Miscarriage- spontaneous termination of pregnancy up to 37 full 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 entire 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 gestation period 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 diagnosed pregnancies. However, only according to clinical data, in the early stages of pregnancy, a spontaneous miscarriage may not be diagnosed. Its frequency increases to 30-60%, when, before the onset of the next menstruation, such highly sensitive methods as determining the level of β-hCG in the blood serum are used to confirm pregnancy. Most often, the diagnosis of "chemical" pregnancy by the level of β-hCG is established in a group of patients with infertility after stimulation of ovulation with hormonal drugs.

From 40 to 80% of miscarriages occurs 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 miscarriages decreases.

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

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

An increase in the risk of miscarriage rates 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 during pregnancy up to 20 weeks, a diagnosis of recurrent 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 provokes miscarriage

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

The main reasons for miscarriage are considered:
- 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 constitute the group of "unexplained" miscarriage.

Characteristics of the most significant risk factors

- Genetic disorders
Genetic disorders leading to spontaneous miscarriage are well studied 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 caused by abnormalities in the chromosomes of the embryo. Early termination of pregnancy can be the result of natural selection, which leads to the death of the pathologically developing embryo and / or fetus.

Chromosomal pathology with 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 married couples with recurrent miscarriage occurs much more often than in women with one miscarriage.

Chromosomal aberrations play a special role in patients with spontaneous miscarriages.

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

Mother's age does not matter for other chromosomal abnormalities that cause spontaneous miscarriages.

Monosomy X causes embryo aplasia. Triploidy and tetraploidy occur with moderate frequency. A structural chromosome abnormality is a translocation transmitted by one of the parents. Among other violations of the karyotype, there are various forms of mosaicism, double trisomies and other pathologies.

Sporadic spontaneous miscarriages during short term pregnancies reflect the universal biological mechanism of natural selection that 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 the karyotype is determined. 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 the mother's 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 enter the fetus.

The hematogenous and contact routes of infection, prevailing in the first trimester of pregnancy, subsequently give way to the ascending spread of infections. An ascending infection from the lower parts of the reproductive organs infects the amniotic membranes, whether their integrity is compromised or not. The fetus becomes infected with contaminated amniotic fluid or infectious agents that spread through 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 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 abortion and a specific pathogenic agent. If a microorganism can be isolated from the tissues of a deceased embryo / fetus, it is almost 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. It is more likely that the fetus becomes infected through the placenta, which leads to chorionamnionitis, release of prostaglandins and increased uterine contractile activity.

There is a relationship between bacterial invasion and the synthesis of cytokines by cells of the amnion, chorion, decidual and fetal tissues. The reproduction 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 of penetration of infection into the embryo / fetus is chorionic biopsy, amniocentesis, fetoscopy, cordocentesis, intrauterine blood transfusion, especially if these manipulations are carried out 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 pathomorphological examination after a spontaneous miscarriage occurred. The diagnosis of primary inflammation is established in the absence of other pathological processes that can cause a violation of uterine pregnancy.

Combined inflammation can be talked about in the case of the simultaneous presence of several etiological factors, the severity of which does not allow distinguishing the sequence of their pathogenic effects. Secondary inflammation is characterized by vascular-cellular reactions against the background of prolonged manifestations of the preceding etiological factors.

The effect of infection on the fetus depends on the state of its body and the gestational age. Given the absence of a formed placental barrier in the first trimester, any types of hematogenous and ascending infection are dangerous. At this time, the most frequent complications of pregnancy are intrauterine infection, fetal abnormalities and spontaneous miscarriage.

The severity of the lesion and the prevalence of the pathological process in the embryo / fetus depend on its ability for an immune response, on the type, virulence and number of penetrated 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 is currently various associations of microorganisms - viral-bacterial, viral-viral and bacterial-bacterial, which is due to the peculiarities of the immune response, in which complete elimination of the pathogen from the body is impossible.

The main source of the gravidar inflammatory process that develops in the first trimester of pregnancy is most often the foci of infection located in the vagina and cervix. 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 presumed factors of a similar inflammatory process in the endometrium. This inflammatory process exacerbates the likelihood of infection of the fetal bladder and thereby 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, but today there is no doubt that opportunistic bacteria prevail among the microbes entering the uterine cavity from the lower reproductive organs, and the imbalance of the vaginal environment is considered as the main reason for the complicated course of pregnancy and fetal IUI. The spectrum of pathogens includes numerous pathogens, such as group A streptococci, opportunistic anaerobes, which are relatively often detected in the vagina.

The action of various infectious agents, as well as unfavorable 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 of great importance in preventing various diseases. Violation of the microbiocenosis of the genital tract is accompanied by an imbalance in the local immune status, 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 in various types of microorganisms and appropriate treatment.

The most common disorder 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 by a mixed flora consisting of anaerobic opportunistic bacteria (Bacteroidesspp., Mobiluncusspp., Peptostreptococcusspp., Peptostreptococcusspp. NS.). The quantitative and qualitative composition of the microflora of the vagina and cervix of the uterus changes both by increasing the intensity of colonization of microorganisms and by increasing the frequency of their excretion.

Immunological weekly sufficiency 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: the activation of 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, supporting 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, to microbiological examination of not only the luminal, but also the parietal microflora of the vagina, which avoids mistakes.

Smear studies help to navigate the possible pathology and determine the need, sequence and volume 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 pronounced dysbiotic disorders of the vagina, a complicated course of pregnancy (the threat of abortion, an abortion that has begun, etc.), as well as structural and functional inferiority of the cervix, it is recommended to use correctors and interferon inductors: KIP-feron (vaginal suppositories) 1 candle 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 in a dose of 25 ml every other day 3 times and / or octagam 2.5 mg intravenously every 2 days 2-3 times is shown.

The drugs of choice for dysbiotic disorders of the vagina in the II trimester are vaginal suppositories and vaginal tablets (terzhinan, betadine, Klion-D, flagil, etc.). At the second stage of treatment, the normal vaginal microbiocenosis is restored with biological products (acilac, 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 androgen secretion (hyperandrogenism);
- diseases of the thyroid gland;
- diabetes.

Defective luteal phase as a cause of endocrine infertility and miscarriage in women was first described in 1949 by G. Jones et al. For a full-fledged secretory transformation and preparation of the endometrium for implantation of a fertilized egg, a sufficient concentration of estrogens, progesterone and the maintenance of their normal ratio during the menstrual cycle and especially in the second phase of the cycle are required.

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

During clinical and endocrinological examination of patients with incomplete luteal phase, it was shown that this pathology arises 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 changes in the pulsating rhythm of the secretion of gonadotropic releasing hormone (luliberin);
- increasing the level of prolactin;
- a decrease in the ovulatory peak of LH and / or the ratio of FSH / LH during the cycle and during ovulation.

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

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

A possible cause of follicular maturation disorders are pathological conditions of the ovaries caused by chronic inflammation of the genitals, surgical interventions on the ovaries, which leads to a decrease in their functional activity, especially in women over 35-36 years old.

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

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

With an inferior luteal phase, natural progesterones are prescribed for several months (dyufaston 200 mg, morning oral 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 threatened abortion and the level of progesterone, it is possible to prescribe duphaston and uterine 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 between three types of hyperandrogenism:
- adrenal;
- ovarian;
- mixed.

Regardless of the type of hyperandrogenism, termination of pregnancy occurs in the early stages and proceeds as anembryonic or non-developing pregnancy. In 40% of patients during pregnancy, functional ICI or low placenta previa occurs. In the II and III trimesters, pregnancy termination 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 is added to the problem of miscarriage.

During pregnancy, patients with hyperandrogenism experience three critical periods when the level of androgens in the mother's body increases 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 testes of the male fetus begin to produce androgens, and at 27-28 weeks, ACTH is secreted by the anterior pituitary gland of the fetus.

In case of hyperandrogenism detected before pregnancy, preparatory therapy with dexamethasone 1/2 tablet (0.25 mg) is carried out once a day in the evening before bedtime, continuously until pregnancy. The dose of the drug changes 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 during this time pregnancy has not occurred, you should think about the occurrence of secondary infertility. During pregnancy, the dose and duration of taking the drug are determined by the peculiarities of the clinical course of pregnancy, the presence of symptoms of the threat of interruption and ICI, as well as the dynamics of the level of DHEA / DHEA sulfate. The timing of discontinuation of dexamethasone ranges 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 ICI, low placentation, and the threat of hypertension and gestosis in the II and III trimesters of pregnancy.

In patients with thyroid diseases of the type of hypo-, hyperthyroidism, autoimmune thyroiditis, etc., it is recommended that the identified disorders be eliminated before the onset of the next pregnancy, as well as the selection of the dose of thyroid homones and clinical and laboratory control during the entire pregnancy.

Pregnancy in women with diabetes mellitus 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 state of health.

- Immune factors
Immune factors of miscarriage are the most common causes of miscarriage and their frequency, according to different authors, is 40-50%. 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 chromosome 6. I class of HLA antigens is represented by antigens A, B, C, which are necessary for recognition of transformed cells by cytotoxic T-lymphocytes. HLA class II antigens (DR, DP, DQ) provide interaction between macrophages and T-lymphocytes in the course of the immune response. Carriage of some HLA antigens is believed to be associated 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 links of immunity.

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

The second, no less complex mechanism of miscarriage is due to violations 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-abortive effect in a woman's body and helps to maintain pregnancy.

What are the immunological mechanisms that cause early termination of pregnancy? To this end, one should recall the features of the formation of an embryo after fertilization of an egg with a sperm. A sperm cell, formed from an embryonic cell and passing through a number of developmental stages, contains half of the total set of chromosomes (23 chromosomes). A similar set of 23 chromosomes contains an ovum produced by ovulation. Accordingly, a fertilized egg already contains a set of 46 genetically programmed chromosomes.

In peripheral blood lymphocytes, progesterone receptors are normally present. 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 indicators outside of pregnancy.

It is believed that unexplained forms of miscarriage can be caused by disorders in the cellular and humoral links of immunity. Much attention is paid to cell-mediated immune mechanisms as possible etiological factors of spontaneous abortion; 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 response helps maintain a normal pregnancy, while the TX1 response is antagonistic to pregnancy and can cause abortion.

Despite the fact that at present the mechanism for the development of spontaneous miscarriage has not been finally clarified, 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 transplant, the number of cells containing progesterone receptors is comparable to that of 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 associated with the presence of an embryo, which acts as an alloantigenic stimulant.

In a pregnant woman, under the influence of antigens of the embryo, against the background of the 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 effect of PIBP concerns both cellular and humoral immune mechanisms. PIBP at the cellular level affects the synthesis of cytokines in T-helper lymphocytes. With a normal pregnancy, there is a shift towards an increase in TX2 and their production of cytokines, while a decrease in TX1. This mechanism contributes to the maintenance of pregnancy.

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

When PIBP was administered to animals, the emergence 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 PIBP and the number of asymmetric molecules - IgG. In the absence of pregnancy, the PIBP level and the number of asymmetric antibodies are low.

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

As a result of studies devoted to the study of the mechanism of action of PIBP, it was shown that this substance:
- affects the balance of cytokines, as a result of which the production of TX1 cytokines decreases and the level of TX2 cytokines increases;
- reduces the activity of natural killer cells and ensures a normal pregnancy outcome.

The blockade of progesterone receptors leads to a decrease in the production of PIBP, which results in an increase in the production of TX1 cytokines, an increase in natural killer cells and the onset of spontaneous abortion.

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

At present, three main pathways have been described along which the embryo is rejected by the mother's body.

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

Increased natural killer activity. These cells are converted into LAK cells under the influence of 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, the opposite processes must be provided in the body. Thus, immunomodulation aimed at protecting the embryo also includes three protection pathways.

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

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

There is no release of TNF α and IL-2, and killer cells are not transformed 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 PIBP, which provides the processes described above.

A number of studies have shown that progesterone significantly 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, TNF α, and therefore this hormone is considered a natural immunosuppressant. Since progesterone inhibits the production of TX1 cytokines and stimulates the production of TX2 cytokines, it has been proposed to use progesterone or its analogs in women with recurrent miscarriage of unknown etiology, when a shift towards the prevalence of TX1 cytokines is observed in the body.

It has been shown that stimulation of progesterone receptors with endogenous progesterone or dydrogesterone (dyufastone) stimulates the production of PIBP, 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 decrease in 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 genitals during miscarriage is of two types: congenital and acquired.

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

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

The mechanism of termination of pregnancy with malformations of the uterus is associated with a violation of the processes of implantation of the ovum, inadequate secretory transformations of the endometrium due to reduced vascularization, close spatial relationships of the internal genital organs, functional features of the myometrium, increased excitability of the infantile uterus. The threat of termination is observed at all stages of pregnancy.

With an intrauterine septum, the risk of spontaneous abortion is 60%. Miscarriages are more likely to occur 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.

Abnormalities in the discharge 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 synechiae are the cause of abortion in 60-80% of women, which depends on the location of the synechiae and the degree of their severity.

The pathogenesis of habitual spontaneous abortion in the presence of uterine fibroids is associated with absolute or relative progesterone sufficiency, 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 data, gynecological examination, results of hysterosalpingography, ultrasound scanning, hysteroscopy and laparoscopy. Currently, most of the organic pathology that causes the habitual spontaneous abortion is treated with the help of hysteroscopic operations. During hysteroscopy, you can remove the submucous myomatous node, destroy the intra-uterine synechia, remove the intrauterine septum. With intrauterine synechiae and uterine septum, transcervical metroplasty is also performed under ultrasound control.

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

Pregnancy in the case of ICI usually proceeds without symptoms of threatened termination. The pregnant woman has no complaints; palpation reveals a normal tone of the uterus. With a vaginal examination, the shortening and softening of the cervix is ​​determined, the cervical canal freely passes the finger beyond the area of ​​the internal pharynx. When viewed in the mirrors, a gaping external cervical os with flaccid edges is visible, prolapse of the fetal bladder is possible. With an increase in intrauterine pressure, the 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 an increase in the frequency of functional ICI, which occurs in endocrine disorders (defective luteal phase, hyperandrogenism).

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

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

Methods for surgical removal of ICI (cervical suture) are described in detail in the manuals for operative obstetrics. The question of suturing the cervix with a prolapsing fetal bladder, low placenta and multiple pregnancy should be decided individually in each specific clinical situation.

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

Symptoms of Miscarriage

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

If you find these symptoms in yourself, immediately contact your obstetrician-gynecologist.

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. The gynecological history reveals the presence of inflammatory diseases of the genitals, viral infection, methods of therapy, especially menstrual and reproductive functions (abortion, childbirth, spontaneous miscarriages, including complicated ones), other gynecological diseases and surgical interventions.

Clinical examination consists of examination, assessment of the condition of the skin, the degree of obesity according to the body mass index, the state of the thyroid gland. According to the hirsut 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 data of rectal temperature and menstrual calendar.

Laboratory and instrumental methods studies are as follows.
- Hysterosalpingography - performed on the 17-23rd day of the menstrual cycle and allows to exclude uterine malformations, intrauterine synechiae, ICI.

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

Infection 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-hCG, anticardiolipin antibodies are determined, and the features of the hemostasis system are analyzed.

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

If there is a suspicion of the presence of intrauterine pathology and / or pathology of the endometrium, separate diagnostic curettage is performed under the control of hysteroscopy.

If there is a suspicion of genital endometriosis, tube pathology and adhesions in the small pelvis, with uterine myoma and scleropolycystic ovaries, operative laparoscopy is indicated.

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

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

Treatment of Miscarriage

If the miscarriage is complete and the uterus is clear, then usually no special treatment is required. Sometimes the uterus is not completely cleansed, then the procedure for scraping 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 certain medications that will cause your body to reject the contents of the uterus. This method can be ideal for those who want to avoid surgery and who are in stable health.

Forecast
Prediction 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 the threat of termination of pregnancy and loss of a child.

Prevention of Miscarriage

Prophylaxis consists in a thorough examination of women in order to identify the causes of miscarriage and conduct rehabilitation therapy to prepare for 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 uterine malformations, intrauterine synechiae, isthmic-cervical insufficiency; functional diagnostic tests to assess hormonal balance; bacteriological examination of the contents of the cervical canal, examination for toxoplasmosis, cytomegalovirus, etc., determination of the 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 a study of his sperm. If at the first stage of the examination, the reasons for miscarriage are not identified, the woman is sent to specialized offices of the antenatal clinic or polyclinic, where hormonal, medical and genetic research is carried out. If the causes of miscarriage still remain unclear, an examination is necessary in specialized institutions or in hospitals, where a deeper study of the endocrine system, the immune system and other special studies is carried out.

31.07.2018

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

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All 9 months, the expectant mother has to carefully monitor her condition, noting any changes, so that in case of complications, immediately consult a doctor. Unfortunately, it cannot always help: miscarriage is diagnosed in about 10-20% of cases.

Miscarriage in obstetrics and gynecology is called spontaneous abortion, which occurred before 37 weeks. Half of all such cases occur in the first trimester. Since it is the most dangerous, almost all medications are prohibited, emotional and physical overload, and sometimes bed rest is required. A spontaneous interruption that occurs before 22 weeks is called. At a later date -.

The classification of miscarriage is most often carried out by timing.

Up to 22 weeks - spontaneous abortion:

• Up to 11 weeks and 6 days - early abortion.
• From 12 weeks to 21 weeks and 6 days - late abortion.
• From 12 weeks to any date, provided that the fetal body weight is less than 500 g - late abortion.

From 12 to 36 weeks and 6 days - premature birth:

• From 22 weeks to 27 weeks and 6 days, with a fetal weight from 500 to 1000 grams - early premature birth.
• From 28 weeks to 36 weeks and 6 days, with a fetus weighing more than 1000 grams - premature birth.

Also, miscarriage is divided into stages:

1. Threatened abortion- the stage at which the fetus grows and develops normally, but exists.
2. Started abortion- the ovum is already peeling off a little, but the pregnancy can still be saved.
3. Abortion on the go- the ovum is separated from the walls of the uterus and is located in its cavity or in the cervix, it is no longer possible to keep the pregnancy.
4. Incomplete abortion- a part of the ovum remains in the uterine cavity, causing its inflammation and the development of infection.
5. Complete abortion- the ovum completely leaves the woman's body, only a doctor's supervision is required.
6. Failed abortion- the fetus dies inside the womb, but is not expelled for a long time.

Antiphospholipid syndrome

Antiphospholipid syndrome refers to an autoimmune disorder that leads to miscarriage. This disease is found in 27% of cases of spontaneous interruption.

Phospholipids are components of the cell walls of blood vessels, platelets, brain and lung tissues. In antiphospholipid syndrome, the immune system attacks membranes, causing damage to cells and tissues. As a result, thrombosis, thrombocytopenia, headaches, stroke, heart attack, hypertension and other diseases can develop.

Early embryo miscarriage occurs due to impaired implantation of the ovum or its rejection. Vascular thrombosis of the placenta leads to intrauterine fetal death.

Other reasons

Other causes of miscarriage include:

• injuries of a pregnant woman;
• intense emotional experiences, stress;
• diseases of internal organs (heart, blood vessels, kidneys, liver);
• complications of pregnancy, such as acute fatty;
• exposure to harmful substances during production, in areas with poor environmental conditions;
• husband's diseases leading to ejaculate pathologies.

Symptoms

Symptoms of miscarriage include:

• pulling pain in the lower abdomen;
• sudden attacks of intense pain in the lower abdomen;
• bleeding from the vagina;
• pain in the lumbar region and sacrum;
• dizziness and weakness;
• nausea and vomiting;
• temperature increase.

If such symptoms are found, you should immediately seek medical help: go to an appointment with a gynecologist out of turn or call an ambulance. If the risk of termination is confirmed, then in the future the woman will be consulted by a doctor on miscarriage.

Diagnostics

In case of miscarriage, the diagnosis is carried out before conception and after spontaneous interruption. The examination helps to find out the possible and existing causes of the complication.

It includes:

• a clinical survey, which clarifies and clarifies complaints: when the symptoms began, what kind of nature they are, what could cause them, etc.;
• collection of information about gynecological diseases, operations, abortions, pregnancies, etc. (obstetric and gynecological history);
• collection of information about: how long does it take, when the period first began, when was the last time, etc.;
• examination in order to study the characteristics of the physique, the degree of obesity, the state of the thyroid gland;
• examination on a gynecological chair;
• Ultrasound of the pelvic organs in each phase of the cycle;
• blood test to detect TORCH infections:, and;
• research to identify urogenital infectious diseases (sexually transmitted diseases);
• study of hormones that affect the bearing of pregnancy (thyroid gland, ovaries, adrenal cortex);
• study of the blood coagulation system (coagulogram);
• genetic examination (set of chromosomes, their changes);
• spermatogram;
• a blood test to detect autoimmune diseases;
• cytogenetic study of the remains of the ovum;
• consultations of narrow specialists: endocrinologist, geneticist, psychotherapist, psychologist.

The choice of the necessary tests for miscarriage is carried out by the doctor individually. The survey data, obstetric and gynecological history, general health of the woman are taken into account.

Treatment

Treatment for miscarriage depends on the cause and stage. When the threat of interruption is identified, strict bed rest with an elevated position of the legs is required. Most often, a hospital stay is required. To prevent natural abortion, hormonal agents are prescribed (, etc.). They must be used strictly according to the medical scheme, exceeding the dosage can affect the child's sexual differentiation, and a sudden cessation of admission can provoke a miscarriage.

Depending on the causes of miscarriage, treatment may include taking sedatives and neurotropics, vitamins, anticoagulants, antibiotics, antiviral drugs, etc.

Helping the family in case of miscarriage is to create a calm and friendly atmosphere in the house, to prevent any physical and emotional overload of the expectant mother.

When intrauterine fetal death occurs without expulsion from the uterus, a procedure is performed to remove the ovum using a special suction. The woman is placed on a gynecological chair, local or general anesthesia is performed, the cervix is ​​dilated and a vacuum tube is inserted. Negative pressure is created and the ovum is released.

In case of incomplete miscarriage, when the fetus is expelled, but parts of the fetal membrane remain, it is carried out. During this procedure, the uterus is cleansed using a curette - an instrument that resembles a spoon with a hole. All manipulations are performed under general anesthesia. In some cases, curettage can be replaced by vacuum aspiration, and in the second trimester, by the administration of oxytocin. This hormone causes uterine contractions similar to those occurring during natural childbirth.

The protocol for the treatment of miscarriage includes monitoring the woman's condition for 3-4 days after a spontaneous abortion. This is necessary in order to eliminate possible complications in time: bleeding, the development of infection, etc. When chills, fever, and lining of the tongue appear, antibiotics are prescribed.

Complications

With miscarriage, rejection and expulsion of the fetus from the uterine cavity occurs.

Miscarriage and premature birth can cause the following complications:

• profuse bleeding, which can lead to a critical condition - weakness, decreased blood pressure, confusion and loss of consciousness, and in severe cases - to death;
• infection of the abdominal cavity, peritonitis;
• blood poisoning (sepsis).

Due to the risk of complications, inpatient observation is necessary for several days after spontaneous abortion. With timely medical assistance, it is possible to stop all symptoms and preserve the woman's reproductive health.

Prophylaxis

Prevention of miscarriage is based on maintaining the health of the woman and a comprehensive examination during planning. If the spontaneous interruption has already occurred, then you need to find out its cause. For this, there are several types of diagnostics: the study of genetic and chromosomal abnormalities, hormonal abnormalities, immunological and anatomical pathologies. All procedures can be carried out in specialized centers for the prevention and treatment of miscarriage.

Once the cause of the miscarriage has been identified, treatment is necessary before the next pregnancy occurs. It may include taking medication, physical therapy, and in some cases, surgery.

If a woman has not yet encountered the problem of miscarriage, then prevention is to maintain health. It is necessary to strengthen the immune system by all means, observe sanitary and hygienic rules, avoid casual sexual intercourse, timely identify and treat diseases of internal organs. For preventive purposes, you need to visit a gynecologist every six months.

Miscarriage is the spontaneous termination of pregnancy before 37 weeks. Depending on the term, it can be called a miscarriage or premature birth. There are many reasons for this complication: hormonal, anatomical, genetic, immunological, infectious.

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Catad_tema Pathology of pregnancy - articles

Actual problems of miscarriage

V.M. Sidelnikova, G.T. Dry

A guide for practitioners

Moscow 2009

Introduction
	Physiology of the reproductive system
	Formation and functioning of the mother-placenta-fetus system
	2.1. Fertilization and the processes of implantation and placentation
	2.2. Placenta formation
	2.3. Hormones of the placenta, decidua and fetal membranes
	2.4. Development of the embryo and fetus.
	2.5. Features of steroidogenesis in the mother-placenta-fetus system.
	2.6. Adaptive changes in the mother's body during pregnancy.
	Epidemiology of miscarriage
	Genetic causes of miscarriage
	Endocrine aspects of miscarriage
	5.1. Defective luteal phase
	5.2. Hyperandrogenism and pregnancy
	5.3. Thyroid and pregnancy
	5.4. Diabetes and pregnancy
	5.5. Hyperprolactinemia and pregnancy
	5.6. Sensitization to human chorionic gonadotropin as a cause of habitual pregnancy loss.
	5 .7. Sensitization to progesterone in patients with recurrent pregnancy loss.
	Thrombophilic disorders and habitual pregnancy loss
	6.1. Physiology of the hemostasis system and methods of its assessment
	6.2. The main methods for diagnosing disorders in the hemostasis system
	6.3. Features of the hemostasis system in uncomplicated pregnancy
	6.4. Antiphospholipid syndrome
	6.4.1. Features of the hemostasis system in pregnant women with APS
	6.4.2. Tactics of preparation for pregnancy in patients with APS
	6.4.3. Pregnancy management tactics for patients with APS
	6.4.4. Catastrophic APS
	6.5. Hereditary thrombophilia in obstetric practice
	6.6. Disseminated intravascular coagulation syndrome (DIC)
	6.7. Coagulopathic disorders. Bleeding during pregnancy (causes, tactics, management)
	6.7.1 Chorionic detachment.
	6.7.2. Premature placental abruption in II and III trimesters
	6.7.3 Chorionic presentation
	6.7.4. Retention of the embryo / fetus in the uterus after death
	Alloimmune mechanisms of repeated pregnancy losses
	7.1. The HLA system and its role in human reproduction
	7.2. Role of HLA-G in recurrent miscarriage
	7.3. The Role of Blocking Anti-Paternal Antibodies in Miscarriage
	7.4. Features of the immune status in patients with recurrent miscarriage
	7.5. Methods of therapy for alloimmune disorders
	Infectious aspects of miscarriage
	8.1. Pregnancy preparation tactics and its management
	8.2. Cytomegalovirus infection in patients with recurrent miscarriage
	8.3. Herpes simplex virus infection
	8.4. Coxsackie virus infection
	8.5. Bacterial infection
	8.6. Tactics of preparing for pregnancy in patients with miscarriage of infectious genesis
	8.7. Immunomodulatory therapy for recurrent miscarriage
	8.8. Pregnancy management tactics in patients with infectious genesis of recurrent miscarriage
	Pathology of the uterus - as a cause of miscarriage
	9.1. Malformations of the uterus
	9.2. Ingenious infantilism
	9.3. Myoma of the uterus
	9.4. Intrauterine synechiae
	9.5. Isthmico-cervical insufficiency
	Paternal causes of miscarriage
	Examination of patients with recurrent miscarriage
	Clinical options for termination of pregnancy. Management tactics
	Premature birth
	13.1. The role of infection in the development of preterm labor
	13.2. Premature rupture of amniotic fluid in premature pregnancy
	13.3. The role of isthmic-cervical insufficiency in preterm labor
	13.4. Stimulating role of corticotropin-releasing hormone in the development of preterm labor
	13.5. Multiple pregnancy - risk of premature birth
	13.6. Diagnostics of threatened premature birth
	13.7. Management and treatment of threatened premature birth
	13.8. Respiratory Distress Syndrome (RDS) Prevention
	13.9. Features of the course and management of spontaneous premature birth
	13.10. Management of preterm labor
	13.11. Prevention of premature birth
	Premature rupture of amniotic fluid in premature pregnancy
Literature

Introduction

The problem of protecting the health of mothers and children is considered as an essential component of health care, which is of paramount importance for the formation of a healthy generation of people from the earliest period of their life. Among the most important problems of practical obstetrics, one of the first places is occupied by the problem of miscarriage.

Miscarriage - spontaneous termination of pregnancy in the period from conception to 37 weeks, counting from the first day of the last menstruation. Termination of pregnancy in the period from conception to 22 weeks is called spontaneous abortion (miscarriage). Termination of pregnancy between 28 weeks and 37 weeks is called preterm labor. The gestation period from 22 weeks to 28 weeks according to the WHO nomenclature is referred to as very early premature birth, and in most developed countries, perinatal mortality is calculated from this gestational age. In our country, it is planned to switch to the WHO nomenclature in the near future.

Spontaneous abortion belongs to the main types of obstetric pathology. The frequency of spontaneous miscarriages is 15 to 20% of all desired pregnancies. It is believed that the statistics do not include a large number of very early and subclinical miscarriages.

Many researchers believe that spontaneous abortions of the first trimester are a tool of natural selection, since in the study of abortions, 60 to 80% of embryos with chromosomal abnormalities are found.

The causes of sporadic spontaneous abortion are extremely varied and not always clearly defined. These include a number of social factors: bad habits, harmful production factors, unsettled family life, hard physical labor, stressful situations, etc. Medical factors: genetic damage to the karyotype of parents, embryos, endocrine disorders, uterine malformations, infectious diseases, previous abortions and etc.

Habitual miscarriage (miscarriage) – spontaneous termination of pregnancy two or more times in a row.

In a number of countries, 3 or more spontaneous interruptions are considered a habitual miscarriage, but examination to identify the causes of abortion is recommended after 2 interruptions. The frequency of recurrent miscarriage in the population ranges from 2% to 5% of the number of pregnancies. In the structure of miscarriage, the frequency of habitual miscarriage is from 5 to 20%.

Habitual miscarriage is a polyetiological complication of pregnancy, which is based on violations of the reproductive system. The most common causes of recurrent miscarriage are endocrine disorders of the reproductive system, erased forms of adrenal dysfunction, damage to the receptor apparatus of the endometrium, clinically manifested in the form of an inferior luteal phase (LF); chronic endometritis with persistence of opportunistic microorganisms and / or viruses; isthmic-cervical insufficiency, uterine malformations, intrauterine synechiae, antiphospholipid syndrome and other autoimmune disorders. Chromosomal pathology for patients with recurrent miscarriage is less significant than for sporadic abortions; nevertheless, in spouses with recurrent miscarriage, structural abnormalities of the karyotype occur 10 times more often than in the population and amount to 2.4%.

The reasons for sporadic abortion and recurrent miscarriage may be identical, but at the same time, a married couple with recurrent miscarriage always has a more pronounced pathology of the reproductive system than with sporadic interruption. When managing patients with habitual loss of pregnancy, it is necessary to examine the state of the reproductive system of a married couple outside of pregnancy.

The problem of recurrent miscarriage cannot be solved during pregnancy. In order for the treatment to maintain pregnancy to be effective, it is necessary to know the causes and a deeper understanding of the pathogenesis of those disorders that lead to the termination of pregnancy.

This can be found out only with a thorough examination outside of pregnancy, for rehabilitation therapy and more rational management of pregnancy. Only such an approach, individual in each specific observation, can ensure a successful pregnancy and the birth of a healthy child.

Premature birth is one of the most important issues in this problem, as it determines the level of perinatal morbidity and mortality. Premature babies account for up to 70% of early neonatal mortality and 65-75% of child mortality. Stillbirth in premature birth is 8-13 times more likely than in timely delivery.

According to B. Guyer et al. (1995), in the United States, prematurity and its complications are the leading cause of death in fetuses and newborns without developmental abnormalities and account for 70% of total perinatal mortality. Long-term consequences of prematurity: disorders of psychomotor development, blindness, deafness, chronic lung diseases, cerebral palsy, etc. - are well known. According to M. Hack et al. (1994), children born weighing less than 1500 g are 200 times more likely to die as newborns and, if they survive, 10 times more likely to have neurological and somatic complications than children born weighing more than 2500 g. And even if the neonatal period passes without complications , then during school years, most of these children have problems. Over the past 30 years, great success has been achieved in the care of premature babies in the world, as a result of which infant mortality, immediate and distant morbidity has been significantly reduced, but the frequency of preterm birth has not decreased in recent years, but, on the contrary, is increasing, especially in developed countries.

According to K. Damus (2000), in the USA over the past 10 years, the incidence of preterm birth has increased from 10% to 11.5%, and this is due to the increase in the number of multiple pregnancies after IVF programs and other methods of stimulating ovulation, as well as the wider spread of harmful habits (tobacco, drugs, alcohol).

The problem of premature birth has a psychosocial aspect, since the birth of a premature baby, his illness and death are severe mental trauma. Women who have lost a child feel fear for the outcome of a subsequent pregnancy, a sense of their own guilt, which ultimately leads to a noticeable decrease in their vitality, conflicts in the family, and often to refusal of subsequent pregnancy. In this regard, the problem of premature birth has not only medical but also great social significance.

The problem of preterm birth is acquiring enormous social significance, given the high cost of nursing premature babies. According to A. Antsaklis (2008), the cost of medical care for premature newborns is $ 16.9 billion - $ 33,200 per one premature baby. According to J. Rogowski (2000), the average cost of nursing a 500 g child is more than USD 150,000, and only 44% of them survive. With a child weighing 1251-1500 g, the average cost of nursing is approximately US $ 30,000 and a survival rate of 97%. But there is no data on the non-medical cost of maintaining these children for the family and society as a whole (Bernstein P., 2000).

Apparently, the solution to the problems of a premature baby, both medically and socially, lies in the problem of preventing premature birth. This is not a simple problem, and many attempts have been made to develop such programs in the world (Papiernik E., 1984), but, unfortunately, N. Eastmen's statement, made back in 1947, remains valid: “Only when the factors underlying the basis of prematurity, will be fully understood, attempts can be made to prevent them. "

In recent years, many of the causes of premature birth and the mechanisms of their development have become clear, and this gives rise to certain hopes.

Premature birth is not just a delivery that is not on time, it is delivery to a sick mother, a sick child.

In this regard, most of the book is devoted to modern aspects of the etiology of miscarriage, as well as the principles of examination and treatment outside of pregnancy of a married couple suffering from habitual loss of pregnancy.

The book also discusses the modern basic principles of hormonal, immune relationships in the mother-placenta-fetus system, the role of genetic disorders in abortion.

A large section is devoted to the prevention and treatment of infection in patients with recurrent miscarriage. The book focuses on thrombophilic complications in obstetric practice, in particular antiphospholipid syndrome, sensitization to chorionic gonadotropin. Much attention is paid to the problem of premature birth, tactics of their management and prevention.

The book presents data from the literature of recent years, the authors' own observations, the results of the work of the teams of the department of therapy and prevention of miscarriage and the laboratory of immunology, who are currently working and have left to work in other teams after defending their dissertations.

The book uses materials obtained in joint research with E.M. Demidova, L.E. Murashko, S.I.Sleptsova, S.F. Ilovaiskaya, L.P. Zatsepina, A.A. Agadzhanova, Z.S. Khodzhaeva, P.A. Kiryushchenkov, O.K. Petukhova, A.A. Zemlyana, N.F. Loginova, I.A.Stadnik, T.I.Shubina. Former graduate and doctoral students of the department: V.N. Moshin, V. Bernat, N. M. Mamedalieva, A. T. Raisova, R. I. Chen, E. Kulikova, M. Rasulova, A. S. Kidralieva, T. V. Khodareva, N.B. Kramarskaya, N. Karibaeva, Zh.Z.Ballyeva, N.V. Khachapuridze, L.G. Dadalyan, R. Skurnik, O.V. Rogachevsky, A.V. Borisova, N.K. Tetruashvili, N.V. Tupikina, R.G. Shmakov, V.V. Gnipova, K.A. Gladkova, T.B. Ionanidze, Y. Shahgyulyan, S.Yu. Baklanova.

For many years we have been conducting clinical and scientific work in close cooperation with other laboratories of the Center and all clinical departments of the Center. This book reflects the results of joint research. The authors are deeply grateful to these teams for their constant assistance in scientific and clinical work and hope that this monograph will be useful to obstetricians-gynecologists in their practical work and will accept all comments with gratitude.

We are especially grateful to O.S. Borisova. for technical assistance in preparing the book.

Miscarriage is not only a physical trauma for a woman, but also a moral one. It is for this reason that the article below has collected the maximum amount of information about the diagnosis, causes, symptoms, treatment, and prevention of spontaneous miscarriage.

Early miscarriage is very sad and, unfortunately, quite common. According to statistics, every eighth woman has a pregnancy terminated in the first twelve weeks. Most of them miscarry without realizing that they were pregnant. And some of them talk about the possibility of losing the fetus already at the first consultations and are advised to go to preservation.

It is considered the least influencing on the reproductive function and health of the woman. It is very important not to miss the deadline.

The termination of pregnancy may not be noticed by a woman in the early stages. The delay in menstruation is simply written off as a delay, and then profuse bleeding begins, which is accompanied by a feeling of pain. When the fetus is completely released, the bleeding and pain stop, and the woman may never know that she was pregnant.

If the fetus does not come out completely, which is the cause of prolonged bleeding, women, as a rule, turn to a specialist who ascertains miscarriage. Most doctors, in order to restore the female body, after such a case, prescribe a course of medical therapy.

Causes

The reasons for miscarriage can be as follows:

• Hormonal disbalance.
• Genetic abnormalities.
• Infectious diseases.
• Rh factor.
• Medications.
• Injuries.
• Abortions in the past.

The threat of termination of pregnancy in the second trimester is markedly reduced. According to statistics, in the second trimester, a miscarriage occurs only in every fiftieth woman.

So, let us consider in more detail the reasons for miscarriage listed above.

Hormonal disbalance

In the female body, hormones and their correct balance are a prerequisite for the normal course of the pregnancy process. In some cases, a failure in the hormonal background can result in a breakdown. Experts identify progesterone as a very important hormone that is required to maintain pregnancy. If its shortage was identified in a timely manner, the woman is prescribed this hormone in the form of medications, as a result, the fetus can be saved.

In addition, the androgen balance affects the safety of the fetus. With their excess in the body of a pregnant woman, the production of estrogen and progesterone is inhibited, and this is also the threat of miscarriage.

Infectious diseases

In preparation for pregnancy, a woman should engage in therapy for all existing chronic diseases. In addition, it is recommended to avoid infectious diseases. Indeed, when a pathogen enters the female body, the temperature can rise sharply, which will also provoke miscarriage.

Sexually transmitted diseases are a separate threat to the fetus. Therefore, future parents in preparation for pregnancy should be examined and tested for these diseases. Due to the fact that this type of infection gets to the fetus through the blood, in most cases, in the presence of pathology, miscarriage is diagnosed.

Genetic abnormalities

The lion's share of all miscarriages occurs for this very reason. Doctors cite a figure of 73% of their total. In the modern world, this factor plays a huge role. Poor quality products, radiation contamination, polluted ecology - all this affects the female body every day.

Today, preparing for pregnancy, many women are trying to leave the polluted bustling city and spend this time in the most suitable environment. Although these factors are not easily eliminated, the associated mutations are not considered to be hereditary, the next pregnancy may be successful.

Rhesus factor

This factor almost always provokes early termination of pregnancy. For this reason, if a woman and a man are positive, this state of affairs can provoke a Rh conflict and, as a result, miscarriage.

To date, medicine has learned to cope with this problem by introducing progesterone into the female body. In this way, the fetus is protected from the aggressive female immune system. However, in this case, the problem of miscarriage may arise.

Medications

Experts recommend avoiding taking medications during this period, especially in the early stages. It is very important to exclude all analgesics and hormonal drugs. It is also undesirable to use folk recipes in which St. John's wort, nettle, cornflowers and parsley are present as ingredients.

Stress factors

Sudden grief, family quarrels, or stress at work are all causes of early miscarriage. These factors should be minimized or, if possible, avoided. An important role in creating a calm environment for a woman belongs to a man. If it is not possible to avoid the action of stress factors, then doctors in this case prescribe mild sedatives.

Bad habits

Before conception, you need to stop drinking alcohol and quit smoking. Smoking can negatively affect the cardiovascular system of the fetus. It is recommended to build a consistent system of healthy nutrition, with a set of essential minerals and vitamins. It is also necessary to adjust the daily routine.

Trauma

Along with the factors listed above, early miscarriage can provoke a violent blow, fall or lift of heavy objects. Therefore, you should behave as carefully as possible.

Abortions in the past

This is not only an argument used to intimidate young women, but also a real factor in future problems. In some cases, abortion can lead to infertility and cause chronic miscarriage.

Diagnosis

Miscarriage is a multifactorial disease in which in many patients it is combined with several pathogens at the same time. For this reason, the examination of patients should be carried out in a comprehensive manner and include all modern laboratory, instrumental and clinical methods.

In the process of examination, not only the causes of spontaneous miscarriage are established, but also the condition is assessed for the subsequent prevention of the appearance of such a condition.

Examination before pregnancy

The anamnesis includes clarification of the presence of somatic, oncological, hereditary diseases and neuroendocrine pathology. A gynecological history allows us to find out the presence of a viral infection, inflammatory diseases of the genitals, features of reproductive and menstrual function (spontaneous miscarriages, childbirth, abortion), methods of therapy and other surgical interventions, gynecological diseases.

During the clinical examination, an examination is carried out, an assessment of the condition of the skin, thyroid gland and the degree of obesity in accordance with the body mass index. According to the hirsut number, the degree of hirsutism is determined, the condition of the internal organs is assessed, as well as the gynecological status. The absence or presence of ovulation, the ovaries are analyzed according to the menstrual calendar and rectal temperature.

Laboratory and instrumental research methods

Diagnosis of miscarriage consists of the following studies:

• Hysterosalpinography - carried out after the menstrual cycle on the 17-13th day, allows to exclude intrauterine synechiae, uterine malformations, ICI.
• Ultrasound - determines the presence of adenomyosis, cysts, uterine fibroids, assesses the state of the ovaries. Clarifies the state of the endometrium: endometrial hyperplasia, polyps, chronic endometritis.
• Infectious screening - it includes microscopic examination of smears of the vagina, urethra, cervical canal and bacteriological examination of the contents of the cervical canal, PCR diagnostics, research for virus carriers.
• Hormonal research. It is carried out on the 5th or 7th day of the cycle, subject to regular menstruation, in patients with oligo- and amenorrhea - on any day. The content of 17-hydroxyprogesterone, DHEA-sulfate, cortisol, testosterone, FGS, LH, prolactin is determined. Progesterone can be determined only in patients with a regular cycle: in the first phase of the cycle on days 5-7, in the second phase of the cycle - on days 6-7 of the rise in rectal temperature. In women with adrenal hyperandrogenism, a small test with dexamethasone is performed in order to determine the optimal therapeutic dose.
• To determine the risk of miscarriage, it is necessary to determine the presence of anticardiolipin antibodies, anti-HCG and to analyze the features of the hemostasis system.
• If there is a suspicion of the presence and / or intrauterine pathology under the control of hysteroscopy,
• If you suspect the presence of adhesive stress in the small pelvis, tube pathology, genital endometriosis, with sclerocystic ovaries and uterine myoma, operative laparoscopy is indicated.
• The examination of a man includes the determination of a hereditary history, analysis of an expanded spermogram, the presence of neuroendocrine and somatic diseases, as well as clarification of inflammatory and immune factors.

After the causes of the habitual miscarriage of pregnancy have been identified, a set of therapeutic measures is prescribed.

Examination during pregnancy

Monitoring during pregnancy should begin immediately after its onset, and it consists of the following research methods:

Prophylaxis

According to statistics, the incidence of spontaneous miscarriage is 1 in 300 pregnancies. Despite the fact that the probability of miscarriage decreases with an increase in the term, in the last trimester this figure is about 30%. It also often happens that premature birth and miscarriage in a woman occurs repeatedly. As a result, the diagnosis is established - habitual miscarriage (treatment will be discussed below).

The causes of this disease are diverse, in most cases a whole complex of them leads to premature birth or miscarriage. Moreover, their action can be either sequential or simultaneous. A woman who has a tiring job combined with nervous and physical overload or a low socio-economic status automatically falls into the risk group.

In addition, the factors that increase the likelihood of pathology include diabetes mellitus, kidney disease, bronchial asthma, vascular and heart disease, regular intoxication with drugs, alcohol, and tobacco smoke. If a woman has complications of pregnancy, or an obstetric history is aggravated, then this also applies to risk factors for spontaneous miscarriage or termination of pregnancy. It is important to remember that in the short term, spontaneous interruption can be a biological mechanism of natural selection, for this reason, a miscarriage is not yet a harbinger of a subsequent unsuccessful pregnancy.

In fact, prevention of miscarriage comes down to two main points:

1. Timely examination of the body of a woman and a man.
2. Healthy lifestyle.

It is very important to determine the presence of hereditary diseases, infections in a man, conduct a semen analysis and complete the treatment of all existing problems.

The woman is faced with a more difficult task. It should be clarified whether there were any somatic, neuroendocrine, oncological diseases, how things are with hereditary pathologies.

Also, within the framework of prevention, the features of the reproductive and menstrual function are studied, the presence of obesity and its degree are found out, the condition of the skin is assessed.

It is advisable to apply for a rather informative hysterosalpingography, which is performed in the second half of the menstrual cycle. As a result, it is possible to find out whether the patient has intrauterine pathologies. The results of ultrasound of the pelvic organs make it possible to diagnose the presence of endometriosis, fibroids, cysts, and also to assess the condition of the ovaries.

It is important to examine swabs from the urethra, cervical canal and vagina. It is advisable to perform hormonal research in the first half of the menstrual cycle. In addition, you need to think about having a blood test that will include clotting indicators. This will determine the presence of antibodies such as anti-HCG, anticardiolipin and lupus.

Treatment

Treatment of miscarriage occurs in the following sequence: clarification and subsequent elimination of the cause.

One of the reasons is the infection of the fetus, which occurs as a result of infection of the amniotic fluid or penetration of pathogens through the placenta. In this case, spontaneous termination of pregnancy occurs later on the contractile activity of the uterus, which is triggered as a result of acute intoxication or outpouring of amniotic fluid prematurely, which is due to a change in the structure of the membranes under the influence of infectious agents. Treatment in such a situation can be successful, since the child's ability to withstand negative factors increases with the duration of pregnancy.

It is necessary to include consultations of an endocrinologist in measures for the prevention of this ailment, since hormonal deficiency can lead to pathological restructuring of the endometrium and its depletion, which is also considered a prerequisite for miscarriage. Hyperandrogenism (pathological condition) is also characterized by a hormonal nature and can be the cause of spontaneous interruption.

Acquired or congenital organic pathology of the organs of the reproductive system is also the cause of miscarriage. In addition, the causes of this disease include psychological overload, stress, the actions of certain drugs, diseases of a different nature, intimate life during pregnancy.

Even when a habitual miscarriage is diagnosed, the possibility of spontaneous abortion can be noticeably reduced, subject to constant monitoring by specialists and comprehensive prevention.

Update: October 2018

Today, miscarriage is considered one of the most important problems in obstetrics, given the variety of causes and an ever-increasing percentage of perinatal losses. According to statistics, the number of reported cases of miscarriage is 10 - 25%, with 20% of them related to habitual miscarriage, and 4 - 10% are premature births (relative to the total number of births).

What does this term mean

• The duration of pregnancy is 280 days or 40 weeks (10 obstetric months).
• Delivery on time is considered to be those deliveries that occurred within 38 - 41 weeks.
• Miscarriage is called spontaneous termination of pregnancy, which occurred in the period from fertilization (conception) to 37 weeks.

The habitual miscarriage includes cases of spontaneous abortion, which have occurred twice or more times in a row (including frozen pregnancy and antenatal fetal death). The frequency of recurrent miscarriage in relation to the total number of all pregnancies reaches 1%.

The risk of miscarriage is directly proportional to the number of previous spontaneous interruptions in the history. So, it has been proven that the risk of terminating a new pregnancy after the first spontaneous abortion is 13 - 17%, after two miscarriages / premature births it reaches 36 - 38%, and after three spontaneous abortions it is 40 - 45%.

Therefore, every married couple who has had 2 spontaneous abortions should be carefully examined and treated at the stage of pregnancy planning.

In addition, it has been proven that a woman's age is directly related to the risk of early miscarriage. If in women in the age category from 20 to 29 years the possibility of spontaneous abortion is 10%, then at 45 years and after it reaches 50%. The risk of termination of pregnancy with increasing age of the mother is associated with the "aging" of eggs and an increase in the number of chromosomal abnormalities in the embryo.

Classification

The classification of miscarriage includes several points:

Depending on the date of occurrence

• spontaneous (spontaneous or sporadic) abortion is divided into early (up to 12 weeks of gestation) and late from 12 to 22 weeks. Spontaneous miscarriages include all cases of termination of pregnancy that happened before 22 weeks or with a fetus weighing less than 500 grams, regardless of the presence / absence of signs of its life .;
• premature births, which are distinguished by timing (according to WHO): from 22 to 27 weeks, very early preterm labor, births that happened from 28 to 33 weeks are called early preterm labor and from 34 to 37 weeks - premature birth.

Depending on the stage, abortion and premature birth are divided into:

• spontaneous abortion: threatened abortion, abortion in progress, incomplete abortion (with remnants of the ovum in the uterus) and complete abortion;
• premature birth, in turn, is classified as: threatening, incipient (at these stages, labor can still be slowed down) and incipient.

Separately, an infected (septic) abortion, which can be criminal, and a failed abortion (a frozen or undeveloped pregnancy) are distinguished.

Causes of miscarriage

The list of reasons for miscarriage is very numerous. It can be divided into two groups. The first group includes social and biological factors, which include:

To the second group refers to medical reasons that are caused either by the state of the embryo / fetus or by the state of health of the mother / father.

Genetic causes of miscarriage

Genetic miscarriage is noted in 3 - 6% of cases of pregnancy loss, and for this reason, about half of pregnancies are terminated only in the first trimester, which is associated with natural selection. When examining spouses (karyotype research), about 7% of failed parents show balanced chromosomal rearrangements that do not affect the health of the husband or wife, but with meiosis, difficulties arise in the processes of mating and chromosome separation. As a result, unbalanced chromosomal rearrangements are formed in the embryo, and it becomes either unviable and the pregnancy is terminated, or is a carrier of a severe chromosomal abnormality. The possibility of giving birth to a child with severe chromosomal abnormalities in parents who have balanced chromosomal rearrangements is 1-15%.

But in many cases, genetic factors of miscarriage (95) are represented by a change in the set of chromosomes, for example, monosomy, when one chromosome is lost or trisomy, in which there is an extra chromosome, which is the result of errors in meiosis due to the influence of harmful factors (medication, radiation, chemical hazards and others). Polyploidy also belongs to genetic factors, when the chromosomal composition increases by 23 chromosomes or a complete haploid set.

Diagnostics

Diagnostics of the genetic factors of recurrent miscarriage begins with the collection of anamnesis from both parents and their close relatives: are there hereditary diseases in the family, are there relatives with congenital anomalies, have / have children with mental retardation in spouses, have spouses or their relatives have infertility or miscarriage of unknown genesis, as well as cases of idiopathic (non-refined) perinatal mortality.

From special examination methods, a mandatory study of the karyotype of spouses is shown (especially when a child is born with congenital malformations and in the presence of habitual miscarriage in the early stages). Also shown is a cytogenetic study of abortion (determination of the karyotype) in cases of stillbirth, miscarriage and infant mortality.

If changes are found in the karyotype of one of the parents, a consultation with a geneticist is shown, who will assess the risk of having a sick child or, if necessary, recommend using a donor egg or sperm.

Pregnancy management

In case of pregnancy, mandatory prenatal diagnostics (chorionic biopsy, cordocentesis or amniocentesis) are carried out in order to identify gross chromosomal pathology of the embryo / fetus and possible termination of pregnancy.

Anatomical causes of miscarriage

The list of anatomical causes of miscarriage includes:

• congenital malformations (formation) of the uterus, which include its doubling, two-horned and saddle-shaped uterus, uterus with one horn, intrauterine septum, complete or partial;
• anatomical defects that appeared during life (intrauterine synechiae, submucous myoma, endometrial polyp)
• isthmic-cervical insufficiency (cervical incompetence).

Habitual miscarriage due to anatomical reasons is 10 - 16%, and the share of congenital malformations is 37% in the bicornuate uterus, 15% in the saddle uterus, 22% in the septum in the uterus, 11% in the double uterus and 4.4% in the uterus with with one horn.

Miscarriage in anatomical uterine abnormalities is due either to unsuccessful implantation of a fertilized egg (directly on the septum or next to the myomatous node) or insufficient blood supply to the uterine mucosa, hormonal disorders or chronic endometritis. Isthmico-cervical insufficiency is highlighted in a separate line.

Diagnostics

The anamnesis contains indications of late miscarriages and premature birth, as well as pathology of the urinary tract, which often accompanies uterine malformations and the formation of the menstrual cycle (there was a hematometer, for example, with a rudimentary uterine horn).

Additional examination methods

Additional methods for miscarriage caused by anatomical changes are:

• metrosalpingography, which allows you to determine the shape of the uterine cavity, identify the existing submucosal myomatous nodes and endometrial polyps, as well as determine the presence of synechiae (adhesions), intrauterine septum and tube patency (performed in phase 2 of the cycle);
• allows you to see with the eye the uterine cavity, the nature of the intrauterine anomaly, and, if necessary, dissect the synechiae, remove the submucosal node or endometrial polyps;
• Ultrasound of the uterus allows you to diagnose submucosal fibroids and intrauterine synechiae in the first phase, and in the second it reveals a septum in the uterus and a bicornuate uterus;
• in some difficult situations, magnetic resonance imaging of the pelvic organs is used, which makes it possible to identify abnormalities in the development of the uterus with concomitant atypical localization of organs in the small pelvis (especially in the case of a rudimentary uterine horn).

Treatment

Treatment of recurrent miscarriage due to the anatomical pathology of the uterus consists in surgical excision of the uterine septum, intrauterine synechiae and submucosal myomatous nodes (preferably during hysteroscopy). The effectiveness of surgical treatment for this type of miscarriage reaches 70 - 80%. But in the case of women with a normal course of pregnancy and childbirth in the past, and then with repeated miscarriages and having uterine malformations, surgical treatment does not have an effect, which may be due to other causes of miscarriage.

After surgical treatment in order to improve the growth of the uterine mucosa, the use of combined oral contraceptives is indicated for 3 months. Physiotherapy is also recommended (,).

Pregnancy management

Pregnancy against the background of a two-legged uterus or with its doubling proceeds with the threat of miscarriage at different times and with the development of placental insufficiency and delayed fetal development. Therefore, already from an early date, when bleeding occurs, bed rest, hemostatics (dicinone, tranexam), antispasmodics (magne-B6) and sedatives (motherwort, valerian) are recommended. Also shown is the reception of gestagens (morning, dyufaston) up to 16 weeks.

Isthmico-cervical insufficiency

ICI is one of the most frequent factors of miscarriage in late stages, mainly in the 2nd trimester. Isthmico-cervical insufficiency is regarded as an inconsistency of the cervix, when it cannot be in a closed position, and as it progresses, it shortens and opens, and the cervical canal expands, which leads to prolapse of the fetal bladder, its opening and discharge of water and ends with late miscarriage or premature birth ... There are ICI functional (hormonal disruptions) and organic (post-traumatic) nature. This reason for recurrent miscarriage occurs in 13 - 20% of cases.

Diagnostics

It is impossible to assess the risk of developing a functional ICI before pregnancy. But in the presence of post-traumatic ICI, metrosalpingography is indicated at the end of phase 2 of the cycle. If an enlargement of the internal pharynx is diagnosed more than 6 - 8 mm, the symptom is regarded as unfavorable, and the woman with the onset of pregnancy is included in the group of high risk of miscarriage.

During pregnancy, it is shown weekly (starting from 12 weeks) to assess the condition of the cervix (examination in the mirrors, ultrasound scanning of the cervix and determining its length, as well as the state of the internal pharynx using transvaginal ultrasound).

Treatment

Treatment of miscarriage before pregnancy consists in surgical intervention on the cervix (with post-traumatic insufficiency), which consists in cervical plasty.

When pregnancy occurs, surgical correction of the cervix (suturing) is performed in the period from 13 to 27 weeks. Indications for surgical treatment are softening and shortening of the neck, expansion of the external pharynx and the opening of the internal pharynx. In the postoperative period, vaginal smears are monitored and, if necessary, the vaginal microflora is corrected. In the case of an increased tone of the uterus, tocolytics are prescribed (ginipral, partusisten). Subsequent pregnancy management includes examination of the cervical stitches every 2 weeks. The stitches are removed at 37 weeks or in case of an emergency (leakage or outpouring of water, the appearance of bleeding from the uterus, cutting of the stitches, and in case of the onset of regular contractions, regardless of gestational age).

Endocrine causes of miscarriage

Miscarriage due to hormonal causes occurs in 8 - 20%. In the forefront are pathologies such as luteal phase failure, hyperandrogenism, hyperprolactinemia, thyroid dysfunction and diabetes mellitus. Among the habitual miscarriage of endocrine genesis, luteal phase insufficiency occurs in 20-60% and is due to a number of factors:

• failure of the synthesis of FSH and LH in the 1st phase of the cycle;
• an early or late burst of LH release;
• hypoestrogenism, as a reflection of the inadequate maturation of follicles, which is caused by hyperprolactinemia, an excess of androgens, etc.

Diagnostics

When studying the anamnesis, attention is paid to the late formation of menstrual function and irregularity of the cycle, a sharp increase in body weight, existing infertility or habitual spontaneous abortions in the early stages. The examination assesses the physique, height and weight, hirsutism, the severity of secondary sexual characteristics, the presence of "stretch marks" on the skin, mammary glands to exclude / confirm galactorrhea. The basal temperature graph is also evaluated for 3 cycles.

Additional examination methods

• Determination of hormone levels

In phase 1, the content of FSH and LH, thyroid-stimulating hormone and testosterone, as well as 17-OP and DHES are examined. In phase 2, the level of progesterone is determined.

Ultrasound monitoring is in progress. In phase 1, endometrial pathology and the presence / absence of polycystic ovaries are diagnosed, and in phase 2, the thickness of the endometrium is measured (normally 10-11 mm, which coincides with the level of progesterone).

• Endometrial biopsy

To confirm the insufficiency of the luteal phase, endometrial aspiration is performed on the eve of menstruation.

Treatment

In case of confirmation of the insufficiency of the luteal phase, it is necessary to identify and eliminate its cause. With NLF against the background of hyperprolactinemia, an MRI of the brain or X-ray of the skull is indicated (to evaluate the Turkish saddle - to exclude a pituitary adenoma, which requires surgery). If no pituitary pathology is found, functional hyperprolactinemia is diagnosed and bromocriptine therapy is prescribed. After the onset of pregnancy, the drug is canceled.

If hypothyroidism is diagnosed, treatment with sodium levothyroxine is prescribed, which is continued after pregnancy.

Direct NLF therapy is carried out in one of the following ways:

• stimulation of ovulation with clomiphene from 5 to 9 days of the cycle (no more than 3 cycles in a row);
• substitution treatment with progesterone drugs (utrozhestan, dyufaston), which supports the full secretory transformation of the endometrium in the case of preserved ovulation (after pregnancy, progesterone therapy is continued).

After using any method of treatment for NLF and the onset of pregnancy, treatment with progesterone drugs is continued for up to 16 weeks.

Adrenal hyperandrogenism or adrenogenital syndrome

This disease is hereditary and is caused by a violation of the production of hormones of the adrenal cortex.

Diagnostics

The anamnesis contains indications of a late menarche and an extended cycle up to oligomenorrhea, spontaneous abortions in the early stages, and possibly infertility. Examination reveals acne, hirsutism, a male physique, and an enlarged clitoris. Based on the basal temperature charts, anovulatory cycles are determined, alternating with ovulatory ones against the background of NLF. Hormonal status: high content of 17-OP and DHES. Ultrasound data: the ovaries are not changed.

Treatment

Therapy consists in the appointment of glucocorticoids (dexamethasone), which suppress excess androgen production.

Pregnancy management

Dexamethasone treatment continues after pregnancy until delivery.

Ovarian hyperandrogenism

Another name for the disease is polycystic ovary disease. The anamnesis contains indications of a late menarche and a violation of the cycle by the type of oligomenorrhea, rare and ending with early miscarriages, prolonged periods of infertility. On examination, there is increased hair growth, acne and striae, and overweight. According to the basal temperature charts, the periods of anovulation alternate with ovulatory cycles against the background of NLF. Hormonal levels: high levels of testosterone, possibly increased FSH and LH, and ultrasound reveals polycystic ovaries.

Treatment

Therapy for ovarian hyperandrogenism consists in normalizing weight (diet, exercise), stimulating ovulation with clomiphene and supporting phase 2 of the cycle with gestagenic drugs. According to the indications, surgery is performed (wedge-shaped excision of the ovaries or laser treatment).

Pregnancy management

When pregnancy occurs, progesterone preparations are prescribed for up to 16 weeks and dexamethasone for up to 12-14 weeks. The condition of the cervix is ​​checked and, with the development of ICI, it is sutured.

Infectious causes of miscarriage

The question of the significance of an infectious factor as a cause of repeated pregnancy losses is still open. In the case of primary infection, pregnancy ends early, due to damage to the embryo, which is incompatible with life. However, in most patients with recurrent miscarriage and existing chronic endometritis, several types of pathogenic microbes and viruses predominate in the endometrium. The histological picture of the endometrium in women with a habitual miscarriage in 45 - 70% of cases indicates the presence of chronic endometritis, and in 60 - 87% there is an activation of conditionally pathogenic flora, which provokes the activity of immunopathological processes.

Diagnostics

In case of miscarriage of an infectious genesis in the anamnesis, there are indications of late miscarriages and premature birth (for example, up to 80% of cases of premature discharge of water are the result of inflammation of the membranes). Additional examination (at the stage of pregnancy planning) includes:

• smears from the vagina and cervical canal;
• tank. sowing the contents of the cervical canal and quantifying the degree of seeding with pathogenic and opportunistic bacteria;
• detection of genital infections by PCR (gonorrhea, chlamydia, trichomoniasis, herpes virus and cytomegalovirus);
• determination of the immune status;
• determination of immunoglobulins in cytomegalovirus and herpes simplex virus in the blood;
• study of interferon status;
• determination of the level of anti-inflammatory cytokines in the blood;
• endometrial biopsy (curettage of the uterine cavity) in phase 1 of the cycle, followed by histological examination.

Treatment

Treatment of miscarriage of an infectious nature consists in the appointment of active immunotherapy (plasmapheresis and gonovaccine), antibiotics after provocation, and antifungal and antiviral drugs. Treatment is selected individually.

Pregnancy management

At the onset of pregnancy, the state of the vaginal microflora is monitored, and studies are carried out for the presence of pathogenic bacteria and viruses. In the first trimester, immunoglobulin therapy is recommended (the introduction of human immunoglobulin three times every other day) and the prevention of placental insufficiency is carried out. In the 2nd and 3rd trimesters, courses of immunoglobulin therapy are repeated, to which the administration of interferon is added. In case of detection of pathogenic flora, antibiotics are prescribed and the simultaneous treatment of placental insufficiency. With the development of the threat of interruption, the woman is hospitalized.

Immunological causes of miscarriage

To date, it is known that approximately 80% of all "incomprehensible" cases of repeated abortions, when genetic, endocrine and anatomical reasons were excluded, are due to immunological disorders. All immunological disorders are divided into autoimmune and alloimmune, which lead to recurrent miscarriage. In the case of an autoimmune process, there is a "hostility" of immunity to the woman's own tissues, that is, antibodies are produced against their own antigens (antiphospholipid, antithyroid, antinuclear autoantibodies). If the production of antibodies by the woman's body is directed to the antigens of the embryo / fetus, which he received from the father, they speak of alloimmune disorders.

Antiphospholipid syndrome

The frequency of APS among the female population reaches 5%, and the cause of recurrent miscarriage of APS is in 27 - 42%. The leading complication of this syndrome is thrombosis; the risk of thrombotic complications increases with the progression of pregnancy and after childbirth.

Examination and medical correction of women with APS should begin at the planning stage of pregnancy. A test is performed for lupus anticoagulant and the presence of antiphospholipid antibodies, if it is positive, the test is repeated after 6 to 8 weeks. If a positive result is obtained again, before the onset of pregnancy, treatment should be started.

Treatment

APS therapy is prescribed individually (the severity of the activity of the autoimmune process is assessed). Antiplatelet agents (acetylsalicylic acid) are prescribed together with vitamin D and calcium preparations, anticoagulants (enoxaparin, sodium dalteparin), small doses of glucocorticoid hormones (dexamethasone), according to plasmapheresis indications.

Pregnancy management

Starting from the first weeks of pregnancy, the activity of the autoimmune process is monitored (lupus anticoagulant, antiphospholipid antibody titer, hemostasiograms are evaluated) and an individual treatment regimen is selected. Against the background of treatment with anticoagulants in the first 3 weeks, a CBC is prescribed and the platelet count is determined, and then the platelet count is monitored twice a month.

Ultrasound of the fetus is performed from 16 weeks and every 3 to 4 weeks (assessment of fetometric indicators - the growth and development of the fetus and the amount of amniotic fluid). In the 2nd - 3rd trimesters, the study of the work of the kidneys and liver (presence / absence of proteinuria, the level of creatinine, urea and liver enzymes).

Doppler sonography to exclude / confirm placental insufficiency, and from 33 weeks CTG to assess the condition of the fetus and resolve the issue of the timing and method of delivery. In childbirth and on the eve of the control of the hemostasiogram, and in the postpartum period, the course of glucocorticoids is continued for 2 weeks.

Prevention of miscarriage

Non-specific preventive measures for miscarriage include giving up bad habits and abortions, maintaining a healthy lifestyle and thorough examination of the married couple and correcting the identified chronic diseases when planning pregnancy.

If there are indications of spontaneous abortion and premature birth in the history, the woman is included in a high-risk group for recurrent miscarriage, and spouses are recommended to undergo the following examination:

• blood groups and Rh factor in both spouses;
• genetic consultation and karyotyping of spouses with a history of early miscarriages, antenatal fetal death, birth of a child with intrauterine developmental anomalies and existing hereditary diseases;
• examination for genital infections for both spouses, and a woman for TORCH infection;
• determination of the hormonal status in a woman (FSH, LH, androgens, prolactin, thyroid-stimulating hormones);
• exclude diabetes mellitus in a woman;
• in case of revealing the anatomical reasons for miscarriage, carry out surgical correction (removal of myomatous nodes, intrauterine synechiae, plastic of the cervix, etc.);
• pregravid treatment of identified infectious diseases and hormonal correction of endocrine disorders.