Background. Pelvic inflammatory disease (PID) is a significant gynecological problem. The main treatment strategy involves antibacterial drugs to eliminate the infection in combination with anti-inflammatory, infusion, transfusion, anticoagulant, and desensitization therapy. Chronic inflammatory processes can induce changes in the immune system, thus reducing the effectiveness of treatment, causing adhesions, obstruction of the fallopian tubes, and infertility. It emphasizes the importance of developing new PID treatment methods, including using agents with immunomodulatory, antioxidant, and enzymatic activity that can increase the body's overall resistance to infections. Aim. To evaluate the effectiveness of Longidase® in treating pelvic adhesions to improve the outcomes in chronic PID. Materials and methods. The study included 50 women of reproductive age with established chronic PID and adhesions aged 18 to 42 years with a mean age of 29.4±5.8 years. The subjects were randomly assigned to two groups comparable in their main prognostic features. Patients of the main group (30 people) received treatment with Longidase® 3000 IU 1 suppository rectally once every 3 days, 10 doses, then 1 suppository once every 5 days, 5 doses (the total course is 15 doses of Longidase suppositories 3000 IU). Patients in the control group (20 people) received placebo. The treatment course was 55 days. The patients were followed up for up to 140 days from the start of therapy. Results. The results show no significant changes and the negative effect of the treatment on the blood chemistry parameters in both groups. In 35% of patients in the main group, the level of peptide-bound oxyproline did not change; 46% responded to therapy with its increase and 11% with a decrease, which indicates the activation of the decomposition of collagen proteins and a decrease in their synthesis. Analysis of individual levels of circulating immune complexes (CIC) before and after treatment showed a significant decrease in CIC in the main group (Longidase) vs. control group (36.1±1.4 and 30.8±0.8, respectively), which indicates a decrease in the severity of the inflammation. The pain relief, more pronounced during treatment in the main group than in the control group (30% vs. 15%), is probably due to the resolution of the chronic inflammation and correlates with changes in CIC. The onset of pregnancy in 10 (33.3%) patients in the main group indicates the effectiveness of bovhyaluronidase azoximer (Longidase®) as an anti-inflammatory and anti-fibrotic agent. Conclusion. The study showed the possibility of using Longidase 3000 IU suppositories in the complex therapy of patients with pelvic adhesions due to chronic PID

Aim. To assess the functional state of the liver and endothelium in patients with menopausal metabolic syndrome, depending on the degree of obesity. Materials and methods. 70 patients with menopausal metabolic syndrome and obesity of varying degrees with an average age of 49.9±1.1 years and 30 practically healthy women without obesity and liver pathology with an average age of 47.3±2.6 years (comparison group) who were in the early postmenopausal period were examined. All women underwent biometric and laboratory-instrumental examination, including assessment of biometric indicators, determination of estradiol levels in the blood, biochemical markers of cytolysis and cholestasis, markers of endothelial dysfunction, assessment of microvascular tone reaction with calculation of the thermal vasodilation index, ultrasound examination of the liver and calculation of the Hepatic steatosis index (HSI). Results. All patients with menopausal metabolic syndrome had a genoid type of obesity and hypoestrogenism. The level of estradiol decreased more significantly during the transition to the 1st degree of obesity (p=0.001). According to ultrasound and the HSI index, signs of liver steatosis were found in all patients with menopausal metabolic syndrome. Functional liver tests were within the reference values, 13% had an increase in the level of alkaline phosphatase, more significant in the group with grade 3 obesity (p=0.034). Laboratory markers of endothelial dysfunction were significantly higher in patients with menopausal metabolic syndrome than in the comparison group. The muscular and neurogenic index of thermal vasodilation significantly decreased in women with grade 1 obesity compared to the group with “pre-obesity“ (p=0.041 and 0.047). The lowest endothelial response was observed at the transition to the 1st degree of obesity in comparison with women with excess body weight. Conclusion. For patients with menopausal metabolic syndrome to assess the condition of the liver, it is recommended to conduct a comprehensive instrumental laboratory examination, including ultrasound examination of the liver, biochemical parameters and calculation of the steatosis index.

Aim. To determine the clinical significance of the level of nitric oxide in exhaled air (NOex) for optimizing the control of bronchial asthma (BA) in pregnant women in order to reduce asthma-associated obstetric complications. Materials and methods. A cohort comparative study was conducted with the participation of 80 pregnant women in the third trimester of pregnancy against the background of asthma with varying degrees of severity and level of control, with an assessment of the frequency of asthma-associated obstetric complications. The main group consisted of 40 patients with a prospective determination of the level of BA control and inflammatory activity against the background of inhaled glucocorticosteroid + long-acting b2-agonist using a study of nitric oxide levels in exhaled air. The comparison group included 40 patients undergoing therapy with inhaled glucocorticosteroids + long-acting b2-agonist or monotherapy with inhaled glucocorticosteroids with standard methods of outpatient monitoring of pregnancy against the background of asthma (without determining the level of NOex). The instrumental examination was presented by the determination of a surrogate noninvasive marker of inflammation – nitric oxide in exhaled air was determined using a portable NOex detection device (NIOX MONO; Aerocrine AB, Sweden). Results. The study of nitric oxide in exhaled air demonstrated the presence of poorly controlled inflammation of the mucous membrane of the respiratory tract in 22.5% of patients at the beginning of the third trimester, the average NOex values were – 18.75±2.86 ppb. A strong correlation was determined between the values of nitric oxide levels in exhaled air and systolic blood pressure in the third trimester in patients from the main group (Rs=0.84; Rs 0.05=0.31). Decrease in NOex averages (14.87±1.65 ppb) in pregnant women, it occurred as a result of changes in the volume of pharmacotherapy with inhaled glucocorticosteroids and measures to control the strict adherence of patients to anti-asthmatic therapy. Achieving complete control of asthma as a result of screening determination of nitric oxide in exhaled air and selection of optimal anti-asthmatic therapy was accompanied by a 2-fold decrease in the frequency of asthma-associated hypertensive disorders and surgical deliveries in pregnant women from the main group. Conclusion. Modern approaches to the monitoring and therapy of pregnant women with asthma should be based on the study of subclinical inflammation of the mucous membrane of the respiratory tract. The screening method for determining the level of a biomarker of inflammation of the bronchial tree epithelial mucosa – nitric oxide in exhaled air allows to determine the level of BA control, meets the requirements of maximum safety and minimally invasive for use in pregnant women.

Aim. Evaluation and correction of local antimicrobial protection factors in women with type 2 diabetes mellitus (DM 2) and chronic recurrent vulvovaginal candidiasis (rVVC). Materials and methods. The study involved 100 women undergoing outpatient follow-up at the age of 40.9±5.8 years, with a body mass index of 29.8±3.5. The period was 2022–2023. The examination included anamnesis, collection of anthropometric data, calculation of body weight, microscopic examination of smears from the cervical canal and vagina, Gram-stained before treatment, in the 1st and 3rd months after its completion, identification pathogenic microorganisms using PCR, colposcopy, ultrasound of the pelvic organs. Indicators of glycosylated hemoglobin in the subjects at the control points of the study: at 1 month the average values were 5.9±2.9%, at 3 months – 5.9±3.0%, the average value was 5.9±3.1%. Candida species were identified by the bacteriological method using Sabouraud dextrose agar (growth of colonies of fungi of the genus Candida in an amount of more than 103 CFU/ml). Immunological methods for studying antimicrobial protection factors included studying the number of neutrophil granulocytes (NG) on the surface of the mucous membranes of the vulva and vagina, their phagocytic and NBT-reducing activity in a latex test. Randomization of patients into groups: group 1 included 50 (50%) women with DM 2 who, as part of complex therapy for rVVC received the drug Genferon® 1 intravaginal suppository of 500 thousand units 2 times a day for 10 days and fluconazole 150 mg orally three times with an interval of 72 hours at the first stage of treatment; group 2 included 50 (50%) women who received therapy with fluconazole 150 mg three times with an interval of 72 hours. The maintenance anti-relapse course therapy in both groups included the use of fluconazole 150 mg once a week for 6 months. In group 1st anti-relapse therapy was supplemented by the administration of the drug Genferon® 1 intravaginal suppository of 500 thousand units at night 3 times a week for 3 months, after which the vaginal microbiota was corrected for 2 weeks using vaginal suppositories, containing Lactobacillus acidophilus in an amount of at least 108 CFU. In group 2nd, basic anti-relapse antimycotic therapy was not accompanied by the prescription of any immunomodulatory or probiotic drugs. Results. The etiological agents of rVVC in women of late reproductive age in 79% (n=79) и 28% (n=28), respectively, were C. albicans and C. glabrata, which during the period of acute of the disease were detected by culture in the vaginal discharge at more than 104 CFU/ml. Chronic recurrent course of vulvovaginal candidiasis in women with DM 2 was characterized by exacerbations 4 or more times a year, accompanied by the corresponding clinical picture: white or yellowish-white cheesy discharge from the genital tract, itching or burning in the anogenital area, discomfort in the external genital area, dyspareunia, dysuria, decreased phagocytic activity of NG in vaginal secretions by 25.8%, impairment of their spontaneous and latex-induced NBT-reducing activity by 35.2%, functional reserve by 23.0% relative to reference values. The use of the drug Genferon® as part of complex therapy for rVVC contributed to a decrease in the number of Candida spp. in 1st and 3d months of observation after completion of anti-relapse therapy, normalization of cellular factors of innate immunity of the mucous membranes, faster resolution of the clinical manifestations of an episode of the disease. The decrease in the number of relapses over a 12-month observation period compared to the control group was also facilitated by an increase in the protective properties of the vaginal mucosa due to the restoration of the vaginal microbiota with the help of lactobacilli acidophilus. Conclusion. The etiological agents of rVVC in women of late reproductive age are C. albicans and C. glabrata. Subcompensated DM 2 is a risk factor for rVVC, which requires additional monitoring of microbiological parameters of the vaginal microbiota. rVVC in women with DM 2 is associated with an increase in the number of NG in the vaginal secretion, a decrease in their phagocytic activity and functional reserve compared to the reference values. Combination therapy of rVVC with topical recombinant interferon α2b, benzocaine and taurine in the formulation of Genferon® (suppositories) is an effective method to improve the clinical and immunological efficacy of therapy.

Background. In recent decades, the frequency of surgical interventions on reproductive system organs has been steadily increasing. In gynecological practice, preference is given to minimally invasive surgery and precision treatments, especially involving ovaries. Despite the modern approach, it is not always possible to preserve this endocrine organ, which leads to post-surgical menopause (PSM). The relatively high incidence of total hysterectomy-associated PSM and primary hypothyroidism in late reproductive age often leads to their combination. Clinical manifestations aggravating each other form an unfavorable vicious circle. Aim. To study the features of the PSM course with concomitant primary hypothyroidism. Materials and methods. A prospective clinical study included 130 women aged 45 to 55 years with a history of PSM. The main group consisted of 70 patients with PSM with subclinical primary hypothyroidism. A control group included 60 PSM patients without thyroid disorders. We assessed the effect of hypothyroidism on the PSM course by comparing several indicators in the main and control groups. Results. It was found that in the main group patients, severe 26.5% and moderate 38.8% menopausal syndrome prevailed, while in the control group patients, such forms were twice as common. In the women of the main group, the levels of triglycerides were higher than those in the control group by 1.3 times (2.6±0.86 mmol/L and 1.43±0.33 mmol/L, respectively). The total serum alkaline phosphatase activity in patients in the study groups was 29.8% higher than in healthy women. Conclusion. It can be concluded that the severity of menopausal disorders depends on the thyroid status, with more severe in patients of the main group with hypothyroidism. In addition, in patients of the main group with hypothyroidism, dyslipidemia is more pronounced, which predisposes them to severe diseases in the future, in particular cardiovascular disorders, the unfavorable course of metabolic syndrome, and the development of postmenopausal osteoporosis.

Aim. To develop and evaluate the effectiveness of complex therapy of vulvar lichen sclerosus (VLS), considering the clinical and immunological variant (CIV) of the disease. Materials and methods. A randomized prospective study included 292 patients 20-70 years old with different CIVs of the VLS course: atrophic (n=101), sclerosing (n=154), scleroatrophic (n=37), as well as 35 females with VLS in the comparison group of the same age category. Based on the clinical, immunological, and morphological features of the VLS course, a complex anti-relapse therapy was developed, the effectiveness of which was evaluated after a year of follow-up in comparison with the standard of care (SoC) of patients (from the comparison group) based on the number of disease relapses and the results of the Vulvar Quality of Life Index Questionnaire (VQLI) survey of women with vulvar diseases. Results. In patients with the sclerosing variant of VLS, short courses of topical glucocorticoids during exacerbations are justified; in patients with the scleroatrophic variant – topical calcineurin inhibitors, in the atrophic variant – a protein-peptide complex from porcine blood leukocytes (vaginal suppositories and cream-balsam with lanolin) containing interleukin-1, 6, tumor necrosis factor α, transforming growth factor, macrophage migration inhibitory factor. Patients with any variant of VLS are instructed to follow household and hygienic recommendations, use emollients daily, take prophylactic doses of vitamins A, E, and D to correct its deficiency or insufficiency, as well as use local enzyme therapy, as indicated, aimed at preventing or treatment of cicatricial changes. Local estrogens were prescribed only to women with genitourinary menopausal syndrome in the peri- and postmenopausal period. The developed complex anti-relapse therapy of VLS showed greater clinical efficacy compared to SoC: 3.7-fold decrease in episodes of disease exacerbation, as well as a significant (p=0.001) 1.3-fold decrease in the negative effect of VLS on the QoL of patients in the main clinical group (15.4 points according to the VQLI assessment – a mild effect on QoL) compared to SoC with the average score of 27.6, which corresponded to a strong negative effect of the disease on QoL. Conclusion. The results of the study support the distinction of VLS CIVs and the need to consider their features when choosing an effective therapy for the disease. Properly selected complex, supportive therapy of VLS can significantly increase the QoL of patients, minimize the number of relapses, and prevent the development of complications, including, probably, the risk of malignant transformation.

Postpartum hemorrhage (PPH) is one of the leading causes of maternal mortality in Russia and worldwide. Accurate calculation of circulating blood volume (CBV) and personalized estimation of the extent of blood loss (EBL) play vital roles in the early diagnosis of PPH. Visual assessment of BL in childbirth is an available diagnostic method, but it has a high error rate compared to the gravimetric method. A dynamic assessment of the shock index (SI) as an indicator that reflects hemodynamic disorders early enough can be used as an additional diagnostic method for PPH and a test that allows predicting the need for transfusion of blood products. Aim. To review current literature on the assessment of BL in childbirth and the diagnosis of PPH. Materials and methods. The search for publications by Russian and foreign authors was carried out in the information electronic databases PubMed, PubMed Central, Scopus, MEDLINE, ScienceDirect, Cochrane Library, and eLibrary from 2016 to January 2024 using the keywords "obstetric blood loss," "PPH," and "SI." Results. When assessing the CBV, its correlation with the body mass index was revealed. Subjective methods for the PPH assessment have a large margin of error, which does not depend on the experience and seniority of the healthcare provider. The gravimetric method is more accurate, but it can underestimate the clinical situation when physiological blood loss is exceeded. Dynamic assessment of SI is an early marker of hemodynamic disorders and makes it possible to identify patients with a high risk of adverse outcomes more reliably than other parameters. Conclusion. In order to provide timely and adequate emergency medical care for excessive obstetric blood loss, a personalized approach should be used to calculate the EBL, taking into account the woman's body mass index, as well as a systematic assessment of the BL, including at least the extent of blood loss and monitoring of the SI.

Aim. To evaluate the clinical efficacy of complex antioxidant therapy (CAT) in the treatment of patients with pelvic varicose veins (PVV). Materials and methods. Patients with PVV (n=150) were divided into groups 1 and 2 of 75 subjects; the groups were comparable. Treatment in both groups included standard therapy with one of the venotropic agents (60 days). Patients of group 1 additionally received CAT for 30 days (1 course), in total 3 courses with 2-month intervals. Results. When assessing the parameters of the lipoperoxidation system (antioxidant protection) in group 1 during CAT combined with standard venotropic therapy, there was a statistically significant decrease in the levels of lipid hydroperoxides (p0.0001), diene conjugates (p=0.001), malonic dialdehyde (p0.0001), an increase in the levels of catalase (p0.0001), superoxide dismutase (p0.0001), glutathione peroxidase (p0.0001), glutathione reductase (p0.0001), glutathione-S-transferase (p=0.002) and the reduced glutathione content (p=0.032) compared to levels before treatment. The above group showed a decrease in the diameter of the pelvic varicose veins: internal iliac (p0.001), ovarian (p0.0001) and arcuate (p0.001), an increase in their blood flow velocity (p=0.003, 0.041, and 0.040, respectively), a decrease in the duration of retrograde flow to 0.3 cm. There was a decrease in pelvic pain (p0.0001), dysmenorrhea (p=0.024), dyspareunia (p=0.037), the frequency of irregular menstruation (p=0.031), an improvement in quality of life (p=0.047), pregnancy rate (p=0.013), the number of live births (p=0.004), and the duration of remission (p=0.047). Conclusion. The use of a combination of antioxidants superoxide dismutase 250 mg 2 times a day, acetyl-glutathione at 100 mg 2 times a day, and astaxanthin 400 mg/day for 30 days in 3 courses with 2-month intervals combined with venotropic therapy can significantly improve the treatment outcomes of patients with PVV.

Background. Paraurethral injection of bulking agents in women is one of the minimally invasive technologies for the treatment of stress urinary incontinence (SUI). The effectiveness and safety of this method depend on the properties of injected substance. Aim. To evaluate the results of paraurethral injections of 1,4-butanediol diglycidyl ether crosslinked high-density hyaluronic acid (EsteFILL® intim) in the treatment of SUI in women of reproductive and perimenopausal age. Materials and methods. We examined 18 patients aged 45.8±5.0 years with mild SUI in combination with grade I–II genital prolapse. After general clinical and special studies (urination diaries, King and PISQ-12 questionnaires, cough test, complex urodynamic study, urethrovesical segment and pelvic floor ultrasound with compression elastography) paraurethral injection of 4.0 ml EsteFILL® intim drug was performed. The results of therapy were studied 1 and 6 months after the procedure. Results. It was found that the injection of the drug contributed to an increase in the stiffness of paraurethral tissues by 1.5 times within 6 months after injection. According to the results of elastography before treatment, the average value of the strain ratio of paraurethral tissues of the proximal posterior wall of the urethra was 0.66±0.46 (0.42–0.91), after 1 and 6 months – 0.99±0.45 (0.76–1.23) and 1.00±0.36 (0.78–1.22) respectively; p=0.009 and 0.018. The effectiveness of EsteFILL® intim drug in the treatment of mild SUI in women after 1 and 6 months according to the results of a cough test was 88.2 and 71.4%, according to urination diaries – 88.9 and 66.7% respectively. During the entire observation period the patients noted a decrease in the degree of discomfort due to SUI and an improvement in the quality of life. Conclusion. Paraurethral injection of EsteFILL® intim drug helps to increase the stiffness of the urethra supporting structures in patients with SUI. This method of treating SUI is effective for women of reproductive and perimenopausal age with mild severity disease, who do not plan surgical treatment, are interested in achieving a quick result of therapy and are informed that the effect decreases over time after the procedure.

Aim. To analyze the relationship between the expression of proteomic markers [estrogen (ER) and progesterone (PR) receptors, LIF, FOXA1, FOXA2] of endometrial receptivity and indicators of the levels of sex steroids [estradiol (E2) and progesterone (P)] in the peripheral blood during the “implantation window” in women with a history of reproductive dysfunction with “thin” endometrium (TE) and evaluate their significance for the therapeutic effect of using estradiol drugs. Materials and methods. The prospective cohort comparative study was conducted. The main group included 52 patients with TE (7 mm according to ultrasound on preovulatory days), the comparison group consisted of 62 women with normal endometrial thickness (≥7 mm according to ultrasound), women of both groups with reproductive dysfunctions of unknown reason; the control group included 16 healthy women. Aspiration biopsy of the endometrium was performed on the 6–8 days after ovulation (LH +6–8), as well as venipuncture to obtain a sample of peripheral blood to determine the E2, P levels. A combined histological and immunohistochemical study of endometrial samples was performed (ER, PR, LIF, FOXA1, FOXA2). The therapeutic effects of estradiol drugs were assessed in a cohort of women from the main group with TE (n=16 out of 26, those who have not changed their reproductive plans). Results. All women had ovulatory values of progesterone [P≥16.1 nmol/l (LH +6–8)] and normoestrogenemia in the blood (p0.05). According to the results of the correlation analysis, there were no associations between the E2, P levels and the value of M-echo, and no relationships were found between the E2, P levels and the expression of ER, PR, LIF, FOX-proteins. It was revealed that there are significant positive relationships between M-echo and FOXA2 expression in the endometrium (r=0.422; p0.001). Conditional threshold values for the ER, PR expression (LH +6–8) were determined, the excess of which is associated with abnormal expression of LIF, FOX-proteins: for PR in the glands – 105 and 285, for ER in glands – 145, for ER in the stroma – 155. It was found that usual doses of estradiol drugs (1–1.5 mg/day) are capable of increasing endometrial proliferation in women with TE, provided that the expression of ER, PR, LIF, FOX-proteins in their endometrium is similar to healthy women. Increased doses of estradiol drugs (4 mg/day) in women with TE had a significant effect in the form of an increase M-echo value and/or pregnancy in cases where the endometrial expression of LIF, FOX-proteins was comparable with healthy women, even in the presence of hormone-receptor interactions in the endometrium that are different from healthy women. Spontaneous pregnancy in participants of the main group with hypoplastic endometrium in our study occurred in 5 women in whom the expression characteristics of FOXA1 and/or FOXA2 in the endometrium were comparable to healthy women. Conclusion. TE is not the only marker of an imbalance of proteomic molecules, but it determines a greater likelihood of impaired expression of ER, PR, LIF, FOX-proteins in the endometrium. In women with an unclear reason of fertility disorders, it is necessary to conduct an in-depth examination of endometrial samples. Characteristics of endometrial expression ER, PR, LIF, FOX-proteins and the usefulness of hormone-receptor interactions in the TE in women with a history of reproductive disorders can be markers for predicting the effectiveness of the use of exogenous estradiol drugs in women in order to enhance endometrial proliferation with an initially low M-echo.