RU2749290C1 - Method for diagnostics of minor forms of endometriosis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine and is intended for diagnostics of minor forms of endometriosis. Concentration of a pro-inflammatory cytokine, interleukin 6 (IL-6) and a carbohydrate antigen, a CA125 tumour marker, are determined in the venous blood of women. Additionally, the levels of IL-6 and alpha-2-microglobulin of fertility, glycodelin, are determined in the menstrual blood. At an IL-6 concentration of 5.3±2.4 pg/ml and a CA125 concentration of 14.6±3.8 U/L in venous blood, an IL-6 concentration of 8.7±3.1 pg/ml and a glycodelin level of 49.1±5.6 ng/ml in menstrual blood, minor forms of endometriosis are diagnosed.

EFFECT: invention ensures increased accuracy of diagnostics.

1 cl, 2 ex

Description

Endometriosis is a common pathology of the reproductive period of women, which is determined by the benign growth of endometrial tissue in ectopic areas. Endometriosis affects about 10% of women of reproductive age, causing dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. Clinical manifestations can range from asymptomatic and unexplained infertility to severe dysmenorrhea and chronic pain. Endometriosis has become a major economic and clinical burden in the industrialized world. One of the key points in the diagnosis of endometriosis is the fact that, on average, according to different authors, it takes about 7 years from the appearance of the first symptoms to an accurate diagnosis [Dunselman GA, Vermeulen N., Becker C., Calhaz-Jorge C., D'Hooghe T., De Bie B. et al. ESHRE guideline: management of women with endometriosis. Human reproduction (Oxford, England). 2014; 29 (3): 400-12. DOI: 10.1093 / humrep / det457].

The etiology of the disease is not known. However, the widely accepted theory of retrograde menstruation suggests that menstrual blood refluxes into the abdomen through uterine contractions. Once on the peritoneum, endometrial tissue can attach to peritoneal structures, activate angiogenesis, and develop into endometriotic lesions. However, 78-90% of women experience retrograde menstruation, while only 5-10% of women eventually develop the disease [Bulletti C. et al. Endometriosis and infertility. Journal of assisted reproduction and genetics. 2010; 27 (8): 441-447].

This suggests that women who develop endometriosis potentially have a dysfunctional immune response to ectopic endometrial cells, which does not lead to their elimination, but enhances the inflammatory, angiogenic and pathological environment. However, the molecular mechanisms underlying the regulation of the immune system in endometriosis and the early establishment and proliferation of lesions remain poorly understood. There is evidence that various environmental, immunological and hormonal factors are associated with endometriosis and genetic loci that pose the risk of endometriosis, but the relative contribution of these and other causal factors is still unclear [Vercellini P., Viganò P., Somigliana E., Fedele L. Endometriosis: Pathogenesis and treatment. Nat. Rev. Endocrinol. 2014; 10: 261-275. Doi: 10.1038 / nrendo.2013.255].

All organs in the abdominal cavity are washed by peritoneal fluid, which is mainly an ovarian exudate produced by developing follicles and the corpus luteum [Králíčková M., Vetvicka V. Immunological aspects of endometriosis: A review. Ann. Transl. Med. 2015; 3: 153]. Exudate volume and content vary significantly at different phases of the menstrual cycle, since vascular permeability increases with increasing estrogen concentration. Peritoneal fluid contains electrolytes, urea, ovarian steroid hormones such as estrogen and progesterone, and cellular components including endometrial cells, macrophages, lymphocytes, and red blood cells. These cellular components independently secrete some substrates: for example, endometrial cells secrete glycodelins, and macrophages can produce cytokines and growth or angiogenic factors [Mu F., Harris H.R., Rich-Edwards J.W., Hankinson S.E., Rimm E.B., Spiegelman D., Missmer S.A. A Prospective Study of Inflammatory Markers and Risk of Endometriosis. Am J Epidemiol. 2018 Mar 1; 187 (3): 515-522. Doi: 10.1093 / aje / kwx272].

According to modern concepts, endometriosis is a consequence of chronic inflammation caused by an abnormal peritoneal environment. The volume of peritoneal fluid is significantly higher in infertile women with endometriosis than in women without the disease. In endometriosis, many aspects of the immune system are altered, including inhibited T-cell cytotoxicity towards endometrial cells, low NK cell activity, and increased numbers of activated macrophages and pro-inflammatory cytokines. These changes create an oxidative and immunotolerant microenvironment for the survival of endometrioid implants [Wang XM, Ma ZY, Song N. Inflammatory cytokines IL-6, IL-10, IL-13, TNF-α and peritoneal fluid flora were associated with infertility in patients with endometriosis ... Eur Rev Med Pharmacol Sci. 2018 May; 22 (9): 2513-2518. doi: 10.26355 / eurrev-201805-14899].

The interaction between foci of endometriosis and its local immune environment has been considered [Bossuyt PM, Shaikh R, Farquhar C, Jordan V, Scheffers CS, Mol BW, Johnson N, Hull ML. Blood biomarkers for the non-invasive diagnosis of endometriosis. Nisenblat V. Cochrane Database Syst Rev. 2016 May 1; (5): CD012179. Epub 2016 May 1]. Endometrioid heterotopies secrete estradiol, progesterone, alpha-2-microglobulin fertility (glycodelin), carbohydrate antigens (CA125, CA19-9), monocyte chemoattractant protein (MCP-1), transforming growth factor (TGF-β), vascular endothelial growth factor ( VEGF) and pro-inflammatory cytokines such as interleukin - 1 (IL 1), IL 6 and IL 8, as well as tumor necrosis factor alpha (TNF-α) and others. This cocktail of secretions in the peritoneal fluid promotes a proliferative and angiogenic environment that enhances the development and progression of endometriosis [Istrate-Ofiţeru A.M., Pirici D., Niculescu M., Berceanu C., Berceanu S., Voicu N.L. et al. Clinical, morphological and immunohistochemical survey in different types of endometriosis. Rom. J. Morphol. Embryol. 2018; 59 (4): 1133-53].

Endometrioid ovarian cysts can alter ovarian function through spatial and local exposure. The cystic fluid within the endometrioma is a rich source of pro-inflammatory cytokines (IL 6, IL 8), iron, reactive oxygen species, growth factors such as TGF-β, and matrix metalloproteases. The active elements of the cystic fluid can influence the function of neighboring ovaries through diffusion into the surrounding tissues. Structural changes were found in adjacent ovarian endometrioma tissue with lower follicular density, greater fibrosis, and loss of cortex-specific stroma. In addition, cortical biopsy of ovaries containing endometriotic cysts revealed atresia of early follicles with increased cleavage of immunostimulating caspase-3, which was not observed in contralateral ovaries without endometriomas. Increased oxidative stress due to local inflammatory reactions is observed in the ovarian cortex surrounding endometrioid cysts [Khan K.N., Fujishita A., Kitajima M., Hiraki K., Nakashima M., Masuzaki H. Occult microscopic endometriosis: undetectable by laparoscopy in normal peritoneum. J Hum reprod. 2014; 29 (3): 462–72. doi: 10.1093 / humrep / det438].

The follicular fluid forms a special microenvironment inside the ovaries and contains cytokines produced by granulosa and local immune cells. The follicular fluid of patients with endometriosis who underwent IVF after stimulation with gonadotropin contains high levels of IL 1β, IL 6, IL 8 and IL 18 [Wilson RB. Hypoxia, cytokines and stromal recruitment: parallels between pathophysiology of encapsulating peritoneal sclerosis, endometriosis and peritoneal metastasis. PleuraPeritoneum. 2018 Mar 21; 3 (1): 20180103. Doi: 10.1515 / pp-2018-0103. eCollection 2018 Mar 1]. It has been established that the follicular fluid of naturally mature follicles (without stimulation by gonadotropins) in patients with endometriosis has higher levels of IL 1β and IL 6 [De Andrade VT, Nácul AP, Dos Santos BR, Lecke SB, Spritzer PM, MorschDM. Circulating and peritoneal fluid interleukin-6 levels and gene expression in pelvic endometriosis. ExpTher Med. 2017 Sep; 14 (3): 2317-2322. Doi: 10.3892 / etm.2017.4794. Epub 2017 Jul 13]. The abnormal presence of intrafollicular IL 1β and IL 6 may affect the development of follicles in patients with endometriosis, since a low level of intrafollicular IL 6 is associated with a higher pregnancy rate [Sikora J, Mielczarek-Palacz A, Kondera-AnaszZ. 1β and Peritoneal Inflammation-Role in Pathogenesis of Endometriosis. J ClinLabAnal. 2016 Nov; 30 (6): 831-837. Doi: 10.1002 / jcla.21944. Epub 2016 Mar 28].

The endometrium, blood serum and peritoneal fluid of women with endometriosis have high levels of inflammatory cytokines (TNF, IL 1β, 6, 8, 18, etc.), angiogenic growth and adhesion factors, fertility suppressor proteins (in particular, glycodelin), as well as cancer molecules (eg CA125, CA19-9) [Liang Y., Yang X., Lan Y., Lei L., Li Y., Wang S. Effect of Endometrioma cystectomy on cytokines of follicular fluid and IVF outcomes. J Ovarian Res. 2019 Oct 21; 12 (1): 98. Doi: 10.1186 / s13048-019-0572-7]. It is believed that these soluble factors are predominantly involved in the initiation and progression of the disease. IL 1β has a proliferative effect on endometrioid cells, which does not occur in healthy endometrial cells. This cytokine stimulates the production of IL 6 and IL 8 in endometrioid cell cultures, which additionally induce proliferation and reduce the rate of apoptosis. In addition, higher levels of IL 6 may indicate a transition from acute to chronic inflammation [Nanda A., Banerjee P., Dutta M., Wangdi T., Sharma P., Chaudhury K., Jana S.K. Cytokines, Angiogenesis, and Extracellular Matrix Degradation are Augmented by Oxidative Stress in Endometriosis. Ann Lab Med. 2020 Sep; 40 (5): 390-397. Doi: 10.3343 / alm.2020.40.5.390].

Identifying biomarkers that can assist in the non-invasive diagnosis and monitoring of endometriosis remains challenging due to the heterogeneous nature of the disease process and its manifestations, as well as the influence of comorbidities. There is insufficient evidence to recommend any systemic or local biomarker or diagnostic complex for widespread implementation in clinical practice. Although a large number of registered markers highlight women with and without endometriosis in small pilot studies, many do not demonstrate compelling potential as a diagnostic test when evaluated in larger studies by different research groups. The diagnostic value of these tests has not previously been fully systematically assessed and summarized using Cochrane methods. Currently, there is no simple minimally invasive test for early detection of endometriosis, which has proven itself in clinical practice [Banerjee J., Sharma R., Agarwal A., Maitra D., Diamond M.P., Abu-Soud H.M. IL-6 and mouse oocyte spindle. PLoSOne. 2012; 7 (4): e35535. Doi: 10.1371 / journal.pone.0035535. Epub 2012 Apr 20].

The development of new highly informative methods for the early diagnosis of small forms of endometriosis, which have a blurred clinical picture and show a higher efficiency in treatment, should be carried out taking into account the leading pathogenetic systemic and local mechanisms involved in the implementation of this disease.

A known method for early diagnosis of external genital endometriosis in women with infertility [Bespalova Zh.V., Volkov NI, Kulakov V.I. Early diagnosis of external genital endometriosis in women with infertility. Journal of Obstetrics and Women's Diseases. 2004. T. 53, No. 2. S. 11-15].

In the known method, on the basis of clinical and anamnestic data, the probability of the presence of endometriosis in women with infertility is calculated. Patients are assessed: history data, clinical manifestations, menstrual and reproductive functions. Mathematical processing of these signs using the total probability formula allows you to calculate the statistical probability of endometriosis in the presence of each sign separately and in case of their random combination.

The disadvantage of this method is the impossibility of identifying in the general group of women who do not suffer from infertility, patients with small forms of endometriosis. Therefore, this technique is not specific enough for early diagnosis. Disease history and vaginal bimanual pelvic examination play a role in the diagnosis of endometriosis, but heterogeneity in the clinical picture, high prevalence of asymptomatic endometriosis (2% to 50%), and a weak relationship between symptom manifestation and disease severity contribute to the low diagnostic accuracy of a method based solely on data history and clinical symptoms.

A known method for the diagnosis of endometriosis using ultrasound criteria for combined genital endometriosis [Kalinkina OB, Zazulin Ya.A., Sreseli GM, Mikheeva EM. Diagnostics and anti-relapse therapy of genital endometriosis in preparation for the implementation of assisted reproductive technologies. Bulletin of the Samara Scientific Center of the Russian Academy of Sciences. 2014.Vol. 16, No. 5-4. S. 1449-1452].

In the known method, on the basis of the developed ultrasound markers, endometriosis is diagnosed in women with stages II-III of the disease, which have combined forms and clinical manifestations.

The disadvantage of this method is the reduced accuracy of the diagnosis of endometriosis due to the low sensitivity and specificity of ultrasound criteria in relation to small forms of endometriosis, in the absence of pronounced structural changes in the tissues surrounding the foci of endometriosis.

A known method for early diagnosis of endometriosis using diagnostic laparoscopy [Koleva N.N. Laparoscopy is an effective way to diagnose and treat endometriosis. In the collection: Problems of implementing the results of innovative developments. Collection of articles of the International Scientific and Practical Conference. Orenburg: Publishing house Omega Sains, 2018. S. 134-136].

In the known method, the diagnosis is carried out by visualizing the foci of endometriosis during laparoscopic surgery, followed by biopsy and histological verification.

The disadvantage of the known method for the early diagnosis of endometriosis is the significant invasiveness of the diagnostic laparoscopic procedure, the need for general anesthesia, the possibility of adhesion formation, low, but the risk of vascular damage (0.001%), internal organs, mortality (0.0001%), only a third of women have endometriosis , the rest of the patients are unnecessarily exposed to surgical risk. In addition, the reliability of laparoscopy for early diagnosis of endometriosis is highly dependent on the skill of the surgeon.

A highly informative non-invasive biomarker detection of endometriosis can lead to the diagnosis of endometriosis without the need for surgery or significantly reduce the need for diagnostic surgery.

Closest to the claimed is a method of early diagnosis of small forms of endometriosis by registering in the blood of women the levels of pro-inflammatory cytokine and carbohydrate antigen - a tumor marker [Ivanov N.V., Shcherbakova L.N., Panina O.B., Bugerenko E.Yu., Shimanovsky N.L, Fomina M.G. Cytokines and tumor markers in the diagnosis of small forms of endometriosis. Questions of gynecology, obstetrics and perinatology. 2012. T. 11, No. 4. S. 47-52].

In this method of early diagnosis of endometriosis in the blood serum of women, the concentration of the pro-inflammatory cytokine - IL 6 and the content of the oncomarker CA125 are determined and the possible presence of small forms of endometriosis is judged by deviations from the norm. In this method for diagnosing endometriosis, its high sensitivity (93%) and specificity (88%) are declared.

The disadvantage of this, the closest to the claimed, method of early diagnosis of small forms of endometriosis is that extragenital pathology and any systemic infectious and inflammatory processes (diseases of the liver, kidneys, gastrointestinal tract, autoimmune processes, ARVI, etc.) can affect the highly sensitive result. ), leading to an increase in the levels of IL 6 and CA125 in the body. This method does not take into account local changes in the organs of the reproductive system, namely, the local cytokine status and changes in the regulatory proteins of fertility against the background of a chronic inflammatory process that plays a key role in the formation and development of early forms of endometriosis.

The problem solved by the invention is a minimally invasive method for early diagnosis of small forms of endometriosis by biomarkers.

The technical result consists in improving the diagnostic accuracy. The specified technical result is achieved by the fact that in the method of early diagnosis of small forms of endometriosis by determining in women in the venous blood of the pro-inflammatory cytokine - IL 6 and the carbohydrate antigen CA125, additionally the determination of the content of glycodelin (alpha-2-microglobulin fertility) and IL 6 in the menstrual blood is carried out When these indicators change in comparison with the norm, small forms of endometriosis are diagnosed.

The method for early diagnosis of small forms of endometriosis is carried out as follows.

A woman with suspected endometriosis is examined taking into account the revealed significant differences in the studied parameters in the absence of endometriosis and in the presence of small forms of endometriosis. For convenience, the sampling from the cubital vein of venous blood and menstrual blood to determine laboratory parameters is carried out in a woman on an empty stomach during menstruation in one day.

The survey is carried out by determining:

in venous blood

- the concentration of interleukin 6 (IL 6)

- the concentration of the tumor marker CA125

in menstrual blood

- concentration of IL 6

- concentration of glycodelin (alpha-2-fertility microglobulin).

The data presented were obtained by determining the concentrations of IL 6, CA125, glycodelin in the blood serum by the method of enzyme-linked immunosorbent assay using the Architect i2000 system (Abbott, USA) using reagents from Abbott (Ireland). When diagnosing the stages of endometriosis, the criteria presented in the latest clinical guidelines were taken into account [Adamyan LV, ed. Endometriosis: diagnosis, treatment and rehabilitation, clinical guidelines for the management of patients. Moscow, 2016].

Laboratory parameters are presented in accordance with various clinical options: norm and minor forms of endometriosis.

In a healthy woman, the above parameters had the following quantitative characteristics:

in venous blood

- IL 6 (pkg / ml) - 1.7 ± 0.6

- CA125 (U / ml) - 7, 2 ± 2.7

in menstrual blood

- IL 6 (pkg / ml) - 3.5 ± 0.9

- glycodelin (ng / ml) - 13.8 ± 2.5.

For small forms of endometriosis, the following values are characteristic:

in venous blood

- IL 6 (pkg / ml) - 5.3 ± 2.4

- CA125 (U / ml) - 14.6 ± 3.8

in menstrual blood

- IL 6 (pkg / ml) - 8.7 ± 3.1

- glycodelin (ng / ml) - 49.1 ± 5.6.

The proposed diagnostic method examined 86 women with suspected endometriosis. Positive examination results, according to the proposed method, were recorded in 78 patients, who underwent diagnostic laparoscopy to verify the diagnosis, followed by a histological examination of the biopsy specimen. Results: the diagnosis of "minor forms of endometriosis" was confirmed in 73 women, in 5 patients the diagnosis of endometriosis was not confirmed. From the standpoint of evidence-based medicine, the calculation of clinical epidemiology tests was carried out, which confirmed the high information content and reliability of the proposed method for early diagnosis of endometriosis: the sensitivity was 95.8%, the specificity was 91.9%, the accuracy was 92.5%, the predictive value of a positive result was 89. 5%, the predictive value of a negative result is 93.78%.

Example 1. Patient M., 29 years old, applied to the antenatal clinic with complaints of secondary infertility. Examination in the mirrors revealed no foci of external genital endometriosis. In a bimanual study of data for the volumetric formation of appendages, infiltrates in the small pelvis, indirect signs of adhesions of the small pelvis were not obtained. The uterus is sensitive to palpation, spherical, not enlarged. According to vaginal ultrasound examination, there is a slight asymmetry of the walls of the uterus, heterogeneous myometrium, no thickening of the basement membrane of the endometrium, the veins of the small pelvis are not dilated.

There were no operations. Menarche at the age of 12, the menstrual cycle was established immediately, menstruation was regular in 27-28 days, lasting 5-6 days with episodes of bleeding, moderately painful, abundant. Pregnancy - 1 to 26 years, ended in spontaneous abortion at 8-9 weeks. In marriage, one partner, tested for STIs - negative, smear for flora - 2 degree of purity, oncocytology - without atypia. The patient lives a regular sex life, does not use any methods of contraception, after a miscarriage, pregnancy did not occur.

For this patient with suspected endometriosis, diagnostic laparoscopy is required to verify the diagnosis according to the standard of management. However, given the patient's reluctance to conduct laparoscopy in order to diagnose the cause of infertility, it was decided in favor of performing a minimally invasive method for detecting endometriosis using the proposed biomarkers.

The following results were obtained: in the venous blood, the content of IL 6 was 6.9 pkg / ml, CA125 — 17.1 U / ml; in menstrual blood, the content of IL 6 was 10.2 pkg / ml, glycodelin - 53.7 ng / ml.

During the examination, all indicators are characteristic of the presence of small forms of endometriosis, which served as the rationale for the appointment of a diagnostic laparoscopy to the patient, which confirmed the small forms of endometriosis on the ovaries and peritoneum of the small pelvis. After complex treatment (surgical removal of visible foci of endometriosis and a drug course of treatment with dienogest for 6 months), the patient, 4 months after the end of treatment, had a uterine pregnancy, which ended in urgent delivery at 39 weeks. This example demonstrates the capabilities of the proposed method for early diagnosis of small forms of endometriosis.

Example 2. Patient D., 32 years old, came to the antenatal clinic with complaints of heavy menstruation up to 7-8 days, sometimes disturbing cramping pains in the right groin area. Menstruation from 13 years old, regular in 30-31 days, profuse, moderately painful. Single. The patient's mother was previously operated on with a diagnosis of bilateral endometrioid ovarian cysts, and her sister was also treated for endometriosis. When viewed in mirrors - no peculiarities, with a bimanual examination, the right ovary is slightly enlarged, painless, dense. When examining by ultrasound - echo signs of a cyst of the right ovary up to 2.5 cm with blood flow, diffusely heterogeneous endometrium. In the general analysis of blood - hemoglobin 107 g / l, the risk index for malignancy of masses of the ovaries, thyroid hormones, androgens, prolactin, progesterone - within the reference values.

To verify the diagnosis according to the standard of management, it is necessary to perform diagnostic laparoscopy. However, given the lack of indications for surgical removal of the ovarian cyst and the possibility of dynamic observation, the patient was given a minimally invasive method for verifying endometriosis. The following survey results were obtained, according to the proposed method: in the venous blood, the content of IL 6 - 1.4 pkg / ml, CA125 - 5.6 U / ml; in menstrual blood, the content of IL 6 was 3.2 pkg / ml, glycodelin - 12.5 ng / ml.

The obtained parameters of biomarkers in this patient correspond to normal values. The diagnosis of external genital endometriosis, endometriotic cyst of the right ovary is not confirmed. Despite the results of the examination, the woman insisted on a diagnostic laparoscopy - a follicular cyst of the right ovary of small size was revealed. Conservative treatment of the follicular cyst was carried out, after 2 months, according to ultrasound data, the right ovary was of normal size, there were no echo signs of the cyst.

This clinical example demonstrates the advantage of the proposed method for early diagnosis of endometriosis, in comparison with the assessment of anamnestic risk factors and the results of ultrasound, and made it possible to avoid the unreasonable appointment of hormonal therapy for endometriosis in this patient, and to choose the correct medical tactics.

Thus, the use of a diagnostic complex for the early diagnosis of small forms of endometriosis with the determination of markers of local chronic inflammatory process - the proinflammatory cytokine IL 6 and the regulatory protein of the functional state of the ovaries, fallopian tubes and endometrium - glycodelin, along with the determination of the proinflammatory cytokine IL 6 and the oncomarker CA125 in the systemic blood flow, significantly expands the diagnostic capabilities of the method, allows timely recording of changes in the early stages of the pathological process, which contributes to an increase in the effectiveness of treatment and preservation of the quality of life.

The reduced accuracy of early diagnosis of endometriosis at the initial stages of the disease only by the presence of appropriate blood levels of IL 6 and CA125 is due to the fact that these parameters, determined in the general blood flow, without taking into account local changes in the organs of the reproductive system, have low specificity for endometriosis, and also, they can change in case of systemic infectious and inflammatory processes, pronounced somatic pathology, which makes it difficult to interpret the examination results.

Changes in the indicators proposed for the minimally invasive method of diagnosing endometriosis (determination of IL 6 and glycodelin in menstrual blood) provides a timely pathogenetically substantiated possibility of judging about violations of the pro-inflammatory activity of cytokines, regulatory proteins of the endometrium and deaptation of the immune system to increased proliferative ability of ectopically developing cells with altered receptor status ...

The positive effect of the proposed method for detecting endometriosis by biomarkers provides new opportunities for early diagnosis of the initial stages of endometriosis with high efficiency due to the assessment of previously unused parameters. The method is non-invasive, safe for the health of women and is widely available for modern outpatient clinics.

As of the date of filing the application, the applicants did not find a diagnostic method with the stated set of features, as a result of which we conclude that the proposed technical solution meets the criteria of the invention “novelty”.

According to the results of a comparative analysis, the set of features of the proposed diagnostic method provides it with new properties in the form of improved diagnostic accuracy, that is, according to the applicants, it ensures that the proposed method meets the criterion of "inventive step"

The criterion of the invention "industrial applicability" is confirmed by the fact that the claimed diagnostic method can be successfully applied in mass examinations of women with the identification of accurate and early signs of endometriosis.

Claims (1)

A method for diagnosing small forms of endometriosis, including determining the concentration of a pro-inflammatory cytokine - interleukin 6 (IL-6) and a carbohydrate antigen - tumor marker CA125 in the venous blood of women, followed by data analysis, characterized in that additionally, the levels of IL-6 and alpha-2-microglobulin fertility - glycodelin, and with the value of these indicators: the concentration of IL-6 (pkg / ml) - 5.3 ± 2.4, the concentration of CA125 (U / L) - 14.6 ± 3.8 in the venous blood; the concentration of IL-6 (pkg / ml) is 8.7 ± 3.1, the level of glycodelin (ng / ml) is 49.1 ± 5.6 in menstrual blood, minor forms of endometriosis are diagnosed.