Uterine pathology as a cause of habitual miscarriage

In most women with reproductive dysfunction, uterine malformations are combined with hormonal disorders with the formation of an incomplete luteal phase of the cycle. This may be due to the effect on the gonads of the same damaging factor that led to uterine malformations. The mechanism of termination of pregnancy with uterine malformations is associated with disorders in the process of implantation of the fertilized egg, insufficient development of the endometrium due to insufficient vascularization of the organ, close spatial relationships, and functional features of the myometrium.

Malformations of the uterus

Malformations of the uterus play a major role in the etiology of habitual miscarriage, especially in the termination of pregnancy in the second and third trimesters. The frequency of malformations of the uterus in the population is only 0.5-0.6%. Among women suffering from habitual miscarriage, the frequency of uterine anomalies is from 10 to 15%, according to various authors.

The frequency of uterine defects among patients examined in the Center's clinics due to habitual miscarriage is 10.8-14.3% in different years. Most researchers see the causes of reproductive dysfunction in the anatomical and physiological inferiority of the uterus, the accompanying isthmic-cervical insufficiency and the inadequate luteal phase of the cycle.

The origin of various malformations of the uterus depends on the stage of embryogenesis at which the teratogenic factor acted or hereditary traits were realized. The rudiments of the genitals appear in humans approximately at the end of the 1st month of embryonic development. The paramesonephric (Müllerian) ducts, from which the uterus, fallopian tubes and proximal part of the vagina are formed, are laid simultaneously on both sides of the mesoderm at 4-6 weeks of intrauterine development. Gradually, the paramesonephric ducts approach each other, their middle sections are located obliquely and merge with their distal sections into an unpaired canal. The uterus and proximal part of the vagina are formed from the merged sections of these ducts, and the fallopian tubes are formed from the unmerged sections. Under the influence of unfavorable factors during embryogenesis, the fusion of the ducts is disrupted, resulting in various uterine anomalies. The causes of adverse effects on the development of the genitals are varied: hyperthermia, infections, ionizing radiation, pregnancy complications, and a hereditary cause of uterine malformations cannot be ruled out. The literature indicates the effect of the drug diethylstilbestrol in utero, taken by the mother to maintain pregnancy. This drug causes uterine malformations: T-shaped uterus, thin convoluted tubes, absence of vaginal vaults, etc. The severity of uterine malformations depends on the dose and duration of the drug used. Other causes of malformations are not precisely known.

Malformations of female genital organs are often combined with malformations of the urinary system (for example, with a unicornuate uterus, there is often no kidney on the side of the missing horn), since these systems are characterized by a common ontogenesis. In case of miscarriage, the most common types of malformations of the uterus are: intrauterine septa (usually incomplete, less often complete), bicornuate, saddle-shaped, unicornuate, double uterus. More severe forms of malformations of the uterus (rudimentary, bicornuate with a rudimentary horn) are observed very rarely. These forms of malformations are characterized by infertility rather than miscarriage.

The following classification of uterine malformations observed in women with miscarriage is proposed.

• Type I - agenesis or hypoplasia;
• Type II - unicornuate uterus;
• Type III - double uterus;
• Type IV - bicornuate uterus;
• Type V - intrauterine septum;
• Type VI - after intrauterine exposure to diethylstilbestrol.

Moreover, it is indicated that with an intrauterine septum, pregnancy is often lost in the first trimester due to failure of placentation, and other developmental defects most often lead to termination of pregnancy in the second and third trimesters.

Genital infantilism

Often, termination of pregnancy can be caused by uterine hypoplasia due to genital infantilism, which is a particular manifestation of a complex pathological process. It is characterized by underdevelopment of the genitals and various disorders in the hypothalamus-pituitary-ovaries-uterus system.

The pathogenesis of genital infantilism is complex and not fully understood. Sexual infantilism is associated with a large number of complications (menstrual cycle disorders, sexual life and reproductive function). According to most researchers, underdevelopment of the reproductive system is caused by insufficient sex hormones. Menstrual cycle disorders are observed in 53% of women with uterine hypoplasia, and ovarian hypofunction is determined during examination using functional diagnostic tests.

Infantile uterus is formed during childhood and can be caused by inflammatory diseases suffered in childhood, in pre- and post-pubertal periods, disorders of nervous and endocrine regulation of the uterus and changes in local tissue metabolism. When studying the reproductive function and features of the course of pregnancy in women with genital infantilism, it was found that patients with miscarriage, as a rule, have normal anthropometric data and well-defined secondary sexual characteristics. All women were found to have an infantile uterus (hypoplastic uterus, long cervix), which was confirmed by clinical data, hysterosalingography methods and ultrasound data.

According to research data, when examining women with genital infantilism using functional diagnostic tests for 3-4 menstrual cycles, all women were found to have a 2-phase menstrual cycle with an incomplete luteal phase. During hormonal examination, the hormone levels corresponded to the fluctuations characteristic of a normal menstrual cycle.

The discrepancy between the level of hormones in the blood plasma and the tests of functional diagnostics allowed us to assume the presence of an inadequate tissue response to hormones produced by the ovaries. Determination of the levels of reception in the endometrium made it possible to confirm this assumption. A decrease in the content of estradiol in the cytosol and nuclei of cells, the number of cytoplasmic and nuclear receptors was revealed, therefore, ovarian hypofunction was clinically determined.

However, in this nosological form it is more correct to speak not about ovarian hypofunction, but about insufficiency or inferiority of the endometrium. In the mechanism of pregnancy termination in genital infantilism, the leading factor is the uterine factor: insufficient preparation of the endometrium for implantation due to the insufficiency of the receptor link of the endometrium, increased excitability of the myometrium of the infantile uterus, close spatial relationships.

The threat of miscarriage is observed at all stages of pregnancy in women with genital infantilism, as well as in women with uterine malformations. In the second trimester of pregnancy, the most common complication is isthmic-cervical insufficiency. At later stages, mild excitability of the uterus, increased tone, and placental insufficiency often develops. Against the background of genital infantilism and uterine malformations, the adverse effects of other factors of spontaneous miscarriage often manifest.

Cervical insufficiency and miscarriage

In the structure of miscarriage in the second trimester of pregnancy, isthmic-cervical insufficiency accounts for 40%, and in the third trimester of pregnancy, isthmic-cervical insufficiency occurs in every third case of premature birth. Insufficiency of the cervix is caused by structural and functional changes in the isthmic section of the uterus, the size of which depends on cyclic changes in the woman's body. Thus, with a two-phase menstrual cycle, in the 1st phase, an increase in the tone of the uterine muscles and, accordingly, an expansion of the isthmic section is noted, and in the 2nd - a decrease in the tone of the uterus and a narrowing of its isthmic section.

A distinction is made between organic and functional isthmic-cervical insufficiency. Organic, or post-traumatic, or secondary, isthmic-cervical insufficiency occurs as a result of previous curettage of the uterine cavity, accompanied by preliminary mechanical expansion of the cervical canal, as well as pathological births, including with the use of minor obstetric operations that led to deep ruptures of the cervix.

The pathogenesis of functional isthmic-cervical insufficiency has not been studied sufficiently. A certain role in its development is played by irritation of alpha- and inhibition of beta-adrenoreceptors. The sensitivity of alpha-receptors increases with hyperestrogenism, and beta-receptors - with an increase in the concentration of progesterone. Activation of alpha-receptors leads to a contraction of the cervix and expansion of the isthmus, the opposite situation is observed with activation of beta-receptors. Functional isthmic-cervical insufficiency, therefore, occurs with endocrine disorders. With hyperandrogenism, functional isthmic-cervical insufficiency occurs in every third patient. In addition, functional isthmic-cervical insufficiency can occur as a result of a violation of the proportional relationship between muscle tissue, the content of which increases to 50% (with a norm of 15%), which leads to early softening of the cervix and connective tissue, as well as changes in the reaction of the structural elements of the cervix to neurohumoral stimuli.

Congenital isthmic-cervical insufficiency is very often observed in women with genital infantilism and uterine malformations.

Diagnosis of isthmic-cervical insufficiency is based on clinical, anamnestic, instrumental and laboratory data. With free insertion of the Hegar dilator No. 6 into the cervical canal in the secretory phase of the menstrual cycle, a diagnosis of isthmic-cervical insufficiency is made. One of the widely used diagnostic methods is radiographic, which is performed on the 18th-20th day of the cycle. In this case, in women with isthmic-cervical insufficiency, the average width of the isthmus is 6.09 mm, with the norm being 2.63 mm. It should be noted that an accurate diagnosis of isthmic-cervical insufficiency, according to a number of authors, is possible only during pregnancy, since in this case there are objective conditions for a functional assessment of the state of the cervix and its isthmic section.

The mechanism of termination of pregnancy in isthmic-cervical insufficiency, regardless of its nature, is that due to shortening and softening of the cervix, gaping of the internal os and cervical canal, the fertilized egg has no support in the lower segment of the uterus. With an increase in intrauterine pressure as pregnancy develops, the fetal membranes protrude into the dilated cervical canal, become infected and open. Infectious pathology plays a significant role in the pathogenesis of premature termination of pregnancy in isthmic-cervical insufficiency. In this case, the mechanism of termination of pregnancy is the same for both organic and functional isthmic-cervical insufficiency.

Infection of the lower pole of the amniotic sac by the ascending route can become a "producing" cause of premature termination of pregnancy: metabolites of the inflammatory process have a cytotoxic effect on the trophoblast, cause detachment of the chorion (placenta), and in the second half of pregnancy affect pathogenetic mechanisms that increase the excitability of the uterus, which leads to the onset of labor and premature termination. It can be said that with isthmic-cervical insufficiency, favorable conditions are created for ascending infection, as a result of which the potential threat of intrauterine infection in pregnant women suffering from cervical insufficiency is quite high.

Uterine fibroids

Many women with uterine myoma have normal reproductive function, pregnancy and childbirth without complications. However, many researchers note that the threat of miscarriage is observed in 30-75% of patients with uterine myoma. According to research, in 15% of women, uterine myoma was the cause of pregnancy termination.

Termination of pregnancy in women with uterine myoma may occur if the size of the uterus and the location of the nodes are unfavorable for the course of pregnancy. Particularly unfavorable conditions for the development of pregnancy are created with intermuscular and submucous localization of nodes. Submucous myoma most often complicates the course of pregnancy in the first trimester. Large intermuscular myomas can deform the uterine cavity and create unfavorable conditions for its continuation. The location of the myoma nodes and the localization of the placenta in relation to the tumor nodes are of great importance. The most unfavorable option is when placentation occurs in the area of the lower segment and on the myomatous nodes.

Hormonal disorders in patients with uterine myoma are no less important in the genesis of miscarriage. Thus, some researchers believe that uterine myoma is accompanied by absolute or relative progesterone deficiency, which may be one of the contributing factors to spontaneous termination of pregnancy.

Premature termination of pregnancy can be caused by high bioelectrical activity of the myometrium and increased enzymatic activity of the contractile complex of the uterus.

Often, the threat of termination of pregnancy is caused by a disruption in the nutrition of myomatous nodes, the development of edema, or necrosis of the node. During pregnancy, myomatous nodes may undergo changes. Many researchers note that pregnancy is associated with an increase in tumor size, the myoma softens, becomes more mobile. Others believe that the tumor becomes larger due to increased vascularization of the uterus, dilation of blood and lymphatic vessels, leading to stagnation of lymph and blood.

When deciding on preserving pregnancy in patients with uterine myoma, an individual approach is necessary. It is necessary to take into account age, duration of the disease, heredity data, and the presence of concomitant extragenital pathology.

Uterine myoma is often combined with endometriosis. According to research, such a combination is observed in 80-85% of patients with uterine myoma. Endometriosis has an adverse effect on the course and outcome of pregnancy, spontaneous abortions and premature births are often observed. Other studies have shown no connection between the frequency of spontaneous termination and the presence of endometriosis, and the treatment of endometriosis, reducing the incidence of infertility, does not reduce the incidence of miscarriage. However, according to our data, the presence of endometriosis even after hormonal and / or surgical treatment complicates the course of pregnancy, whether in patients with a history of infertility or with habitual miscarriage. Apparently, the peculiarities of hormonal changes, presumably the autoimmune nature of this pathology lead to a complicated course of pregnancy at all its stages.

Intrauterine adhesions

Intrauterine adhesions formed after instrumental interventions or endometritis are diagnosed radiologically in 13.2% of women examined for habitual miscarriage in our clinic.

Clinical manifestations of intrauterine adhesions syndrome depend on the degree of endometrial damage by adhesions, their localization and the duration of the disease. After the occurrence of intrauterine adhesions, only 18.3% of patients maintain a two-phase menstrual cycle; most women experience an incomplete luteal phase of varying severity, which is typical for patients with habitual miscarriage.

It should be noted that if the basal layer of the endometrium is damaged and scars appear, it is almost impossible to restore it, therefore, with large adhesions, persistent infertility may develop.