Phase of endometrial desquamation. Histological examination of endometrial scrapings

05.04.2020 -

During uterine cycle ovarian hormones, formed in the follicle and corpus luteum, affect the cyclic changes in the tone, excitability and blood filling of the uterus. More significant cyclic changes occur in the endometrium. Their essence lies in a correctly repeating process of proliferation, in a qualitative change, rejection and restoration of the layer of the mucous membrane, which faces the lumen of the uterus. This layer, which undergoes cyclic changes, is called the functional layer of the endometrium. The layer of mucous membrane adjacent to the muscular membrane of the uterus does not undergo cyclic changes and is called the basal layer.

The uterine cycle, like the ovarian cycle, lasts 28 days (less often 21 or 30-35 days). It consists of: desquamation phase, regeneration phase, proliferation phase and secretion phase.

Desquamation phase manifested by the release of blood, lasting 3-5 days (menstruation). The functional layer of the mucous membrane, under the influence of enzymes, disintegrates, is rejected and released outward along with the contents of the uterine glands and blood from ruptured vessels. The phase of endometrial desquamation coincides with the beginning of the death of the corpus luteum in the ovary.

Regeneration phase mucous membrane begins during the period of desquamation and ends on the 5th-6th day from the onset of menstruation. The restoration of the functional layer of the mucous membrane occurs due to the growth of the epithelium of the remnants of the glands located in the basal layer, and by the proliferation of other elements of this layer (stroma, blood vessels, nerves). Regeneration is due to the influence formed in the follicle, the development of which begins after the death of the corpus luteum.

Proliferation phase the endometrium coincides with the maturation of the follicle in the ovary and continues until the 14th day of the cycle (with a 21-day cycle up to 10-11 days). Under the influence of the estrogen hormone, which affects the nerve elements and metabolic processes in the uterus, there is a proliferation or growth of the stroma and the growth of the mucous membrane. The glands are elongated, then wriggle like a corkscrew, but do not contain a secret. The mucous membrane of the uterus thickens during this period by 4-5 times.

Secretion phase coincides with the development of the corpus luteum in the ovary and continues from the 14-15th to the 28th day, i.e. until the end of the cycle.

Under the influence of the corpus luteum hormone, important qualitative transformations occur in the uterine mucosa. The glands produce a secret, their cavity expands, bay-like protrusions form in the walls. The stromal cells are enlarged and slightly rounded, resembling the decidual cells formed during pregnancy. Glycogen, phosphorus, calcium and other substances are deposited in the mucous membrane.

As a result of these changes in the mucous membrane, conditions are created that are favorable for the development of the embryo if fertilization occurs. At the end of the secretion phase, serous impregnation of the stroma is noted, diffuse leukocyte infiltration of the functional layer appears. The vessels of this layer lengthen, acquire a spiral shape, extensions form in them, and the number of anastomoses increases.

One of the most common functional diagnostic tests is the histological examination of endometrial scrapings. For the purposes of functional diagnostics, the so-called “dash scraping” is usually used, in which a small strip of the endometrium is taken with a small curette. Clinical, morphological and differential diagnosis of the phases of the 28-day menstrual cycle according to the structures of the endometrium is clearly presented in the work of O. I. Topchieva (1967) and can be recommended for practical use. The whole is divided into 3 phases: proliferation, secretion, bleeding, and the phases of proliferation and secretion are divided into early, middle and late stages, and the bleeding phase into desquamation and regeneration.

When assessing the changes occurring in the endometrium, it is necessary to take into account the duration of the cycle, its clinical manifestations (the presence or absence of premenstrual and postmenstrual bleeding, the duration of menstrual bleeding, the amount of blood loss, etc.).

Early stage phases of proliferation(5-7th day) is characterized by the fact that the surface of the mucosa is lined with cuboidal epithelium, the endometrial glands look like straight tubes with a narrow lumen, on the cross section the contours of the glands are round or oval; the epithelium of the glands is prismatic, low, the nuclei are oval, located at the base of the cells, intensely stained. The stroma consists of spindle-shaped cells with large nuclei. The spiral arteries are slightly tortuous.

In the middle stage (8-10th day), the surface of the mucosa is lined with high prismatic epithelium. The glands are slightly tortuous. Numerous mitoses are determined in the nuclei. On the apical edge of some cells, a border of mucus may be found. The stroma is edematous, loosened.

In the late stage (11-14th day), the glands acquire a sinuous outline. Their lumen is expanded, the nuclei are located at different levels. In the basal sections of some cells, small vacuoles containing glycogen begin to be detected. The stroma is juicy, the nuclei increase, round and stain less intensely. Vessels take on a convoluted shape.

The described changes, characteristic of a normal cycle, can occur in pathology: a) during the second half of the menstrual cycle in anovulatory cycles; b) with dysfunctional uterine bleeding due to anovulatory processes; c) with glandular hyperplasia - in various parts of the endometrium.

If tangles of spiral vessels are found in the functional layer of the endometrium of the proliferation phase, this indicates that the previous cycle was two-phase, and during the next menstruation, the entire functional layer was not rejected and it only underwent reverse development.

Early stage secretion phases(15-18th day) subnuclear vacuolization is found in the epithelium of the glands; vacuoles push the nuclei into the central parts of the cell; nuclei are located on the same level; vacuoles contain glycogen particles. The lumen of the glands is enlarged, traces of the secret can already be determined in them. The stroma of the endometrium is juicy, loose. The vessels become even more tortuous. A similar structure of the endometrium can occur with the following hormonal disorders: a) with an inferior corpus luteum at the end of the menstrual cycle; b) with a delayed onset of ovulation; c) with cyclic bleeding that occurs as a result of the death of the corpus luteum, which has not reached the flowering stage; d) with acyclic bleeding due to the early death of an inferior corpus luteum.

In the middle stage of the secretion phase (19-23rd day), the lumen of the glands is expanded, their walls become folded. Epithelial cells are low, filled with a secret that separates into the lumen of the gland. In the stroma, by the 21st-22nd day, a decidua-like reaction begins to occur. Spiral arteries are sharply tortuous, form tangles, which is one of the most reliable signs of a full-fledged luteal phase. A similar structure of the endometrium can be observed with prolonged and increased function of the corpus luteum or when taking large doses of progesterone, with an early uterine period (outside the implantation zone), with a progressive ectopic pregnancy.

In the late stage of the secretion phase (24-27th day), due to the regression of the corpus luteum, the juiciness of the tissue decreases; the functional layer decreases in height. The folding of the glands increases, acquiring a sawtooth shape in longitudinal and star-shaped in transverse sections. In the lumen of the glands is a secret. Perivascular decidua-like reaction of the stroma is intense. Spiral vessels form coils closely adjacent to each other. By the 26-27th day, the venous vessels are full of blood with the formation of blood clots. In the stroma of the compact layer, leukocyte infiltration occurs; focal hemorrhages and areas of edema appear and grow. A similar condition must be differentiated from endometritis, in which the cellular infiltrate is localized mainly around the vessels and glands.

In the bleeding (menstruation) phase, the desquamation stage (28-2nd day) is characterized by an increase in the changes noted for the late secretory stage. Rejection of the endometrium begins with the surface layers and is focal in nature. Complete desquamation is completed by the third day of menstruation. A morphological sign of the menstrual phase is the discovery in the necrotic tissue of collapsed glands with stellate outlines. Regeneration (3-4th day) occurs from the tissues of the basal layer. By the fourth day, the mucosa is normally epithelized. Violation of rejection and regeneration of the endometrium may be due to a slowdown in the process or incomplete rejection with the reverse development of the endometrium.

The pathological state of the endometrium is characterized by the so-called hyperplastic proliferative changes (glandular hyperplasia, glandular-cystic hyperplasia, mixed form of hyperplasia, adenomatosis) and hypoplastic conditions (resting, non-functioning endometrium, transitional endometrium, dysplastic, hypoplastic, mixed endometrium).

Pathological anatomical diagnosis of the state of the endometrium by biopsies / Pryanishnikov V.A., Topchieva O.I. ; under. ed. prof. OK. Khmelnitsky. - Leningrad.

Diagnosis by biopsy of the endometrium 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, the endometrial tissue is distinguished by an exceptional variety of morphological structures, depending on the level of steroid hormones secreted by the ovaries in normal conditions and under pathological conditions associated with endocrine dysregulation.

Pathological anatomical diagnosis of the state of the endometrium by biopsies: guidelines

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PATHOLOGICAL AND ANATOMICAL DIAGNOSIS OF ENDOMETRIUM CONDITIONS BY BIOPSY

Accurate microscopic diagnosis of 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 by biopsy of the endometrium 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 in normal and pathological conditions associated with endocrine regulation.

Experience shows that a responsible and complex diagnosis of changes in the endometrium by 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 pathoanatomical diagnostics and includes such histochemical reactions as a reaction to glycogen, alkaline and acid phosphatases, monoamine oxidase, etc. The use of these reactions allows you to more accurately assess the degree of imbalance of estrogens and progestogens in the body women, and also makes it possible to determine the degree and nature of endometrial hormone sensitivity in hyperplastic processes and tumors, which is of great importance when choosing methods for treating these diseases.

METHOD OF OBTAINING AND PREPARATION OF MATERIAL FOR STUDY

Important for the correct microscopic diagnosis of endometrial scrapings is the observance of a number of conditions when collecting material.

The first condition is the correct determination of the time that is most favorable for the production of scraping. There are the following indications for scraping:

a) in case of sterility with suspected insufficiency of the corpus luteum or anovulatory cycle - 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, scraping is taken 5-10 days after the onset of menstruation;
c) in case of dysfunctional uterine bleeding such as metrorrhagic scrapings should be taken immediately after the onset of bleeding.

The second condition is the technically correct curettage of the uterine cavity. The "accuracy" of the pathologist's answer depends largely on how the endometrial scraping is taken. If small, fragmented pieces of tissue are received for research, then it is extremely difficult or even impossible to restore the structure of the endometrium. This can be eliminated with the correct work of curettage, the purpose of which is to obtain as large as possible, non-crushed strips of tissue of 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. In the event that the curette is not removed every time, then the mucous membrane separated from the uterine wall is crushed with repeated movements of the curette and part of it remains in the uterine cavity.

Complete diagnostic curettage of the uterus is performed after the expansion 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 the fixative liquid in two separate jars, marked where it came from.

In the presence of bleeding, especially in women who are in menopause or menopause, it is necessary to scrape out the tubal corners of the uterus with a small curette, remembering that it is in these areas that polyposis growths of the endometrium can be localized, in which areas of malignancy are most common.

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 the so-called dashed 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, to determine the causes of a woman's sterility. To obtain trains, a small curette is used without first expanding the cervical canal. When taking a train, it is necessary to hold the curette to the very bottom of the uterus so that the mucous membrane gets into the strip of dashed scraping from top to bottom, i.e., lining all parts of the uterus. To obtain the correct answer from the histologist for the train, as a rule, it is enough to have 1-2 strips of the endometrium.

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

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, I do not allow negative results of aspiration biopsy! to reject with confidence the initial forms of asymptomatic cancer. In this regard, if cancer of the uterine body 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 examination must fill out accompanying direction l about our proposed form.

The direction should indicate:

a) the duration of the menstrual cycle characteristic of this woman (21-28, or 31-day cycle);
b) the date of the onset of bleeding (on the date of the expected menstruation, ahead of time or late). In the presence of menopause or amenorrhea, it is necessary to indicate its duration.

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 the function of the thyroid gland and adrenal cortex),
c) Has the patient been subjected to hormonal therapy, about what, with what hormone and in what dosage?
d) whether methods of hormonal contraception were used, the duration of the use of contraceptives.

Histological processing 6-iopsium material includes fixation in 10% neutral formalin solution, followed by dehydration and paraffin embedding. You can also use the accelerated method of pouring into paraffin according to G.A. Merkulov with fixation in formalin, heated to 37°C in a thermostat in within 1-2 hours.

In everyday work, you can limit yourself to staining preparations with hematoxylin-eosin, according to Van Gieson, mucicarmine or alcian oitaim.

For a finer diagnosis of the state of the endometrium, especially when addressing issues of the cause of sterility associated with inferior ovarian function, as well as to determine the hormone sensitivity of the endometrium in hyperplastic processes and tumors, it is necessary to use histochemical methods that allow detecting glycogen, assessing the activity of acid, alkaline phosphatases and a number of other enzymes.

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

To conduct histological and histochemical studies from endometrial biopsies on cryostat sections, the pathoanatomical laboratory must be equipped with the following equipment: MK-25 cryostat, liquid nitrogen or carbon dioxide (“dry ice”), Dewar vessels (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 co-workers (1974).

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

Pieces of the endometrium (without prior washing with water and without fixation) are placed on a strip of filter paper moistened with water and gently immersed in liquid nitrogen for 3-5 seconds.
Filter paper with pieces of endometrium frozen in nitrogen is transferred to the cryostat chamber (-20°C) and carefully frozen to the microtome block holder with a few drops of water.
Sections 10 µm thick obtained in the cryostat are mounted in the cryostat chamber on cooled glass slides or coverslips.
The sections are straightened by melting the sections, which is achieved by touching a warm finger to the lower surface of the glass.
Glass with thawed sections is quickly removed from the cryostat chamber (do not allow the sections to freeze again), dried in air, and fixed in 2% solution of glutaraldehyde (or vapor form) or in a mixture of formaldehyde - alcohol - acetic acid - chloroform in a ratio of 2: 6 :1:1.
Fixed media are stained with hematoxylin-eosin, dehydrated, cleared, and mounted in polystyrene or balm. The choice of the level of the studied histological structure of the endometrium is made on temporary preparations (non-fixed 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 the content and localization of glycogen, air-dried cryostat sections are fixed in acetone cooled to +4°C for 5 minutes, dried in air, and stained according to the McManus method (Pearce 1962).

To identify hydrolytic enzymes (acid and alkaline phosphatase), cryostat sections are used, fixed in 2% chilled to a temperature of +4°C. neutral formalin solution for 20-30 minutes. After fixation, the sections are rinsed in water and immersed in an incubation solution to detect acid or alkaline phosphatase activity. Acid phosphatase is determined by the method of Bark and Anderson (1963), and alkaline phosphatase is determined by the method of Burston (Burston, 1965). Sections may be counterstained with hematoxylin prior to imaging. It is necessary to store drugs in a dark place.

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

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

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

Basal the layer contains a few narrow glands lined with a cylindrical single-row epithelium, the cells of which have oval nuclei that are intensely stained with hematoxylin. The response of the tissue of the basal layer 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 in 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. In 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 marked.

The cyclic changes in the morphological picture of the endometrium observed during the menstrual cycle are based on the ability of sex steroids-estrogens to cause characteristic changes in the structure and behavior of the mucosal tissue of the uterine body.

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

Progesterone has an effect on the endometrium only after prior 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 features were taken 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
- The middle stage (the most pronounced secretion) - 19-23 days
- Late stage (beginning regression) - 24-25 days
- Regression with ischemia - 26-27 days
3) phase of bleeding - 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 duration of the cycle in this woman (28- or 21-day cycle);
2) the period of ovulation that has occurred, which under normal conditions is 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 of 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 extended or shortened within 3 days. The changes observed in the endometrium of the proliferation phase result from the action of an increasing amount of estrogens secreted by the growing and maturing follicle.

The most pronounced morphological changes in the proliferation phase are noted in the glands. In the early stage, the glands look like straight or cast convoluted tubules with a narrow lumen, the contours of the glands are rounded or oval. The epithelium of the glands is single-row low cylindrical, the nuclei are oval, located at the base of the cells, intensely stained with hematoxylin. In the late stage, the glands acquire a sinuous, sometimes corkscrew-shaped outline with a somewhat expanded lumen. The epithelium becomes high prismatic, there is a large number of mitoses. As a result of intensive division and an increase in the number of epithelial cells, their nuclei are at different levels. The epithelial cells of the glands of the early phase of proliferation are characterized by the absence of glycogen and moderate activity of alkaline phosphatase. By the end of the proliferation phase in the glands, the appearance of small dust-like glycogen granules and high activity of alkaline phosphatase are noted.

In the stroma of the endometrium, 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 nicle, may reflect hormonal disorders if they are detected:

1) during the second half of the menstrual cycle; this may indicate an anovulatory monophasic cycle or an abnormal, prolonged proliferative phase with delayed ovulation. in a biphasic cycle:
2) with glandular hyperplasia of the endometrium in various parts of the hyperplastic mucosa;
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 of the secretion phase by more than two days in women in the reproductive period should be considered a pathological condition, since such cycles are sterile.

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

So, on the 2nd day after ovulation (16th day of the cycle) in the epithelium of the glands appear 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), the vacuoles partially move from the basal to the apical regions, and by the 5th day (19th day of the cycle), almost all vacuoles move to the apical regions of the cells, and the nuclei shift to the basal departments. On the following 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 noted in the cells of the epithelium of the glands, as a result of which apical “ Paradise cells have, as it were, notches, uneven. The lumen of the glands during this period is usually expanded, filled with eosinophilic secretion, 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 made it possible to establish that subnuclear vacuoles contain large glycogen granules, which are released into the lumen of the glands by apocrine secretion during the early and early middle stages of the secretion phase. Along with glycogen, the lumen of the glands also contains acid mucopolysaccharides. With the accumulation of glycogen and its secretion into the lumen of the glands, there is a clear decrease in the activity of alkaline phosphatase in the epithelial cells, which almost completely disappears by the 20-23rd day 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 stroma of the compact layer 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 sections 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 progestogen 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 the mixed hypoplastic endometrium with dysfunctional uterine bleeding in women of any age, including the period of menopause (O. I. Topchieva, 1962). However, in the endometrium, where the occurrence of vacuoles is not associated with ovulation, they are contained in individual glands or in a group of glands, as a rule, only in a part of the cells. The vacuoles themselves have a different 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, in conjunction with the onset of regression of the corpus luteum and a decrease in the level of progesterone in the blood, morphological signs of regression are observed in the endometrium, and on 26 th and 27th day signs of ischemia join. As a result of wrinkling of the stroma of the functional layer of the gland, they acquire star-shaped outlines on transverse sections and sawtooth on longitudinal ones.

In the phase of bleeding (menstruation), processes of desquamation and regeneration occur in the endometrium. A morphological feature characteristic of the endometrium of the menstrual phase is the presence, in the hemorrhagic, decaying tissue, 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 IN DISTURBANCE OF THE ENDOCRINE FUNCTION OF THE OVARIAN

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

Changes in the endometrium in violation of secretion estrogenic hormones.
Changes in the endometrium in violation of secretion progestative hormones.
Changes in the endometrium of the “mixed type”, in which structures are simultaneously found that reflect the effects of estrogen and progestative hormones.

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

A special place in its extremely important clinical significance is occupied by uterine bleeding in women in menopause, since among the various causes that cause such bleeding, about 30% are malignant neoplasms of the endometrium (V.A. Mandelstam 1971).

1. Changes in the endometrium in violation of the secretion of estrogen hormones

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

a) in an insufficient amount of estrogens and the formation of a non-functioning (resting) endometrium.

Under physiological conditions, the resting endometrium briefly exists during menstrual cycles - after regeneration of the mucosa before the onset of proliferation. Non-functioning endometrium is also observed in elderly women with the extinction of the hormonal function of the ovaries and is a stage of transition to atrophic endometrium. Morphological signs of a non-functioning endometrium - the glands look like straight or slightly twisted tubules. 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. When these changes are stressed, the endometrium turns from non-functioning to atrophic with small glands lined with cuboidal epithelium.

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

As a rule, the endometrium with dyshormonal proliferation is thickened, its height reaches 1-1.5 cm or more. Microscopically, there is no division of the endometrium into layers - compact and spongy, there is also no correct distribution of glands in the stroma; Characteristics of racemose enlarged glands. The number of glands (more precisely glandular tubules) does not increase (as opposed to atypical glandular hyperplasia - adenomatosis). But in connection with the 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 hyperplasia of the endometrium, which does not contain racemose enlarged 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” estrogens). The active form is characterized by a large number of mitoses both in the epithelial cells of the glands and in the cells of the stroma, high activity of alkaline phosphatase, and the appearance of accumulations of “light” cells in the glands. All of these signs point to 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 low levels of estrogen hormones on the endometrium. Under these conditions, the endometrial tissue acquires similarities with a resting, non-functioning endometrium: the nuclei of the epithelium 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 in the menopause, with the extinction of ovarian function.

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

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

2. Changes in the endometrium in violation of the 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).

Hypolyutein cycles with corpus luteum insufficiency are shortened in 25% of cases; ovulation usually occurs on time, but the secretory phase can be shortened to 8 days. Coming ahead of time, menstruation is associated with the premature death of an inferior corpus luteum and the cessation of secretion of testerone.

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

Predecidual transformations of the connective tissue cells are very weak or absent at all, the 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 reduced secretion of progesterone by the wooly corpus luteum.

In the first case, the changes that occur in the endometrium were called ultramenstrual hypertrophy and are similar to structures seen in early pregnancy. The mucosa is thickened up to 1 cm, the secretion is intense, there is a pronounced decidua-like transformation of the stroma and the development of spiral arteries. Differential diagnosis with impaired pregnancy (in women of reproductive age) is extremely difficult. The possibility of such changes in the endometrium of menopausal women (in which pregnancy can be excluded) is noted.

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

The microscopic picture of scrapings of the endometrium obtained with such bleeding after the 5th day seems to be very variegated: the scrapings show areas of necrotic tissue, areas in a state of regression, secretory and proliferative endometrium. Such changes in the endometrium can be found in women with acyclic dysfunctional uterine bleeding who are in the menopause.

Sometimes exposure to low concentrations of progesterone leads to a slowdown in its rejection, involution, i.e., the reverse development of the deep sections 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 there are three amenorrheas due to the so-called “hidden cycles” or hidden menstruation (E.I. Kvater 1961).

3. Endometrium “mixed type”

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 glands of an indifferent type, and also areas with secretory changes, mitoses are extremely rare.

Such an endometrium occurs in women of reproductive age with ovarian hypofunction, in menopausal women with dysfunctional uterine bleeding, and in menopausal bleeding.

Glandular hyperplasia of the endometrium with pronounced signs of exposure to progestogen hormones can be attributed to hyperplastic mixed endometrium. If among the tissues of glandular hyperplasia of the endometrium, along with typical glands that reflect the estrogenic effect, there are areas with groups of glands in which secretory signs, then such a structure of the endometrium is called a mixed form of glandular hyperplasia. Along with secretory changes in the glands, there are also changes in the stroma, namely: focal decidua-like transformation of connective tissue cells and the formation of tangles of spiral vessels.

PRECANCER CONDITIONS AND ENDOMETRIAL CANCER

Despite the great inconsistency of data on the possibility of endometrial cancer on the background of glandular hyperplasia, most authors believe that the possibility of a direct transition of glandular hyperplasia to 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 appear that resemble malignant growths. Adenomatosis is divided according to prevalence into diffuse and focal, and according to the severity of proliferative processes - into mild and pronounced forms (B.I. Zheleznoy, 1972).

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

The glands are strongly convoluted, often have numerous branches with numerous papillary protrusions 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 staining nuclei with signs of polymorphism. Structures corresponding to endometrial adenomatosis can be found over a large extent or in limited areas against the background of endometrial glandular hyperplasia. Sometimes in the glands, nested groups of light cells are found that have a morphological similarity to the squamous epithelium - adenoid acanthosis. Foci of pseudosquamous structures are sharply demarcated from the cylindrical 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, there is an accumulation of a large number of “light” cells (ciliated epithelium) in the epithelium of the glands.

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

However, due to the lack of clear morphological criteria for this form of endometrial cancer (unlike a similar form of cervical cancer), the use of this term in the diagnosis of 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 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 latest International Classification of 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 (mucoepidermoid) cancer.
e) Undifferentiated cancer.

It should be emphasized that more than 80% of malignant epithelial tumors of the endometrium are adenocarcinomas of varying degrees of differentiation.

A distinctive feature of tumors with histological structures of highly differentiated endometrial cancers is that the glandular structures of the tumor, although they have signs of atypia, nevertheless still resemble normal endometrial epithelium. Glandular growths of the endometrium of the epithelium with papillary outgrowths 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 mild polymorphism and relatively rare mitoses.

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

According to histochemical features, highly differentiated glandular cancers resemble the 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. Bohman, O. F. Che-pick 1976). Much less often, such a differentiating effect of gestagens develops in cells of moderately differentiated endometrial cancers.

CHANGES IN THE ENDOMETRIUM DURING THE PRESENTATION OF 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 of estrogens and gestagens, it is possible to artificially obtain morphological changes in the human endometrium that are characteristic of one or another phase of the menstrual cycle with normally functioning ovaries. The principles underlying the hormone therapy of dysfunctional uterine bleeding and amenorrhea are based on the general patterns inherent in the action of estrogens and progestogens on normal human endometrium.

The introduction of estrogen leads, depending on the duration and dose, to the development of proliferative processes in the endometrium up to glandular hyperplasia. With prolonged use of estrogens against the background of proliferation, abundant acyclic uterine bleeding may occur.

The introduction of progesterone in the proliferative phase of the cycle leads to inhibition of the proliferation of the epithelium of the glands 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:

- the 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.

With the joint administration of estrogens and progestogens, changes in the endometrium depend on the quantitative ratio of hormones, as well as on the duration of their administration. So, for the proliferating endometrium under the influence of estrogens, 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 a 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 progestogens in the treatment of menstrual disorders and pathological conditions of the endometrium should be carried out under histological control, by sampling repeated endometrial trains.

When using combined hormonal contraceptives in the normal endometrium of a woman, regular morphological changes occur, depending primarily on the duration 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 contained in them inhibit the proliferation processes in the glands, as a result of which the latter do not reach their full development, as is the case with a normal cycle. Secretory changes that develop in such glands have an unexpressed abortive character,

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

Thus, when taking combined hormonal contraceptives in the endometrium of women, there are pronounced deviations from the morphological picture of the endometrium of the corresponding phases of the normal cycle. However, as a rule, after discontinuation of the drugs, there is a gradual and complete restoration of the 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 ENDOMETRIUM ARISING DURING PREGNANCY AND ITS TERMINATION

When pregnancy occurs, implantation of a fertilized egg - a blastocyst occurs on the 7th day after ovulation, that is, on the 20th - 22nd day of the menstrual cycle. At this time, the recurrent reaction of the endometrial stroma is still very weakly expressed. The most rapid formation of decidual tissue occurs in the zone of blastocyst implantation. As for changes in the endometrium outside of implantation, the decidual tissue becomes clearly expressed 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 in both uterine and ectopic pregnancy.

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

In the compact layer of decidual tissue in early pregnancy, two types of cells are found: large, vesicle-shaped cells with a pale staining 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 in the exceptionally strong development of the glands, which are closely adjacent to each other and form a tissue, the general appearance of which may have some resemblance to an adenoma.

When making histological diagnosis based on scrapings and tissues released spontaneously from the uterine cavity, it is necessary to distinguish between trophoblast cells and decidual cells, especially when it comes to differential diagnosis between uterine and ectopic pregnancy.

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

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

In case of violation of pregnancy, the formed tissue of the decidual shell becomes necrotic and is usually completely rejected. If the pregnancy is violated in the early stages, when the decidual tissue is still completely undeveloped, then it undergoes reverse development. An undoubted sign that the endometrial tissue was subjected to 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 violation of pregnancy, one of the most important questions that a morphologist has to answer is the question of uterine or ectopic pregnancy. The absolute signs of uterine pregnancy are the presence in the scraping of chorionic villi, decidual tissue with invasion of the chorionic epithelium, the deposition of fibrinoid in the form of foci and strands in the decidual tissue and in the walls of venous vessels.

In those cases when decidual tissue without chorion elements is found in the scraping, this is possible both with 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 last menstruation, when the area of the fetal egg is large enough, then chorionic villi are almost always found in the uterine form of pregnancy. Their absence suggests an ectopic pregnancy.

At an earlier pregnancy, the absence of chorion elements in the scraping does not always indicate an ectopic pregnancy, since an unnoticed spontaneous miscarriage cannot be ruled out: during bleeding, a small fetal egg could stand out completely even before curettage.

All-Union Scientific and Methodological Center for the Pathological and Anatomical Service of the Institute of Human Morphology of the USSR Academy of Medical Sciences
Leningrad State Order of Lenin Institute for the Improvement of Physicians. CM. Kirov
I Leningrad Order of the Red Banner of Labor Medical Institute. I. P. Pavlova

Editor - Professor O. K. Khmelnitsky

The menstrual cycle of a woman includes several phases (follicular phase, ovulatory phase, luteal phase). Each woman has “her own” individual duration of the menstrual cycle, and, accordingly, the number of days of each phase also differ. To calculate the "safe" days when the ability to conceive is minimal, or, on the contrary, the most "dangerous" days, gynecologists are recommended to keep a calendar of the female menstrual cycle, by which it is possible to determine all of its days. It is from the day of the menstrual cycle that not only the female fertility (the possibility of pregnancy), but also her psycho-emotional state will depend.

About the phases of the menstrual cycle

The first day of the menstrual cycle is the first day of menstruation. In an ideal situation, the duration of the menstrual cycle in a woman is 28 days.

There are four phases in the menstrual cycle:

follicular phase;
ovulatory phase;
luteal phase;
desquamative phase.

Follicular phase

The beginning of the follicular (proliferative) phase is the first day of menstruation. The duration of the first phase of the female menstrual cycle usually depends on its duration. On average (with a twenty-eight-day monthly cycle), the follicular phase lasts fourteen days, but can be from seven to twenty-two days. In the first phase of the menstrual cycle, under the influence of the pituitary follicle-stimulating hormone, estrogens begin to be produced in the female ovary, which ensure the process of follicle growth and further maturation of the main (dominant) follicle among them, from which a mature egg will later come out, which is capable of fertilization. During the same phase, proliferative processes are carried out in the endometrium of the uterus, it begins its growth and thickening.

During the first or second day of the menstrual cycle, a woman usually feels aching pain in the lower abdomen, dyspepsia, headaches, and irritability are likely.

The third to sixth day of the menstrual cycle is often characterized by the stabilization of the woman's mood, as well as her physical condition.

During the seventh to eleventh days of the menstrual cycle, the fair sex is in a great mood, she is happy with life, makes her plans for the future and the present.

ovulatory phase

With a twenty-eight-day menstrual cycle, the ovulatory phase lasts from 36 to 48 hours, it occurs on the fourteenth to fifteenth day. During the ovulatory phase, the level of estrogen reaches its peak, which stimulates the production of luteinizing hormone in the pituitary gland, under the influence of which the dominant follicle breaks.

After that, a mature egg is released into the abdominal cavity from it. Then the level of estrogen begins to gradually decrease. During the ovulatory phase, a small (usually one or two drops of blood on underwear) ovulatory bleeding is likely to occur.

The ovulatory phase is the most favorable period for conception (the egg is viable for twenty-four hours).

During the twelfth to fifteenth days of the menstrual cycle, a woman unconsciously carefully monitors her appearance, she becomes more passionate (due to increased sexual desire), as well as more feminine. She is in excellent health.

luteal phase

It should be noted that the luteal or secretory phase is more or less constant. It continues on average (with a twenty-eight-day cycle) thirteen to fourteen days. After the rupture of the main follicle, its walls collapse. Then a corpus luteum begins to form at this place, producing progesterone. The luteal phase takes place under the action of the luteinizing hormone of the pituitary gland. Under the influence of progesterone, so-called secretory phenomena occur in the mucous membranes of the uterus, the endometrium at this time becomes edematous and then loosens (preparation for the probable implantation of a fertilized egg).

During the period of the eighteenth to twenty-second day of the monthly cycle, a woman feels great, she has a surge of strength.

In the period from the twenty-third to the twenty-eighth day of the menstrual cycle, the fair sex begins premenstrual syndrome. The woman becomes capricious, irritable, prone to tearfulness and depression. The mood is unstable and changes several times a day. Probably the appearance of swelling on the legs and face, pain in the lumbar region, swelling and increased sensitivity of the chest.

Desquamation phase

The last phase of desquamation is the rejection of the functional layer of the endometrium, or menstruation. The first day of menstruation or the first day of the menstrual cycle.

Today, one of the most common tests in the field of functional diagnostics is a histological examination of endometrial scrapings. For functional diagnostics, the so-called “stroke scraping” is often used, which involves taking a small strip of the endometrium with a small curette. The entire female menstrual cycle is divided into three phases: proliferation, secretion, bleeding. In addition, the phases of proliferation and secretion are divided into early, middle, and late; and the bleeding phase - for desquamation, as well as regeneration. Based on this study, we can say that the endometrium corresponds to the phase of proliferation or some other phase.

When evaluating the changes that occur in the endometrium, one should take into account the duration of the cycle, its main clinical manifestations (absence or presence of postmenstrual or premenstrual blood compartments, duration of menstrual bleeding, volume of blood loss, etc.).

Proliferation phase

The endometrium of the early stage of the proliferation phase (fifth-seventh day) has the form of straight tubes with a small lumen; on its transverse section, the contours of the glands are round or oval; the epithelium of the glands is low, prismatic, the nuclei are oval, located at the base of the cells, intensely stained; The mucosal surface is lined with cuboidal epithelium. The stroma includes spindle-shaped cells with large nuclei. But the spiral arteries are weakly tortuous.

In the middle stage (eighth to tenth day), the surface of the mucosa is lined with high prismatic epithelium. The glands are slightly tortuous. There are many mitoses in the nuclei. On the apical edge of certain cells, a border of mucus may be revealed. The stroma is edematous, loosened.

In the late stage (eleventh to fourteenth day) the glands get a tortuous outline. Their lumen is already expanded, the nuclei are located at different levels. In the basal section of some cells, small vacuoles containing glycogen begin to appear. The stroma is juicy, its nuclei increase, stain and round with less intensity. Vessels become convoluted.

The described changes are characteristic of the normal menstrual cycle, may be observed in pathology

during the second half of the monthly cycle with an anovulatory cycle;
with dysfunctional uterine bleeding due to anovulatory processes;
in the case of glandular hyperplasia - in different parts of the endometrium.

When tangles of spiral vessels are detected in the functional layer of the endometrium corresponding to the proliferation phase, then this indicates that the previous menstrual cycle was two-phase, and during the next menstruation the process of rejection of the entire functional layer did not occur, it only underwent reverse development.

Secretion phase

During the early stage of the secretion phase (fifteenth to eighteenth day), subnuclear vacuolization is detected in the epithelium of the glands; vacuoles are pushed into the central sections of the nucleus cell; nuclei are located on the same level; vacuoles contain particles of glycogen. The lumens of the glands are enlarged, traces of secretion may already be revealed in them. The stroma of the endometrium is juicy, loose. The vessels become even more tortuosity. A similar structure of the endometrium is usually found in such hormonal disorders:

in the case of an inferior corpus luteum at the end of the monthly cycle;
in case of delayed onset of ovulation;
in the case of cyclic bleeding that occurs due to the death of the corpus luteum, which has not reached the flowering stage;
in the case of acyclic bleeding, which is due to the early death of an still inferior corpus luteum.

During the middle stage of the secretion phase (nineteenth to twenty-third days), the lumen of the glands is expanded, they have folded walls. Epithelial cells are low, filled with a secret that is separated into the lumen of the gland. In the stroma during the twenty-first to twenty-second day, a decidua-like reaction begins to appear. Spiral arteries are sharply tortuous, form tangles, which is one of the most reliable signs of an absolutely full luteal phase. This structure of the endometrium can be noted:

with increased prolonged function of the corpus luteum;
due to taking large doses of progesterone;
during the early period of uterine pregnancy;
in the case of a progressive ectopic pregnancy.

During the late stage of the secretion phase (twenty-fourth to twenty-seventh day), due to the regression of the corpus luteum, the juiciness of the tissue is minimized; the height of the functional layer decreases. The folding of the glands increases, getting a sawtooth shape. In the lumen of the glands is a secret. The stroma has an intense perivascular decidua-like reaction. Spiral vessels form coils that are closely adjacent to each other. On the twenty-sixth to twenty-seventh days, the venous vessels are filled with blood with the appearance of blood clots. Infiltration by leukocytes of the appearance of a compact layer in the stroma; focal hemorrhages arise and grow, as well as areas of edema. This condition must be differentiated from endometritis, when the cellular infiltrate is located mainly around the glands and blood vessels.

Bleeding phase

In the phase of menstruation or bleeding for the stage of desquamation (twenty-eighth - second day), the increase in changes that are noted for the late secretory stage is characteristic. The process of rejection of the endometrium begins with the surface layer and has a focal character. Fully desquamation ends by the third day of menstruation. The morphological sign of the monthly phase is the discovery of collapsed star-shaped glands in necrotic tissue. The regeneration process (third-fourth day) is carried out from the tissues of the basal layer. By the fourth day, the normal mucosa is epithelialized. Impaired rejection and regeneration of the endometrium can be caused by slow processes or incomplete rejection of the endometrium.

The abnormal state of the endometrium is characterized by the so-called hyperplastic proliferative changes (glandular cystic hyperplasia, glandular hyperplasia, adenomatosis, mixed form of hyperplasia), as well as hypoplastic conditions (non-functioning, resting endometrium, transitional endometrium, hypoplastic, dysplastic, mixed endometrium).

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