the patient. Usually treatment includes three stages:
- general immunocorrection and treatment of associated diseases;
- preparation for pregnancy;
- treatment during pregnancy.
Detection of ASAT in tservikalny slime demands regular application of condoms for an exception of hit of sperm in a genital tract and specifications of the reasons of immune reactions against spermatozoa: ASAT at the husband, an infection, hormonal violations, etc. Treatment includes measures of specific and nonspecific character, as an additional way of treatment the intrauterine insemination can be recommended by the husband`s sperm. At detection of significant quantities of ASAT in blood serum treatment can demand for a long time the period. To Insemination and EKO before normalization of quantity of ASAT in blood are not recommended.to
the General immunocorrection and treatment of associated diseases it is directed to elimination of the immunodeficiency revealed at inspection of the patient, treatment of inflammatory diseases of genitals and genital infections, elimination of an intestinal dysbiosis and a vagina, carrying out the all-strengthening treatment and psychological rehabilitation. At the same time it must be kept in mind that now, despite quite significant amount of the preparations possessing immunomodulatory properties, their application at treatment of pregnant women is sharply limited. Immunocytotherapy - introduction to the woman of lymphocytes of the husband or the donor is Still actively applied. The method can successfully be applied as at excess reactions of immune system of mother against a fruit, and at coincidence of a genotype of spouses on HLA.
the Most successful treatment of not incubation of pregnancy happens when immunological preparation for pregnancy begins at least a month before the protection termination. Concrete medical actions are defined by the gynecologist. Irrespective of initial violations, after pregnancy approach periodic research of indicators of a hemostasis and blood test on an autoantitel with carrying out adequate correction in case of detection of deviations is of great importance.
the Own experience and data of scientific literature demonstrate that the infertility and complications of pregnancy connected with violation of the regulating function of immune system are in most cases curable now.