The endometrium of the early stage of the proliferation phase has a normal structure. Why does proliferation processes slow down? Changes in the endometrium observed during the two-phase menstrual cycle

To find out what proliferative endometrium is, it is necessary to understand how the female body functions. Interior The uterus, lined with endometrium, experiences cyclical changes throughout menstrual period.

The endometrium is a mucous layer covering the inner plane of the uterus, abundantly supplied with blood vessels and serving to supply the organ with blood.

Purpose and structure of the endometrium

According to its structure, the endometrium can be divided into two layers: basal and functional.

The peculiarity of the first layer is that it hardly changes and is the basis for the regeneration of the functional layer in the next menstrual period.

It consists of a layer of cells tightly adjacent to one another, connecting tissues (stroma), equipped with glands and a large number of branched blood vessels. IN in good condition its thickness varies from one to one and a half centimeters.

Unlike the basal layer, the functional layer constantly experiences changes. This is due to damage to its integrity as a result of peeling due to blood leakage during menstruation, the birth of a child, artificial termination of pregnancy, and curettage during diagnostics.

The endometrium is designed to perform several functions, the main one of which is to provide the necessary conditions for the onset and successful course of pregnancy, when the number of glands and blood vessels included in the structure of the placenta increases. One of the purposes of a child's place is to supply the embryo with nutrients and oxygen. Another function is to prevent the opposing walls of the uterus from sticking together.

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IN female body changes occur monthly, during which favorable conditions for conception and gestation. The period between them is called the menstrual cycle and lasts from 20 to 30 days. The beginning of the cycle is the first day of menstruation.

Any deviations that arise during this period indicate the presence of any disturbances in the woman’s body. The cycle is divided into three phases:

• proliferation;
• secretion;
• menstruation.

Proliferation is the process of cell reproduction by division, leading to the growth of body tissues. Endometrial proliferation is an increase in the tissue of the mucous membrane inside the uterus as a result of the division of normal cells. The phenomenon may occur as part menstrual cycle, and have a pathological origin.

The duration of the proliferation phase is about 2 weeks. The changes that occur in the endometrium during this period arise due to an increase in the amount of the hormone estrogen, which is produced by the maturing follicle. This phase includes three stages: early, middle and late.

For early stage, which lasts from 5 days to 1 week, is characterized by the following: the surface of the endometrium is covered epithelial cells cylindrical in appearance, the glands of the mucous layer resemble straight tubes, in cross section the outlines of the glands are oval or round; the epithelium of the glands is low, the cell nuclei are located at their base, have oval shape and intense color. Cells connecting tissues (stroma) are spindle-shaped with large nuclei. The blood arteries are almost not tortuous.

The middle stage, which occurs on the eighth to tenth day, is characterized by the fact that the plane of the mucosa is covered with tall epithelial cells of a prismatic appearance.

The glands take on a slightly convoluted shape. The nuclei lose color, increase in size, and are different levels. Appears big number cells obtained indirect division. The stroma becomes loose and edematous.

The late stage, lasting from 11 to 14 days, is characterized by the fact that the glands become tortuous, the nuclei of all cells are at different levels. The epithelium is single-layered, but with many rows. In some cells, small vacuoles appear that contain glycogen. The vessels become tortuous. The cell nuclei take on a more rounded shape and greatly increase in size. The stroma is infused.

The secretory phase of the cycle is divided into stages:

• early, lasting from 15 to 18 days of the cycle;
• medium, with the most pronounced secretion, occurring from 20 to 23 days;
• late (decay of secretion), occurring from 24 to 27 days.

The menstrual phase consists of two periods:

• desquamation, which occurs from 28 to 2 days of the cycle and occurs if fertilization does not occur;
• regeneration, lasting from days 3 to 4 and starting until the functional layer of the endometrium is completely separated, but together with the beginning of the growth of epithelial cells of the proliferation phase.

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Normal structure of the endometrium

Using hysteroscopy (examination of the uterine cavity), you can evaluate the structure of the glands, assess the degree of formation of new blood vessels in the endometrium, and determine the thickness of the cell layer. IN different phases During the menstrual period, examination results differ from each other.

Normally, the basal layer has a thickness of 1 to 1.5 cm, but can increase to 2 cm at the end of the proliferation phase. On hormonal influences his reaction is weak.

During the first week, the inner mucous surface of the uterus is smooth, colored light pink, with small particles of the unseparated functional layer of the previous cycle.

In the second week, thickening of the endometrium of a proliferative type is observed, associated with active division healthy cells.

It becomes impossible to see the blood vessels. Due to the uneven thickening of the endometrium on internal walls folds appear in the uterus. In the proliferation phase, normally the posterior wall and bottom have the thickest mucous layer, and the anterior wall and Bottom part the child's seat is the thinnest. The thickness of the functional layer ranges from five to twelve millimeters.

Normally, there should be a complete rejection of the functional layer almost to the basal layer. In reality, complete separation does not occur; only the outer sections are rejected. If not clinical disorders phases of menstruation, then we are talking about the individual norm.

The endometrium is the mucous inner layer of the uterus, which forms optimal conditions for the attachment of the fertilized egg and changes its thickness during the menstrual period.

The minimum thickness is observed at the beginning of the cycle, the maximum - in its last days. If fertilization does not occur during the menstrual cycle, a section of the epithelium is detached and an unfertilized egg is released with the menstrual cell.

Speaking accessible language we can say that the endometrium influences the volume of discharge, as well as the frequency and cyclicity of menstruation.

In women, under the influence negative factors, thinning of the endometrium is possible, which not only negatively affects the attachment of the embryo, but can also lead to infertility.

In gynecology, there are cases of arbitrary miscarriage if the egg was placed on a thin layer. Competent enough gynecological treatment so that problems that negatively affect conception and the safe course of pregnancy are eliminated.

Thickening of the endometrial layer (hyperplasia) is characterized by a benign course and may be accompanied by the appearance of polyps. Deviations in the thickness of the endometrium are detected during a gynecological examination and prescribed examinations.

If there are no symptoms of the pathology, and infertility is not observed, treatment may not be prescribed.

Forms of hyperplasia:

• Simple. Glandular cells predominate, leading to the appearance of polyps. Treatment uses drugs and surgery.
• Atypical. Accompanied by the development of adenomatosis (malignant disease).

Women's menstrual cycle

Changes occur in the female body every month that help create optimal conditions for conceiving and bearing a child. The period between them is called the menstrual cycle.

On average, its duration is 20-30 days. The beginning of the cycle is the first day of menstruation.

At the same time, the endometrium is renewed and cleansed.

If women experience abnormalities during the menstrual cycle, this indicates serious violations in organism. The cycle is divided into several phases:

• proliferation;
• secretion;
• menstruation.

Proliferation refers to the processes of reproduction and cell division that contribute to the growth of internal tissues of the body. During the proliferation of the endometrium, normal cells begin to divide in the mucous membrane of the uterine cavity.

Such changes may occur during menstruation or have a pathological origin.

The duration of proliferation is on average up to two weeks. In a woman’s body, estrogen begins to increase rapidly, which is produced by an already mature follicle.

This phase can be divided into early, middle and late stages. At an early stage (5-7 days) in the uterine cavity, the surface of the endometrium is covered with epithelial cells, which have a cylindrical shape.

Wherein blood arteries remain unchanged.

Classification of endometrial hyperplasia

According to the histological variant, there are several types of endometrial hyperplasia: glandular, glandular-cystic, atypical (adenomatosis) and focal (endometrial polyps).

Glandular hyperplasia of the endometrium is characterized by the disappearance of the division of the endometrium into functional and basal layers. The border between the myometrium and endometrium is clearly expressed, an increased number of glands is noted, but their location is uneven and their shape is not the same.

Pathoanatomical diagnosis of the condition of the endometrium using biopsies / Pryanishnikov V.A., Topchieva O.I. ; under. ed. prof. OK. Khmelnitsky. - Leningrad.

Diagnosis from endometrial biopsies is often very difficult due to the fact that the same very similar microscopic picture of the endometrium can be caused by for various reasons(O.I. Topchieva 1968). In addition, endometrial tissue is distinguished by an exceptional variety of morphological structures, depending on the level steroid hormones, secreted by the ovaries under normal conditions and under pathological conditions associated with disruption of endocrine regulation.

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PATHOLOGANATOMICAL DIAGNOSIS OF ENDOMETRIAL CONDITIONS BY BIOPSY

Accurate microscopic diagnosis from endometrial scrapings is of great importance for the daily work of an obstetrician-gynecologist. Biopsies (scrapings) of the endometrium make up a significant part of the material sent by obstetric and gynecological hospitals for microscopic examination.

Diagnosis from endometrial biopsies often presents great difficulties due to the fact that the same very similar microscopic picture of the endometrium can be due to various reasons (O. I. Topchieva 1968). In addition, endometrial tissue is distinguished by an exceptional variety of morphological structures, depending on the level of steroid hormones secreted by the ovaries under normal conditions and under pathological conditions associated with impaired endocrine regulation.

Experience shows that responsible and complex diagnosis of endometrial changes from scrapings is complete only if there is close contact in the work between the pathologist and the gynecologist.

The use of histochemical methods, along with classical morphological research methods, significantly expands the possibilities of pathological diagnosis and includes such histochemical reactions as the reaction to glycogen, alkaline and acid phosphatases, monoamine oxidase, etc. The use of these reactions allows a more accurate assessment of the degree of imbalance of estrogens and gestagens in the body women, and also makes it possible to determine the degree and nature of endometrial hormonal sensitivity during hyperplastic processes and tumors, which is of great importance when choosing methods for treating these diseases.

METHOD OF OBTAINING AND PREPARING MATERIAL FOR RESEARCH

Important for correct microscopic diagnostics based on endometrial scrapings, a number of conditions are met when collecting material.

The first condition is the correct determination of the time, which is most favorable for curettage. There are the following indications for curettage:

• a) in case of sterility with suspected insufficient function of the corpus luteum or an anovulatory cycle - a scraping is taken 2-3 days before menstruation;
• b) with menorrhagia, when delayed rejection of the endometrial mucosa is suspected; depending on the duration of bleeding, the scraping is taken 5-10 days after the start of menstruation;
• c) in case of dysfunctional uterine bleeding such as metrogynous, scraping should be taken immediately after the start of bleeding.

The second condition is technically correct execution curettage of the uterine cavity. The “accuracy” of the pathologist’s answer in to a large extent depends on how the endometrial scraping is taken. If small, crushed pieces of tissue are received for research, it is extremely difficult or even impossible to restore the structure of the endometrium. This can be eliminated with proper curettage, the purpose of which is to obtain as large, uncrushed strips of tissue as possible from the uterine mucosa. This is achieved by the fact that after passing the curette along the wall of the uterus, it must be removed from the cervical canal each time, and the resulting mucosal tissue is carefully folded onto gauze. If the curette is not removed every time, then the mucous membrane separated from the uterine wall is crushed during repeated movements of the curette and part of it remains in the uterine cavity.

Complete diagnostic curettage the uterus is performed after dilation of the cervical canal to the 10th number of the Hegar dilator. Usually, curettage is carried out separately: first, the cervical canal, and then the uterine cavity. The material is placed in a fixing liquid in two separate jars, marked where it was taken from.

If there is bleeding, especially in women who are in menopause or in menopause, you should scrape out the tubal angles of the uterus with a small curette, remembering that it is in these areas that polypous growths of the endometrium, in which areas of malignancy are most often found, can be localized.

If a large amount of tissue is removed from the uterus during curettage, then it is necessary to send the entire material to the laboratory, and not part of it.

Tsugi or so called line scrapings are taken in cases where it is necessary to determine the reaction of the uterine mucosa in response to the secretion of hormones by the ovaries, to monitor the results of hormone therapy, and to determine the causes of a woman’s sterility. To obtain trains, use a small curette without preliminary expansion cervical canal. When taking a train, it is necessary to carry the curette to the very bottom of the uterus so that the mucous membrane from top to bottom gets into the strip of streaked scraping, i.e., lining all parts of the uterus. To obtain the correct answer from a histologist regarding the train, as a rule, it is enough to have 1-2 strips of endometrium.

The train technique should under no circumstances be used in the presence of uterine bleeding, since in such cases it is necessary to have endometrium from the surface of all uterine walls for examination.

Aspiration biopsy- obtaining pieces of endometrial tissue by suction from the uterine cavity can be recommended for mass preventive examinations of women in order to identify precancerous conditions and endometrial cancer in “high-risk groups.” At the same time negative results I don’t allow aspiration biopsy! confidently reject initial forms asymptomatic cancer. In this regard, if uterine body cancer is suspected, the most reliable and only indicated diagnostic method remains [complete curettage of the uterine cavity (V. A. Mandelstam, 1970).

After performing a biopsy, the doctor sending the material for research must fill out accompanying direction l about the form we propose.

The direction must indicate:

• a) the duration of the menstrual cycle characteristic of a given woman (21-28, or 31-day cycle);
• b) date of onset of bleeding (at the time of expected menstruation, ahead of schedule or late). If there is menopause or amenorrhea, its duration must be indicated.

Information about:

• a) the constitutional type of the patient (obesity is often accompanied by pathological changes in the endometrium),
• b) endocrine disorders(diabetes, changes in function thyroid gland and adrenal cortex),
• c) did the patient undergo hormone therapy, for what, with what hormone and in what dosage?
• d) whether methods were used hormonal contraception, duration of contraceptive use.

Histological processing 6opsies of material include fixation in a 10% neutral formalin solution, followed by dehydration and embedding in paraffin. Can also be used accelerated method pouring into paraffin according to G.A. Merkulov with fixation in formaldehyde heated to 37°C in a thermostat V within 1-2 hours.

IN daily work You can limit yourself to staining the preparations with hematoxylin-eosin, according to Van Gieson, mucicarmine or Alcian oitaim.

For more fine diagnostics state of the endometrium, especially when solving questions about the cause of sterility associated with defective ovarian function, as well as to determine the hormonal sensitivity of the endometrium in hyperplastic processes and tumors, it is necessary to use histochemical methods that allow identifying glycogen, assessing the activity of acid, alkaline phosphatases and a number of other enzymes.

Cryostat sections, obtained from unfixed endometrial tissue frozen at liquid nitrogen temperature (-196°) can be used not only for research using conventional histological staining methods (hematoxylin-eosin, etc.), but also to determine the glycogen content and enzyme activity in morphological structures uterine mucosa.

To conduct histological and histochemical studies of endometrial biopsies on cryostat sections, the pathological laboratory must be equipped with the following equipment: MK-25 cryostat, liquid nitrogen or carbon dioxide (“dry ice”), Dewar flasks (or household thermos), PH meter, refrigerator at +4°C, thermostat or water bath. To obtain cryostat sections, you can use the method developed by V.A. Pryanishnikov and his colleagues (1974).

According to this method, the following stages of preparing cryostat sections are distinguished:

1. Pieces of endometrium (without prior washing with water and without fixation) are placed on a strip of filter paper moistened with water and carefully lowered into liquid nitrogen for 3-5 seconds.
2. Filter paper with pieces of endometrium frozen in nitrogen is transferred to a cryostat chamber (-20°C) and carefully frozen to the microtome block holder using a few drops of water.
3. Sections 10 µm thick obtained in a cryostat are mounted in the cryostat chamber on cooled slides or coverslips.
4. The straightening of the slices is carried out by melting the slices, which is achieved by touching the bottom surface of the glass with a warm finger.
5. The glass with thawed sections is quickly (do not allow the sections to freeze again) removed from the cryostat chamber, dried in air, and fixed in a 2% solution of glutaraldehyde (or steam form) or in a mixture of formaldehyde - alcohol - acetic acid - chloroform in a ratio of 2:6 :1:1.
6. Fixed media are stained with hematoxylin-eosin, dehydrated, cleared and embedded in polystyrene or balsam. The choice of the level of the histological structure of the endometrium to be studied is made on temporary preparations (unfixed cryostat sections) stained with toluidine blue or methylene blue and enclosed in a drop of water. Their production takes 1-2 minutes.

For histochemical determination of glycogen content and localization, air-dried cryostat sections are fixed in acetone cooled to +4°C for 5 minutes, air-dried and stained using the McManus method (Pearce 1962).

To identify hydrolytic enzymes (acid and alkaline phosphatase), cryostat sections are used, fixed in 2% cooled to a temperature of +4°C. neutral formaldehyde solution for 20-30 minutes. After fixation, the sections are rinsed in water and immersed in an incubation solution to determine the activity of acid or alkaline phosphatases. Acid phosphatase is determined by the method of Bark and Anderson (1963), and alkaline phosphatase by the Burston method (Burston, 1965). Before conclusion, sections can be counterstained with hematoxylin. The drugs must be stored in a dark place.

CHANGES IN THE ENDOMETRIA OBSERVED DURING THE TWO-PHASE MENSTRUAL CYCLE

The mucous membrane of the uterus, lining its various sections - the body, isthmus and cervix - has typical histological and functional features in each of these sections.

The endometrium of the uterine body consists of two layers: basal, deeper, located directly on the myometrium and superficial - functional.

Basal the layer contains a few narrow glands lined with cylindrical single-row epithelium, the cells of which have oval nuclei that are intensely stained with hematoxylin. The response of the basal layer tissue to hormonal influences is weak and inconsistent.

From the tissue of the basal layer, the functional layer is regenerated after various violations of its integrity: rejection during the menstrual phase of the cycle, with dysfunctional bleeding, after abortion, childbirth, and also after curettage.

Functional the layer is a tissue with a special, biologically determined high sensitivity to sex steroid hormones - estrogens and gestagens, under the influence of which its structure and function change.

The height of the functional layer in mature women varies depending on the phase of the menstrual cycle: about 1 mm at the beginning of the proliferation phase and up to 8 mm in the secretion phase, at the end of the 3rd week of the cycle. During this period, in the functional layer, the deep, spongy layer, where the glands are located more closely, and the superficial-compact layer, in which the cytogenic stroma predominates, are most clearly identified.

Based on cyclical changes morphological picture endometrium observed throughout the menstrual cycle is the ability of sex steroids-estrogens to cause characteristic changes in the structure and behavior of the tissue of the uterine mucosa.

So, estrogens stimulate the proliferation of glandular and stromal cells, promote regenerative processes, have a vasodilating effect and increase the permeability of endometrial capillaries.

Progesterone has an effect on the endometrium only after preliminary exposure to estrogens. Under these conditions, gestagens (progesterone) cause: a) secretory changes in the glands, b) decidual reaction of stromal cells, c) development of spiral vessels in the functional layer of the endometrium.

The above morphological characteristics were used as the basis for the morphological division of the menstrual cycle into phases and stages.

According to modern concepts, the menstrual cycle is divided into:

• 1) proliferation phase:
  • Early stage - 5-7 days
  • Middle stage - 8-10 days
  • Late stage - 10-14 days
• 2) secretion phase:
  • Early stage (first signs of secretory transformations) - 15-18 days
  • Middle stage (most pronounced secretion) - 19-23 days
  • Late stage (beginning regression) - 24-25 days
  • Regression with ischemia - 26-27 days
• 3) bleeding phase - menstruation:
  • Desquamation - 28-2 days
  • Regeneration - 3-4 days

When assessing the changes occurring in the endometrium according to the days of the menstrual cycle, it is necessary to take into account:

• 1) the length of a given woman’s cycle (28- or 21-day cycle);
• 2) the date of ovulation, which is normal conditions observed on average from the 13th to the 16th day of the cycle; (therefore, depending on the time of ovulation, the structure of the endometrium at one or another stage of the secretion phase varies within 2-3 days).

The proliferation phase lasts 14 days, however, and under physiological conditions it can be lengthened or shortened within 3 days. The changes observed in the endometrium of the proliferation phase arise as a result of the action of an increasing amount of estrogens secreted by the growing and maturing follicle.

The most pronounced morphological changes during the proliferation phase are observed in the glands. In the early stage, the glands look like straight or molded convoluted tubes with a narrow lumen, the contours of the glands are round or oval. The epithelium of the glands is single-row, low cylindrical, the nuclei are oval, located at the base of the cells, intensively stained with hematoxylin. In the late stage, the glands acquire tortuous, sometimes corkscrew-shaped outlines with a slightly expanded lumen. The epithelium becomes high prismatic, a large number of mitoses are noted. As a result of intensive division and increase in the number of epithelial cells, their nuclei are located at at different levels. Glandular epithelial cells in the early proliferation phase are characterized by the absence of glycogen and moderate alkaline phosphatase activity. Towards the end of the proliferation phase, the appearance of small dust-like granules of glycogen and high activity alkaline phosphatase.

In the endometrial stroma, during the proliferation phase, there is an increase in dividing cells, as well as thin-walled vessels.

Endometrial structures corresponding to the proliferation phase, observed under physiological conditions in the first half of the biphasic cycle, may reflect hormonal disorders, if they are detected:

• 1) during the second half of the menstrual cycle; this may indicate an anovulatory single-phase cycle or an abnormal, prolonged proliferation phase with delayed ovulation. In a biphasic cycle:
• 2) with glandular hyperplasia of the endometrium in various areas hyperplastic mucous membrane;
• 3) three dysfunctional uterine bleeding in women at any age.

The secretion phase, directly related to the hormonal activity of the menstrual corpus luteum and the corresponding secretion of progesterone, lasts 14 ± 1 days. Shortening or lengthening the secretion phase by more than two days in women in the reproductive period should be considered a pathological condition, since such cycles turn out to be sterile.

During the first week of the secretion phase, the day of ovulation is determined by changes in the epithelium of the glands, while in the second week this day can most accurately be determined by the state of the endometrial stromal cells.

So, on the 2nd day after ovulation (16th day of the cycle), subnuclear vacuoles. On the 3rd day after ovulation (17th day of the cycle), subnuclear vacuoles push the nuclei into the apical sections of the cells, as a result of which the latter are at the same level. On the 4th day after ovulation (18th day of the cycle), vacuoles partially move from the basal to the apical sections, and by the 5th day (19th day of the cycle), almost all vacuoles move to the apical sections of the cells, and the nuclei shift to the basal -th departments. In the subsequent 6th, 7th and 8th days after ovulation, i.e. on the 20th, 21st and 22nd days of the cycle, pronounced processes of apocrine secretion are observed in the epithelial cells of the glands, as a result of which apical “ The cell paradises have a sort of jagged, uneven appearance. The lumen of the glands during this period is usually expanded, filled with eosinophilic secretion, and the walls of the glands become folded. On the 9th day after ovulation (23rd day of the menstrual cycle), the secretion of the glands is completed.

The use of histochemical methods has made it possible to establish that subnuclear vacuoles contain large glycogen granules, which are released through apocrine secretion into the lumen of the glands during the early and early middle stages of the secretion phase. Along with glycogen, the lumen of the glands also contains acidic mucopolysaccharides. As glycogen accumulates and is secreted into the lumen of the glands, there is a clear decrease in the activity of alkaline phosphatase in epithelial cells, which almost completely disappears by days 20-23 of the cycle.

In the stroma characteristic changes for the secretion phase begin to appear on the 6th, 7th day after ovulation (20th, 21st day of the cycle) in the form of a perivascular decidua-like reaction. This reaction is most pronounced in the cells of the compact layer stroma and is accompanied by an increase in the cytoplasm of the cells, they acquire polygonal or rounded outlines, and glycogen accumulation is noted. Characteristic of this stage of the secretion phase is also the appearance of tangles of spiral vessels not only in the deep parts of the functional layer, but also in the superficial compact layer.

It should be emphasized that the presence of spiral arteries in the functional layer of the endometrium is one of the most reliable signs that determine the full gestagenic effect.

On the contrary, subnuclear vacuolization in the epithelium of the glands is not always a sign indicating that ovulation has occurred and the secretion of progesterone by the corpus luteum has begun.

Subnuclear vacuoles can sometimes be found in the glands of mixed hypoplastic endometrium during dysfunctional uterine bleeding in women of any age, including menopause (O. I. Topchieva, 1962). However, in the endometrium, where the appearance of vacuoles is not associated with ovulation, they are contained in individual glands or in a group of glands, usually only in some cells. The vacuoles themselves vary in size, most often they are small.

In the late stage of the secretion phase, from the 10th day after ovulation, i.e. on the 24th day of the cycle, with the onset of regression of the corpus luteum and a decrease in the level of progesterone in the blood in the endometrium, morphological signs of regression are observed, and on 26 On the 1st and 27th days, signs of ischemia appear. As a result of wrinkling of the stroma of the functional layer of the gland, they acquire a star-shaped outline in transverse sections and a sawtooth in longitudinal sections.

During the bleeding phase (menstruation), desquamation and regeneration processes occur in the endometrium. Morphological feature characteristic of the endometrium menstrual phase, is the presence, in the disintegrating tissue riddled with hemorrhages, of collapsed glands or their fragments, as well as tangles of spiral arteries. Complete rejection of the functional layer usually ends on the 3rd day of the cycle.

Regeneration of the endometrium occurs due to the proliferation of cells of the basal glands and ends within 24-48 hours.

CHANGES IN THE ENDOMETRIUM DURING DISORDERS OF THE ENDOCRINE FUNCTION OF THE OVARIES

From the point of view of etiology, pathogenesis, and also taking into account clinical symptoms morphological changes in the endometrium that occur when the endocrine function of the ovaries is disrupted can be divided into three groups:

1. Changes in the endometrium due to impaired secretion estrogenic hormones.
2. Changes in the endometrium due to impaired secretion progestational hormones.
3. Changes in the endometrium are of a “mixed type,” in which structures simultaneously occur that reflect the effects of estrogenic and progestational hormones.

Regardless of the nature of the above-mentioned disorders of the endocrine function of the ovaries, the most common symptoms encountered by clinicians and morphologists are uterine bleeding and amenorrhea.

A special place due to its exceptional importance clinical significance occupy uterine bleeding in women in menopause, because among various reasons that cause such bleeding, about 30% turn out to be malignant neoplasms of the endometrium (V.A. Mandelstam 1971).

1. Changes in the endometrium due to impaired secretion of estrogen hormones

Violation of the secretion of estrogen hormones manifests itself in two main forms:

a) insufficient amounts of estrogens and the formation of a non-functioning (resting) endometrium.

Under physiological conditions, the resting endometrium exists briefly during menstrual cycles, after mucosal regeneration before the onset of proliferation. Non-functioning endometrium is also observed in older women when the hormonal function of the ovaries is fading and is a stage of transition to an atrophic endometrium. Morphological signs of a non-functioning endometrium - the glands look like straight or slightly convoluted tubes. The epithelium is low, cylindrical, the cytoplasm is basophilic, the nuclei are elongated, occupying most of the cell. Mitoses are absent or extremely rare. The stroma is rich in cells. As these changes progress, the endometrium turns from nonfunctional to atrophic with small glands lined with cuboidal epithelium.

b) in the prolonged secretion of estrogens from persistent follicles, accompanied by anovulatory monophasic cycles. Extended single-phase cycles resulting from long-term persistence of the follicle lead to the development of dishormonal proliferation of the endometrium glandular or glandular cystic hyperplasia.

As a rule, the endometrium with dishormonal proliferation is thickened, its height reaches 1-1.5 cm or more. Microscopically, there is no division of the endometrium into compact and spongy layers; there is also no correct distribution of glands in the stroma; Characteristics of racemose dilated glands. The number of glands (more precisely, glandular tubes) does not increase (in contrast to atypical glandular hyperplasia - adenomatosis). But due to increased proliferation, the glands acquire a convoluted shape and on a section passing through individual turns of the same glandular tube, the impression of a large number of glands is created.

The structure of glandular endometrial hyperplasia, which does not contain racemose dilated glands, is called “simple hyperplasia.”

Depending on the severity of proliferative processes, endometrial glandular hyperplasia is divided into “active” and “resting” (which correspond to the states of “acute” and “chronic” estrogenism). For active form characterized by a large number of mitoses both in the epithelial cells of the glands and in the stromal cells, high activity of alkaline phosphatase and the appearance of clusters of “light” cells in the glands. All these signs indicate intense estrogen stimulation (“acute estrogenism”).

The “resting” form of glandular hyperplasia, corresponding to the state of “chronic estrothenia,” occurs under conditions of prolonged exposure to the endometrium of low levels of estrogen hormones. Under these conditions, endometrial tissue acquires features similar to the resting, non-functioning endometrium: the epithelial nuclei are intensely stained, the cytoplasm is basophilic, mitoses are very rare or do not occur at all. The “resting” form of glandular hyperplasia is most often observed during menopause, when ovarian function declines.

It should be remembered that the occurrence of glandular hyperplasia, especially its active form, in women many years after menopause, with a tendency to relapse, should be regarded as unfavorable factor in a relationship possible occurrence endometrial cancer.

It is also necessary to keep in mind that dyshormonal proliferation of the endometrium can also occur in the presence of cilioepithelial and pseudomucinous ovarian cysts, both malignant and benign, as well as with some other ovarian neoplasms, for example, with a Brenner tumor (M. F. Glazunov 1961).

2. Changes in the endometrium due to impaired secretion of gestagens

Violation of the secretion of hormones of the menstrual corpus luteum appears both in the form of insufficient secretion of progesterone, and with its increased and prolonged secretion (persistence of the corpus luteum).

Hypoluteal cycles with corpus luteum deficiency are shortened in 25% of cases; Ovulation usually occurs on time, but the secretory phase can be shortened to 8 days. Menstruation occurring ahead of time is associated with the premature death of the defective corpus luteum and the cessation of the secretion of testerone.

Histological changes in the endometrium during hypoluteal cycles consist of uneven and insufficient secretory transformation of the mucosa. So, for example, shortly before the onset of menstruation, in the 4th week of the cycle, along with the glands characteristic of the late stage of the secretory phase, there are glands that are sharply lagging behind in their secretory function and correspond only to the beginning phases secretion.

Predecidual transformations of connective tissue cells are extremely weakly expressed or absent altogether, and spiral vessels are underdeveloped.

Persistence of the corpus luteum may be accompanied by full secretion of progesterone and prolongation of the secretion phase. In addition, there are cases with decreased secretion progesterone woolly yellow body.

In the first case, changes occurring in the endometrium were called ultramenstrual hypertrophy and have similarities to structures observed in early pregnancy. The mucous membrane is thickened to 1 cm, secretion is intense, there is a pronounced deciduate-like transformation of the stroma and the development of spiral arteries. Differential diagnosis with impaired pregnancy (in women reproductive age) is extremely difficult. The possibility of similar changes occurring in the endometrium of menopausal women (in whom pregnancy can be excluded) is noted.

In the case of a decrease in the hormonal function of the corpus luteum, when it undergoes incomplete gradual regression, the process of endometrial rejection slows down and is accompanied by lengthening phases bleeding in the form of menorrhagia.

The microscopic picture of endometrial scrapings obtained during such bleeding after the 5th day appears to be very varied: the scraping reveals areas of necrotic tissue, areas in a state of reverse development, secretory and proliferative endometrium. Such changes in the endometrium can be detected in women with acyclic dysfunctional uterine bleeding who are in menopause.

Sometimes exposure to low concentrations of progesterone leads to a slowdown in its rejection, involution, i.e., the reverse development of the deep parts of the functional layer. This process creates conditions for the return of the endometrium to the original structure that was before the onset of cyclic changes and three amenorrheas occur, caused by the so-called “hidden cycles” or hidden menstruation (E.I. Kvater 1961).

3. “Mixed type” endometrium

The endometrium is called mixed if its tissue contains structures that simultaneously reflect the effects of estrogen and progestogen hormones.

There are two forms of mixed endometrium: a) mixed hypoplastic, b) mixed hyperplastic.

The structure of the mixed hypoplastic endometrium presents a motley picture: the functional layer is poorly developed and is represented by indifferent type glands, as well as areas with secretory changes; mitoses are extremely rare.

Such endometrium is found in women of reproductive age with ovarian hypofunction, in menopausal women with dysfunctional uterine bleeding, and with bleeding during menopause.

Glandular endometrial hyperplasia with pronounced signs effects of gestagenic hormones. If among the tissues of glandular endometrial hyperplasia along with typical glands, reflecting the estrogenic effect, there are areas with groups of glands in which there are secretory signs, then this structure of the endometrium is called a mixed form of glandular hyperplasia. Along with secretory changes in the glands, changes in the stroma are also observed, namely: focal decidua-like transformation of connective tissue cells and the formation of tangles of spiral vessels.

PRE-CANCER CONDITIONS AND ENDOMETRIAL CANCER

Despite the great inconsistency of data on the possibility of endometrial cancer arising against the background of glandular hyperplasia, most authors believe that the possibility of a direct transition of glandular hyperplasia into endometrial cancer is unlikely (A. I. Serebrov 1968; Ya. V. Bokhmai 1972), However, unlike the usual (typical) glandular hyperplasia of the endometrium, the atypical form (adenomatosis) is considered by many researchers as a precancer (A. I. Serebrov 1968, L. A. Novikova 1971, etc.).

Adenomatosis is a pathological proliferation of the endometrium, in which the features characteristic of hormonal hyperplasia are lost and atypical structures that resemble malignant growths appear. Adenomatosis is divided according to its prevalence into diffuse and focal, and according to the severity of proliferative processes - into mild and pronounced forms (B.I. Zheleznoy, 1972).

Despite the significant diversity of morphological signs of adenomatosis, most forms encountered in the practice of a pathologist have a number of characteristic morphological signs.

The glands are highly convoluted and often have numerous branches with numerous papillary projections into the lumen. In some places, the glands are closely located next to each other, almost not separated by connective tissue. Epithelial cells have large or oval, elongated, pale-stained nuclei with signs of polymorphism. Structures corresponding to endometrial adenomatosis can be found over a large area or in limited areas against the background of glandular endometrial hyperplasia. Sometimes in the glands nested groups of light cells are found that have morphological similarities with squamous epithelium - adenoacanthosis. Foci of pseudosquamous structures are sharply demarcated from the columnar epithelium of the glands and connective tissue cells of the stroma. Such foci can occur not only with adenomatosis, but also with endometrial adenocarcinoma (adenoacanthoma). In some rare forms of adenomatosis, an accumulation of a large number of “light” cells (ciliated epithelium) is observed in the epithelium of the glands.

Significant difficulties arise for the morphologist when trying to carry out a differential diagnosis between pronounced proliferative forms of adenomatosis and highly differentiated variants of endometrial cancer. Severe forms of adenomatosis are characterized by intense proliferation and atypia of the glandular epithelium in the form of an increase in the size of cells and nuclei, which allowed Hertig et al. (1949) name such forms of adenomatosis “ zero stage” endometrial cancer.

However, due to the lack of clear morphological criteria for this form of endometrial cancer (in contrast to similar shape cervical cancer) the use of this term when diagnosing by endometrial scrapings does not seem justified (E. Novak 1974, B.I. Zheleznov 1973).

Endometrial cancer

Most of the existing classifications of epithelial malignant tumors of the endometrium are based on the principle of the degree of severity of tumor differentiation (M.F. Glazunov, 1947; P.V. Simpovsky and O.K. Khmelnitsky, 1963; E.N. Petrova, 1964; N.A. Kraevsky , 1969).

The same principle underlies the latter International classification endometrial cancer, developed by a group of experts from the World Health Organization (Poulsen and Taylor, 1975).

According to this classification, the following morphological forms of endometrial cancer are distinguished:

• a) Adenocarcinoma (highly, moderately and poorly differentiated forms).
• b) Clear cell (mesonephroid) adenocarcinoma.
• c) Squamous cell carcinoma.
• d) Glandular squamous cell (mucoepidermoid) cancer.
• e) Undifferentiated cancer.

It must be emphasized that more than 80% of malignant epithelial endometrial tumors are adenocarcinomas varying degrees differentiation.

A distinctive feature of tumors with the histological structure of well-differentiated endometrial cancers is that glandular structures the tumors, although they have signs of atypia, nevertheless still resemble ordinary endometrial epithelium. Glandular growths of the endometrial epithelium with papillary processes are surrounded by scanty layers of connective tissue with a small number of vessels. The glands are lined with high- and low-prismatic epithelium with weakly expressed polymorphism and relatively rare mitoses.

As differentiation decreases, glandular cancers lose the characteristics characteristic of endometrial epithelium; glandular structures of an alveolar, tubular or papillary structure begin to predominate in them, which do not differ in structure from glandular cancers of other localizations.

According to histochemical characteristics, well-differentiated glandular cancers resemble endometrial epithelium, since they contain glycogen in a significant percentage and react to alkaline phosphatase. In addition, these forms of endometrial cancer are highly sensitive to hormone therapy with synthetic gestagens (17-hydroxyprogesterone capronoate), under the influence of which secretory changes develop in tumor cells, glycogen accumulates, and alkaline phosphatase activity decreases (V. A. Pryanishnikov, Ya. V. Bokhman, O. F. Che-pik 1976). Much less often, such a differentiating effect of gestagens develops in the cells of moderately differentiated endometrial cancers.

CHANGES IN THE ENDOMETRIA WHEN PRESCRIBED WITH HORMONAL DRUGS

Currently, estrogen and gestagen preparations are widely used in gynecological practice for the treatment of dysfunctional uterine bleeding, some forms of amenorrhea, and also as contraceptives.

Using various combinations estrogens and gestagens can be artificially obtained in the human endometrium, morphological changes characteristic of one or another phase of the menstrual cycle with normally functioning ovaries. The principles underlying hormonal therapy for dysfunctional uterine bleeding and amenorrhea are based on general principles inherent in the action of estrogens and gestagens on the normal human endometrium.

The administration of estrogens leads, depending on the duration and dose, to the development of proliferative processes in the endometrium, up to glandular hyperplasia. With long-term use of estrogens against the background of proliferation, heavy acyclic uterine bleeding may occur.

The administration of progesterone in the proliferative phase of the cycle leads to inhibition of proliferation of the glandular epithelium and suppresses ovulation. The effect of progesterone on the proliferating endometrium depends on the duration of hormone administration and manifests itself in the form of the following morphological changes:

• - stage of “stopped proliferation” in the glands;
• - atrophic changes in the glands with decidua-like transformation of stromal cells;
• - atrophic changes in the epithelium of the glands and stroma.

When estrogens and gestagens are administered together, changes in the endometrium depend on the quantitative ratio of hormones, as well as on the duration of their administration. Thus, for the endometrium, which proliferates under the influence of estrogen, the daily dose of progesterone, which causes secretory changes in the glands in the form of accumulation of glycogen granules, is 30 mg. In the presence of severe glandular hyperplasia of the endometrium, to achieve similar effect it is necessary to administer 400 mg of progesterone daily (Dallenbach-Helwig, 1969).

It is important for a morphologist and clinician-gynecologist to know that the selection of the dosage of estrogens and gestagens in the treatment of menstrual disorders and pathological conditions of the endometrium should be carried out under histological control, by collecting repeated endometrial trains.

When using combined hormonal contraceptives V normal endometrium women undergo natural morphological changes, depending primarily on the duration of use of the drug.

First of all, there is a shortening of the proliferative phase with the development of defective glands, in which abortive secretion subsequently develops. These changes are due to the fact that when taking these drugs, the gestagens they contain inhibit the proliferation processes in the glands, as a result of which the latter do not reach their full development, as is the case during a normal cycle. Secretory changes developing in such glands have an abortifacient, unexpressed nature,

Another typical feature of changes in the endometrium when taking hormonal contraceptives is a pronounced focality, diversity of the morphological picture of the endometrium, namely: the existence of sections of glands and stroma of different degrees of maturity that do not correspond to the day of the cycle. These patterns are characteristic of both the proliferative and secretory phases of the cycle.

Thus, when taking combined hormonal contraceptives, pronounced deviations from the morphological picture of the endometrium of the corresponding phases of the normal cycle occur in the endometrium of women. However, as a rule, after drug withdrawal there is a gradual and full recovery morphological structure of the uterine mucosa (the only exception is cases when the drugs were taken for a very long time - 10-15 years).

CHANGES IN THE ENDOMETRIA ARISING FROM PREGNANCY AND ITS INTERRUPTION

When pregnancy occurs, implantation of a fertilized egg - a blastocyst - occurs on the 7th day after ovulation, i.e. on the 20th - 22nd day of the menstrual cycle. At this time, the pericidial reaction of the endometrial stroma is still very weakly expressed. Most fast education decidual tissue occurs in the blastocyst implantation zone. As for changes in the endometrium beyond implantation, decidual tissue becomes clearly visible only from the 16th day after ovulation and fertilization, i.e., when menstruation is already delayed by 3-4 days. This is observed in the endometrium equally during both uterine and ectopic pregnancy.

In the decidua, which lines the walls of the uterus throughout its entire length, with the exception of the blastocyst implantation zone, a compact layer and a spongy layer are distinguished.

In the compact layer of decidual tissue in the early stages of pregnancy, two types of cells are found: large, vesicle-shaped with a pale-colored nucleus and smaller oval or polygonal cells with a darker nucleus. Large decidual cells are the final form of development of small cells.

The spongy layer differs from the compact layer only strong development glands that are closely adjacent to each other and form tissue, the general appearance of which may have some resemblance to an adenoma.

During histological diagnosis using scrapings and tissues released spontaneously from the uterine cavity, it is necessary to distinguish trophoblast cells from decidual cells, especially when the question is about differential diagnosis between uterine and ectopic pregnancy.

Cells trophoblast, the components of the formation are polymorphic with a predominance of small polygonal ones. There are no vessels, fibrous structures, or leukocytes in the formation. If among the cells that make up the layer there are single large syncytial formations, then this immediately resolves the question of whether it belongs to the trophoblast.

Cells decidual fabrics also have different sizes, but they are larger and oval. The cytoplasm is homogeneous, pale; the nuclei are vesicular. The layer of decidual tissue contains blood vessels and leukocytes.

If pregnancy is disrupted, the formed tissue of the decidua becomes necrotic and is usually completely rejected. If pregnancy is disrupted in the early stages, when the decidual tissue is still completely undeveloped, then it undergoes reverse development. An undoubted sign that endometrial tissue has undergone reverse development after pregnancy, disturbed in the early stages, is the presence of tangles of spiral arteries in the functional layer. A characteristic, but not absolute sign is also the presence of the Arias-Stella phenomenon (the appearance in the glands of cells with a very large hyperchromic nucleus).

In case of pregnancy disorders, one of the most important issues, which the morphologist has to answer, is the question of uterine or ectopic pregnancy. Absolute signs of intrauterine pregnancy are the presence of chorionic villi in the scraping, decidual tissue with invasion of the chorionic epithelium, deposition of fibrinoid in the form of foci and strands in the decidual tissue and in the walls of the venous vessels.

In cases where scraping reveals decidual tissue without chorion elements, this is possible in both uterine and ectopic pregnancy. In this regard, both the morphologist and the clinician should remember that if curettage was performed no earlier than 50 days after the previous last menstrual period When the area where the fertilized egg is located is large enough, then in the uterine form of pregnancy, chorionic villi are almost always found. Their absence suggests an ectopic pregnancy.

At an earlier stage of pregnancy, the absence of chorion elements in the scraping does not always indicate an ectopic pregnancy, since in this case an undetected spontaneous miscarriage cannot be excluded: during bleeding, a small fetal egg could be completely released even before curettage.

All-Union Scientific and Methodological Center of Pathological Service of the Institute of Human Morphology of the USSR Academy of Medical Sciences
Leningrad State Order of Lenin Institute for Advanced Training of Doctors named after. CM. Kirov
I Leningrad Order of the Red Banner of Labor medical school them. I. P. Pavlova

Editor - Professor O. K. Khmelnitsky

Early stage of the proliferation phase. In this phase of the menstrual cycle, the mucous membrane can be traced in the form of a narrow echo-positive strip ("traces of the endometrium") of a homogeneous structure, 2-3 mm thick, located centrally.

Colpocytology. The cells are large, light-colored, with medium-sized nuclei. Moderate folding of cell edges. The number of eosinophilic and basophilic cells is approximately the same. Cells are placed in groups. There are few leukocytes.

Endometrial histology. The surface of the mucous membrane is covered with flattened columnar epithelium, which has a cubic shape. The endometrium is thin, there is no division of the functional layer into zones. The glands look like straight or somewhat winding tubes with a narrow lumen. In cross sections they have a round or oval shape. The epithelium of the glandular crypts is prismatic, the nuclei are oval, located at the base, and stain well. The cytoplasm is basophilic, homogeneous. The apical edge of the epithelial cells is smooth and clearly defined. On its surface, using electron microscopy, long microvilli are identified, which contribute to an increase in the surface of the cell. The stroma consists of spindle-shaped or stellate reticular cells with delicate processes. There is little cytoplasm. It is barely noticeable around the nuclei. In stromal cells, as in epithelial cells, single mitoses appear.

Hysteroscopy. In this phase of the menstrual cycle (up to the 7th day of the cycle), the endometrium is thin, smooth, pale pink, in some areas small hemorrhages are visible, isolated areas of the endometrium are visible in a pale pink color, which have not been rejected. The eyes of the fallopian tubes are clearly visible.

Middle proliferation phase. The middle stage of the proliferation phase lasts from 4-5 to 8-9 days after menstruation. The thickness of the endometrium continues to increase to 6-7 mm, its structure is homogeneous or with a zone of increased density in the center - the zone of contact of the functional layers of the upper and lower walls.

Colpocytology. A large number of eosinophilic cells (up to 60%). Cells are placed scatteredly. There are few leukocytes.

Endometrial histology. The endometrium is thin, there is no separation of the functional layer. The surface of the mucous membrane is covered with high prismatic epithelium. The glands are somewhat tortuous. The nuclei of epithelial cells are located in places at different levels, and numerous mitoses are observed in them. Compared to the early phase of proliferation, the nuclei are enlarged, less intensely colored, and some of them contain small nucleoli. From the 8th day of the menstrual cycle, a layer containing acidic mucoids forms on the apical surface of epithelial cells. Alkaline phosphatase activity increases. The stroma is swollen, loosened, and a narrow strip of cytoplasm is visible in the connective tissues. The number of mitoses increases. The stromal vessels are single, with thin walls.

Hysteroscopy. In the middle stage of the proliferation phase, the endometrium gradually thickens, becomes pale pink, and no vessels are visible.

Late stage of proliferation. In the late stage of the proliferation phase (lasts approximately 3 days), the thickness of the functional layer reaches 8-9 mm, the shape of the endometrium is usually teardrop-shaped, the central echo-positive line remains unchanged throughout the first phase of the menstrual cycle. Against the general echo-negative background, it is possible to distinguish short, very narrow echo-positive layers of low and medium density, which reflect the delicate fibrous structure of the endometrium.

Colpocytology. The smear contains predominantly eosinophilic superficial cells (70%), few basophilic ones. In the cytoplasm of eosinophilic cells there is granularity, the nuclei are small and pyknotic. There are few leukocytes. Characterized by a large amount of mucus.

Endometrial histology. There is some thickening of the functional layer, but there is no division into zones. The surface of the endometrium is covered with tall columnar epithelium. The glands are more tortuous, sometimes corkscrew-like. Their lumen is somewhat expanded, the epithelium of the glands is high, prismatic. The apical edges of the cells are smooth and distinct. As a result of intensive division and increase in the number of epithelial cells, the nuclei are at different levels. They are enlarged, still oval, and contain small nucleoli. Closer to the 14th day of the menstrual cycle, you can see a large number of cells containing glycogen. The activity of alkaline phosphatase in the epithelium of the glands reaches its highest level. The nuclei of connective tissue cells are larger, rounded, less intensely colored, and an even more noticeable halo of cytoplasm appears around them. The spiral arteries that grow from the basal layer at this time already reach the surface of the endometrium. They are still slightly tortuous. Under the microscope, only one or two peripheral vessels located nearby are identified.

Psteroscopy. In the late phase of proliferation, certain areas of the endometrium appear as thickened folds. It is important to note that if menstrual cycle proceeds normally, then in the proliferation phase the endometrium can have different thicknesses, depending on the location - thickened in the days and posterior wall of the uterus, thinner on the anterior wall and in the lower third part of the uterine body.

Early stage of the secretion phase. In this phase of the menstrual cycle (2-4 days after ovulation), the thickness of the endometrium reaches 10-13 mm. After ovulation, due to secretory changes (the result of the production of progesterone by the menstrual corpus luteum of the ovary), the structure of the endometrium becomes homogeneous again until the onset of menstruation. During this period, the thickness of the endometrium increases faster than in the first phase (by 3-5 mm).

Colpocytology. Characteristic deformed cells are wavy, with curved edges, as if folded in half; the cells are located in dense clusters, layers. The cell nuclei are small and pyknotic. The number of basophilic cells increases.

Histology of the endometrium. The thickness of the endometrium increases moderately compared to the proliferation phase. The glands become more tortuous, their lumen is expanded. Most characteristic feature phases of secretion, in particular its early stage - the appearance of subnuclear vacuoles in the epithelium of the glands. Glycogen granules become large, cell nuclei move from the basal to the central sections (indicating that ovulation has occurred). The nuclei are pushed aside by vacuoles into central departments the cells are initially at different levels, but on day 3 after ovulation (day 17 of the cycle), the nuclei, which lie above large vacuoles, are located at the same level. On the 18th day of the cycle, in some cells glycogen granules move to the apical sections of the cells, as if bypassing the nucleus. As a result of this, the nuclei again descend down to the base of the cell, and glycogen granules are located above them, which are located in the apical parts of the cells. The kernels are more rounded. There are no mitoses in them. The cytoplasm of the cells is basophilic. Acid mucoids continue to appear in their apical sections, while alkaline phosphatase activity decreases. The endometrial stroma is slightly swollen. Spiral arteries are tortuous.

Hysteroscopy. In this phase of the menstrual cycle, the endometrium is swollen, thickened, and forms folds, especially in upper third body of the uterus. The color of the endometrium becomes yellowish.

Middle stage of secretion phase. The duration of the middle stage of the second phase is from 4 to 6-7 days, which corresponds to days 18-24 of the menstrual cycle. During this period, the greatest severity of secretory changes in the endometrium is observed. Echographically, this is manifested by a thickening of the endometrium by another 1-2 mm, the diameter of which reaches 12-15 mm, and its even greater density. At the border of the endometrium and myometrium, a rejection zone begins to form in the form of an echo-negative, clearly defined rim, the severity of which reaches its maximum before menstruation.

Colpocytology. Characteristic folding of cells, curved edges, accumulation of cells in groups, the number of cells with pyknotic nuclei decreases. The number of leukocytes increases moderately.

Endometrial histology. The functional layer becomes higher. It is clearly divided into deep and superficial parts. The deep layer is spongy. It contains highly developed glands and a small amount of stroma. The surface layer is compact, it contains less tortuous glands and many connective tissue cells. On the 19th day of the menstrual cycle, most of the nuclei are located in the basal part of the epithelial cells. All kernels are round and light. The apical section of the epithelial cells becomes dome-shaped, glycogen accumulates here and begins to be released into the lumen of the glands by apocrine secretion. The lumen of the glands expands, their walls gradually become more folded. The epithelium of the glands is single-row, with basally located nuclei. As a result of intense secretion, the cells become low, their apical edges are vaguely expressed, as if with teeth. Alkaline phosphatase disappears completely. In the lumen of the glands there is a secret that contains glycogen and acidic mucopolysaccharides. On day 23, the secretion of the glands ends. A perivascular decidual reaction of the endometrial stroma appears, then the decidual reaction becomes diffuse, especially in superficial sections compact layer. The connective tissue cells of the compact layer around the vessels become large, round and polygonal in shape. Glycogen appears in their cytoplasm. Islands of predecidual cells are formed. A reliable indicator of the middle stage of the secretion phase, which indicates high concentration progesterone, are changes in the spiral arteries. Spiral arteries are sharply tortuous, form “skeins”, they can be found not only in the spongy, but also in the superficial parts of the compact layer. Until the 23rd day of the menstrual cycle, the tangles of the spiral arteries are most clearly expressed. Insufficient development of “coils” of spiral arteries in the endometrium of the secretory phase is characterized as a manifestation of weak function of the corpus luteum and insufficient preparation of the endometrium for implantation. The structure of the endometrium of the secretory phase, the middle stage (22-23 days of the cycle), can be observed with prolonged and increased hormonal function of the menstrual corpus luteum - persistence of the corpus luteum, and in the early stages of pregnancy - during the first days after implantation, with intrauterine pregnancy outside the implantation zone ; with progressive ectopic pregnancy evenly in all parts of the mucous membrane of the uterine body.

Hysteroscopy. In the middle phase of the secretion stage, the hysteroscopic picture of the endometrium does not differ significantly from that in the early phase of this stage. Often, endometrial folds take on a polyp-like shape. If the distal end of the hysteroscope is placed tightly to the endometrium, the glandular ducts can be seen.

Late stage of the secretion phase. Late stage of the second phase of the menstrual cycle (lasts 3-4 days). In the endometrium, pronounced trophic disorders occur due to a decrease in the concentration of progesterone. Sonographic changes in the endometrium associated with polymorphic vascular reactions in the form of hyperemia, spasms and thrombosis with the development of hemorrhages, necrosis and others dystrophic changes, slight heterogeneity (spotting) of the mucous membrane appears due to the appearance of small areas (dark “spots” - zones vascular disorders), the rim of the rejection zone (2-4 mm) becomes clearly visible, and the three-layer structure of the mucosa, characteristic of the proliferative phase, is transformed into a homogeneous tissue. There are cases when echo-negative zones of the endometrial thickness in the preovulatory period are mistakenly assessed by ultrasound as pathological changes.

Colpocytology. The cells are large, pale-colored, foamy, basophilic, without inclusions in the cytoplasm, the contours of the cells are indistinct and blurry.

Endometrial histology. The folding of the walls of the glands is enhanced, it has a dust-like shape on longitudinal sections, and a star-like shape on transverse sections. The nuclei of some epithelial cells of the glands are pyknotic. The stroma of the functional layer shrinks. Predecidual cells are close together and located around the spiral vessels diffusely throughout the compact layer. Among the predecidual cells there are small cells with dark nuclei - endometrial granular cells, which are transformed from connective tissue cells. On the 26-27th day of the menstrual cycle, in the superficial areas of the compact layer, lacunar expansion of capillaries into the stroma is observed. In the premenstrual period, spiralization becomes so pronounced that blood circulation slows down and stasis and thrombosis occur. A day before the onset of menstrual bleeding, a state of the endometrium occurs, which Schroeder called “anatomical menstruation.” At this time, you can find not only dilated and congested blood vessels, but also spasm and thrombosis, as well as small hemorrhages, edema, and leukocyte infiltration of the stroma.

Psteroscopy. In the late phase of the secretion stage, the endometrium acquires a reddish tint. Due to the pronounced thickening and folding of the mucosa, the eyes of the fallopian tubes cannot always be seen. Just before menstruation, the appearance of the endometrium can be mistakenly interpreted as endometrial pathology (polypoid hyperplasia). Therefore, the time of hysteroscopy must be recorded for the pathologist.

Bleeding phase (desquamation). During menstrual bleeding, due to a violation of the integrity of the endometrium due to its rejection, the presence of hemorrhages and blood clots in the uterine cavity, the echographic picture changes during the days of menstruation as parts of the endometrium with menstrual blood are discharged. At the beginning of menstruation, the rejection zone is still visible, although not completely. The structure of the endometrium is heterogeneous. Gradually, the distance between the walls of the uterus decreases and before the end of menstruation they “close” with each other.

Colpocytology. The smear contains foamy basophilic cells with large nuclei. A large number of erythrocytes, leukocytes, endometrial cells, and histocytes are also found.

Endometrial histology(28-29 days). Tissue necrosis and autolysis develop. This process starts with surface layers endometrium and is flammable in nature. As a result of vasodilation, which occurs after a long spasm, endometrial tissue receives significant amount blood. This leads to rupture of blood vessels and detachment of necrotic sections of the functional layer of the endometrium.

Morphological signs characteristic of the endometrium of the menstrual phase are: the presence of tissue permeated with hemorrhages, areas of necrosis, leukocyte infiltration, a partially preserved area of ​​the endometrium, as well as tangles of spiral arteries.

Hysteroscopy. In the first 2-3 days of menstruation, the uterine cavity is filled big amount scraps of endometrium from pale pink to dark purple, especially in the upper third. In the lower and middle third of the uterine cavity, the endometrium is thin, pale pink, with pinpoint hemorrhages and areas of old hemorrhages. If the menstrual cycle was full, then already before the second day of menstruation there is almost complete rejection of the uterine mucosa, only in certain areas of it small fragments of the mucous membrane are detected.

Regeneration(3-4 days of the cycle). After rejection of the necrotic functional layer, regeneration of the endometrium from the tissues of the basal layer is observed. Epithelization of the wound surface occurs due to the marginal glands of the basal layer, from which epithelial cells move in all directions onto the wound surface and close the defect. With normal menstrual bleeding under normal conditions two-phase cycle the entire wound surface is epithelialized on the 4th day of the cycle.

Hysteroscopy. During the regeneration stage, against a pink background with areas of hyperemia of the mucosa, small hemorrhages are visible in some areas, and isolated areas of the endometrium of a pale pink color may be encountered. As the endometrium regenerates, areas of hyperemia disappear, changing color to pale pink. The angles of the uterus are clearly visible.

Content

The endometrium covers the entire uterus from the inside and has a mucous structure. It is updated monthly and performs several important functions. The secretory endometrium has numerous blood vessels that supply blood to the body of the uterus.

The structure and purpose of the endometrium

The endometrium is basal and functional in structure. The first layer remains practically unchanged, and the second regenerates the functional layer during menstruation. If there are no pathological processes in a woman’s body, then its thickness is 1-1.5 centimeters. The functional layer of the endometrium changes regularly. Such processes are associated with the fact that during menstruation in the uterine cavity, individual sections of the walls peel off.

Damage appears during labor, during mechanical abortion or diagnostic sampling of material for histology.

The endometrium performs an extremely important function in a woman’s body and helps to have a successful pregnancy. The fruit is attached to its walls. They arrive at the embryo nutrients and oxygen necessary for life. Thanks to the mucous layer of the endometrium, the opposite walls of the uterus do not stick together.

Women's menstrual cycle

Changes occur in the female body every month that help create optimal conditions for conceiving and bearing a child. The period between them is called the menstrual cycle. On average, its duration is 20-30 days. The beginning of the cycle is the first day of menstruation. At the same time, the endometrium is renewed and cleansed.

If women experience abnormalities during the menstrual cycle, this indicates serious disorders in the body. The cycle is divided into several phases:

• proliferation;
• secretion;
• menstruation.

Proliferation refers to the processes of reproduction and cell division that contribute to the growth of internal tissues of the body. During the proliferation of the endometrium, normal cells begin to divide in the mucous membrane of the uterine cavity. Such changes may occur during menstruation or have a pathological origin.

The duration of proliferation is on average up to two weeks. In a woman’s body, estrogen begins to increase rapidly, which is produced by an already mature follicle. This phase can be divided into early, middle and late stages. At an early stage (5-7 days) in the uterine cavity, the surface of the endometrium is covered with epithelial cells, which have a cylindrical shape. In this case, the blood arteries remain unchanged.

The middle stage (8-10 days) is characterized by the covering of the plane of the mucous membrane with epithelial cells, which have a prismatic appearance. The glands are distinguished by a slightly convoluted shape, and the nucleus has a less intense shade and increases in size. A huge number of cells appear in the uterine cavity, which arose as a result of division. The stroma becomes swollen and quite loose.

The late stage (11-15 days) is characterized by a single-layer epithelium, which has many rows. The gland becomes tortuous, and the nuclei are located at different levels. Some cells contain small vacuoles that contain glycogen. The vessels have a tortuous shape, the cell nuclei gradually acquire a rounded shape and greatly increase in size. The stroma becomes engorged.

The endometrium of the secretory type uterus can be divided into several stages:

• early (15-18 days of the menstrual cycle);
• medium (20-23 days, pronounced secretion is observed in the body);
• late (24-27 days, secretion gradually fades away in the uterine cavity).

The menstrual phase can be divided into several periods:

1. Desquamation. This phase occurs from day 28 to day 2 of the menstrual cycle and occurs when fertilization has not occurred in the uterine cavity.
2. Regeneration. This phase lasts from the third to fourth day. It begins before the complete separation of the functional layer of the endometrium along with the beginning of the growth of epithelial cells.

Normal structure

Hysteroscopy helps the doctor examine the uterine cavity to assess the structure of the glands, new blood vessels and determine the thickness of the endometrial cell layer.

If the study is carried out at different phases of the menstrual cycle, the test result will be different. For example, towards the end of the proliferation period, the basal layer begins to increase, and therefore does not respond to any hormonal influences. At the very beginning of the cycle, the internal mucous cavity of the uterus has a pinkish tint, a smooth surface and small areas of the functional layer that has not completely separated.

At the next stage, a proliferative type of endometrium begins to grow in a woman’s body, which is associated with cell division. Blood vessels located in folds and arise as a result of uneven thickening of the endometrial layer. If there are no women in the body pathological changes, then the functional layer should be completely rejected.

Forms of deviation

Any deviations in endometrial thickness arise as a result of functional causes or pathological changes. Functional disorders appear in the early stages of pregnancy or a week after fertilization of the egg. In the uterine cavity, the baby's place gradually thickens.

Pathological processes arise as a result of chaotic division of healthy cells, which form excess soft tissue. In this case, neoplasms and malignant tumors form in the body of the uterus. These changes most often occur as a result of hormonal imbalance due to endometrial hyperplasia. Hyperplasia comes in several forms.

1. Glandular. In this case, there is completely no clear separation between the basal and functional layer. The number of glands increases.
2. Glandular-cystic form. A certain part of the glands forms a cyst.
3. Focal. In the uterine cavity, epithelial tissue begins to grow and numerous polyps form.
4. Atypical. In a woman’s body, the structure of the endometrium changes and the number of connective cells decreases.

Endometrium of the uterus secretory type appears in the second phase of the menstrual cycle; in case of conception, it helps the fertilized egg attach to the wall of the uterus.

Secretory type

During the menstrual cycle, most of the endometrium dies, but when menstruation occurs, it is restored through cell division. After five days, the structure of the endometrium becomes renewed and is quite thin. The endometrium of the secretory type uterus has an early and late phase. It has the ability to grow and with the onset of menstruation it increases several times. In the first stage, the inner lining of the uterus is covered with cylindrical low epithelium, which has tubular glands. In the second cycle, the endometrium of the secretory type uterus is covered with a thick layer of epithelium. The glands in it begin to lengthen and take on a wavy shape.

In the secretory stage, the endometrium changes its original shape and increases significantly in size. The structure of the mucous membrane becomes saccular, glandular cells appear through which mucus is secreted. The secretory endometrium is characterized by a dense and smooth surface with a basal layer. However, he does not show activity. The secretory type of endometrium coincides with the period of formation and further development of follicles.

Glycogen gradually accumulates in the stromal cells, and a certain part of them is transformed into decidual cells. At the end of the period corpus luteum begins to involute, and progesterone stops working. In the secretory phase of the endometrium, glandular and glandular-cystic hyperplasia can develop.

Causes of glandular cystic hyperplasia

Glandular cystic hyperplasia occurs in women of all ages. In most cases, formations occur in the secretory type of endometrium during the period of hormonal changes.

Congenital causes of glandular cystic hyperplasia include:

• hereditary genetic abnormalities;
• hormonal imbalance during puberty in adolescents.

Acquired pathologies include:

• problems of hormonal dependence - endometriosis and mastopathy;
• inflammatory processes in the genital organs;
• infectious pathologies in the pelvic organs;
• gynecological manipulations;
• curettage or abortion;
• violations in proper operation endocrine system;
• excess body weight;
• polycystic ovary syndrome;
• arterial hypertension;
• depressed function of the liver, mammary gland and adrenal glands.

If one of the women in the family was diagnosed with glandular cystic endometrial hyperplasia, then other girls need to be especially careful about their health. It is important to regularly come for a preventive examination to a gynecologist, who can promptly identify possible abnormalities or pathological disorders in the uterine cavity.

Clinical manifestations

Glandular cystic hyperplasia, which forms in the secretory endometrium, is manifested by the following symptoms.

• Menstrual irregularities. Spotting bloody issues between menstruation.
• The discharge is not profuse, but with bloody, dense clots. With prolonged blood loss, patients may experience anemia.
• Pain and discomfort in the lower abdomen.
• Lack of ovulation.

Pathological changes can be determined at the next preventive examination at the gynecologist. Glandular cystic hyperplasia of the secretory endometrium does not resolve on its own, so it is important to seek help from a qualified doctor in a timely manner. Only after complex diagnostics the specialist will be able to prescribe therapeutic treatment.

Diagnostic methods

Glandular cystic hyperplasia of the secretory endometrium can be diagnosed using following methods diagnostics

• Diagnostic examination by a gynecologist.
• Analysis of the patient’s medical history, as well as determination of hereditary factors.
• Ultrasound examination of the uterine cavity and pelvic organs. A special sensor is inserted into the uterus, thanks to which the doctor examines and measures the endometrium of the secretory type of uterus. He also checks for polyps, cystic formations or nodules. But, ultrasonography doesn't give maximum exact result, therefore, patients are prescribed other examination methods.
• Hysteroscopy. This examination is carried out with a special medical optical apparatus. During diagnosis, differential curettage of the secretory endometrium of the uterus is performed. The resulting sample is sent for histological examination, which will determine the presence pathological processes and type of hyperplasia. This technique should be carried out before the onset of menstruation. The results obtained are the most informative, so gynecologists will be able to make a correct and accurate diagnosis. With the help of hysteroscopy, you can not only determine the pathology, but also perform surgery patients.
• Aspiration biopsy. During gynecological examination The doctor scrapes the secretory endometrium. The resulting material is sent for histology.
• Histological examination. This diagnostic method determines the morphology of the diagnosis, as well as the type of hyperplasia.
• Laboratory tests to determine the level of hormones in the body. If necessary, hormonal disorders are checked in the thyroid gland and adrenal glands.

Only after careful and comprehensive examination the doctor will be able to diagnose correct diagnosis, and also assign effective treatment. The gynecologist will individually select medications and their exact dosages.