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On July 17, 2021, Advisory Board with the participation of more than 60 leading reproductive specialists and healthcare executives was held. The primary task was to discuss the real world data on the first Russian biosimilar follitropin alfa and the possibilities of import substitution of follitropin alfa drugs. The information about drug development stages, experience of usage in ovarian stimulation for artificial insemination and assisted reproductive technologies (ART), the results of the largest Russian study in reproduction "FОLLITROPIN" (2020), where biosimilar recombinant human follicle stimulating hormone (FSH) was studied in 5484 IVF cycles in real clinical practice, experience of drug use in leading ART medical centers have been provided in research reports. After discussion the Advisory Board Resolution has been developed.

The article discusses the development of a production technique for recombinant follicle-stimulating hormone used in the treatment of infertility, in the culture of Chinese hamster ovary cells. As part of the creation of the technological platform receiving hormone the bioprocess in wave-induced motion bioreactor has been optimized. A number of parameters that influence on the bioprocess was studied, as follows: optimal cell density, concentration of metabolites, temperature shift and its duration.

OBJECTIVE. The study identified predictors of endocrine detection of sperm in case of open testicular biopsy in patients with non-obstructive azoospermia. MATERIAL AND METHODS. The research was based on the results of examination and testicular biopsy of 76 patients with secretory azoospermia aged from 20 to 55 years old. The instrumental, laboratory, physical methods of research were carried out for all the patients before performing of the open biopsy for testicular sperm extraction. Hormone levels were determined in blood plasma such as luteinizing hormone, follicle stimulating hormone, prolactin, total and free testosterone, estradiol and sex steroid binding globulin. Patients were divided into two groups. The first group consisted of patients (n =43) whom sperms were found in testicular biopsies. The second group included patients (n = 33) whom sperms weren’t detected. RESULTS. Сonсentration of follicle stimulating hormone in blood plasma was the most significant hormone predictor. It was found that follicle stimulating hormone level between 12 and 16 IU/L indicated to the low probability of sperm presence in testicular biopsies and in case it was less than 17 IU/L the probability was extremely low. There was also established that elevated follicle stimulating hormone levels in patients older than 26 years pointed to the low probability of finding sperm using open testicular sperm extraction. CONCLUSIONS. Increase of luteinizing hormone, follicle stimulating hormone or their correlation in blood plasma indicates to a low probability of finding sperm by open testicular sperm extraction. The concentrations of testosterone, sex steroid binding globulin, prolactin and estradiol in the blood plasma weren’t reliable predictors of finding sperm in testicular biopsies.

Background: 2025 is going to be the 100th anniversary of the first historical description of Turner syndrome - complex of  genomic abnormalities, congenital gonadal disruption and hypergonadotropic hypogonadism. Total estrogenic deficiency triggers development of age-related comorbidities. There is no doubt that personalized search for replicative markers of cellular aging among females with Turner syndrome is needed., Aim: To evaluate features of replicative (telomere length) and biochemical (lipid profile, calcium-phosphate album, thyroid hormones, markers cytolysis and cholestasis, carbohydrate metabolism, nitrogenic metabolism, electrolytes, FSH) markers among females with Turner syndrome., Materials and Methods: Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022. Females with non-iatrogenic hypergonadotropic hypogonadism caused by Turner syndrome (45,X0; 45,X/46,XX; 45,X/46,X,r(X); 13-40 y.o.; n=26) and primary ovarian insufficiency (18-39 нyears=26); healthy females of reproductive age (15-49 y.o.; n=24). Patients have undergone laboratory genetic (leucocyte telomere length), biochemical (fasting glycaemia, urea, creatinine, common/conjugated bilirubin, ALT, AST, gamma-glutamyl transferase, triglycerides, HDL-P, LDL-P, common cholesterol, common/ionized calcium, phosphate, vitamin D, sodium/potassium/chlorides, FSH, HbA1c) analyses. Body measurements - body mass, body height. DNA extraction - provided with Qiagen DNA blood mini kit (Germany). Leukocyte telomere length - with real-time polymerase chain reaction PCR (Flow-fish). Soft program IBM SPSS Statistics (version 26,0 for Windows)., Results: 1. Females with Turner syndrome have significantly lower mean telomere length (8,22 kB [6,63-9,30]) than with primary ovarian insufficiency (10, 34 кБ [8,41-13,08], p<0,001) and healthy reproductive age females (10,77 kB [9,95-13,16], р>0,05).2. Telomere length correlates directly and significantly with longevity of menopausal hormonal therapy among females with primary ovarian insufficiency (ρ = 505; p<0,001).3. Patients with Turner syndrome are inclined to vitamin D deficiency (р<0,001), dyslipidemia (р=0,01); increase of levels of aminotransferases, cholestasis markers, phosphate and FSH (р<0,001)., Conclusion: Turner syndrome is serious genetic disease that leads not only to infertility but to significant decrease of quality/life longevity out of "healthy aging" conception.

Infertility is a polyetiological disease and requires modern universal markers, studying of which could allow determination of the appropriate tactics of treatment of patients with impaired fertility, evaluation of prognosis, and prospects of treatment. Besides, there is an evident trend towards widening of indications to apply auxiliary reproductive technologies in treatment of patients with the most serious factors of male infertility. Inhibin, that is a hormone composed of two subunits, may act as one of such markers that allow judging of the morphological and functional state of the testicular parenchyma. Inhibin B that is produced with Sertoli cells and young spermatogenous cells in the seminiferous tubules is a known endocrine marker for evaluation of spermatogenesis. The review includes analysis of results of the studies that investigated the value of determination of the level of inhibin B in the course of diagnostics of male infertility as well as in the course of prognosis of results of testicular sperm extraction. It has been demonstrated that on the whole inhibin B is a more sensitive marker than the follicle-stimulating hormone. According to a number of authors, due to its high sensitivity and specificity, inhibin B may become the alternative to testicular biopsy, as well as a marker of differential diagnosis of male infertility in future. At the same time, the level of inhibin B in serum may not be used as a singular marker of males with non-obstructive azoospermia. Ambiguous results received require further studies.

Pathochemical characteristic features of facial nerve neuropathy (FNN) have been more accurately defined. Heterogeneous patochemical pattern of facial nerve neuropathy has been shown to be dependent on the severity of the disease, intensity of free radical oxidation processes, and hormonal status of the patient. We have found reliable distinctions in dynamics of free radical oxidation processes, and hormo-nal status in the blood of the patients with moderately severe and severe forms of facial nerve neuropathies. In facial nerve neuropathies we observed regulatory effects of cortisol and somatotropic hormone; in facial nerve neuropathywith moderate severity the hormones of thyroid group were seen to be switching off, falling out the processes regulating metabolism. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were found to have regulating effects, especially in the acute phase of the disease. Different dynamics of the hormones in patients with high and low free radical oxidation levels suggests that the oxidative stress intensity could be associated with regulatory effects of the hormones . The results of correlation analysis confirm the reliable distinctions in free radical oxidation characteristics andand cortisole levels, STH, FSH and LH levels.

The purpose of research was to study the significance of the levels of inhibin B, folliclestimulating hormone (FSH) and anti-muller hormone (AMH) as a prognostic marker hormones vasomotor disturbances of climacteric syndrome and the effectiveness of the appointment of menopausal hormone therapy (MHT) for the treatment and prevention of these disorders.Materials and methods. The study included 90 women aged 45 to 55 years old, appealed for outpatient care in connection with the tides and menstrual irregularities different nature. We studied the functional state of ovaries and ovarian reserve with endocrine markers.Results. The effective use of the complex endocrine markers "inhibin B, FSH and AMH" to predict the potential of menopausal disorders.Conclusion. Efficiency of prophylactic MGT premenopausal patients is rated and discussed.

Background: One of the most dangerous reproductive pathologies is primary ovarian insufficiency (POI). Except manifestation in the age <40 years old it leads to demographical losses, decrease of chances for healthy aging. POI can be characterized as summary of secondary amenorrhea, total estrogenic deficiency and hypergonadotropic hypogonadism. Hence, POI has probably harmful effect on telomere length. Telomere length determining and sex steroid replacement therapy may be promising and effective to prevent decrease of life quality/ longevity among females with POI., Aim: To evaluate features of replicative (telomere length) and biochemical (metabolic syndrome) markers among females with primary ovarian insufficiency., Materials and Methods: Research has been provided in collaboration between Endocrinology Research Centre of the Russian Ministry of Health and Lomonosov Moscow State University Medical Research and Educational Centre in the period since 10.01.2021 until 01.08.2022. Females with non-iatrogenic hypergonadotropic hypogonadism caused by primary ovarian insufficiency (n=33); healthy females of reproductive age (18-49 y.o.; n=24). Patients have undergone laboratory genetic (leucocyte telomere length), biochemical analyses. DNA extraction - with Qiagen DNA blood mini kit (Germany).Leukocyte telomere length - with real-time polymerase chain reaction PCR (Flow-fish). Soft program IBM SPSS Statistics (version 26,0 for Windows)., Results: Females with POI due to estrogenic deficiency have slightly shorter mean telomere length (10,0 [7,9-10,7] kB, than healthy females of reproductive age (10,8 [10,0-13,1] кБ, р<0,001). Females with POI due to estrogenic deficiency have higher chances for development of carbohydrate metabolism disturbances (prediabetes) (р<0,043), increasement of FSH level (р<0,001). FSH level correlates moderately and negatively (ρ=0,434) with leukocyte telomere length (р<0,001)., Conclusions: Female with POI and receiving sex steroid replacement therapy have decrease of telomere length and increase of chances for carbohydrate metabolism disturbances in opposite to healthy reproductive females.

Functioning gonadotroph adenomas are rare pituitary tumors secreting one or two gonadotropins (follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH)), which are hormonally active. In the majority of cases, gonadotroph tumors are endocrinologically "silent" and make up more than a half of non-functioning pituitary adenomas. In this article we describe a rare clinical case of LH/FSH-secreting pituitary macroadenoma with bitemporal hemianopsia in a 62-year-old man. The patient underwent transnasal transsphenoidal adenomectomy, leading to remission. The distinctive feature of this case is the presence of secondary erythrocytosis due to endogenous hyperandrogenism, which required several blood exfusions to normaliza the level of hematocrit before surgery. It is noteworthy that clinical signs of erythrocytosis were present long before visual impairment. This clinical case demonstrates difficulties in the early diagnosis of functioning gonadotroph adenomas.

Background: The problem of differential diagnosis of constitutional delay of puberty/CDP and hypogonadotropic hypogonadism/HH in boys is discussed, as boys have similar genetic mechanisms and appearance., Aims: to determine accuracy of the criteria for the differential diagnosis of CDP and HH., Materials: The study included 56 boys 14.4±0.7 years old with delayed puberty (G1P1-3/testicular volume <3 сm3). We excluded patients with hypergonadotropic hypogonadism, treated with sex steroids or gonadotropins for 12 months, with endocrine/somatic diseases affecting puberty. At the first visit, we evaluated anthropometric data, bone age, testicular volume, hormones and the results of the gonadotropin-releasing hormone test (GnRH) agonist test and the human chorionic gonadotropin test (hCG) test. The HH was defined by a testicular volume <3 сm3 after 2 years follow-up. The patients were divided into two groups: the first group with CDP and testicles ≥3 cm3 (n=50) and the second group with HH and testicles <3 cm3 (n=6)., Results: At the first visit in boys with CDP corrected target height was less (Me SDS –1.8 vs –0,4, р=0.02), bone age was less (Ме SDS –2.5 vs –0.2 р=0.03), testicular volume was more (Ме 1.9 vs 0.5, p=0.0003), hormones were significantly higher, such as LH (Ме 1.1 vs 0.1 mIU/ml, p=0.0002), FSH (Ме 1.9 vs 0.2 IU/l, p=0.00007), inhibin B (Ме 142.3 vs 31.3 pg/ml, p=0.00009), max LH (Ме 18.9 vs 0.6 mIU/ml, p=0.00007), max LH/FSH (Ме 2.3 vs 0.4, p=0.0002) on the GnRH agonist test and Δ testosterone (Ме 14.4 vs 1.1 nmol/l, p=0.0001) on the hCG test than in boys with HH. The LH ≥0.3 mIU/ml had 86% sensitivity, 100% specificity; max LH/FSH ≥1 – 92% sensitivity, 100% specificity; Δ testosterone ≥2.7 nmol/l on the hCG test – 98% sensitivity, 100% specificity for differential diagnosis of CDP and HH in boys. However, max LH ≥3.5 mIU/ml on the GnRH agonist test, FSH ≥0.5 IU/l, inhibin B ≥58 pg/ml had 100% sensitivity and specificity for diagnosis of CDP., Conclusions: The inhibin B ≥58 pg/ml, LH ≥0.3 mIU/ml, FSH ≥0.5 IU/l or max LH ≥3.5 mIU/ml, max LH/FSH ≥1,0 on the GnRH agonist test, Δ testosterone ≥2.7 nmol/l on the hCG test have an excellent accuracy for the differential diagnosis of CDP and HH in prepubertal boys with delayed puberty.

The inability to use hormone replacement therapy in women requires the search for effective non-pharmacological methods for the correction of menopausal disorders. Purpose of work. To assess the effect of non-drug programs for the correction of age-related disorders in women with metabolic syndrome (MS) on the level of sex hormones. Of the 330 women 45-50 years old with menopausal syndrome (CS) and MS, 5 groups were formed. Applied: basic treatment, physiotherapy, balneotherapy, multivitamins and minerals, physiotherapy (vibration therapy, chromotherapy, melotherapy, aromatherapy, aeroionotherapy) in various combinations. The levels of follicle-stimulating (FSH) and luteinizing (LH) hormones, estradiol were determined. In patients with mild CS, when using physiotherapy, after 3 months of treatment, FSH, LH decreased, estradiol increased. In patients with moderate KS, the best results were achieved using a full set of physiotherapeutic factors: after 6 months, FSH decreased by 19,3% (p<0,0001) and LH by 23,9% (p<0,0001), estradiol increased by 22,3% (p=0,0084). Comprehensive non-drug correction has a positive effect on the functioning of the hypothalamic-pituitary system in patients with CS and MS. In moderate-grade CS, a program with the use of vibration therapy, chromotherapy, melotherapy, aromatherapy and aeroionotherapy is a priority.

From 14 to 54% of all pituitary adenomas are nonfunctioning pituitary adenomas (NPAs), their prevalence is estimated as 7.041.3 cases per 100 000 population. The most common type of NPAs (73% of cases) are gonadotropinomas. In most cases, gonadotropinoma is characterized by secretion of biologically inactive hormones, so the release of gonadotropins does not lead to the development of any clinical symptoms. For this reason the diagnosis of gonadotropinomas is most often performed on the basis of immunohistochemical analysis. However, in rare cases, gonadotropinomas secrete biologically active hormones, most often follicle-stimulating (FSH). Ovarian hyperstimulation syndrome due to gonadotropin-secreting pituitary tumors occurs in about 3% of women with hormonally inactive pituitary adenomas at reproductive age and in 8% of patients with verified gonadotropinomas. This clinical case describes a young patient with a rare pathology: FSH/LH-secreting macroadenoma of the pituitary, which led to the development of ovary hyperstymulation symdrome. The diagnosis of pituitary adenoma was performed due to the identified hyperprolactinemia one month before the development of visual impairment, which can be considered a late diagnosis. Surgical treatment of gonadotropinomy was carried out successfully and without complications, remission of the disease was achieved, visual function was restored, the patient successfully became pregnant.

Aim: To compare ovarian reserve in healthy women of reproductive age - carriers of antithyroid antibodies (ATA) and in healthy women of reproductive age negative for ATA., Materials and Methods: 70 healthy women of young reproductive age in the state of euthyroidism (from 18 to 38 years old) were examined. Participants were divided into equal groups (n=35) depending on the status of the presence of antithyroid antibodies (AT-TPO, AT-TG). On the 2nd-4th days of the menstrual cycle, the following markers of the ovarian reserve were determined: serum levels of anti-Müllerian hormone (AMG), inhibin B, FSH, LH, estradiol, testosterone and progesterone, as well as ultrasound parameters - the number of antral follicles and the volume of the ovaries. In addition, to determine the predisposition to premature ovarian failure, an analysis was performed to the number of CGG repeats in the FMR1 gene., Results and Discussion: Statistically significantly differs such parameters as the level of estradiol and testosterone, while the differences were not clinically significant. All the parameters evaluated were within the normal range, the main predictors of the ovarian reserve (levels of AMG and inhibin B, the number of antral follicles) remained in the normal range. An increase in the number of repeats of CGG in the FMR1 gene was not detected in any of the participants in the study., Conclusion: In healthy young reproductive age women, the status of ATA does not have a direct effect on the ovarian reserve.

Aim: To reveal the changes in the pituitary-thyroid, pituitary-gonadal, adrenal components and in the prolactinergic system of neuroendocrine regulation in patients with severe obstructive sleep apnea syndrome (OSAS)., Material and Methods: The study involved 51 men aged 46-55 years. The main group (BG) included 37 patients with severe OSAS. The duration of clinical manifestations of OSAS was 10.5±1.5 years. OSAS was verified on the basis of clinical and functional studies and polysomnographic monitoring in accordance with the AASM criteria (2014). The control group (CG) consisted of 14 age-matched men without sleep-disordered breathing. The body mass index in BG was 34.2±1.8 compared to 28.2±2.1 kg/m 2 in CG. Serum concentrations of thyroid-stimulating hormone (TTG), free thyroxine (T4), triiodothyronine (T3), cortisol, prolactin, testosterone, luteonizing (LH) and follicle-stimulating (FSH) hormones were determined by the immunoradiological method using the standard DIA test system (Russia) and the analyzer 'Immunotest-800'., Results: Patients with severe OSAS had decreased concentration of free thyroxine (T4) and decreased activity of thyroid stimulating hormone (TSH) (р<0.001), increased concentration of prolactin and cortisol (р<0.001), decreased concentration of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone compared to the controls (р<0.001)., Conclusion: The changes in the hypothalamic-pituitary-gonadal system are a manifestation of disturbances of the mechanisms of self-regulation and compensation that indicates the presence of maladaptive reactions of the neuroendocrine system.