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AIM: To compare the efficiency of using different interventional procedures for a barren marriage in case of secretory azoospermia (SAS)/MATERIAL AND METHODS: The trial enrolled 110 patients aged 25 to 54 years with SAS. The levels of sexual hormones were determined; ovarian punch biopsy was performed/RESULTS: Decreased volume of the ovaries was noted in 85.3% of the patients; diffuse or focal changes in their parenchyma were seen in 65.7%. There was an increase of follicle-stimulating hormone levels and a reduction in testosterone ones. Hyperestrogenemia was identified in 26.5% of the patients. The level of inhibin B was lower in all the patients. The efficiency of standard testicular sperm extraction for cryopreservation was achieved in 28.7% of the patients and that of a microsurgical technique was in 56.7%. The wives of 37 out of the 57 patients included in an assisted reproductive technology program were more than 12 weeks pregnant after 95 intracytoplasmic sperm injection cycles/CONCLUSION: The microsurgical technique is most effective in achieving the successful treatment of patients with azoospermia in order to prevent male infertility.

Aim. To study the influence of long-term of vardenafil use on endothelial and erectile functions in patients with arteriogenic erectile dysfunction (ED) Subjects and methods. The study included 74 arteriogenic ED patients (mean age 57.4 ± 4.7 years). In addition to a comprehensive andrological examination, all the patients underwent the estimation of the endothelial function of cavernous arteries, the indicator of which is the percentage increase in the diameter of cavernous arteries. The patients were divided into 3 groups: 1) 24 patients receiving vardenafil on demand in a dose of 10 mg; 2) 26 patients taking the drug on demand in a dose of 20 mg; and 3) 24 patients regularly using the agent in a dose of 10 mg every other day. Endothelial and erective functions were re-estimated 1, 3, and 6 months after the initiation of vardenafil therapy and a month following its discontinuation. Results. Erectile function improvement was noted just a month after the initiation of vardenafil therapy and achieved the maximum values by month 6. The highest erectile function parameters were observed in Group 3. There was a significant endothelial function improvement only in Group 3; the peak effect was achieved by month 6 of treatment. Conclusion. The long-term use of vardenafil contributes to the improvement of both erectile and endothelial functions in patients with arteriogenic ED.

Introduction. Hyperhomocysteinemia (HHC) is one of the arms in the pathogenesis of thrombotic complications in female cancer patients.Aim: to assess an HHC-related impact to developing thrombotic complications in patients with malignant neoplasms of the female genital organs and breast cancer.Materials and Methods. There were retrospectively evaluated the data collected from 236 patients: with ovarian tumors (n = 63), cervical cancer (n = 51), breast tumors (n = 64), malignant neoplasms of the uterine body (n = 58). The control group consisted of 50 women without malignant neoplasms. The analysis of homocysteine (HC) concentration, the frequency of polymorphisms of the genes encoding folate cycle enzymes MTHFR C677T, MTHFR A1298C, MTRR A66G, MTR A2756G as well as the rate of thrombotic complications was carried out. A risk of blood HC level-related thrombotic complications was assessed.Results. Plasma HC concentration comprised ≥ 22 μmol/l in 30.5 % of patients. Thrombotic complications within one year after discharge from the hospital were developed in 15.3 % cases. The risk of thrombotic complications turned out to be higher in patients with elevated plasma HC level (≥ 22 μmol/l) (odds ratio = 2.99; 95 % confidence interval = 1.11–8.08). No significantly increased prevalence of polymorphisms in the genes encoding folate cycle enzymes among female cancer patients was detected.Conclusion. Monitoring HC level in female cancer patients contributes separately to predict a likelihood of thrombotic complications. Prescribing drugs that reduce HC level (folic acid) and monitoring its concentration in female cancer patients during therapy, including chemotherapy, can potentially lower an incidence of thrombotic complications.

Introduction. Studies evidence about a relation between increased circulating free DNA (cfDNA) concentrations and chemotherapy, the majority of which have been focused on considering a tumor as a source of cfDNA. It has been suggested that neutrophils also contribute to this process, as cancer-related cfDNA characteristics resemble those of neutrophil extracellular traps (NETs). Therefore, the elevated concentration of cfDNA observed in chemotherapy patients may be associated with NETosis.Aim: assessment of NETosis markers in surgical treatment and adjuvant chemotherapy of patients with malignant neoplasms of the female reproductive system.Materials and Methods. A prospective non-randomized interventional controlled study was carried out by enrolling 111 patients with malignant breast diseases and female genital organs of various localizations and stages hospitalized for elective surgical treatment or chemotherapy course. The control group included 33 healthy women. 69 patients underwent surgical treatment. Adjuvant chemotherapy with paclitaxel and carboplatin was performed in 25 patients with ovarian cancer and 17 patients with breast cancer. In cancer patients, citrullinated histone H3 (citH3) and myeloperoxidase (MPO) were chosen as NETosis biomarkers allowing to distinguish NETs from other tumor-derived cfDNA thereby improving quality of research study. The concentration of NETosis markers was assessed before surgery or onset of chemotherapy upon admission to hospital and 14 days after surgery or 14 days after the second course of chemotherapy.Results. In all patients, the concentrations of NETosis markers before the start of therapy were significantly increased compared to the control group as well as 14 days after surgical treatment and 14 days after the second course of chemotherapy. However, in surgical patients, no significantly increased concentration of NETosis markers postvs. pre-surgery magnitude was observed. Upon that, patients underwent 2 courses of chemotherapy vs. baseline level were found to have significantly elevated magnitude of NETosis markers.Conclusion. The study revealed the relationship between administration of paclitaxel-containing chemotherapy in patients with ovarian cancer and breast cancer and a rise in NETs level. Chemotherapy is an essential component for management of patients with malignant neoplasms of the female reproductive system, therefore, development of new strategies to lower a risk of thrombosis and resistance to it is of crucial importance.

Hypercoagulation is a typical condition for cancer patients. In addition, various arms of the hemostasis system become involved in tumor growth, invasion, metastasis, neoangiogenesis as well as immunoevasion. The magnitude of activated hemostasis is driven by tumor phenotype. Parameters characterizing coagulation, intensity of fibrinolysis processes, platelet aggregation and activation as well as endothelial activation mirror magnitude of hemostasis activation in oncological process, but may also be considered as candidate markers of tumor progression and predictors of oncological diseases outcome. This review summarizes the study data assessing a value of predictive hemostasis biomarkers for overall survival and response to therapy in oncogynecology and mammology. The most promising biomarkers have been identified and used in the future for risk stratification as well as personalized patient management.

Introduction. One of the leading causes in the mortality pattern of cancer patients is accounted for by thrombotic complications. Recent studies have shown that neutrophil extracellular traps (NETs) are involved in the activation of coagulation, contribute to the initiation and progression of thrombosis. In addition, NET-related effect on tumor progression and metastasis has been actively studied.Aim: to evaluate NET-related procoagulant activity in gynecological cancer patients.Materials and Methods. From April 2020 to October 2022, a prospective controlled interventional non-randomized study was conducted with 120 women. The main group included 87 patients aged 32 to 72 years with malignant neoplasms of the female genital organs and mammary glands who were hospitalized for elective surgical treatment or chemotherapy: uterine body cancer (subgroup 1; n = 18), ovarian cancer (subgroup 2; n = 26), cervical cancer – adenocarcinoma of the cervical canal (subgroup 3; n = 13), breast cancer (subgroup 4; n = 30). The control group consisted of 33 healthy women aged 32 to 68 years. In all women, plasma concentrations of citrullinated histone H3 (citH3), myeloperoxidase antigen (MPO:Ag), D-dimer, and thrombin–antithrombin (TAT) complexes were evaluated.Results. The magnitude of NETosis in cancer patients, assessed by level of citH3 (2.5 ± 0.7; 1.9 ± 0.8; 2.5 ± 0.7; 0.7 ± 0.5 ng/ml in four subgroups, respectively) and MPO:Ag (29.5 ± 13.1; 12.8 ± 3.7; 22.8 ± 8.7; 6.6 ± 2.5 ng/ml in four subgroups, respectively) was significantly higher compared to women in the control group (0.3 ± 0.1 ng/ml; p = 0.0001 and 2.5 ± 0.2 ng/ml; p = 0.0001). In parallel with increased NETosis markers in accordance with the disease stage, there was an increase in the concentration of hemostasis activation markers – D-dimer (1.7 ± 0.6; 2.0 ± 0.7; 1.4 ± 0.5; 1.5 ± 0.7 µg/ml in four subgroups, respectively) and TAT complexes (729.8 ± 43.9; 794.1 ± 164.8; 636.2 ± 149.5; 699.6 ± 165.7 pg/ml in four subgroups, respectively) exceeding their level in the control group (respectively, 0.4 ± 0.1 μg/ml; p = 0.0001 and 362.3 ± 0.1 pg/ml; p = 0.0001). The maximum values of parameters occurred at later stages according to the Classification of Malignant Tumours (tumor, nodus, metastasis, TNM). A significant correlation between TAT level and the concentrations of citH3 (r = 0.586; р = 0.04) and MPO:Ag was revealed (r = 0.631; р = 0.04).Conclusion. Tumor tissue creates milieu that stimulates NETs release, which, in turn, not only contribute to the creating a procoagulant state, but also might act as one of the factors that ensure tumor progression and metastasis. The development of targeted therapies acting on NETs has a potential to affect hemostasis in cancer patients and reduce rate of tumor growth and metastasis.

Introduction. Neutrophil extracellular traps (NETs) and von Willebrand factor (vWF) are integral players in thrombosis and inflammation in cancer patients. It has been increasingly evident that an active interplay exists between NETs and vWF. Some studies suggest that NETs cause decrease in ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity, being an arm in the pathogenesis of both thrombotic microangiopathies (TMA) and other thrombotic complications during oncological process.Aim: to assess a crosstalk between NETs, vWF, and ADAMTS-13 in uterine, ovarian, breast malignant neoplasms as well as cervical canal adenocarcinoma.Materials and Methods. From September 2019 to July 2022, a prospective controlled interventional non-randomized study was carried out with 106 patients hospitalized for planned surgical treatment aged 30 to 72 years. The main group included 73 patients with malignant neoplasms of the female genital organs and mammary glands, stage I–III: uterine cancer (subgroup 1; n = 18), ovarian cancer (subgroup 2; n = 21), cervical cancer – adenocarcinoma of cervical canal (subgroup 3; n = 9) and breast cancer (subgroup 4; n = 25). The control group consisted of 33 women with female genital tract and breast benign neoplasms. In all patients, serum levels of vWF, citrullinated histone H3 (citH3), MPO (myeloperoxidase) antigen, ADAMTS-13 activity, ADAMTS-13 antigen, and D-dimer were evaluated.Results. The study revealed significant differences in the concentration of NETosis markers between the main and control groups. Patients with uterine cancer and adenocarcinoma of the cervical canal peaked at NETosis markers. At the same time, there were significant differences in citH3 concentration among patients with «early» (stage I) and «not early» (stage II–III) disease forms. While assessing level of von Willebrand factor (vWF:Ag), antigen (ADAMTS-13:Ag), and ADAMTS-13 activity (ADAMTS-13:Ac), significant differences were found between the main and control groups (p < 0.0001). The vWF in the main groups was sharply increasedwhereas ADAMTS-13 antigen concentration and activity were decreased. A сorrelation analysis among oncological patients in main group showed that while citH3 level increased, it was also paralleled with rise in vWF:Ag (ρ = 0.80; p < 0.01) and MPO:Ag (ρ = 0.87; p < 0.01); increase in MPO:Ag level was coupled to rise in vWF:Ag (ρ = 0.70; p< 0.01), but increase in vWF:Ag occurred along with decline in ADAMTS-13:Ac (ρ = –0.43; p < 0.01) and ADAMTS-13:Ag (ρ= –0.42; p < 0.01).Conclusion. The interplay between NET, vWF, and ADAMTS-13 leads to a vicious circle, reduces ADAMTS-13 activity by increasing serum vWF concentration, which positively correlates with severity and mortality in TMA, acute ischemic infarction, and COVID-19. Targeting the NETs-vWF axis may pave the way for therapeutic strategies for immunothrombosis in various diseases, including cancer.