[Clinical guidelines for male infertility: controversial issues and the need to reach interdisciplinary consensus].

A review of controversial issues about the terminology on male infertility and reproductive function, which is currently used, as well as proposals for updating clinical guidelines for the diagnosis and treatment of male infertility and men in infertile couples are presented in the article. An algorithm is described, the elements of which ensure referral of patients based on the possibility and timing of restoration of reproductive function, taking into account the reproductive health of a woman, as well as increasing the likelihood of successful treatment aimed at the birth of a healthy child.

[Influence of COVID-19 on male fertility. What is already known?]

A new coronavirus infection caused by SARS-CoV-2 was first identified in December 2019. It has spread quickly and caused a global pandemic. Analysis of demographic factors reveals a disproportionately large number of men with severe forms of the disease. Moreover, mortality rate is also higher in men. The currently available data regarding potential risks to the male reproductive system, including pathophysiological basics, detection of viral RNA in the reproductive tract, risk of orchitis, hypogonadism, possible influence of oxidative stress, etc. are described in the review.

[Why are recommendations on the study of ejaculate not updated?]

In recent years, the quality of germinal cells has been recognized as the main factor determining reproductive potential. Standard sperm analysis is of limited value for predicting both the achievement of a pregnancy and the outcomes of assisted reproductive technologies, which raises the question of the additional significance of functional testing. Most current guidelines recommend to perform additional studies from a scientific point of view, recognizing their importance, but dont include men in the basic diagnostic schemes. In this review, we try to discuss of the relevance of special sperm testing.

[The incidence of AZF deletions, CFTR mutations and long alleles of the ar CAG repeats during the primary laboratory diagnostics in a heterogeneous group of infertily men].

AIM: microdeletions in the AZF region of Y-chromosome, compound heterozygotes of severe and mild CFTR mutations, and long CAG-repeats in the androgen receptor gene (AR) as marker of predisposition are frequently studied as genetic causes of male infertility. A simultaneously testing of the panel including biochemical, immunological, cyto- and molecular genetic markers is often performed during the complex laboratory diagnostics in infertile men. The aim of our work was to identify molecular genetic alterations, which are advisable for simultaneously testing in a man with currently uncertain form of infertility, to increase the informativeness of laboratory diagnostics. MATERIALS AND METHODS: a retrospective study of 885 infertile men was conducted. AZF deletions were determined by multiplex PCR using 10 STS-markers (sY83, sY84, sY86, sY127, sY134, sY143, sY152, sY157, sY254, sY255) and two control loci SRY and AMEL with detection in polyacrylamide gel. Mutations in the CFTR gene (F508del, CFTRdel2.3(21kb), I507del, 1677delTA, 2143delT, 2184insA, 394delTT, W1282X, G542X, N1303K, R334W and 5T) were detected by PCR and SNaPshot. For determination of length of the AR CAG-repeat a fragment analysis of fluorescently labeled PCR products on the 3500xl capillary sequencer was performed. RESULTS: AZF deletions were detected in 8.2% of cases. The largest number of deletions was found in the AZFc subregion (58.9%), while a frequency of deletion in AZFa, AZFb or combined deletions of two and three subregions was 5.5%, 12.3% and 23.3%, respectively. Heterozygous carriage of severe CFTR mutations was detected in 4.7% patients. The most frequent mutation was F508del (83.3%), followed by CFTRdel21kb (7.1%) and W1282X (4.8%). The frequency of the mild splicing 5T mutation was 5.3%, and its incidence was significantly higher than in the previously published control group (p=0.002). AR genotyping revealed that the most prevailing allele was 21 (CAG) (21.5%). Long alleles with 27 or more CAG-trinucleotides were identified in 7.5% of the tested cases. In addition, 7 CAG heterozygotes with Kleinfelter syndrome were found. CONCLUSION: during primary complex laboratory diagnostics in a heterogeneous group of infertile men, it is advisable to detect AZF deletions and the most frequent CFTR mutations, including F508del, CFTRdel21kb, 1677delTA, 2143delT, W1282X and 5T. The more comprehensive analysis of CFTR mutations is justified only in patients with verified obstructive infertility. Sequencing of panels associated with infertility genes using NGS technology is promising.

[Autoantibodies to M2-cholinoreceptors as a potential development factor of arrhythmia in patients with paroxysmal atrial fibrillation].

AIM: We aimed to assess autoantibodies to M2-cholinoceptors (M2-CR) in patients with paroxysmal lone atrial fibrillation (AF) and in patients with AF and arterial hypertension (AH). MATERIALS AND METHODS: 100 patients with lone AF and 84 patients with AF and AH were included. Patients underwent clinical blood and urinalysis, assessment of biochemistry blood panel, 12-lead ECG, 24-hour Holter monitoring, echocardiography and stress - testing (treadmill or stress - echocardiography). Assessment of IgM and IgG autoantibodies to M2-CR was performed by indirect immunoenzyme assay. The following peptide molecules were used as epitopes for detection of autoantibodies: M1 - amino acid sequence YTVIGYWPLGVVCDL (83-98) of the first extracellular loop of M2-CR; M2 - sequence VRTVEDGECYIQFFSNAAVTFGTAI (168-192) of the second extracellular loop of M2-CR; M3 - sequence NTFCAPCIPNTV (410-421) of the third extracellular loop of M2-CR; M4 - short sequence VEDGECYIQFFS (171-182) of the second extracellular loop of M2-CR; M1+M4 - chimeric molecule formed by sequences of the first and the second extracellular loops of M2-CR connected by disulfide bound YTVIGYWPLGVVCDL + VEDGECYIQFFS (83-98 + 171-182). RESULTS: Autoantibodies to M2-CR were found in 45% patients with lone AF and in 35% patients with AF and AH. In patients with lone AF prevalence of increased IgG to M2-CR were greater than in patients with AF and AH (32% vs 20%; p.

[The role of tadalafil in the management of sexual dysfunctions].

Erectile dysfunction (ED) has a significant negative impact on the quality of life of the patients and their partners. The sequence and regimens of ED therapy have become quite evident since the advent of phosphodiesterase type 5 inhibitors (PDE-5). However, there have been continued basic research of the efficacy and safety of these agents and studies aimed at new therapeutic goals. In recent years, the attention of researchers has shifted into a wider range of issues related to the personalized PDE-5 therapy, including sexual satisfaction, psychosocial variables (e.g., confidence, self-esteem, quality of relationships) and other potentially related factors. In particular, there are more and more new data on male sexual dysfunction. This review focuses on the relationship between erectile dysfunction and concomitant conditions: depressive symptoms, libido and sexual satisfaction disorders, ejaculation and orgasm abnormalities. The authors outline the possibilities and potential benefits of PDE-5 for patients with comorbid sexual dysfunction and depression with a special focus on tadalafil.

[Isolated teratozoospermia: is there a role for antioxidant therapy?]

Recently, literature has emerged that offers contradictory findings of idiopathic forms of isolated teratozoospermia that may confuse clinicians. Some researchers argue that at 0-1% of normal forms of spermatozoa, morphology itself cannot be a prognostic indicator of fertility, either in the planning of natural pregnancy, or when used in assisted reproduction. In this connection, the possible causes of teratozoospermia and alternative therapies are being actively sought, in addition to known invasive and costly procedures. There is convincing evidence that reactive oxygen species overproduction is associated with the occurrence of abnormal spermatozoa in the ejaculate. An abnormal morphology can be accompanied by damage to the sperm DNA, impaired chromatin condensation, and associated unsuccessful pregnancy outcomes. Most of the studies show that using antioxidants results in positive changes. This literature review highlights the role of oxidative stress and DNA fragmentation in the formation of morphologically abnormal spermatozoa. The authors discuss drug interventions to treat teratozoospermia and present their own recommendations for antioxidant therapy in the clinical management of idiopathic forms of male infertility.

[PDE-5 inhibitors: patients preferences].

To date, multidisciplinary approach is commonly used to treat erectile dysfunction (ED), and the first line of ED pharmacotherapy, despite its multiple causes, is phosphodiesterase inhibitors of type 5 (PDE-5). They are considered an effective and well tolerated treatment option [1-4]. Concurrently, sildenafil has the largest evidence base for efficacy and safety [5]. The satisfaction of patients with ED therapy is a complex and personal matter, and there are no clearly established and reliable criteria for showing preferences when choosing a PDE-5. Adherence of patients to the PDE-5 therapy is determined not only by the erectile response and side effects, but also by how well the treatment meets the needs and expectations of patients and how it affects the relationship between the partners. This review examines the tolerability and efficacy of the various types of PDE-5 available for treating ED, with a special emphasis on the patient's preferences, and in particular on the new sildenafil orodispersible films. As an alternative route of drug administration, films quickly dissolve in the mouth [6] and have several advantages, improve sexual health and the sense of psychological well-being of patients and their partners.

[A critical incident during marathon competition as a result of metabolic decompensation].

A case of polyorganic insufficiency syndrome associated with coma, convulsive disorder, acute hepato-renal and respiratory dysfunction, hypovolemic shock, and hyperthermal syndrome in a 46 year-old participant ofa marathon competition is reported. The clinical picture was dominated by acute hepatic insufficiency treated with remaxol to activate substrate phosphorylation under effect of exogenous succinate for slowing down the development of energy deficit in mitochondria under condition of oxygen deficit. This case can be regarded as a variant of correction of mitochondrial dysfunction with the use of a mitochondria-targeted medication such as succinate-containing remaxol. This medication reduced AST and ALT activities and utilization of endogenous enzymes for succinate synthesis from alanine and aspartate under hypoxic conditions. Prescription of remaxol as a form of direct substitution therapy was dictated by pathogenetic considerations.

[Contemporary aspects of using sildenafil].

Sildenafil has been thoroughly studied in 74 registered double-blind, placebo-controlled clinical trials assessing the efficacy and safety of the drug in a total of more than 16 000 men with erectile dysfunction (ED). However, practicing urologists have some questions regarding administering the drug in patients with multiple comorbidities. In this review, on a par with the now "classic" research, we outline the latest updates of meta-analyzes and comparative studies relating to the use of sildenafil in different groups of patients. We also discuss the problem of self-discontinuation of sildenafil therapy and the possible risks of using counterfeit phosphodiesterase type 5 inhibitors (PDE-5i).

[Role of Autoantibodies Against 1-Adrenergic Receptor in Cardiovascular Disease].

According to current knowledge, autoantibodies against 1-adrenergic receptors may be involved in pathogenesis of different cardiovascular diseases and are mostly studied in patients with Chagas disease, dilated cardiomyopathy and heart rhythm disorders. They may play an important role in cardiomyocyte apoptosis, alteration of their chrono- and inotropic effects and electrophysiological characteristics. Their effects are transduced via 1-adrenergic receptors and depend on multiple factors as ligand properties, durability of its coupling with the receptor, amount of receptors on the cell surface, their affinity and conformation. Up to the present moment, reasons for autoimmune response and clinical significance of autoantibodies against 1-adrenergic receptors are not thoroughly understood. Autoantibodies against 1-adrenergic receptors can be removed from the bloodstream by immunoadsorption and thus development of validated methods of their identification is relevant.

[Detection of Autoantibodies Against the 1-Adrenergic Receptor in the Sera of Patients via the Competitive cell-Based Enzyme Linked Immunosorbent Assay].

OBJECTIVE: This study aimed to assess the level of anti-1-adrenergic receptor autoantibodies in patients with ventricular arrhythmias with no signs of organic heart disease and with presence of cardiovascular pathology in comparison with a group of healthy volunteers. MATERIAL AND METHODS: The study included 44 patients with ventricular arrhythmias with no signs of organic heart disease ("idiopathic"), 34 patients with diagnosed dilated cardiomyopathy (DCM) of inflammatory origin, 35 patients with coronary heart disease and ventricular arrhythmias, 12patients with coronary heart disease with no ventricular arrhythmias, and 19 healthy volunteers (control group). The level of autoantibodies against the 1-adrenergic receptor was determined by the developed competitive cell-based enzyme-linked immunosorbent assay (ELISA) and by the standard ELISA using peptides corresponding to the second extracellular loop of the 1-adrenergic receptor. RESULTS: Elevated level of autoantibodies detected by a competitive cell-based ELISA was observed in 62% of patients with DCM compared to 21% of healthy volunteers (p=0.0006). In patients with "idiopathic" ventricular arrhythmias, the level of 1-adrenergic receptor autoantibodies was lower than in healthy subjects (p=0.003). Coronary heart disease patients with or without ventricular arrhythmias exhibited no differences from the control group. The number of significantly positive signals in peptide-based ELISA did not exceed 10% in any of the groups. No correlation between the data from competitive cell-based ELISA and peptide-based ELISA was found. CONCLUSIONS: This study demonstrated that competitive cell-based ELISA technique can be applied for detection of 1-adrenergic receptor autoantibodies. The results in DCM patients generally correspond to the expected. Decreased level of autoantibodies in patients with "idiopathic" ventricular arrhythmias indicates that this disease is related to changes in the immune system. Such relation is not observed in the case of coronary heart disease patients.

[MALE PRECONCEPTION CARE].

Planning pregnancy is very important to ensure the most comfortable and optimal conditions for conception, gestation and the subsequent birth of a healthy child. This review examines the effects and mechanisms of the damaging effect of external factors, social habits and certain diseases on the ejaculate quality, as well as ways to overcome them aiming to optimum preparation of a man to conceive. Several studies have shown an inverse relationship between semen quality and common diseases. Unfavorable environmental conditions, varicocele, endocrine causes, such as diabetes, obesity, and metabolic syndrome, are thought to be among the factors that could adversely affect the quality of sperm. Oxidative stress in the testicular microenvironment may lead to suppression of spermatogenesis and sperm DNA damage resulting in a decrease of their mobility and causing morphological abnormalities.

[USE OF SILDENAFIL CITRATE FOR TREATMENT OF ERECTILE DYSFUNCTION OF VARIOUS ETIOLOGY].

Erectile dysfunction is closely linked to the general state of both physical and psychological wellness. Among the major risk factors are heart disease, arterial hypertension, diabetes, hyperlipidemia, as well as sedentary lifestyle, smoking and alcohol abuse. Also, the disease is more frequently found in men undergoing radiation therapy or surgery for prostate cancer. Psychological correlates include anxiety, depression and irritability. Despite a higher prevalence among older men, erectile dysfunction is not considered an inevitable part of aging. Due to polyetiology of the disease, sildenafil is regarded as the gold standard of treatment, and new high quality generic drugs are marketed. The article covers the use of sildenafil in patients with diseases of the cardiovascular system, diabetes, hypogonadism. Effectiveness of sildenafil in patients on chronic hemodialysis as well as in patients undergoing radical prostatectomy is discussed. The issue of addiction to sildenafil is outlined.

[Treatment of exstrophy of bladder in adults].

Exstrophy of bladder in adults is extremely rare, since such anomalies are usually underwent surgery in early childhood. Difficulties in the treatment of adult patients are associated with severe long-term changes of the mucosa and surrounding tissues, chronic urinary infection, as well as a large diastasis between pubic bones and inefficiency of osteotomy. The article describes the methodology and results of the surgery in a patient 33 years old with exstrophy-epispadias after failed previous interventions. During the follow-up period of more than 5 years, there were no complications related to continent reservoir, reconstruction of the anterior abdominal wall, and urinary infection. Decrease in renal function was not observed. Thus, the cystectomy with formation of continent reservoir from the ileum is accompanied by a good functional and cosmetic results. Resection of vesical plate is justified due to severe long-term changes of the mucosa and the surrounding skin, as well as a high risk of malignancy. The use of polypropylene ? allows to reconstruct the anterior abdominal wall without osteotomy and provides a sufficient degree of its strengthening.

[The immune-enzyme analysis based on chimeric molecule and oligopeptide fragmentations to detect autoantibodies to beta-adrenergic receptor in patients with dilation cardiomyopathy].

The article deals with specification of technique of immune-enzyme analysis to detect autoantibodies to beta-adrenergic receptors (beta1-AP) using compound of oligopeptids representing the fragmentations of extracellular sites beta1-AP and chimeric molecule of extracellular section of receptor This technique significantly exceeds the analogues defined in publications by its sensitivity and correlation with diagnosis.

[Synthetic conformational antigen, simulating the extracellular part of M2-muscarinic receptor and its reactivity with sera from patients with idiopathic arrhythmias].

Linear peptides corresponding to fragment 83-98 of the first loop and fragments 168-192 and 171-182 of the second extracellular loops of M2-muscarinic receptor (marker of early cardiac disorders and arrhythmias) were synthesized by Fmoc-SPPS method. A new conformational antigen was synthesized by method of selective ligation of linear peptides by disulfide bond with native localization. Peptides were studied in reaction with sera from patients with idiopathic arrhythmias. A new conformational antigen was recognized by sera from patients with idiopathic arrhythmias with high reactivity.

[Novel conformational peptide antigen, which simulates an immunodominant epitope of the 2nd extracellular loop of ß1-adrenoceptor. Computer simulation, synthesis, spatial structure].

By means of computer simulation has been built polypeptide antigen conformational structure that imitates the immunodominant epitope of the 2nd extracellular loop of ß1-adrenoreceptor. A linear 25-membered peptide corresponding to calculated sequence was synthesized by means of solid-phase methoyd using Fmoc-technology, then directed by the closure ofdisulfide bridges was obtained original bicyclic polypeptide corresponding to the proposed structure of the conformational antigen. With the help of high-resolution NMR spectroscopy 3D structure of synthetic conformational antigen was investigated. It was shown that the structure of the bicyclic polypeptide similar to that of building computer model. Bicyclic conformational antigen was suitable for the detection of autoantibodies in the blood serum of patients with rhythm and conductivity violation without evidence of organic disease of the cardiovascular system.

[Clinical immunological rationale of interferon therapy in chronic bacterial prostatitis].

The study of changes in the immune status of patients with chronic bacterial prostatitis demonstrated changes in immunological parameters reflecting depression of the immune system (subnormal levels of interferon alpha, gamma, sIgA, functional activity of neutrophils, high concentration of IgA, IgG, IgM). Thus, combined treatment of chronic bacterial prostatitis must include administration of immunomodulators.