History of miscarriage. Anatomical causes of miscarriage. Additional examination methods

Miscarriage- spontaneous termination of pregnancy up to 37 completed weeks, counting from the first day of the last menstruation. Miscarriage, ending in the death of the fetus at various stages of pregnancy, is a complex obstetric and gynecological problem and often has serious psychological consequences for the whole family. According to the WHO definition, miscarriage is considered "expulsion or removal from the mother's body of an embryo or fetus weighing 500 g or less", which approximately corresponds to a gestational age of 20-22 weeks and the fetus is still considered unviable.

The frequency of miscarriages is 15-20% of the total number of all clinically detected pregnancies. However, only according to clinical data, in the early stages of pregnancy, spontaneous miscarriage may not be diagnosed. Its frequency increases to 30-60% when highly sensitive methods such as determining the level of β-CHG in the blood serum are used to confirm pregnancy before the next menstruation. Most often, the diagnosis of "chemical" pregnancy by the level of β-CHG is established in the group of patients with infertility after ovulation stimulation with hormonal drugs.

From 40 to 80% of miscarriages occur in the first trimester of pregnancy, and almost every second woman does not even assume that she had a pregnancy. With an increase in the duration of pregnancy (in the II and III trimesters), the frequency of miscarriage decreases.

Miscarriage occurs more often in patients with bloody discharge from the genital tract from early pregnancy (12.4-13.6%) compared with patients without bloody discharge (4.2-6.1%). For women with idiopathic or "unexplained" miscarriage, the most dangerous in terms of termination of pregnancy are 6-8 weeks. It is during this period that 78% of miscarriages occur, and most of them occur before the onset of cardiac activity, that is, the embryo dies, not the embryo. At 8 weeks of gestation, in the presence of a fetal heartbeat, the probability of miscarriage is 2%, pregnancy persists in 98% of patients. At the same time, with a pregnancy of 10 weeks and a normal fetal heart rate, the miscarriage rate is only 0.6%, and the probability of maintaining a pregnancy is 99.4%.

The outcome of pregnancy depends on the age of the patient: if in a 20-year-old patient with a history of two miscarriages the probability of a favorable outcome of a subsequent pregnancy is 92%, then in a 45-year-old woman with a similar number of miscarriages it is 60%.

An increased risk of miscarriage has been described depending on the number of previous miscarriages. So, with one miscarriage, the threat of subsequent termination of pregnancy is 15%, with two - 25%, with three - 45% and with four - 54%. Similarly, the risk of developing secondary infertility increases, which in general for the group is about 35%.

In cases where a woman has three consecutive miscarriages in pregnancy up to 20 weeks, a diagnosis of habitual miscarriage is established. According to statistics, this pathology is 1 in 300 pregnancies. Termination of pregnancy and subsequent curettage of the uterus is the cause of the development of severe inflammatory diseases of the genitals, adhesions, pathology of the uterus and tubes, complex neuroendocrine disorders, recurrent miscarriage and infertility.

What causes miscarriage

Miscarriage, as a rule, is the result of not one, but several causes that act simultaneously or sequentially. In clinical practice, it can be difficult to establish a specific factor that led to spontaneous abortion, as this is prevented by tissue maceration after fetal death, which makes it difficult to chromosomal and morphological studies. A detailed analysis of the reasons that probably caused miscarriage, and the most accurate diagnosis, it seems possible to establish only during the examination after a spontaneous miscarriage. In most foreign clinics, examination and treatment for miscarriage begin only after three miscarriages. Domestic scientists believe that finding out the causes of miscarriage should begin after the first termination of pregnancy.

The main causes of miscarriage are:
- genetic factors;
- sexually transmitted infections (STIs);
- endocrine disorders;
- immune factors;
- congenital and acquired pathology of the uterus;
- other factors.

In almost 45-50% of women, it is not possible to establish the cause of spontaneous miscarriage, and they form the group of "unexplained" miscarriage.

Characteristics of the most significant risk factors

- Genetic disorders
Genetic disorders leading to spontaneous miscarriage have been studied quite well and account for about 5% in the structure of the causes of this pathology. From 40 to 60% of miscarriages occurring in the first trimester of pregnancy are due to abnormal chromosomes of the fetus. Early termination of pregnancy may be the result of natural selection, which leads to the death of a pathologically developing embryo and / or fetus.

Chromosomal pathology in recurrent miscarriage is more common and clinically more significant than in patients with a single miscarriage. The causes of spontaneous miscarriage and recurrent miscarriage may be identical, however, concomitant pathology of the reproductive system in couples with recurrent miscarriage is much more common than in women with a single miscarriage.

A special role in patients with spontaneous miscarriages is assigned to chromosomal aberrations.

Autosomal trisomy, as the most common type of chromosomal pathology, is responsible for more than half of pathological karyotypes. Autosomal trisomies are the result of the absence of chromosome segregation during the first mitotic division of the oocyte, and the frequency of this phenomenon increases with maternal age.

The age of the mother does not matter for other chromosomal abnormalities that cause spontaneous miscarriages.

Monosomy X causes embryonic aplasia. Triploidy and tetraploidy occur with moderate frequency. Structural pathology of chromosomes is a translocation transmitted by one of the parents. Other karyotype disorders include various forms of mosaicism, double trisomies, and other pathologies.

Sporadic spontaneous miscarriages during short term pregnancy are a reflection of the universal biological mechanism of natural selection, which ensures the birth of healthy offspring. More than 95% of mutations are eliminated in utero. Human chromosomal pathology depends not only on the intensity of the mutation process, but also on the efficiency of selection. With age, selection weakens and therefore developmental anomalies are more common.

Chromosomal abnormalities are detected only when determining the karyotype. It is not easy to establish the significance of defects in one gene in the development of spontaneous abortions, since not all medical institutions have the technical ability to detect this pathology. Sex-linked hereditary diseases can lead to spontaneous miscarriage only during pregnancy with a male fetus.

- Inflammatory diseases
The inflammatory genesis of miscarriage is due to the peculiarities of the penetration of microorganisms through the placenta to the fetus from maternal blood. The presence of microorganisms in the mother may be asymptomatic or accompanied by characteristic signs of an inflammatory disease. Often, the pathogen, passing through the placenta, causes the development of placentitis with certain histopathological changes. Thus, bacteria (gram-negative and gram-positive cocci, listeria, treponema and mycobacteria), protozoa (toxoplasma, plasmodia) and viruses can penetrate into the fetus.

The hematogenous and contact routes of infection, which prevail in the first trimester of pregnancy, subsequently give way to the upward spread of infections. An ascending infection from the lower reproductive organs infects the amniotic membranes, regardless of whether their integrity is broken or not. The fetus becomes infected with contaminated amniotic fluid or infectious agents that spread along the amniotic membranes and further along the umbilical cord to the fetus.

Some inflammatory diseases of the mother during pregnancy are characterized by special clinical manifestations or have more severe consequences. Acute infections, accompanied by severe intoxication and hyperthermia, can stimulate the activity of the uterus and thereby lead to termination of pregnancy. In most cases, it is difficult to establish a direct causal relationship between pregnancy termination and a specific pathogenic agent. If any microorganism can be isolated from the tissues of a deceased embryo/fetus, it is practically impossible to determine when the contamination occurred: before or after its death in the uterine cavity.

In general, it is possible that bacteria and viruses can enter the uterine cavity during pregnancy and cause spontaneous miscarriage, but only a few of them directly affect the fetus. More likely is infection of the fetus through the placenta, which leads to chorionamnionitis, the release of prostaglandins and increased uterine contractility.

There is a relationship between bacterial invasion and cytokine synthesis by amnion, chorion, decidual and fetal tissues. The multiplication of microorganisms in the amniotic fluid leads to an increase in the level of lipopolysaccharides, which activate the synthesis of cytokines: TNF, IL-1, -6, -8, etc. pregnancy.

One of the possible ways for infection to enter the embryo/fetus is chorion biopsy, amniocentesis, fetoscopy, cordocentesis, intrauterine blood transfusion, especially if these manipulations are performed transcervically.

In clinical practice, the differential diagnosis between the primary and secondary inflammatory process of the genitals is of great importance, which is carried out according to the data of a pathomorphological study after a spontaneous miscarriage has occurred. The diagnosis of primary inflammation is established in the absence of other pathological processes that can cause a violation of uterine pregnancy.

We can talk about combined inflammation in the case of the simultaneous presence of several etiological factors, the severity of which does not allow us to distinguish between the sequence of their pathogenic effects. Secondary inflammation is characterized by vascular-cellular reactions against the background of long-term manifestations of previous etiological factors.

The effect of infection on the fetus depends on the state of his body and gestational age. Given the absence of a formed placental barrier in the first trimester, any type of hematogenous and ascending infection is dangerous. At this time, the most common complications of pregnancy are intrauterine infection, pathology of fetal development and spontaneous miscarriage.

The severity of the lesion and the prevalence of the pathological process in the embryo / fetus depend on its ability to immune response, on the type, virulence and number of invading microorganisms, the duration of the mother's illness, the state of her protective and adaptive mechanisms and other factors.

A distinctive feature of the etiological structure of infectious diseases at present are various associations of microorganisms - viral-bacterial, viral-viral and bacterial-bacterial, which is due to the characteristics of the immune response, in which complete elimination of the pathogen from the body is impossible.

The foci of infection located in the vagina and cervix are most often the main source of the gravid inflammatory process that develops in the first trimester of pregnancy. The presence of nonspecific inflammatory diseases of the vagina and cervix (acute or chronic endocervicitis, structural and functional inferiority of the cervix) are one of the suggestive factors for a similar inflammatory process in the endometrium. This inflammatory process exacerbates the likelihood of infection of the fetal bladder and thus serves as an indirect cause of early termination of pregnancy.

The state of the vaginal microflora, as a risk factor, has not been given due attention for a long time, however, today there is no doubt that opportunistic bacteria prevail among the microbes penetrating the uterine cavity from the lower parts of the reproductive organs, and the imbalance of the vaginal environment is considered as the main cause of the complicated course of pregnancy and IUI of the fetus. The spectrum of pathogens includes numerous pathogens, such as group A streptococci, opportunistic anaerobes that are relatively common in the vagina.

The action of various infectious agents, as well as adverse factors of a different nature (any form of bleeding during pregnancy, the threat of spontaneous abortion, active sex life, etc.) lead to the loss of mechanisms for controlling the immune response and disturbances in the local immunity system, which is important in preventing various diseases. Violation of the microbiocenosis of the genital tract is accompanied by an imbalance in the local immune status, which is expressed in a decrease in the level of IgG and an increase in the amount of IgA.

Infectious processes in the vagina and cervix belong to a group of diseases, the consequences of which during pregnancy can be largely prevented by screening for infections, timely detection of imbalances of various types of microorganisms and appropriate treatment.

The most common violation of the vaginal microflora, the frequency of which in pregnant women is 10-20%, is dysbiosis, characterized by a sharp decrease in the representatives of the obligate microflora and its replacement with a mixed flora consisting of anaerobic opportunistic bacteria (Bacteroides spp., Mobiluncusspp., Peptostreptococcus spp. and etc.). The quantitative and qualitative composition of the microflora of the vagina and cervix is ​​changing both by increasing the intensity of colonization of microorganisms and by increasing the frequency of their isolation.

Immunological deficiency weakens the compensatory-protective mechanisms of the body as a whole, which largely determines the individual characteristics of the course and outcome of the disease. Thus, a vicious circle is created: activation of the opportunistic vaginal flora and prolonged exposure to an infectious agent contribute to the development of immune disorders, which in turn further aggravate dysbiotic disorders in the vagina, maintaining the inflammatory process and significantly increasing the risk of IUI.

For the correct diagnosis of vaginal dysbiosis, along with the clinical signs of the disease, an important role belongs to laboratory research methods and, above all, microbiological examination of not only the luminal, but also the parietal microflora of the vagina, which helps to avoid errors.

Smear studies help to orient in a possible pathology and determine the need, sequence and scope of additional studies (PCR, ELISA, etc.)

Therapeutic measures in the first trimester of pregnancy are limited due to the danger of using certain medications during embryogenesis. Nevertheless, with severe dysbiotic disorders of the vagina, complicated pregnancy (threatened abortion, incipient abortion, etc.), as well as structural and functional inferiority of the cervix, the use of interferon correctors and inducers is recommended: KIP-feron (vaginal suppositories) 1 suppository 2 times per day for 10 days; viferon (vaginal suppositories) 1 suppository 1 time per day for 10 days. At a high risk of infection, intravenous drip of human immunoglobulin at a dose of 25 ml every other day 3 times and / or octagons of 2.5 mg intravenously every 2 days 2-3 times is indicated.

The drugs of choice for dysbiotic disorders of the vagina in the second trimester are vaginal suppositories and vaginal tablets (terzhinan, betadine, klion-D, flagyl, etc.). At the second stage of treatment, the normal microbiocenosis of the vagina is restored with biological products (acylac, lactobacterin), as well as the activation of local immunity factors using immunomodulators (vaginal or rectal suppositories viferon, KIP-feron, etc.).

Treatment of candidiasis is carried out from the first trimester of pregnancy with pimafucin orally (1 tablet 2 times a day for 10 days) and / or vaginally (1 suppository for 10 days).

- Endocrine factors
The endocrine factors of miscarriage, which are detected in 17-23% of cases, include:
- defective luteal phase;
- violation of secretion of androgens (hyperandrogenism);
- diseases of the thyroid gland;
- diabetes.

Inferior luteal phase as a cause of endocrine infertility and miscarriage in women was first described in 1949 by G. Jones et al. For a complete secretory transformation and preparation of the endometrium for implantation of a fertilized egg, a sufficient concentration of estrogen, progesterone and maintaining their normal ratio during the menstrual cycle and especially in the second phase of the cycle are necessary.

The results of a hormonal examination indicate the presence of an inferior luteal phase of the cycle in 40% of women with habitual miscarriage and in 28% of women with infertility and a regular rhythm of menstruation.

During the clinical and endocrinological examination of patients with an incomplete luteal phase, it was shown that this pathology occurs as a result of disorders at various levels of the hypothalamic-pituitary-ovarian and adrenal systems and manifests itself in the form of:
- a decrease in the amplitude and a change in the pulsating rhythm of the secretion of gonadotropic releasing hormone (luliberin);
- increase in the level of prolactin;
- decrease in the ovulatory peak of LH and / or the ratio of FSH / LH during the cycle and during the period of ovulation.

The disorder of the mechanisms of regulation of the menstrual cycle at the level of the hypothalamic-pituitary region is the main cause of:
- disruption of growth and full maturation of follicles;
- defective ovulation;
- the formation of a pathological corpus luteum.

As a result of the described disorders, the corpus luteum is formed, which in each subsequent cycle secretes a reduced amount of progesterone. Hormonal ovarian insufficiency is also manifested by a decrease in estrogen levels during the menstrual cycle and a change in the ratio between estrogens and progesterone, especially in the luteal phase.

A possible cause of impaired maturation of follicles is the pathological conditions of the ovaries, caused by a chronic inflammatory process of the genitals, surgical interventions on the ovaries, which leads to a decrease in their functional activity, especially in women older than 35-36 years.

Ultimately, against the background of hypoestrogenism and hypoprogesteronemia, an inferior phase of endometrial secretion develops, which prevents the implantation of a fertilized egg and the normal development of pregnancy.

Thus, dysfunction of the corpus luteum, which secretes a sufficient amount of progesterone for weeks, is the cause of spontaneous miscarriage in the early stages, and defective trophoblast function is the cause of later periods of the first trimester of pregnancy.

In case of an inferior luteal phase, natural progesterones are prescribed for several months (duphaston 200 mg, utrogestan orally 200 mg or intravaginally 300 mg per day) from the 16th to the 25th day of the menstrual cycle. In the early stages of pregnancy, depending on the presence of symptoms of a threatened abortion and the level of progesterone, it is possible to prescribe duphaston and utrogestan in similar doses up to 10-12 weeks of pregnancy.

Hyperandrogenism is a pathological condition caused by an increased level of adrenal and ovarian androgens, which is the cause of spontaneous miscarriage in 20-40% of women. The clinic distinguishes three types of hyperandrogenism:
- adrenal;
- ovarian;
- mixed.

Regardless of the type of hyperandrogenism, abortion occurs early and proceeds as anembryony or non-developing pregnancy. In 40% of patients during pregnancy, functional CI or low placenta previa occurs. In the II and III trimesters, abortion occurs at a critical time. With each subsequent miscarriage, the nature of hormonal disorders becomes more severe, and in 25-30% of cases, secondary infertility joins the problem of miscarriage.

During pregnancy, patients with hyperandrogenism have three critical periods when there is an increase in the level of androgens in the mother's body due to androgens synthesized by the fetus. So, at 12-13 weeks, the adrenal glands of the fetus begin to function; at 23-24 weeks, the testicles of the male fetus begin to produce androgens and at 27-28 weeks, ACTH begins to be secreted by the anterior pituitary gland of the fetus.

With hyperandrogenism detected before pregnancy, preparatory therapy with dexamethasone is carried out, 1/2 tablet (0.25 mg) 1 time per day in the evening before bedtime, continuously until pregnancy occurs. The dose of the drug varies depending on the level of adrenal androgens (DHEA / DHEA sulfate), which are determined once a month (on the 5-7th day of the cycle).

Determination of testosterone against the background of ongoing therapy is impractical, since dexamethasone does not have any suppressive effect on it. The duration of therapy before the onset of pregnancy is 6-12 months, and if pregnancy has not occurred during this time, one should think about the occurrence of secondary infertility. During pregnancy, the dose and duration of taking the drug are determined by the characteristics of the clinical course of pregnancy, the presence of symptoms of threatened abortion and CI, as well as the dynamics of the level of DHEA / DHEA sulfate. The timing of discontinuation of dexamethasone varies from 16 to 36 weeks and is determined individually for each patient.

The most frequent complications of pregnancies caused by endocrine causes of miscarriage, especially against the background of hyperandrogenism, are the threat of early termination, functional CCI, low placentation, the threat of developing hypertension and preeclampsia in the II and III trimesters of pregnancy.

In patients with thyroid diseases such as hypo-, hyperthyroidism, autoimmune thyroiditis, etc., it is recommended to eliminate the identified violations before the next pregnancy, as well as dose selection of thyroid hormones and clinical and laboratory monitoring throughout pregnancy.

Pregnancy in women with diabetes is recommended after examination by an endocrinologist and correction of the underlying disease. During pregnancy, the patient is under the supervision of both an endocrinologist and a gynecologist, and the tactics of pregnancy management and the nature of delivery are decided depending on the patient's health status.

- Immune factors
Immune factors of miscarriage are the most common causes of miscarriage and their frequency, according to different authors, is 40-50%. The recognition of a foreign agent and the development of an immune response in a woman's body are regulated by HLA antigens, which are divided into two classes.

The genes encoding these antigens are located on the 6th chromosome. Class I HLA antigens are represented by antigens A, B, C, necessary for the recognition of transformed cells by cytotoxic T-lymphocytes. HLA class II antigens (DR, DP, DQ) provide interaction between macrophages and T-lymphocytes during the immune response. It is believed that the carriage of certain HLA antigens is combined with a predisposition to certain diseases.

When studying the role of the immunological factor in the clinic of miscarriage, two groups of disorders were identified: in the humoral and cellular immunity.

Violations in the humoral link of immunity are associated with antiphospholipid syndrome.

The second, no less complex mechanism of miscarriage is due to disturbances in the cellular link of immunity, which is manifested by the response of the mother's body to the paternal antigens of the embryo.

In this group of patients, the relationship between hormonal and immune factors is most clearly defined.

It is believed that among these mechanisms, progesterone plays a significant role, which is involved in the normalization of the immune response in the early stages of pregnancy. Under the influence of progesterone, lymphocytes are activated and begin to produce a protein, the so-called progesterone-induced blocking factor (PIBF), which has an anti-abortion effect in a woman's body and helps to maintain pregnancy.

What are the immunological mechanisms that cause abortion in the early stages? To this end, one should recall the features of the formation of the embryo after the fertilization of the egg by the spermatozoon. The spermatozoon, formed from the germ cell and having gone through a number of stages of development, contains half of the total set of chromosomes (23 chromosomes). A similar set of 23 chromosomes is contained in the egg that is formed as a result of ovulation. Accordingly, a fertilized egg already contains a set of 46 genetically programmed chromosomes.

Progesterone receptors are normally present in peripheral blood lymphocytes. In the absence of pregnancy, the number of lymphocytes containing progesterone receptors is negligible. However, the number of these cells increases with the onset of pregnancy and increases in proportion to its duration. Probably, such an increase in the number of progesterone receptors can be caused by the embryo, which acts as an alloantigen that stimulates blood lymphocytes. With spontaneous miscarriage, the number of cells containing progesterone receptors decreases sharply and practically does not differ from the indicators outside of pregnancy.

It is believed that inexplicable forms of miscarriage may be due to disturbances in the cellular and humoral immunity. Much attention is paid to cell-mediated immune mechanisms as possible etiological factors of spontaneous miscarriage; in particular, we are talking about T-helper cells (TX1, TX2) and the cytokines secreted by them. In the body, these cells are activated in turn.

The TX2-mediated response contributes to maintaining a normal pregnancy, while the TX1-mediated response is antagonistic to pregnancy and may induce abortion.

Despite the fact that at present the mechanism of development of spontaneous miscarriage has not been completely elucidated, it is believed that natural killers activated by lymphokines and activated decidual macrophages can play an important role in them.

Returning to the mechanism of the effect of progesterone on the activity of lymphocytes, it should be noted that the number of progesterone receptors increases with allogeneic or mitogenic stimulation of lymphocytes.

It has been established that after a blood transfusion or transplantation, the number of cells containing progesterone receptors is comparable to those during pregnancy. This indicates that in vivo alloantigenic stimulation leads to an increase in progesterone receptors in lymphocytes. It is believed that the increase in the number of progesterone receptors during pregnancy may be due to the presence of the fetus, which acts as an alloantigenic stimulator.

In a pregnant woman, under the influence of antigens of the fetus, against the background of activation of lymphocytes and the appearance of progesterone receptors in them, a mediator protein begins to be produced. This factor is produced by CD56+ cells located on the fetoplacental surface of the membrane.

The immunological influence of PIBF concerns both cellular and humoral immune mechanisms. PIBF at the cellular level affects the synthesis of cytokines in T-helper lymphocytes. In a normal pregnancy, there is a shift towards an increase in TX2 and their production of cytokines, while reducing TX1. This mechanism contributes to the preservation of pregnancy.

In the presence of PIBF, activated lymphocytes produce 8 times more cytokine TX2 (IL-2) than in its absence. An increase in the production of TX2 cytokines leads to an increase in the production of immunoglobulins and affects humoral immunity.

When PIBF was administered to animals, the appearance of a new subgroup of immunoglobulins, asymmetric antibodies, was noted. These antibodies are able to bind to antigens, compete with antibodies of the same specificity and act as "blocking" antibodies. Thus, they protect the embryo and prevent it from being destroyed by the mother's immune system. In pregnant women, a direct relationship is determined between the expression of PIBF and the number of asymmetric molecules - IgG. In the absence of pregnancy, the level of PIBF and the number of asymmetric antibodies are low.

PIBF appears in the blood of women from early pregnancy. Its concentration increases, reaching a maximum by 40 weeks of pregnancy. The content of PIBF drops sharply after childbirth. PIBF is determined by enzyme immunoassay. In miscarriage and out of pregnancy, low levels of PIBF are determined.

As a result of studies on the mechanism of action of PIBF, it was shown that this substance:
- affects the balance of cytokines, resulting in a decrease in the production of TX1 cytokines and an increase in the level of TX2 cytokines;
- reduces the activity of natural killer cells and ensures a normal pregnancy outcome.

Blockade of progesterone receptors leads to a decrease in the production of PIBF, resulting in an increase in the production of TX1 cytokines, an increase in natural killer cells and the onset of spontaneous miscarriage.

In vitro and in vivo experiments found that stimulation of progesterone receptors by endogenous progesterone or its derivatives (dydrogesterone, duphaston) induces the production of PIBF and protects the embryo in the mother's body.

Currently, three main pathways are described for the rejection of the embryo by the mother's body.

allogeneic reaction. Symmetrical (cytotoxic) antibodies bind to embryonic antigens (FAB structures) and then the complement system is activated by the Fc structure of the antigen. As a result, cytotoxicity, phagocytic cellular reactions develop and, as a result, the destruction of the embryo.

The mechanism of embryo destruction caused by TX1. This mechanism is mediated by cytokines: α-TNF, γ-IFN and IL-2, -12, -18. In all cases of abortogenic response of the maternal immune system, the lymphocytic reaction of TX1 prevails over the lymphocytic protective response of the mother's organism, caused by TX2.

Increased activity of natural killers. These cells are converted into LAK cells by IL-2 and TNF-α, which are released by TX1.

Taking into account the data concerning the mechanisms of embryo rejection, it was concluded that in order to maintain its viability, opposite processes must be provided in the body. Thus, immunomodulation aimed at protecting the embryo also includes three protection pathways.

Asymmetric antibodies are introduced that do not match the structure of the antigens of the fetus and do not fully bind to it, as a result of which the cascade of the complement system does not start.

TX2 activation effects predominate, protective cytokines are released, and TX1 activity is suppressed.

There is no release of α-TNF and IL-2, killer cells do not transform into embryonic LAK cells.

The key to such a restructuring of the immune response in the direction of protecting the embryo is the stimulation of the production of PIBF, which provides the processes described above.

A number of studies have shown that progesterone largely blocks and suppresses the activation and proliferation of cytotoxic TX1, the activity of killer cells, as well as the production of γ-IFN, IL-2, α-TNF, and therefore this hormone is considered as a natural immunosuppressant. Since progesterone inhibits the production of TX1 cytokines and stimulates the production of TX2 cytokines, it is proposed to use progestrone or its analogues in women with recurrent miscarriage of unknown etiology, when there is a shift in the body towards the predominance of TX1 cytokines.

It has been shown that stimulation of progesterone receptors with endogenous progesterone or dydrogesterone (duphaston) stimulates the production of PIBF, which in turn affects the balance of cytokines, reducing the production of TX1 cytokines and the number of natural killer cells.

According to the literature, an important role in preventing spontaneous miscarriages and maintaining early pregnancy is played by the effect on progesterone receptors. In this regard, progesterone is prescribed to prepare for pregnancy and prevent spontaneous miscarriages. It is noted that the immunomodulatory effect of hormones is important for maintaining the normal function of the endometrium, stabilizing its functional state and relaxing effect on the muscles of the uterus. It is believed that the protective effect of progesterone, in particular the stabilization and reduction of endometrial tone, is a consequence of a decrease in the production of prostaglandins by endometrial cells, as well as blocking the release of cytokines and other inflammatory mediators.

- Organic pathology of the genital organs
Organic pathology of the genital organs during miscarriage is of two types: congenital and acquired.

Congenital pathology (malformations):
- malformations of the derivatives of the Mullerian ducts;
- ICN;
- anomalies of divergence and branching of the uterine arteries.

Acquired pathology:
- ICN;
- Asherman's syndrome;
- uterine fibroids;
- endometriosis.

The mechanism of abortion in case of malformations of the uterus is associated with a violation of the processes of implantation of the fetal egg, inferior secretory transformations of the endometrium due to reduced vascularization, close spatial relationships of the internal genital organs, functional features of the myometrium, and increased excitability of the infantile uterus. The threat of interruption is observed at all stages of pregnancy.

With an intrauterine septum, the risk of spontaneous abortion is 60%. Miscarriages are more common in the second trimester. If the embryo is implanted in the area of ​​the septum, abortion occurs in the first trimester, which is explained by the inferiority of the endometrium in this area and the violation of the placentation process.

Anomalies in the origin and branching of the uterine arteries lead to impaired blood supply to the implanted embryo and placenta, and as a result, to spontaneous miscarriage.

Intrauterine synechia is the cause of abortion in 60-80% of women, depending on the location of the synechia and their severity.

The pathogenesis of habitual spontaneous abortion in the presence of uterine fibroids is associated with absolute or relative progesterone deficiency, increased bioelectrical activity of the myometrium and increased enzymatic activity of the uterine contractile complex, as well as malnutrition in the myomatous nodes.

The pathogenesis of habitual spontaneous abortion in genital endometriosis is not fully understood and is possibly associated with immune disorders, and in adenomyosis - with the pathological state of the endo- and myometrium.

The diagnosis of malformations and other pathological conditions of the uterus and cervical canal is established on the basis of anamnesis, gynecological examination, results of hysterosalpingography, ultrasound scanning, hystero- and laparoscopy. Currently, most of the organic pathology that causes habitual spontaneous abortion is treated with the help of hysteroscopic operations. During hysteroscopy, it is possible to remove the submucosal myomatous node, destroy the intrauterine synechia, and remove the intrauterine septum. With intrauterine synechia and uterine septum, transcervical metroplasty is also performed under ultrasound control.

Istimiko-cervical weekly sufficiency is more often a consequence of frequent and gross intrauterine interventions and traumatic injuries of the cervix during abortions and childbirth. The frequency of ICI ranges from 7.2 to 13.5% and the relative risk of developing this pathology increases with an increase in the number of induced miscarriages.

Pregnancy in the case of ICI usually proceeds without symptoms of threatened miscarriage. The pregnant woman does not complain, palpation shows normal uterine tone. During vaginal examination, shortening and softening of the cervix is ​​​​determined, the cervical canal freely passes a finger beyond the area of ​​\u200b\u200bthe internal pharynx. When viewed in the mirrors, a gaping external pharynx of the cervix with flaccid edges is visible, prolapse of the fetal bladder is possible. With an increase in intrauterine pressure, the fetal membranes protrude into the dilated cervical canal, become infected and open. In the presence of ICI, termination of pregnancy occurs, as a rule, in the II and III trimesters and begins with the discharge of amniotic fluid.

Currently, there is a tendency to increase the frequency of functional CI, which occurs with endocrine disorders (inferior luteal phase, hyperandrogenism).

Diagnosis of CCI, in addition to anamnestic data and examination data, includes a special examination: outside of pregnancy - hysterosalpingography and echographic examination, and during pregnancy - transvaginal scanning.

Surgical treatment of ICI is carried out in the following cases:
- when ICI of organic origin is detected outside of pregnancy;
- in the presence of signs of progressive weekly sufficiency of the cervix (change - consistency, the appearance of flabbiness, shortening of the cervix);
- with a gradual increase in the "gaping" of the external and the opening of the internal pharynx;
- if there is a history of spontaneous miscarriages or premature births in the II and III trimesters of pregnancy.

Methods for the surgical elimination of CCI (suturing the cervix) are described in detail in the manuals on operative obstetrics. The issue of suturing the cervix with a prolapsing fetal bladder, low placenta and multiple pregnancies should be addressed individually in each specific clinical situation.

Contraindications for the imposition of a circular suture on the cervix are:
- signs of interruption threat;
- diseases in which pregnancy is contraindicated;
- cicatricial deformity of the cervix, its deep ruptures, a sharp shortening of the cervix;
- the presence of pato

Symptoms of miscarriage

Symptoms of miscarriage include:
- Increasing bleeding
- Spasms
- Pain in the lower abdomen
- Elevated temperature
- Weakness
- Vomit
- Lower back pain

If you experience these symptoms, please contact your obstetrician/gynecologist immediately.

Diagnosis of miscarriage

Miscarriage is a multifactorial disease, in which most patients have a combination of several causes at the same time. In this regard, the examination of patients in this group should be comprehensive and include all modern clinical, instrumental and laboratory methods. When examining these patients, it is required not only to establish the cause (s) of spontaneous miscarriage, but also to assess the state of the reproductive system in order to prevent subsequent miscarriages.

Examination before pregnancy
Anamnesis includes clarification of the presence of hereditary, oncological somatic diseases, neuroendocrine pathology. In the gynecological history, the presence of inflammatory diseases of the genitals, viral infection, methods of therapy, features of menstrual and reproductive functions (abortions, childbirth, spontaneous miscarriages, including complicated ones), other gynecological diseases and surgical interventions are revealed.

A clinical examination consists of an examination, an assessment of the condition of the skin, the degree of obesity according to the body mass index, and the condition of the thyroid gland. According to the hirsute number, the degree of hirsutism is determined, the condition of the internal organs is assessed, as well as the gynecological status. The functional state of the ovaries, the presence or absence of ovulation are analyzed according to the rectal temperature and menstrual calendar.

Laboratory and instrumental methods studies are the following.
- Hysterosalpingography - is performed on the 17th-23rd day of the menstrual cycle and allows you to exclude malformations of the uterus, intrauterine synechia, ICI.

Ultrasound - while assessing the condition of the ovaries, the presence of cysts of uterine fibroids, adenomyosis. Clarify the state of the endometrium: chronic endometritis, polyps, endometrial hyperplasia.

infectious screening. Includes microscopic examination of smears from the urethra, cervical canal and vagina, PCR diagnostics, bacteriological examination of the contents of the cervical canal, examination for virus carriers (see section 8.3.2).

Hormonal research. It is carried out on the 5-7th day of the menstrual cycle with regular menstruation and on any day in patients with oligo- and amenorrhea. The content of prolactin, LH, FSH, testosterone, cortisol, DHEA sulfate, 17-hydroxyprogesterone is determined. Progesterone is determined only in women with a regular menstrual cycle: on the 5-7th day in the I phase of the cycle and on the 6-7th day of the rise in rectal temperature in the II phase of the cycle. In patients with adrenal hyperandrogenism, a small test with dexamethasone is performed to determine an adequate therapeutic dose.

In order to clarify the autoimmune genesis of miscarriage, the presence of lupus antigen, anti-CHG, anticardiolipin antibodies is determined, and the features of the hemostasis system are analyzed.

Examination of a spouse includes clarification of hereditary history, the presence of somatic, especially neuroendocrine diseases, analysis of a detailed spermogram, clarification of immune and inflammatory factors.

If intrauterine pathology and / or endometrial pathology is suspected, a separate diagnostic curettage is performed under the control of hysteroscopy.

If you suspect the presence of genital endometriosis, tube pathology and adhesions in the pelvis, with uterine myoma and scleropolycystic ovaries, operative laparoscopy is indicated.

After the examination, a complex of therapeutic measures is planned depending on the identified factors of miscarriage.

Examination during pregnancy
Observation during pregnancy begins immediately after the onset of pregnancy and includes the following research methods:
- ultrasonic scanning;
- periodic determination of HCG in the blood;
- determination of DHEA/DHEA sulfate;
- if necessary, consulting with a psychologist and psychotherapist.

Treatment for miscarriage

If the miscarriage is complete and the uterus is clean, then no special treatment is usually needed. Sometimes the uterus is not completely cleared, then the procedure for curettage of the uterine cavity is performed. During this procedure, the uterus is opened and the remains of the fetus or placenta in it are carefully removed. An alternative to curettage is taking certain medications that will cause your body to reject the contents of your uterus. This method may be ideal for those who wish to avoid surgery and who are in stable health.

Forecast
The prognosis of the course of subsequent pregnancies in women with a history of spontaneous miscarriages, depending on the outcome of the previous one.

It is shown that the most promising in this regard are women with organic pathology of the uterus, endocrine and immune factors.

In conclusion, it should be noted that a thorough and complete examination of women before pregnancy, especially after spontaneous miscarriages, the most accurate diagnosis of the causes of miscarriage, timely and pathogenetically substantiated therapy, dynamic monitoring during pregnancy can significantly reduce the risk of threatened abortion and loss of a child.

Prevention of miscarriage

Prevention consists in a thorough examination of women in order to identify the causes of miscarriage and conduct rehabilitation therapy in preparation for a subsequent pregnancy. Examination in the antenatal clinic includes a consultation with a therapist to identify extragenital diseases in which pregnancy is contraindicated; metrosalpingography and / or hysteroscopy to exclude malformations of the uterus, intrauterine synechia, isthmic-cervical insufficiency; conducting functional diagnostic tests to assess hormonal balance; bacteriological examination of the contents of the cervical canal, examination for toxoplasmosis, cytomegalovirus, etc., determination of blood group and Rh factor. An obligatory component of the examination of a woman with a history of miscarriage is an assessment of her husband's health, including the study of his sperm. If the causes of miscarriage are not identified at the first stage of the examination, the woman is sent to specialized antenatal clinics or polyclinics, where a hormonal, medical and genetic study is carried out. If the causes of miscarriage still remain unclear, an examination is necessary in specialized institutions or in hospitals, where they carry out a deeper study of the endocrine system, the immune system and other special studies.

31.07.2018

In St. Petersburg, the AIDS Center, in partnership with the City Center for the Treatment of Hemophilia and with the support of the Society of Hemophilia Patients of St. Petersburg, launched a pilot information and diagnostic project for patients with hemophilia infected with hepatitis C.

Medical Articles

Almost 5% of all malignant tumors are sarcomas. They are characterized by high aggressiveness, rapid hematogenous spread and a tendency to relapse after treatment. Some sarcomas develop for years without showing anything ...

Viruses not only hover in the air, but can also get on handrails, seats and other surfaces, while maintaining their activity. Therefore, when traveling or in public places, it is advisable not only to exclude communication with other people, but also to avoid ...

Returning good vision and saying goodbye to glasses and contact lenses forever is the dream of many people. Now it can be made a reality quickly and safely. New opportunities for laser vision correction are opened by a completely non-contact Femto-LASIK technique.

Cosmetic preparations designed to care for our skin and hair may not actually be as safe as we think.

Among the most important problems of practical obstetrics, one of the first places is occupied by miscarriage, the frequency of which is 20%, i.e., almost every 5th pregnancy is lost, and does not tend to decrease, despite numerous and highly effective diagnostic and treatment methods developed in last years. It is believed that the statistics do not include a large number of very early and subclinical miscarriages. Sporadic termination of pregnancy at short terms is considered by many researchers as a manifestation of natural selection with a high frequency (up to | 60%) of the abnormal karyotype of the embryo. Habitual pregnancy loss (childless marriage) occurs in 3-5% of couples. With recurrent pregnancy loss, the frequency of abnormal embryonic karyotype is much lower than with sporadic miscarriage. After two spontaneous miscarriages, the frequency of termination of a subsequent pregnancy is already 20-25%, after three - 30-45%. Most specialists dealing with the problem of miscarriage now come to the conclusion that two consecutive miscarriages are enough to classify a married couple as habitual pregnancy loss, followed by a mandatory examination and a set of measures to prepare for pregnancy.

Miscarriage- its spontaneous interruption in terms from conception to 37 weeks. In world practice, it is customary to distinguish between early pregnancy loss (from conception to 22 weeks) and premature birth (from 22 to 37 weeks). Premature births are divided into 3 groups, taking into account the gestational age from 22 to 27 weeks - very early preterm birth, from 28 to 33 weeks - early preterm birth and at 34-37 weeks of gestation - premature birth. This division is quite justified, since the causes of termination, treatment tactics and pregnancy outcomes for the newborn are different during these periods of pregnancy.

As for the first half of pregnancy, it is completely illogical to bring everything into one group (early pregnancy losses), since the causes of termination, management tactics, and therapeutic measures differ even more than with a gestational age after 22 weeks.

In our country, it is customary to single out early and late miscarriages, termination of pregnancy at 22-27 weeks and premature birth at 28-37 weeks. Early pregnancy losses up to 12 weeks make up almost 85% of all losses, and the shorter the gestational age, the more often the embryo dies at first, and then the symptoms of abortion appear.

The causes of abortion are extremely diverse, and often there is a combination of several etiological factors. Nevertheless, there are 2 main problems in terminating a pregnancy in the first trimester:
The first problem is the state of the embryo itself and chromosomal abnormalities that arise de novo or are inherited from parents. Hormonal diseases can lead to chromosomal disorders of the embryo, leading to disturbances in the processes of maturation of the follicle, the processes of meiosis, mitosis in the egg, in the sperm.
The 2nd problem is the state of the endometrium, i.e., a characteristic of the pathology due to many reasons: hormonal, thrombophilic, immunological disorders, the presence of chronic endometritis with the persistence of viruses, microorganisms in the endometrium, with a high level of pro-inflammatory cytokines, a high content of activated immune cells.
However, both in the 1st and 2nd groups of problems, there is a violation of the processes of implantation and placentation, improper formation of the placenta, which subsequently leads either to termination of pregnancy, or when it progresses to placental insufficiency with delayed fetal development and the occurrence preeclampsia and other complications of pregnancy.

In this regard, there are 6 large groups of causes of habitual pregnancy loss. These include:
- genetic disorders (inherited from parents or arising de novo);
- endocrine disorders (insufficiency of the luteal phase, hyperandrogenism, diabetes, etc.);
- infectious causes;
- immunological (autoimmune and alloimmune) disorders;
- thrombophilic disorders (acquired, closely related to autoimmune disorders, congenital);
- pathology of the uterus (malformations, intrauterine synechia, isthmic-cervical insufficiency).

Each stage of pregnancy has its own pain points, which for most women are the leading causes of abortion.

When a pregnancy is terminated up to 5-6 weeks the leading reasons are:

1. Features of the karyotype of parents (translocations and inversions of chromosomes). Genetic factors in the structure of the causes of recurrent miscarriage account for 3-6%. With early pregnancy losses, anomalies in the karyotype of the parents, according to our data, are observed in 8.8% of cases. The probability of having a child with unbalanced chromosomal abnormalities in the presence of balanced chromosomal rearrangements in the karyotype of one of the parents is 1 - 15%. The difference in the data is related to the nature of the rearrangements, the size of the involved segments, the gender of the carrier, and family history. If a couple has a pathological karyotype even in one of the parents, prenatal diagnosis during pregnancy (chorionic biopsy or amniocentesis is recommended due to the high risk of chromosomal abnormalities in the fetus).

2. In recent years, much attention in the world has been paid to the role of the HLA system in reproduction, protecting the fetus from the mother's immune aggression, and in the formation of tolerance to pregnancy. The negative contribution of certain antigens, the carriers of which are men in married couples with early miscarriage, has been established. These include HLA class I antigens - B35 (p< 0,05), II класса - аллель 0501 по локусу DQA, (р < 0,05). Выявлено, что подавляющее число анэмбрионий приходится на супружеские пары, в которых мужчина имеет аллели 0201 по локусу DQA, и/или DQB, имеется двукратное увеличение этого аллеля по сравнению с популяционными данными. Выявлено, что неблагоприятными генотипами являются 0501/0501 и 0102/0301 по локусу DQA, и 0301/0301 по локусу DQB. Частота обнаружения гомозигот по аллелям 0301/0301 составляет 0,138 по сравнению с популяционными данными - 0,06 (р < 0,05). Применение лимфоцитоиммунотерапии для подготовки к беременности и в I триместре позволяет доносить беременность более 90% женщин.

3. It has been established that the immunological causes of early pregnancy losses are due to several disorders, in particular, a high level of pro-inflammatory cytokines, activated NK cells, macrophages in the endometrium, and the presence of antibodies to phospholipids. High levels of antibodies to phosphoserine, choline, glycerol, inositol lead to early pregnancy losses, while lupus anticoagulant and high levels of antibodies to cardiolipin are accompanied by intrauterine fetal death in later pregnancy due to thrombophilic disorders. A high level of pro-inflammatory cytokines has a direct embryotoxic effect on the embryo and leads to chorionic hypoplasia. Under these conditions, pregnancy cannot be maintained, and if pregnancy persists at lower levels of cytokines, then primary placental insufficiency is formed. CD56 endometrial large granular lymphocytes account for 80% of the total immune cell population in the endometrium at the time of embryo implantation. They play an important role in trophoblast invasion, change the mother's immune response with the development of pregnancy tolerance by releasing progesterone-induced blocking factor and activating Tn2 to produce blocking antibodies; provide the production of growth factors and pro-inflammatory cytokines, the balance of which is necessary for trophoblast invasion and placentation.

4. In women with failures in the development of pregnancy, both in recurrent miscarriage and after IVF, the level of aggressive LNK cells, the so-called lymphokine-activated (CD56+l6+ CD56+16+3+), increases sharply, which leads to an imbalance between regulatory and pro-inflammatory cytokines towards the predominance of the latter and to the development of local thrombophilic disorders and abortion. Very often, women with high levels of LNK in the endometrium have a thin endometrium with impaired blood flow in the vessels of the uterus.

With habitual abortion at 7-10 weeks The leading causes are hormonal disorders:

1. insufficiency of the luteal phase of any genesis,
2. hyperandrogenism due to impaired folliculogenesis,
3. hypoestrogenism at the stage of choosing a dominant follicle,
4. defective development or overmaturation of the egg,
5. defective formation of the corpus luteum,
6. defective secretory transformation of the endometrium.
As a result of these disorders, defective invasion of the trophoblast and the formation of an inferior chorion occur. Pathology of the endometrium due to hormonal disorders, not
always determined by the level of hormones in the blood. The receptor apparatus of the endometrium may be disturbed, there may be no activation of the genes of the receptor apparatus.

With habitual miscarriage over 10 weeks The leading causes of violations in the development of pregnancy are:

1. autoimmune problems,
2. closely related thrombophilic, in particular antiphospholipid syndrome (APS). With APS without treatment, in 95% of pregnant women, the fetus dies due to thrombosis, placental infarction, placental abruption, development of placental insufficiency and early manifestations of gestosis.

The thrombophilic conditions during pregnancy, leading to habitual miscarriage, include the following forms of genetically determined thrombophilia:
-deficiency of antithrombin III,
- factor V mutation (Leidin mutation),
-deficiency of protein C,
-deficiency of protein S,
-mutation of the prothrombin gene G20210A,
- hyperhomocysteinemia.

An examination for hereditary thrombophilia is carried out with:
- the presence of thromboembolism in relatives under the age of 40,
- unclear episodes of venous and / or arterial thrombosis under the age of 40 with recurrent thrombosis in the patient and close relatives,
- with thromboembolic complications during pregnancy, after childbirth (repeated pregnancy losses, stillbirths, intrauterine growth retardation, placental abruption, early onset of preeclampsia, HELLP syndrome),
-when using hormonal contraception.

Treatment is carried out with antiplatelet agents, anticoagulants, in case of hyperhomocysteinemia - by prescribing folic acid, vitamins of group B.

During pregnancy after 15-16 weeks the causes of miscarriage of infectious genesis (gestational pyelonephritis), isthmic-cervical insufficiency come to the fore. In connection with the local immunosuppression characteristic of pregnant women during these periods, candidiasis, bacterial vaginosis, and banal colpitis are often detected. Infection by the ascending route in the presence of isthmic-cervical insufficiency leads to premature rupture of amniotic fluid and the development of contractile activity of the uterus under the influence of the infectious process.

Even this by no means small list of reasons shows that it is impossible to solve these problems during pregnancy. It is possible to understand the causes and pathogenesis of interruption only on the basis of a thorough examination of a married couple before pregnancy. And for the examination, modern technologies are needed, i.e., highly informative research methods: genetic, immunological, hemostasiological, endocrinological, microbiological, etc. You also need a high professionalism of a doctor who can read and understand a hemostasiogram, draw conclusions from an immunogram, understand information about genetic markers pathology, based on these data, select etiological and pathogenetic, and not symptomatic (ineffective) therapy.

The greatest discussions are caused by problems arising with a gestational age of 22-27 weeks . According to WHO recommendations, this period of pregnancy is referred to as premature birth. But children born at 22-23 weeks practically do not survive and in many countries births from 24 or 26 weeks are considered premature. As a result, preterm birth rates vary across countries. In addition, during these periods, possible fetal malformations are specified according to ultrasound data, according to the results of fetal karyotyping after amniocentesis, and abortion is performed for medical reasons. Can these cases be classified as preterm births and included in perinatal mortality rates? Often, fetal weight at birth is taken as a marker of gestational age. If the fetus weighs less than 1000 g, it is considered an abortion. However, about 64% of babies under 33 weeks' gestation have intrauterine growth retardation and birth weights that are not appropriate for their gestational age.

The gestational age more accurately determines the outcome of childbirth for a premature fetus than its weight. Analysis of pregnancy losses at 22-27 weeks' gestation at the Center showed that the main immediate causes of abortion are isthmic-cervical insufficiency, infection, prolapse of the membranes, premature rupture of water, multiple pregnancy with the same infectious complications and malformations.
Nursing children born during these terms of pregnancy is a very complex and expensive problem, requiring huge material costs and high professionalism of medical personnel. The experience of many countries, in which preterm births are counted from the above terms of pregnancy, indicates that with a decrease in perinatal mortality during these terms, disability from childhood increases by the same amount.

Pregnancy 28-33 weeks accounts for approximately 1/3 of all preterm births, the rest are preterm births at 34-37 weeks, the outcomes of which for the fetus are almost comparable to those in full-term pregnancy.

An analysis of the immediate causes of abortion showed that up to 40% of preterm births are due to the presence of infection, 30% of births occur due to premature rupture of amniotic fluid, which is also often due to ascending infection.
Isthmic-cervical insufficiency is one of the etiological factors of preterm birth. The introduction into practice of assessing the state of the cervix by transvaginal ultrasound showed that the degree of competence of the cervix can be different and often isthmic-cervical insufficiency manifests itself in late pregnancy, which leads to prolapse of the fetal bladder, to infection and to the onset of labor.
Another significant cause of preterm labor is chronic fetal distress caused by the development of placental insufficiency in preeclampsia, extragenital diseases, and thrombophilic disorders.
Overdistension of the uterus during multiple pregnancy is one of the causes of premature birth and extremely complicated pregnancy in women after the use of new reproductive technologies.

Without knowledge of the causes of preterm labor, there can be no successful treatment. Thus, tocolytic drugs with different mechanisms of action have been used in world practice for more than 40 years, but the frequency of preterm birth does not change.

In most perinatal centers in the world, only 40% of preterm births are spontaneous and pass through the natural birth canal. In other cases, abdominal delivery is performed. The outcome of childbirth for the fetus, the incidence of newborns during abortion by surgery may differ significantly from the outcomes of childbirth for a newborn with spontaneous preterm birth. So, according to our data, in the analysis of 96 preterm births at a period of 28-33 weeks, of which 17 were spontaneous and 79 ended with a caesarean section, the outcome of childbirth for the fetus was different. The stillbirth rate for spontaneous delivery was 41%, for caesarean section - 1.9%. Early neonatal mortality was 30% and 7.9%, respectively.

Given the adverse outcomes of preterm birth for the child, it is necessary to pay more attention to the problem of preventing preterm birth at the level of the entire population of pregnant women. This program should include:

Examination outside of pregnancy of women at risk of miscarriage and perinatal losses and rational preparation of spouses for pregnancy;
- control of infectious complications during pregnancy: in world practice adopted
screening for infections at first visit, followed by bacteriuria and Gram smear evaluation every month. In addition, attempts are being made to determine markers of early manifestations of intrauterine infection (fibronectin IL-6 in the mucus of the cervical canal, TNFa IL-IB in the blood, etc.);
- timely diagnosis of isthmic-cervical insufficiency (ultrasound with a transvaginal sensor, manual assessment of the cervix up to 24 weeks, and with multiple pregnancy up to 26-27 weeks) and adequate therapy - antibacterial, immunotherapy;
- prevention of placental insufficiency from the first trimester in risk groups, control and therapy of thrombophilic disorders, rational therapy of extragenital pathology;
- prevention of preterm birth by improving the quality of management of pregnant women at the level of the entire population.

Two cherished stripes on the test and confirmation of the onset of pregnancy by a gynecologist make a woman happy. But nine months is a long period, and, unfortunately, it does not always end well. The most terrible blow for every pregnant woman is the loss of a child. After all, the most long-awaited, full of pleasant troubles period in life was interrupted.

Unfortunately, the statistics are not encouraging in numbers, and the number of patients who are diagnosed with recurrent miscarriage is growing rapidly.

What is habitual miscarriage: definition

According to the definition of the World Health Organization, a miscarriage is diagnosed when a woman has miscarriages at least three times before 22 weeks. If this happens later, then doctors are already talking about premature birth. The difference is that in the first case it makes no sense to fight for the life of the baby, and in the second case there is a chance to save the life of the child.

Today, however, many doctors agree that two consecutive incidents are enough to make a diagnosis of recurrent miscarriage. However, you should not give up in this situation. In most cases, comprehensive diagnosis and competent treatment help a married couple overcome all difficulties and achieve the desired result - to become parents.

Causes and risk groups

Several factors can provoke spontaneous abortion:

1. Genetic disorders. According to statistics, chromosomal abnormalities are the most common cause of abortion. This happens in 70% of cases, and most of them happen because “defective” sex cells participated in the process of conception. The human genome consists of 23 pairs of chromosomes. But there are cases when their number in germ cells is less (22), or, conversely, more (24). In such a situation, the development of the fetus will occur with a chromosomal abnormality, which will certainly end in abortion.
2. anatomical reasons. This group includes congenital anomalies of uterine development (irregular shape of the organ, the presence of a septum in the uterus, etc.), acquired anatomical defects (intrauterine adhesions; benign formations that deform the uterine cavity (myoma, fibromyoma, fibroma); isthmic-cervical insufficiency ).
3. Endocrine diseases. Thyroid disease, ovarian and placental insufficiency, and adrenal dysfunction lead to hormonal imbalance. Deficiency or excess of biologically active substances become a common cause of miscarriages in the early stages.
4. Immunological disorders. Every human body produces antibodies that help it fight various infections. But sometimes antibodies are formed in the body of a pregnant woman, which begin to destroy "their" cells. This process creates a lot of health problems for the expectant mother and increases the likelihood of spontaneous miscarriage.
5. Infectious diseases . Infection of the genital tract during the gestation period causes inflammation of the uterine mucosa, as well as infection of the fetus and placenta, which often disrupts the development of pregnancy. That is why doctors recommend undergoing an examination and treating infectious diseases of the reproductive system before the planned conception.
6. thrombophilia. A pathological condition characterized by a violation of the blood coagulation system. If one of the relatives had problems with the cardiovascular system (venous insufficiency, heart attack, hypertension, stroke), then there is a risk that a woman will develop thrombophilia during pregnancy. With this disease, microclots can form in the placenta that disrupt blood circulation, which can subsequently lead to miscarriage.

In addition to medical factors, biological and social causes can also influence abortion. These include:

• dissatisfaction with family life;
• low social status and, accordingly, low material income;
• industrial hazards;
• too early age (before 20 years), or late (after 35);
• malnutrition;
• bad habits;
• unfavorable ecological zone of residence.

Treatment

Timely access to a highly professional doctor is the key to a successful pregnancy. Therefore, if you are faced with such a problem as a spontaneous miscarriage, then do not delay a visit to a specialist. Treatment largely depends on the cause of the pathological process. To identify it, the couple must necessarily undergo a complete medical examination. Only after the factor of miscarriage is detected, the doctor will select the most effective method of therapy.

If the cause is congenital genetic disorders, then the doctor may recommend the IVF method, which involves the use of donor germ cells (egg or sperm, depending on which of the spouses has an error in the number or structure of chromosomes).

In case of anatomical disorders in the structure of the uterus, the elimination of structural changes will be required, followed by observation by a specialist throughout the pregnancy. If the cause is weakness of the muscle ring, then a surgical method is used - cervical cerclage, in which special sutures are applied to the cervix.

In case of problems with the hormonal background, the patient is prescribed the use of hormonal drugs. For example, with progesterone deficiency, Utrogestan vaginal suppositories are often used.

With thrombophilia and immunological disorders, drugs are prescribed that help thin the blood. Antibiotic therapy is used for infectious diseases of the reproductive system, while antibiotics are taken by both partners.

Caring for children begins from the moment they are conceived. Therefore, a patient with a diagnosis of "recurrent miscarriage" needs constant monitoring by a doctor. This will eliminate the risk of complications and save the pregnancy.

Especially for - Marina Amiran

According to statistics, miscarriage is recorded in 10-25% of pregnant women.

The cause of miscarriage can be various diseases that are difficult to cure or have become chronic. However, these diseases do not apply to the sexual sphere. An important feature of this kind of pathology is the unpredictability of the process, since for each specific pregnancy it is difficult to determine the true cause of abortion. Indeed, at the same time, the body of a pregnant woman is influenced by many different factors that can act covertly or explicitly. The outcome of pregnancy in case of habitual miscarriage is largely determined by the ongoing therapy. With three or more spontaneous miscarriages at gestational ages up to 20 weeks of gestation, an obstetrician-gynecologist diagnoses habitual miscarriage. This pathology occurs in 1% of all pregnant women.

After the fertilized ovum is “located” in the uterine cavity, the complex process of its engraftment there begins - implantation. The future baby first develops from a fetal egg, then becomes an embryo, then it is called a fetus that grows and develops during pregnancy. Unfortunately, at any stage of bearing a child, a woman may encounter such pathology of pregnancy as her miscarriage.

Miscarriage is the termination of pregnancy between the time of conception and the 37th week.

Risk of primary miscarriage

Doctors note a certain pattern: the risk of miscarriage after two failures increases by 24%, after three - 30%, after four - 40%.

In case of miscarriage, a complete or incomplete (the fetal egg exfoliated from the uterine wall, but remained in its cavity and did not come out) miscarriage occurs in the period up to 22 weeks. At a later date, in the period of 22-37 weeks, spontaneous abortion is called premature birth, and an immature but viable baby is born. Its mass ranges from 500 to 2500 g. Premature, prematurely born children are immature. Their death is often noted. In surviving children, malformations are often recorded. The concept of prematurity, in addition to the short term of pregnancy, includes low birth weight of the fetus, on average from 500 to 2500 g, as well as signs of physical immaturity in the fetus. Only by a combination of these three signs can a newborn be considered premature.

With the development of miscarriage, certain risk factors are indicated.

Modern advances in medicine and new technologies, the timeliness and quality of medical care make it possible to avoid serious complications and prevent premature termination of pregnancy.

A woman with a first trimester miscarriage should undergo a long-term examination before the expected pregnancy and during pregnancy to identify the true cause of the miscarriage. A very difficult situation develops with spontaneous miscarriage against the background of the normal course of pregnancy. In such cases, the woman and her doctor can do nothing to prevent such a course of events.

The most common factor in the development of premature termination of pregnancy are fetal chromosomal abnormalities. Chromosomes are microscopic elongated structures located in the internal structure of cells. Chromosomes contain genetic material that determines all the properties that are characteristic of each “person: eye color, hair, height, weight parameters, etc. There are 23 pairs of chromosomes in the structure of the human genetic code, 46 in total, with one part inherited from the mother organism, and the second - from the father. Two chromosomes in each set are called sex chromosomes and determine the sex of a person (XX chromosomes determine the female sex, XY chromosomes determine the male sex), while the other chromosomes carry the rest of the genetic information about the whole organism and are called somatic.

It has been established that about 70% of all miscarriages in early pregnancy are due to abnormalities of the somatic chromosomes in the fetus, while most of the chromosomal abnormalities of the developing fetus occurred due to the participation of a defective egg or sperm in the process of fertilization. This is due to the biological process of division, when the egg and sperm in the process of their preliminary maturation divide in order to form mature germ cells in which the set of chromosomes is 23. In other cases, eggs or spermatozoa are formed with an insufficient (22) or excess (24) set chromosomes. In such cases, the formed embryo will develop with a chromosomal abnormality, leading to a miscarriage.

The most common chromosomal defect can be considered trisomy, while the embryo is formed by the fusion of the germ cell with chromosome set 24, as a result of which the set of fetal chromosomes is not 46 (23 + 23), as it should be normal, but 47 (24 + 23) chromosomes . Most trisomies involving somatic chromosomes lead to the development of a fetus with malformations that are incompatible with life, which is why spontaneous miscarriage occurs in early pregnancy. In rare cases, a fetus with a similar developmental anomaly lives to a long time.

An example of the most well-known developmental anomaly caused by trisomy is Down's disease (represented by trisomy on chromosome 21).

A woman's age plays an important role in the occurrence of chromosomal disorders. And recent studies show that the age of the father plays an equally important role, the risk of genetic abnormalities increases with the age of the father over 40 years.
As a solution to this problem, couples where at least one partner is diagnosed with congenital genetic diseases are offered mandatory counseling by a geneticist. In certain cases, it is proposed to carry out IVF (in vitro fertilization - artificial insemination in vitro) with a donor egg or sperm, which directly depends on which of the partners revealed such chromosomal disorders.

Causes of primary miscarriage

There can be many reasons for such violations. The process of conceiving and carrying a baby is complex and fragile, it involves a large number of interrelated factors, one of which is endocrine (hormonal). The female body maintains a certain hormonal background so that the baby can develop correctly at each stage of its intrauterine development. If for some reason the body of the expectant mother begins to produce hormones incorrectly, then hormonal imbalances cause a threat of abortion.

Never take hormones on your own. Their intake can seriously disrupt the reproductive function.

The following congenital or life-acquired lesions of the uterus can threaten the course of pregnancy.

• Anatomical malformations of the uterus - duplication of the uterus, saddle uterus, bicornuate uterus, unicornuate uterus, partial or complete uterine septum in the cavity - are congenital. Most often, they prevent the fetal egg from successfully implanting (for example, the egg "sits" on the septum, which is not able to perform the functions of the inner layer of the uterus), which is why a miscarriage occurs.
• Chronic endometritis - inflammation of the mucous layer of the uterus - the endometrium. As you remember from the section that provides information on the anatomy and physiology of a woman, the endometrium has an important reproductive function, but only as long as it is “healthy”. Prolonged inflammation changes the nature of the mucous layer and disrupts its functionality. It will not be easy for a fetal egg to attach and grow and develop normally on such an endometrium, which can lead to pregnancy loss.
• Polyps and hyperplasia of the endometrium - the growth of the mucous membrane of the uterine cavity - the endometrium. This pathology can also prevent the implantation of the embryo.
• Intrauterine synechia - adhesions between the walls in the uterine cavity, which do not allow the fertilized egg to move, implant and develop. Synechia most often occurs as a result of mechanical trauma to the uterine cavity or inflammatory diseases.
• Uterine fibroids are benign tumor processes that occur in the muscular layer of the uterus - myometrium. Fibroids can cause miscarriage if the fetal egg is implanted next to the myoma node, which has broken the tissue of the internal cavity of the uterus, “takes over” the blood flow and can grow towards the fetal egg.
• Isthmic-cervical insufficiency. It is considered the most common cause of perinatal losses in the second trimester of pregnancy (13-20%). The cervix shortens with subsequent dilatation, which leads to pregnancy loss. Typically, isthmic-cervical insufficiency occurs in women whose cervix has been damaged earlier (abortion, rupture in childbirth, etc.), has a congenital malformation or cannot cope with increased stress during pregnancy (large fetus, polyhydramnios, multiple pregnancy, etc.). P.).

Some women have a congenital predisposition to thrombosis (blood clotting, blood clots in the vessels), which makes it difficult for the implantation of the fetal egg and prevents normal blood flow between the placenta, baby and mother.

The expectant mother often does not know about her pathology before pregnancy at all, since her hemostasis system coped well with its functions before pregnancy, that is, without the “double” load that appears with the task of bearing a baby.

There are other causes of miscarriage that need to be diagnosed for timely prevention and treatment. Methods of correction will depend on the identified cause.

The cause of habitual miscarriage can also be normal chromosomes, which do not give problems in the development of both partners, but carry a hidden carriage of chromosomal disorders, which affect the developmental anomalies of the fetus. In such a situation, both parents should have their blood tested for a karyotype in order to identify such chromosomal abnormalities (carriage of non-manifesting chromosomal abnormalities). During this examination, based on the results of karyotyping, a probable assessment of the course of a subsequent pregnancy is determined, and the examination cannot give a 100% guarantee of possible anomalies.

Chromosomal abnormalities are diverse, they can also be the cause of non-developing pregnancy. In this case, only fetal membranes are formed, while the fetus itself may not be. It is noted that the fetal egg is either formed initially, or it stopped its further development in the early stages. For this, in the early stages, the cessation of the characteristic symptoms of pregnancy is characteristic, at the same time, dark brown discharge from the vagina often appears. Ultrasound can reliably determine the absence of a fetal egg.

Miscarriage in the second trimester of pregnancy is mainly due to abnormalities in the structure of the uterus (such as an irregular shape of the uterus, an additional uterine horn, its saddle shape, the presence of a septum, or a weakened cervix that dilates leading to preterm labor). In this case, possible causes of miscarriage in the later stages may be infection of the mother (inflammatory diseases of the appendages and uterus) or chromosomal abnormalities of the fetus. According to statistics, chromosomal abnormalities are the cause of miscarriage in the second trimester of pregnancy in 20% of cases.

Symptoms and signs of primary miscarriage

A characteristic symptom of miscarriage is bleeding. Bloody discharge from the vagina with spontaneous miscarriage usually begins suddenly. In some cases, miscarriage is preceded by pulling pain in the lower abdomen, which resembles pain before menstruation. Together with the release of blood from the genital tract, with the onset of spontaneous miscarriage, the following symptoms are often observed: general weakness, malaise, fever, a decrease in nausea that was present before, emotional tension.

But not all cases of spotting in early pregnancy end in spontaneous miscarriage. In case of bleeding from the vagina, a woman should consult a doctor. Only a doctor will be able to conduct a proper examination, determine the condition of the fetus, find out if the cervix is ​​dilated and choose the right treatment aimed at maintaining pregnancy.

If bloody discharge from the genital tract is detected in the hospital, a vaginal examination is performed first. If the miscarriage is the first and occurred in the first trimester of pregnancy, then the study is carried out shallowly. In the event of a miscarriage in the second trimester or two or more spontaneous abortions in the first trimester of pregnancy, a complete examination becomes necessary.

In this case, the course of a complete examination includes a certain set of examinations:

1. blood tests for chromosomal abnormalities in both parents (clarification of the karyotype) and the determination of hormonal and immunological changes in the blood of the mother;
2. testing for chromosomal abnormalities of aborted tissues (it is possible to determine if these tissues are available - either the woman herself saved them, or they were removed after curettage of the uterus in a hospital);
3. ultrasound examination of the uterus and hysteroscopy (examination of the uterine cavity using a video camera that is inserted through the cervix and displays a picture on the screen);
4. hysterosalpingography (X-ray examination of the uterus;
5. biopsy of the endometrium (inner layer) of the uterus. This manipulation involves taking a small piece of the uterine mucosa, after which a hormonal examination of the tissue is performed.

Treatment and prevention of primary miscarriage

If pregnancy is threatened by endocrine disorders in a woman, then after laboratory tests, the doctor prescribes hormone therapy. In order to prevent unwanted surges in hormones, medications can be prescribed even before pregnancy, with subsequent adjustment of the dosage and drugs already during pregnancy. In the case of hormone therapy, the condition of the expectant mother is always monitored and appropriate laboratory tests (analyzes) are performed.

If miscarriage is due to uterine factors, then appropriate treatment is carried out a few months before the conception of the baby, as it requires surgical intervention. During the operation, synechiae are dissected, polyps of the uterine cavity are removed, fibroids that interfere with the course of pregnancy are removed. Medications before pregnancy treat infections that contribute to the development of endometritis. Isthmic-cervical insufficiency during pregnancy is corrected surgically. Most often, the doctor prescribes suturing the cervix (for a period of 13-27 weeks) if its insufficiency occurs - the cervix begins to shorten, become softer, the internal or external pharynx opens. The stitches are removed at 37 weeks of gestation. A woman with a sutured cervix is ​​shown a gentle physical regimen, the absence of psychological stress, since even on a sutured cervix, amniotic fluid may leak.

In addition to suturing the cervix, a less traumatic intervention is used - putting on the neck of the Meyer ring (obstetric pessary), which also protects the cervix from further disclosure.

The doctor will suggest the most suitable method for each specific situation.

Do not forget that not only ultrasound data is important, but also information obtained during a vaginal examination, since the neck can be not only shortened, but also softened.

For the prevention and treatment of problems associated with the hemostasis system of the expectant mother, the doctor will prescribe laboratory blood tests (mutations of the hemostasis system, coagulogram, D-dimer, etc.). Based on the results of the examination, drug treatment (tablets, injections) can be applied to improve blood flow. Expectant mothers with impaired venous blood flow are recommended to wear therapeutic compression stockings.

There can be many reasons for miscarriage. We did not mention severe extragenital pathologies (diseases that are not related to the genital area), in which it is difficult to bear a child. It is possible that for a particular woman, not one reason “works” for her condition, but several factors at once, which, overlapping each other, give such a pathology.

It is very important that a woman with a miscarriage (three or more losses in history) be examined and undergo medical preparation BEFORE the upcoming pregnancy in order to avoid this complication.

Treatment of such a pathology is extremely difficult and requires a strictly individual approach.

Most women do not need treatment as such immediately after a spontaneous miscarriage in the early stages. The uterus is gradually and completely self-cleansing, as it happens during menstruation. However, in some cases of incomplete miscarriage (partially the remains of the fetal egg remain in the uterine cavity) and when the cervix is ​​bent, it becomes necessary to scrape the uterine cavity. Such manipulation is also required in case of intense and non-stop bleeding, as well as in cases of a threat of the development of an infectious process, or if, according to ultrasound, remnants of the membranes are found in the uterus.

Anomalies in the structure of the uterus is one of the main causes of recurrent miscarriage (the cause is in 10-15% of cases of repeated miscarriage in both the first and second trimesters of pregnancy). Such anomalies of the structure include: the irregular shape of the uterus, the presence of a septum in the uterine cavity, benign neoplasms that deform the uterine cavity (myomas, fibromas, fibromyomas) or scars from previous surgical interventions (caesarean section, removal of fibromatous nodes). As a result of such violations, problems arise for the growth and development of the fetus. The solution in such cases is the elimination of possible structural disorders and very close monitoring during pregnancy.

An equally important role in habitual miscarriage is played by a certain weakness of the muscular ring of the cervix, while the most typical term for termination of pregnancy for this reason is 16-18 weeks of pregnancy. Initially, the weakness of the muscular ring of the cervix can be congenital, and can also be the result of medical interventions - traumatic injuries of the muscular ring of the cervix (as a result of abortions, purges, ruptures of the cervix during childbirth) or a certain kind of hormonal disorders (in particular, an increase in the level of male sex hormones). The problem can be solved by applying a special suture around the cervix at the beginning of a subsequent pregnancy. The procedure is called "cervical seclage".

A significant cause of recurrent miscarriage is hormonal imbalance. Thus, ongoing studies have revealed that low progesterone levels are extremely important in maintaining pregnancy in the early stages. It is the deficiency of this hormone that is the cause of early termination of pregnancy in 40% of cases. The modern pharmaceutical market has been significantly replenished with drugs similar to the hormone progesterone. They are called progestins. The molecules of such synthetic substances are very similar to progesterone, but they also have a number of differences due to modification. Such drugs are used in hormone replacement therapy in cases of corpus luteum insufficiency, although each of them has a certain range of disadvantages and side effects. Currently, there is only one drug that is completely identical to natural progesterone - utrogestan. The drug is very convenient to use - it can be taken orally and injected into the vagina. Moreover, the vaginal route of administration has a large number of advantages, since, being absorbed into the vagina, progesterone immediately enters the uterine bloodstream, therefore, the secretion of progesterone by the corpus luteum is simulated. To maintain the luteal phase, micronized progesterone is prescribed at a dose of 2-3 capsules per day. If, against the background of the use of utrozhestan, pregnancy develops safely, then it is continued, and the dose is increased to 10 capsules (which is determined by the gynecologist). With the course of pregnancy, the dosage of the drug is gradually reduced. The drug is reasonably used until the 20th week of pregnancy.

A pronounced hormonal disorder may be the result of polycystic altered ovaries, resulting in multiple cystic formations in the body of the ovaries. The reasons for recurrent non-violence in such cases are not well understood. Habitual miscarriage is often the result of immune disorders in the body of the mother and fetus. This is due to the specific feature of the body to produce antibodies to fight penetrating infections. However, the body can also produce antibodies against the body's own cells (autoantibodies), which can attack the body's own tissues, causing health problems and premature termination of pregnancy. These autoimmune disorders are responsible for 3-15% of cases of recurrent miscarriage. In such a situation, it is first necessary to measure the existing level of antibodies with the help of special blood tests. Treatment involves the use of small doses of aspirin and drugs that thin the blood (heparin), which leads to the possibility of carrying a healthy baby.

Modern medicine draws attention to a new genetic anomaly - a Leiden mutation of factor V, which affects blood clotting. This genetic trait may also play an important role in recurrent miscarriage. Treatment of this kind of disorders is currently not fully developed.

A special place among the causes of habitual miscarriage is occupied by asymptomatic infectious processes in the genitals. It is possible to prevent premature termination of pregnancy by routine testing of partners for infections, including women, before a planned pregnancy. The main pathogens that cause habitual miscarriage are mycoplasmas and ureaplasmas. Antibiotics are used to treat such infections: ofloxin, vibromycin, doxycycline. The treatment provided must be performed by both partners. A control examination for the presence of these pathogens is performed one month after the end of antibiotic therapy. In this case, a combination of local and general treatment is extremely necessary. Locally, it is better to use broad-spectrum drugs that act on several pathogens at the same time.

In the event that the causes of repeated miscarriage cannot be detected even after a comprehensive examination, the spouses should not lose hope. It has been statistically established that in 65% of cases after miscarriage, spouses have a successful subsequent pregnancy. To do this, it is important to strictly follow the prescriptions of doctors, namely, to take a proper break between pregnancies. For a complete physiological recovery after a spontaneous miscarriage, it takes from several weeks to a month, depending on how long the pregnancy was terminated. For example, certain pregnancy hormones remain in the blood for one or two months after a miscarriage, and menstruation in most cases begins 4-6 weeks after the termination of pregnancy. But psycho-emotional recovery often takes much longer.

It should be remembered that the observation of a pregnant woman with habitual miscarriage should be carried out weekly, and if necessary, more often, for which hospitalization is carried out. After establishing the fact of pregnancy, an ultrasound examination should be performed to confirm the uterine form, and then every two weeks until the period at which the previous pregnancy was terminated. If, according to ultrasound data, fetal cardiac activity is not recorded, it is recommended to take fetal tissues for karyotyping.

Once fetal heart activity is detected, additional blood tests are no longer needed. However, in later pregnancy, an assessment of the level of α-fetoprotein is desirable in addition to ultrasound. An increase in its level may indicate malformations of the neural tube, and low values ​​- chromosomal disorders. An increase in the concentration of α-fetoprotein without obvious reasons at a period of 16-18 weeks of pregnancy may indicate the risk of spontaneous abortion in the second and third trimesters.

Of great importance is the assessment of the fetal karyotype. This study should be carried out not only for all pregnant women over 35 years old, but also for women with recurrent miscarriage, which is associated with an increased likelihood of fetal malformations in subsequent pregnancies.

When treating recurrent miscarriage of an unclear cause, one of the alternatives can be considered the IVF technique. This method allows you to perform a study of germ cells for the presence of chromosomal abnormalities even before artificial insemination in vitro. The combination of the application of this technique with the use of a donor egg gives positive results in the onset of the desired full-fledged pregnancy. According to statistics, a full-fledged pregnancy in women with recurrent miscarriage after this procedure occurred in 86% of cases, and the frequency of miscarriages is reduced to 11%.

In addition to the various methods described for the treatment of recurrent miscarriage, it should be noted that non-specific, background therapy, the purpose of which is to relieve the increased tone of the muscular wall of the uterus. It is the increased tone of the uterus of a different nature that is the main cause of premature miscarriages. Treatment involves the use of no-shpa, suppositories with papaverine or belladonna (introduced into the rectum), intravenous drip of magnesia.

Unfortunately, pregnancy does not always end with the birth of a child at the time set by nature. In such cases, we are talking about miscarriage.

The relevance of this pathology is very high both in the obstetric sense and in the socio-economic sense. Miscarriage causes a decrease in fertility, causes psychological and physiological trauma to a woman, and leads to conflict situations in the family. Despite a lot of scientific research on the causes, treatment and prevention, miscarriage still remains the most important problem of modern obstetrics.

Terminology

In official language, miscarriage is its independent termination at any time from the moment of conception to 36 weeks and 6 days. Based on the gestational age at which the pregnancy was interrupted, the following types of miscarriage are distinguished:

• Miscarriage or spontaneous abortion - up to 21 weeks and 6 days.
• Premature birth - 22-37 weeks.

Spontaneous abortion happens:

• Early (up to 12 weeks of gestation).
• Late (from 13 to 22 completed weeks).

In addition, miscarriage also includes the cessation of fetal development, followed by its death at any time - a missed or non-developing pregnancy.

When a pregnancy is terminated prematurely two or more times, this condition is called "recurrent miscarriage".

Statistics

The frequency of miscarriage is not so small - about a quarter of pregnancies end prematurely. In addition, the rejection of the embryo can occur before the next menstruation (in such cases, the woman may not be aware of the existence of pregnancy), therefore, the occurrence of miscarriage is much more frequent.

Most often, pregnancy is interrupted during the first months - in 75-80% of cases. In the second trimester, the frequency of spontaneous termination of pregnancy decreases to about 10-12% of cases, and in the third - about 5-7%.

Recurrent miscarriage is usually due to severe impairment of female reproductive function and occurs in approximately 20-25% of cases of all spontaneous abortions.

Main reasons

Factors causing a violation of the normal course of pregnancy are very numerous and varied. In most cases, the development of this pathology is influenced by several causes at once, which act either simultaneously or join over time.

The main causes of miscarriage can be grouped into several groups, which will be discussed in detail below:

• Endocrine.
• Anatomical and functional disorders of the female genital organs.
• Complicated course of pregnancy (for example, fetoplacental insufficiency).
• Negative effect of external factors.
• Infection.
• Immunological.
• Genetic.
• Extragenital pathology (acute and chronic somatic diseases of the mother).
• Injuries, surgical interventions during pregnancy of any localization (especially in the abdomen and genitals).

In about one in three women, the exact cause of spontaneous abortion cannot be diagnosed.

The high frequency of fetal loss during the first three months of gestation is due to a kind of "natural selection", since approximately 60% of it is due to genetic causes (chromosomal abnormalities of the embryo, which are often incompatible with life). In addition, during these periods, the fetus, due to the lack of protection (the placenta, which is fully formed at 14–16 weeks), is more susceptible to the negative damaging effects of external factors: infection, radiation, etc.

At later stages, a pregnancy disorder is usually due to its complicated course or anatomical defects of the uterus (for example, isthmic-cervical insufficiency).

Infection

The leading role in the development of miscarriage is played by an infectious factor with concomitant inflammatory diseases of the internal genital organs and the fetal egg (its membranes and placenta).

The causes of the infectious-inflammatory process can be a variety of pathogenic bacteria and viruses, for example:

• Chlamydia.
• Myco- and ureaplasmas.
• Herpes.
• Toxoplasma.
• Cytomegalovirus.
• Rickettsia.
• Trichomonas.
• Enteroviruses.
• Rubella, chicken pox and some others.

The most dangerous primary infection during pregnancy, especially in its first three months. In these cases, a serious damage to the embryo often occurs, which often ends in its death and, accordingly, termination of pregnancy.

At later stages, the influence of infection can also cause damage to the fetus and amniotic membranes. In this case, chorioamnionitis often develops, which is manifested by low or polyhydramnios, premature rupture of the membranes, etc. All this can contribute to abortion.

An important role is also assigned to the conditionally pathogenic flora (UPF), which can manifest its negative properties against the background of physiological immunosuppression (decrease in general and local immunity) in a pregnant woman. In addition, in case of miscarriage, the presence of several infectious pathogens at once (associations of microorganisms) is quite common.

Infection in the uterine cavity can penetrate in several ways, the main of which are:

• Hematogenous - with blood flow.
• Ascending (through the cervical canal from the vagina) is the most common.

The sources of penetration of an infectious agent into the uterine cavity are often any acute and chronic inflammatory processes localized both in the genital area and outside them.

Chronic endometritis

Almost 70% of women suffering from habitual miscarriage are diagnosed with chronic inflammation of the endometrium (endometritis), which is often caused by the persistence (long stay in the body) of various microorganisms. In more than half of these patients, endometritis is due to UPF or its combination with a viral infection. Moreover, in most of these women, the course of the inflammatory process in the uterus is practically asymptomatic.

Predisposing factors for the formation of chronic endometritis are endometrial injuries during intrauterine interventions (for example, curettage of the uterine cavity). A decrease in general and local immunity during pregnancy (aimed at the possibility of carrying it) also creates prerequisites for the activation of a “dormant” infection and the formation of an inflammatory process in the uterus.

endocrine disorders

Hormonal dysfunction of any origin, as the cause of spontaneous abortion, occupies one of the leading positions. The most common hormonal imbalances are:

• Insufficiency of the luteal phase (ovarian hypofunction).
• Hyperandrogenism.
• Disruption of the thyroid gland.
• Diabetes.

The most common are ovarian hypofunction and hyperandrogenism. Consider these endocrine disorders in more detail.

Hypofunction of the ovaries

As you know, normally the ovaries synthesize the most important female sex hormones: estrogen and progesterone. Their production is carried out by a complex chain of biochemical reactions controlled by the brain. Therefore, when a reduced level of female hormones is detected, problems can be at any level: from the hypothalamus to, in fact, the ovaries.

The influence of female sex hormones during pregnancy cannot be overestimated. Their action begins long before conception: they affect the process of maturation and release of the egg, prepare the uterine mucosa for implantation, etc. During pregnancy, estrogens control blood flow in the uterus, increase its functional activity, and prepare the mammary glands for subsequent lactation. Progesterone ensures the rest of the uterus, thus contributing to the bearing of pregnancy. And this is not all types of effects of sex hormones on the female body.

What contributes to the development of ovarian hypofunction:

• Diseases transferred by the mother - various infections, irrational treatment with hormones, some somatic pathology, etc.
• Pathological births and abortions in the past.
• Violation of the normal maturation of the reproductive system in the pre- and pubertal period.
• Infectious and inflammatory diseases, especially chronic ones.

In this condition, a decrease in the synthesis of estrogen and, to a greater extent, progesterone, is often detected. This leads to an increase in the contractile activity of the uterus and abortion in the first trimester. With its progression, insufficient functioning of the placenta is often detected, which often leads to a delay in intrauterine development of the fetus, its hypoxia and contributes to premature birth.

Hyperandrogenism

Normally, in all women, male sex hormones (androgens) are produced in small quantities by the ovaries and adrenal glands. Their increased synthesis is called hyperandrogenism. According to the predominant localization of the pathological synthesis of androgens, it happens:

• Adrenal.
• Ovarian.
• Mixed.

An increase in the level of androgens of any genesis is accompanied by a decrease in the content of progesterone.

The effect of hyperandrogenism on pregnancy is accompanied by such manifestations:

• Spasm of the vessels of the utero-chorial and utero-placental space. This leads to an early disorder of blood flow in these areas, the formation of placental insufficiency, followed by a delay in the development of the fetus (up to its death).
• An increase in the contractile activity of the uterus, which can result in a miscarriage or premature birth.
• Contribute to the formation of isthmic-cervical insufficiency.

Increased or insufficient synthesis of thyroid hormones (hyper- or hypothyroidism) has the most direct impact on the course of pregnancy. Uncompensated dysfunction of this endocrine organ often leads to severe complications:

• Intrauterine fetal death.
• Stillbirth.
• Preeclampsia and others.

All this can ultimately lead to spontaneous abortion at any gestational age.

Anatomical and functional disorders

Almost the entire development cycle, starting from the first weeks of gestation and until the moment of birth, the unborn child passes in the so-called fetal place - the uterus. Accordingly, various violations of its anatomical structure or functional state do not have the most favorable effect on the possibility of normal pregnancy.

The most common anatomical and functional disorders of the uterus include:

• Defects (anomalies) of its development are two-horned, saddle-shaped, one-horned. In addition, sometimes a complete or incomplete doubling of the body or even the entire uterus is diagnosed. Sometimes externally the uterus has an anatomically correct shape and size, and in its cavity a connective tissue or muscular septum is found - partial or complete.
• Asherman's syndrome. This is an acquired anatomical defect of the uterus, in which so-called synechia, or adhesions, of varying severity are formed in its cavity. The most common cause of the formation of this condition are repeated intrauterine interventions, for example, curettage of the uterine cavity.
• Submucosal (submucous) uterine leiomyoma.
• Internal endometriosis or adenomyosis.
• Isthmic-cervical insufficiency.

All of the above anomalies most directly affect the possibility of carrying a pregnancy. So, with unsuccessful implantation of a fertilized egg on the septum of the uterine cavity or near the submucosal node, a violation of the normal blood supply to the embryo occurs, which soon dies. In addition, the presence of leiomyoma and / or adenomyosis is often accompanied by various hormonal disorders (luteal phase deficiency), which aggravate the course of pregnancy.

With anatomical defects of the uterus, pregnancy is usually interrupted in the second or third trimesters. And in severe pathology - and in the first.

Isthmic-cervical insufficiency

The frequency of this pathological condition is quite high - approximately one in five women with habitual pregnancy loss is diagnosed with cervical incompetence. Pregnancy loss usually occurs in the second trimester.

The cervix is ​​normally in a closed state almost until the very term of childbirth. With isthmic-cervical insufficiency (ICN), gaping of the internal (and often external) pharynx is observed, accompanied by a gradual decrease in the length of the neck itself. The insolvency of the cervix develops, and it ceases to fulfill its functions.

There are certain risk factors for the development of ICI:

• Traumatization of the cervix and cervical canal in the past. This can occur during abortions, pathological births (cervical ruptures at the birth of a large fetus, the use of obstetric forceps and some other conditions). In addition, some types of surgical intervention to correct pathologies of the cervix, such as conization or amputation, often lead to ICI.
• Congenital incompetence of the cervix.
• Functional ICN. The reason for its development in such cases are various endocrine disorders, for example, hyperandrogenism.
• Pathological course of pregnancy with multiple pregnancy, large fetus, polyhydramnios.

The main symptom of ICI is the gradual shortening of the cervix, followed by the opening of the internal os. This process is most often not accompanied by any sensations, such as pain. Subsequently, there is a protrusion of the fetal bladder through the "opened" cervix into the vagina and its rupture with the outflow of amniotic fluid. In the future, a miscarriage or premature birth occurs (the child is often born very premature).

Chromosomal abnormalities

Violations of the chromosomal set of the embryo usually lead to a stop in its further development and death. This is the reason for the termination of pregnancy (miscarriage), which usually occurs in the first few months of gestation. According to statistics, the cause of more than 70% of spontaneous abortions in the period up to eight weeks is precisely a genetic anomaly.

It is necessary to know that in the vast majority of cases, chromosomal abnormalities detected in the embryo are not hereditary. The reason for their formation is failures in the process of cell division under the influence of external or internal factors. This can occur both at the stage of formation of germ cells in both parents, and in the process of division of the zygote (early stages of embryo development). Examples of such factors might be:

• Old age of future parents.
• Alcoholism.
• Addiction.
• Unfavorable working conditions (usually in industrial enterprises), etc.

After one miscarriage caused by chromosomal abnormalities in the embryo, subsequent pregnancies usually end normally.

If there are several such cases, a mandatory consultation of a married couple by a medical geneticist is required to identify a hereditary pathology.

Fetoplacental insufficiency

Violation of the normal functioning of the placenta or fetoplacental insufficiency (FPI) plays an important role among the causes of miscarriage. In this pathological condition, almost all functions of the placenta are violated, for example, transport, nutrition, endocrine. As a result, the fetus receives less nutrients, oxygen, the hormonal activity of the placenta is disrupted, etc. All this ultimately leads to the following consequences:

• Intrauterine hypotrophy of the fetus (developmental delay).
• Decreased functional activity of the fetus.
• Hypoxia (oxygen starvation), which can be acute or chronic.
• Premature detachment of the placenta.
• placental infarction.
• Increasing the incidence and mortality of a newborn child.

Many factors lead to the development of FPI. Examples might be:

• Chronic infectious pathology.
• Dysfunction of the endometrium (for example, previous intrauterine manipulations during abortions, miscarriages).
• endocrine disorders.
• Complicated course of pregnancy: threatened miscarriage, preeclampsia, multiple pregnancy, immunological incompatibility, etc.
• Extragenital diseases in the mother: chronic pyelonephritis, hypertension, diabetes mellitus, pathology of the blood and coagulation system, and many others.

Also, a combination of causes that provoke the development of fetoplacental insufficiency is often noted.

The most unfavorable is FPI, which develops in the early stages (up to 16 weeks of pregnancy). It is in such cases that pregnancy is most often interrupted.

Extragenital pathology and external factors

The presence of any acute and chronic somatic diseases in the mother, the influence of external (exogenous) causes, injuries, surgical interventions directly affect the course of pregnancy.

The risk of premature termination of pregnancy increases significantly with severe pathology of the kidneys, heart and lungs, some autoimmune diseases (for example, systemic lupus erythematosus). In addition, such diseases can be a threat to the life of the woman herself.

The association of inflammatory bowel diseases with an increase in the frequency of preterm birth has been noted.

Among the external factors, the greatest influence on the normal course of pregnancy is:

• Bad habits: alcohol, smoking, drugs, caffeine.
• Stress.
• Work in a hazardous industry. The toxic effects of ionizing radiation, lead, mercury and some other compounds are proven causes of possible abortion and its unfavorable course.

Injuries sustained by the mother during pregnancy (especially the abdomen and genitals) can have a very direct impact on the possibility of miscarriage or premature birth.

Immunological factors

Among all the reasons that have a negative impact on fertility, about 20% are accounted for by immunological conflicts.

The principle of the human immune system is built in such a way as to reject and, if possible, destroy all foreign cells that enter the body. During conception, a female egg is fertilized by a sperm cell, which, in fact, carries foreign information. Accordingly, the unborn child will have a chromosome set of both mother and father.

For the body of a pregnant woman, the fetus is a foreign substance. However, for the normal carrying of pregnancy, the evolutionarily established mechanisms for overcoming tissue incompatibility between the mother's body and the fetus are included. Violation of these mechanisms leads to immune conflict.

The most studied immunological conflicts are:

• Isosensitization according to the Rh factor or the ABO system (blood group).
• Antiphospholipid syndrome (APS).
• Autosensitization to human chorionic gonadotropin.

Immunological factors of miscarriage are still insufficiently studied.

Isosensitization

It is formed when the body of the mother and fetus are incompatible for various erythrocyte antigens.

It is known that each person has a certain blood type. Currently, four are known: O (I), A (II), B (III), AB (IV). In addition, the Rh factor is also determined, which, in essence, is a special protein contained in red blood cells. A person can be Rh-positive (the Rh factor is determined) or Rh-negative.

For the occurrence of isosensitization during pregnancy, there must be two conditions:

• Penetration of fetal blood into the mother's bloodstream.
• The presence in the maternal blood of special cells - antibodies.

ABO isosensitization is formed when fetal blood with a different blood type enters the mother's bloodstream. Most often, an immune conflict occurs with the first blood group in the mother, and the second or third in the fetus.

Rh-conflict pregnancy can develop in the absence of the Rh factor in the mother (Rh-negative blood type) and the presence of it in the fetus (inherited from the father).

Throughout pregnancy, there is constant contact between the circulatory system of the mother and the fetus. However, even with a difference in blood group or Rh factor, isosensitization does not always occur. This requires the presence in the mother's bloodstream of special cells - antibodies. There are Rh antibodies and group (alpha and beta). When these antibodies are combined with antigens (receptors on the surface of “foreign” erythrocytes of the fetus), an immune reaction and isosensitization occurs.

Risk factors and manifestations

There are certain factors that increase the risk of developing Rh and group antibodies. These include:

• The presence in the past of pregnancy with a fetus with an Rh-positive type or with a blood type different from the maternal one. It does not matter the outcome of such a pregnancy: childbirth, abortion, miscarriage, ectopic.
• Pathological childbirth - caesarean section, manual examination of the uterine cavity.
• Blood transfusions.
• The introduction of vaccines and sera made on the basis of blood components.

It has been established that each subsequent pregnancy with an Rh-positive fetus in women with a negative Rh factor increases the risk of isosensitization by 10%.

Immune conflicts on the Rh factor are the most severe. At the same time, all the negative consequences of such a pathology are reflected exclusively in the unborn child. The severity of manifestations depends on the level of Rh antibodies in the mother's body. In especially severe cases, fetal death occurs, followed by miscarriage. If the pregnancy progresses, the so-called hemolytic disease of the fetus can develop, and then the newborn. It is characterized by severe damage to almost all systems and organs of the baby (especially the central nervous system suffers). The birth of such a child may be premature.

Antiphospholipid Syndrome (APS)

It is an autoimmune condition in which a woman's body produces antibodies to the endothelium (inner shell) of her own blood vessels. As a result of this, their damage occurs, in which a cascade of various biochemical reactions is triggered. This leads to an increase in blood coagulation and, ultimately, to the development of thromboembolic complications (the formation of blood clots in small and large vessels).

The reasons for the appearance of such antibodies have not yet been identified. There are studies on the role of some viruses and their effect on lymphocytes, as one of the parts of the immune system.

According to statistics, APS is detected in almost 40% of women with recurrent miscarriage. Interruption occurs more often in the second or third trimesters. It is natural that the gestational age decreases with each subsequent interrupted pregnancy.

The main manifestations of APS during pregnancy:

• Dysfunction of the placenta (fetoplacental insufficiency) due to multiple microthrombosis of the placental vessels. As a result, intrauterine growth retardation of the fetus develops, its hypoxia up to death.
• Much or little water.
• Premature rupture of membranes.
• Complications of the course of pregnancy: preeclampsia, eclampsia, HELLP syndrome, etc.
• Premature detachment of a normally located placenta.

Even at the birth of a full-term baby, he may develop various pathological conditions that significantly worsen the course of the neonatal period and can even lead to death (hyaline membrane syndrome, cerebrovascular accident, respiratory distress syndrome, etc.).

To diagnose this serious pathology, a number of diagnostic tests are used, the leading of which is the determination of specific antibodies (anticardiolipin and antiphospholipid).

Prevention

Prevention of miscarriage lies, first of all, in the competent approach of future parents to the birth of offspring. To this end, a number of activities have been developed, which is called "pregravid preparation". To reduce the risk of problems with conception and subsequent pregnancy, a married couple is recommended:

• Undergo an examination to identify abnormalities in both somatic and reproductive areas.
• It is mandatory to maintain a healthy lifestyle: giving up bad habits, minimizing the influence of environmental factors (for example, occupational hazards), avoiding stress, etc.
• If any foci of infection are detected, they should be sanitized.

If a woman has already had cases of abortion at any time, it is necessary to find out the possible reasons for this as fully as possible and carry out the necessary correction. The treatment of this pathology is carried out by a gynecologist with the possible involvement of doctors of other specialties, depending on the identified violations.