RU2726971C1 - Method of non-invasive early diagnosis of endometriosis - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, namely to gynecology, and aims at non-invasive early diagnosis of endometriosis. Diagnosing endometriosis involves chemical analysis of six amino acids in blood serum – glycine, alanine, valine, proline, serine and tryptophan in the range of concentrations from 0.5 to 10.0 mcg/ml. Obtained analytical signal values are normalized to the valine analytical signal. Comparison of normalized values of concentrations of five amino acids with average normalized values for groups of patients and healthy. If the obtained values of normalized concentration values for glycine are less than 1.85, for alanine less than 1.14, for proline is less than 1.07 and serine is less than 1.93, and for tryptophan is more than 1.79, endometriosis is diagnosed. If the obtained values for glycine are more than 1.85, for alanine is more than 1.14, for proline is more than 1.07 and serine is more than 1.93, and for tryptophan is less than 1.79, the disease is not diagnosed. If these relationships are not complied with, further analysis is required to specify the diagnosis.EFFECT: use of the invention provides higher accuracy and specificity of non-invasive early diagnosis of endometriosis in females, which enables timely prescribing the corresponding adequate pathogenetic therapy.1 cl, 2 tbl, 1 dwg

Description

The invention relates to medicine, namely to gynecology, and will find wide application for an objective early diagnosis of endometriosis.

The introduction in the last 20-30 years into practice of instrumental, endoscopic, genetic, immunological methods has expanded the diagnostic capabilities in the examination of patients with endometriosis. The frequency of detection of endometriosis in patients of reproductive age ranges from 7 to 50%. The most common deficiencies in diagnosis are: non-recognition of endometriosis, erroneous diagnosis in some cancer and neurological patients in the absence of endometriosis, late diagnosis. The "gold" standard for the diagnosis of endometriosis is laparoscopy and hysteroscopy with subsequent histological examination of biopsied tissues. However, the frequency of histological confirmation of the diagnosis ranges from 70 to 85%. A positive result confirms the diagnosis of endometriosis, while a negative result does not completely exclude endometrioid disease, since only individual pieces of tissue that are devoid of the characteristic morphological signs of endometriosis can get into the study (Baskakov V.P., Tsvelev Yu.V., Kira E.F. . Endometrioid disease. St. Petersburg, 2002, 448 p.). Currently, there is no reliable non-invasive diagnosis of small forms of endometriosis (Kennedy S., Bergqvist A., Chapron C., D'Hooghe T., Dunselman G., Greb R. et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod 2005, Vol. 20, P. 2698-704; Rogers PA, D'Hooghe TM, Fazeabas A., Garget CE, Giudice LC, Montgomery GW, Rombauts L., Salamoonsen LA, Zondervan KT Priorities for endometriosis research: recommendations from an international consensus workshop. Reprod Sci 2009, Vol. 16, P. 335-346), which leads to an increase in the time interval between the first manifestation of symptoms of pain, infertility and surgical confirmation of the diagnosis (Chernukha G.E. Endometriosis and chronic pelvic pain: causes and consequences.Problems of reproduction, 2011, No. 5, pp. 83-89; Sinaii N., Plumb K., Cotton L., Lambert A., Kennedy S., Zondervan K. et al. Differences in characteristics among 1,000 women with endometriosis based on the extent of diseae Fertil Steril 2008, Vol. 89, P. 5 38-45; Gajbhiye R., Sonawani A., Khan S., Suryawanshi A., Kadam S., Warty N., Raut V., Khole V. Identification and evaluation of new serum markers for early diagnosis of endometriosis. Human Reprodaction 2012, no. 2 (26), p. 35-45). An analysis of the patent and scientific medical literature made it possible to establish that the existing methods for diagnosing endometriosis are mainly invasive.

Ultrasound diagnostics firmly entered medical practice as one of the objective methods of diagnostics and dynamic observation of gynecological patients. But transvaginal ultrasound scanning, according to a number of researchers, does not allow detecting superficial implants on the peritoneum of the small pelvis, sacro-uterine ligaments (Adamyan L.V., Kulakov V.I., Andreeva E.N. Endometriosis: doctors' guide. M., Medicine, 2006, 416 pp .; Ishchenko A.I., Kudrina E.A.Endometriosis: modern aspects.M., Medicine, 2008, 176 pp .; Steinkeler JA, WoodField SA, Hillstrom MM Female Infertility: A Systematic Approach to Radiologic Imaging and Diagnosis. Radio Graphics 2009, Vol. 29, No. 5, P. 1353-1370).

Currently, MPT diagnostics is used for endometrioid ovarian cysts, endometriosis of the rectovaginal space, but using this method it is impossible to detect foci of endometriosis on the pelvic peritoneum (small forms of endometriosis) (Kulakov V.I., Adamyan L.V., Volobuev A.I. . et al. Magnetic resonance imaging in the diagnosis of various forms of endometriosis. Bulletin of roentgenology and radiology 2003, No. 4, pp. 45-59; Trufanov GE, Panov VO Guidelines for radiation diagnostics in gynecology. 2008, p. 200 -204; Seeber B, Sammel MD, Fan X. Panel of markers can accurately predict endometriosis in a subset of patients. Fertil Steril. 2008, Vol. 89, P. 1073-1081; Al-Jefout M, Dezamaulds G, Cooper M , et al. Diagnosis of endometriosis by detection of nerve fibers in an endometrial biopsy: a double blind study. Hum Reprod. 2009, Vol. 24; P. 3019-3024).

The present invention relates to practical medicine, namely to gynecology, and can be used to diagnose endometriosis in patients. External genital endometriosis is one of the most common conditions associated with infertility. However, with its small forms and at an early stage, diagnosis by non-invasive methods is extremely difficult.

Endometrioid cysts, retrocervical endometriosis can be verified using bimanual, ultrasound, magnetic resonance imaging, however, external endometriosis of the pelvic peritoneum (small forms of external genital endometriosis) can be diagnosed only during laparoscopy and subsequent histological examination.

The problem of external genital endometriosis, especially in women with infertility, is extremely important, since it is a very common disease of women of reproductive age, the frequency of which reaches 10% in the population (Adamyan L.V., Kulakov V.I., Andreeva E.N. Endometriosis: A Guide for Physicians. - M .: Medicine, 2006. - 416 p .; Giudice LC Endometriosis. // N. Engl. J. Med. - 2010. - Vol. 362. - P. 2389-2398). In turn, infertility, which is largely (up to 39%) due to endometriosis (Kulakov V.I., Ovsyannikova T.V. Problems and prospects for the treatment of infertility in marriage // Obstetrics and gynecology. - 1997. - No. 3. - S. 5-8, Ustinkina T.I. Etiological and pathogenetic structure of infertility in the family: Abstract of the thesis.Doctor of medical sciences. - L., 1990. - 36 p.), Has not only medical, but also social value.

In the absence of diagnostic markers, the delay of invasive instrumental examination (laparoscopy or laparotomy) for confirmation of endometriosis from the onset of pain syndrome can be up to 8 years. However, even in these cases, the frequency of histological confirmation of the diagnosis ranges from 70 to 85%, and often only in the late stages of the disease (Sinaii N., Plumb K., Cotton L., Lambert A., Kennedy S., Zondervan K. et al. Differences in characteristics among 1,000 women with endometriosis based on the extent of disease // Fertil Steril. - 2008. - Vol. 89. - P. 538-545).

Among the methods for diagnosing external genital endometriosis known in the scientific, medical and patent literature, the following can be noted.

There is a known method for diagnosing external genital endometriosis (patent RU No. 2164687, G01N 33/53, G01N 33/48, priority date 02/20/2001, publication date 03/27/2001) by examining peripheral blood, characterized in that spontaneous HCT activity is determined in the blood of neutrophils after their incubation with PAMG-2 and at rates of 24% or more, external genital endometriosis is diagnosed. The disadvantages of this method are: the subjectivity of the method for assessing the spontaneous NBT activity of neutrophils, since the calculation of the diagnostic indicator is carried out using light microscopy; the use in the reaction of PAMG-2, which does not have a certificate and is not related to the number of chemicals included in the "Register of new medical devices approved for use by the Ministry of Health of the Russian Federation".

A known method for diagnosing external genital endometriosis (patent RU No. 2211454, G01N 33/53, priority date 10/29/2001, publication date 08/27/2003) in women by examining biological material, characterized in that the concentration of interferon is determined in a serum sample of peripheral venous blood γ and with its content equal to 1000 pg / ml or less, external genital endometriosis is diagnosed. The disadvantages of this method are: nonspecificity, since the content of interferon-γ in the blood changes depending on many endo- and exogenous factors: stress, the presence of autoimmune diseases, viral infections, immunodeficiency states and even periodontal inflammation (Ershov F.I. The interferon system is normal and in pathology. - M .: Medicine, 1996. - 240 p.), which occurs in very many people and is characterized by insufficiently high accuracy (77%).

A known method for diagnosing the severity of external genital endometriosis (patent RU No. 2219548, G01N 33/48, priority date 01/28/2002, publication date 12/20/2003) by spectrophotometric determination in the peritoneal fluid of the level of molecules of average weight and at a wavelength of 280 nm and extinction rates in within 0.100-0.210 p.p. stage I external genital endometriosis is diagnosed; 0.211-0.310 dp - external genital endometriosis stage II; 0.311-0.526 dp - external genital endometriosis stage III; 0.527-0.726 dp - external genital endometriosis stage IV. The disadvantage of this method is its invasiveness (taking peritoneal fluid); nonspecificity (change in the level of average weight molecules, as a marker of endogenous intoxication, takes place in various pathological and even functional states of the body) (Encyclopedia of Clinical Laboratory Tests. Edited by N. Tit. - M .: Publishing House "Labinform". - 1997. - 960 p.); insufficient sensitivity (measurement of the determined products in relative values of optical density).

A known method for diagnosing the stage of external genital endometriosis (patent RU No. 2242002, G01N 33/53, priority date 13.05.2003, publication date 10.12.2004) by examining blood serum, characterized in that the content of macroglobulin is determined and at its level from 600.0 mg / dl and above, stage I is diagnosed, with a value from 599.0 to 480.0 mg / dl - stage II endometriosis, from 479.0 to 360.0 mg / dl - stage III endometriosis and from 359.0 mg / dL - endometriosis stage IV. The disadvantages of this method are low specificity, since a change in the content of α2-macroglobulin in blood serum can be a reflection of inflammatory processes not only in reproductive tissues, but also in any other organ (liver, pancreas, gastrointestinal tract) (Encyclopedia of Clinical Laboratory Tests. Edited by N. Tit. M .: Publishing house "Labinform", - 1997. - 960 pp. Ivanova OM The value of α2-macroglobulin in the pathogenesis of coronary heart disease. - Bulletin of new medical technologies. - 2008. - No. 4. - S. 109-112; Zorina VN et al. The role of alpha-2-macroglobulin in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus. - Bulletin of Siberian medicine. - 2010. - No. 5. - P. 39-44). The sensitivity and reliability of the method are not indicated.

Also, the method for the early diagnosis of external genital endometriosis in women by examining the endometrial biopsy (patent RU No. 2247391, G01N 33/68, priority date 05/13/2003, publication date 02/27/2005) is also not without drawbacks, characterized in that cathepsin activity is determined in a tissue sample D and with its value 0.1 U. farms, act / h and less diagnose external genital endometriosis. The method is invasive (taking the CUG of the endometrium), characterized by limited information content (using one enzyme only from the group of acidic lysosomal endopeptidases without taking into account neutral exopeptidases), insufficient accuracy and specificity. The extremely low relative values of the reaction products (tenths and hundredths) indicate the low sensitivity of the method.

Known diagnostic test, which determines the content of the main fibroblast growth factor-2 in serum and peritoneal fluid, the increase in which in both biological fluids is used to diagnose external genital endometriosis (Burlev V.A., Larsson A., Olovsson M. Fibroblast growth factor -2 in the diagnosis of peritoneal endometriosis // Obstetrics and gynecology. - 2007. - No. 3. - P. 50-54). The disadvantages of the method are: its invasiveness (study of the peritoneal fluid); non-specificity - it plays an important role not only for angiogenesis in the endometrium, but also for angiogenesis in all tissues of the human body (Ferriari RA, Charnock-Jones DS, Prentice A. et al. Immunohistochemical localization of acidic and basic firoblast growth factors in normal human endometrium and endometriosis and the detection of their mRNA by polymerase chain reaction. // Hum. Reprod. - 1993. - Vol. 8. - P. 11-16, Moller B., Rasmusessen C, Lindblom B., Olovsson M. Expression of the angiogenic growth factors VEGF, FGF-2, EGF and their receptors in normal human endometrium during the menstrual cycle // Mol. Hum. Reprod. - 2001. - Vol. 5. - P. 681-684); limited possibilities of using the method (only in large perinatal centers, a highly qualified specialist is required to perform it).

There is a known method for the diagnosis of genital endometriosis (patent RU No. 2363000, G01N 33/68, priority date 08/03/2007, publication date 07/27/2009), including the study of blood serum and peritoneal fluid, characterized in that in the samples obtained by the enzyme-linked immunosorbent method, the content of vascular endothelial growth factor (VEGF) and if the ratio of VEGF in serum to VEGF in peritoneal fluid exceeds 4.35, external genital endometriosis is diagnosed. The disadvantages of the method include its invasiveness (study of the peritoneal fluid), as well as insufficient specificity, since angiogenic VEGF plays a very important role not only in local processes of angiogenesis in the endometrium, but also at the systemic level in a woman's body (Costa N., Paramanathan S., Mac Donald D., Wierzbicki AS, Hampson G. Factors regulating circulating vascular endothelial growth factor (VEGF): association with bone mineral density (BMD) in post-menopausal osteoporosis. // Cytokine. - 2009. - Vol. 46, N 3 - P. 376-381; Thielemann A., Baszczuk A., Kopczynski Z., Kopczynski P., Grodecka-Gazdecka S. Clinical usefulness of assessing VEGF and soluble receptors sVEGFR-1 and sVEGFR-2 in women with breast cancer / / Ann. Agric Environ Med. - 2013. - Vol. 20, N 2. - P. 293-297).

A known method for diagnosing external genital endometriosis in women with infertility (patent RU No. 2291439, G01N 33/577, priority date 07/04/2005, publication date 01/10/2007) by examining peripheral venous blood, characterized in that the relative amount of CD 16 is determined in the blood + monocytes in the monocytic gate and with values of this indicator equal to or less than 45%, external genital endometriosis is diagnosed. This method, like the previous ones, has a number of disadvantages:

- nonspecificity, since the number of CD 16+ monocytes varies significantly in venous blood in various diseases, pathological and extreme conditions (viral infections, autoimmune diseases, gastroenterological diseases, inflammatory processes, stress) (Mamedova L.N. Clinical and pathogenetic rationale for optimizing diagnostics and Treatment of Inflammatory Bowel Diseases: Diss. Can. of Medical Sciences. - Rostov on Don, 2014. - 180 pp. Recent advances in clinical immunology. Edited by RA Thompson. M .: Medicine, 1983. - 199 pp. );

- insufficient sensitivity (measurement of a diagnostic indicator in relative quantities);

- insufficient accuracy (reduced due to the lack of absolute values), almost 20% are false positive and false negative results.

Known diagnostic test, which takes into account the absolute number of macrophages in the peritoneal fluid - 13⋅10 ⁶ , allowing to diagnose the presence of endometriosis (Oosterlynk DJ, Lacquaet FA, Waer M. et al. Lymphokine - activated killer activity in women with endometriosis // Gyn. Obstet Invest. - 1994. - Vol. 37, # 3. - P. 185-190). The disadvantage of the above method should be attributed to its invasiveness, since for the diagnosis of endometriosis by this method, it is necessary to obtain peritoneal fluid, for which laparoscopy is performed. If the diagnosis is confirmed, repeated laparoscopy should be performed. At the same time, a highly professional specialist should be involved in calculating the absolute number of macrophages in the peritoneal fluid.

A known method for the diagnosis of genital endometriosis by studying the functional activity of basophils in the peripheral blood of a patient in the presence of an aqueous extract of endometrioid tissue with a protein concentration of> 200 μg / ml. With an indicator> 12%, genital endometriosis is diagnosed (Patent 2004910. Kulakov V.I., Sukhikh G.T., Pshenichnikova T.Ya., Volkov N.I., Ionov I.D. Russian Research Center of Perinatology, Obstetrics and gynecology. Method for the diagnosis of genital endometriosis. Bulletin "Inventions", - 1993. - 45-46. - p. 164.). Disadvantages of the method:

- Isolation of basophilic leukocytes requires taking a large amount of blood (18 ml) due to the relative small number of basophils in human peripheral blood (0.5-1%)

- the extract of endometrioid tissue proposed for use is not a standardized preparation and is not included in the "Register of new medical devices and products approved for use by the Ministry of Health of the Russian Federation";

- the method does not provide for the diagnosis of various forms of genital endometriosis (external, internal), because this method is used to diagnose all forms of genital endometriosis;

- the accuracy of the method is not indicated.

A known method for the diagnosis of external genital endometriosis by determining the spontaneous release of histamine from the basophils of the peripheral blood. With a value of this indicator of 49% or more, external genital endometriosis is diagnosed (Author's certificate 1534397. Ionov ID, Volkov NI, Sukhikh GT, Pshenichnikova T.Ya. All-Russian Research Institute for Maternal and Child Health. diagnostics of external genital endometriosis. - Bulletin "Inventions." - 1990. - 1. - P. 180). The method has several disadvantages:

- the isolation of basophils requires the collection of a large amount of blood (18 ml) due to the relative paucity of basophils in the peripheral blood of humans (0.5-1%) and the low content of histamine in them;

- the proposed method is nonspecific, since an increase in the release of histamine by basophils occurs in other pathological conditions, in particular inflammation and allergic reactions of any type;

- the method does not make it possible to establish the severity of the disease and is only qualitative;

- the accuracy of the method is not indicated.

There are a number of methods for diagnosing the uterus based on the study of the blood serum of patients. A method for diagnosing internal endometriosis of the uterus (patent RU 2117296, G01N 33/68, priority date 12/27/1995, publication date 08/08/1998), including a biochemical study of the patient's blood serum, characterized in that the level of acid phosphatase is determined in the blood serum and when it is detected values of 50.91 + 6.95 mmol / l diagnose internal endometriosis of the uterus. A method for diagnosing external genital endometriosis in women with infertility (patent RU 2655812, G01N 33/50, priority date 06/06/2017, publication date 05/29/2018), including a blood test, characterized in that the content of agmatine in the serum of a woman is determined and a value below 2.2 μg / ml is diagnosed with external genital endometriosis. A method for diagnosing external genital endometriosis in patients with infertility (patent RU 2599019, G01N 33/53, G01N 33/48, priority date 04/06/2015, publication date 10/10/2016), including measuring the concentration of coenzyme Q10 and α-tocopherol in blood plasma, and when the value of coenzyme Q10 is less than 1.057 μg / ml and α-tocopherol is less than 18.00 μg / ml, severe or moderate forms of external genital endometriosis are diagnosed; at concentrations of coenzyme Q10 from 1.057 μg / ml to 1.352 μg / ml and α-tocopherol from 18.00 μg / ml and up to 21.03 μg / ml - small forms of external genital endometriosis; at concentrations of coenzyme Q10 more than 1.352 μg / ml and α-tocopherol more than 21.03 μg / ml, external genital endometriosis is excluded.

The disadvantages of this group of methods include the following:

- insufficient accuracy of methods for diagnosing endometriosis in the early stages;

- a high probability of occurrence as false positive results (for example, an increase in the level of acid phosphatase in women may be associated with hyperparathyroidism, Gaucher disease, breast cancer and bone metastases (Bull H, Murray PG, Thomas D, Fraser AM, Nelson PN. Acid phosphatases. Mol Pathol. 2002 Apr; 55 (2): 65-72. doi: 10.1136 / mp.55.2.65.) and false negative results (for example, elevated serum agmatine levels may be associated with autoimmune thyroid disease). glands (Song J, Shan Z, Mao J, Teng W. Serum polyamine metabolic profile in autoimmune thyroid disease patients. Clin Endocrinol (Oxf). 2019 May; 90 (5): 727-736. doi: 10.1111 / cen. 13946. ) or even taking a dietary supplement containing agmatine).

- insufficient specificity, since these markers may relate to other pathological conditions of the body.

The closest in technical essence and the achieved result to the proposed invention is a method for diagnosing external genital endometriosis (patent RU 2526823, G01N 33/53, G01N 33/50, G01N 33/48, priority date 08/05/2013, publication date 08/27/2014), including a study of blood serum by a biochemical method with the determination of the level of high density lipoproteins (HDL), at a value of 0.77 mmol / l and above, external genital endometriosis is diagnosed. The disadvantages of this method are:

- study of the total content of lipoproteins, and not of individual specific compounds, which can give false positive results, for example, under the influence of differences in the patient's diet;

- lack of specificity to endometriosis, since an increase in HDL can be caused by genetic diseases, chronic alcoholism, chronic liver diseases such as primary biliary cirrhosis (cholangitis), hyperthyroidism and the action of drugs (such as corticosteroids, insulin, phenytoin, estrogens ) (MSD Manuals, https://www.msdmanuals.com/professional).

These disadvantages are proposed to be eliminated in the claimed method.

The problem to be solved by the present invention is to identify signs of the disease in early diagnosis.

This problem is solved by the achievement of early diagnosis of signs of endometriosis disease by the method of chemical analysis of metabolites in blood serum, including the analysis of 6 amino acids.

The technical result obtained in the course of using the invention consists in increasing the accuracy and specificity of non-invasive early diagnosis of endometriosis in women, which will allow timely prescribing an appropriate adequate pathogenetic therapy.

The novelty of the proposed method lies in the fact that instead of the biochemical analysis of biological samples, a chemical analysis of metabolites in blood serum is carried out, including the analysis of 6 amino acids - glycine, alanine, valine, proline, serine and tryptophan in the concentration range from 0.5 to 10.0 μg / ml, the subsequent normalization of the obtained values of the analytical signal to the analytical signal of valine to exclude the possible error in determining the concentration of amino acids in the calculation and comparison of the normalized values of the concentrations of 5 amino acids with the average normalized values for the groups of patients and healthy people. If the obtained values of the normalized values of the concentrations of glycine, alanine, proline and serine are not less than 1.4 times lower, and tryptophan is higher than the average values for the reference group of healthy people, then the possibility of diagnosing endometriosis is confirmed if the obtained values correspond to the average values for the reference group. healthy, the disease is not diagnosed. In case of deviation from the ratio of the superiority or insufficiency of the concentration of tryptophan with the concentration of other amino acids, additional studies of patients are carried out.

A detailed description of the method and examples of its clinical implementation.

The method is carried out as follows.

The method of gas chromatography-mass spectrometry, using a gas chromatography-mass spectrometer Shimadzu GCMS-TQ8040 or similar, is not inferior in characteristics, with preliminary preparation of the sample by derivatization, the concentration of 6 amino acids in the blood serum of patients is determined. Values for 5 amino acids are normalized by dividing their concentrations by the valine concentration, and normalized concentration values are obtained for each amino acid.

As a result of determining the normalized concentrations according to this scheme for the control group of healthy (14 people) and the control group of patients with a preliminary diagnosis with confirmation of the diagnosis based on the results of histological examination (14 people), the previously obtained average values of normalized concentrations for both control groups (figure). The figure shows a comparison of the average normalized concentrations of 5 amino acids for patients of the control group with a confirmed diagnosis of endometriosis and the healthy control group (Ala - alanine, Gly - glycine, Pro - proline, Ser - series, Trp - tryptophan). The normalized values of the concentrations of glycine, alanine, proline and serine are not less than 1.4 times lower, and tryptophan is higher for the control group of patients with a preliminary diagnosis of endometriosis.

A further calculation method is based on comparing the normalized concentrations for a sample of patients with an unknown diagnosis with the normalized concentrations for the control group of healthy patients, which are shown in Table 1, which presents the cutoff values of the normalized concentrations of 5 amino acids used to establish or refute the diagnosis of endometriosis, taking into account coefficient 1.4. For the convenience of subsequent comparison in table 1, the boundary values of the normalized concentrations of 5 amino acids are calculated, which are used to formulate or refute the diagnosis of endometriosis, taking into account the coefficient 1.4.

Table 2 shows the application of the proposed diagnostic method for the example of 3 patients with an unknown diagnosis, which illustrates the diagnosis for 3 patients with an unknown diagnosis according to the method described above.

From the table it can be noted that when analyzing 6 amino acids, the normalized concentration values for glycine were less than 1.85, for alanine less than 1.14, for proline less than 1.07 and serine less than 1.93, and for tryptophan more than 1.79 , then the possibility of diagnosing endometriosis is confirmed, if the obtained values for glycine are more than 1.85, for alanine more than 1.14, for proline more than 1.07 and serine more than 1.93, and for tryptophan less than 1.79, the disease is not diagnosed. If these dependencies are not met, then additional studies are required to clarify the diagnosis of patients.

Claims (2)

1. A method for non-invasive early diagnosis of endometriosis, including the study of blood serum, characterized in that a chemical analysis of metabolites in the blood serum is carried out, in which six amino acids are analyzed - glycine, alanine, valine, proline, serine and tryptophan in the concentration range from 0.5 up to 10.0 μg / ml, subsequent normalization of the obtained values of the analytical signal to the analytical signal of valine to exclude the possible error in determining the concentration of amino acids in the calculation and comparison of the normalized values of the concentrations of five amino acids with the average normalized values for the healthy group, when obtaining the values of the normalized concentrations for glycine less than 1.85, for alanine less than 1.14, for proline less than 1.07 and serine less than 1.93, and for tryptophan more than 1.79, confirm the possibility of a diagnosis of endometriosis, if the values for glycine are more than 1.85, for alanine is more than 1.14, for proline is more than 1.07 and serine is more than 1.93, and for tryptophan is less than 1.79, the disease is not diagnosed. 2. The method of non-invasive early diagnosis of endometriosis according to claim 1, characterized in that in case of deviation from the ratio of the superiority or insufficiency of the concentration of tryptophan with the concentration of the remaining amino acids, additional studies are carried out.

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