[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.

[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.

[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).

[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.

[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.

[Vitaprost plus in the treatment of chronic bacterial prostatitis].

Our study has demonstrated that compound medicine vitaprost plus in therapy of chronic bacterial prostatitis (CBP) reduces intensity of prostatic inflammation, significantly relieves symptoms of chronic prostatitis and pain syndrome. The absence of unwanted side effects, significant changes in clinical and biochemical blood and urine parameters evidences for good tolerance and safety of the drug. Thus, rectal suppositories vitaprost plus can be recommended for treatment of chronic bacterial prostatitis caused by both gram-positive and gram-negative bacteria in patients of different age and clinical symptoms.

[Administration of oral vitaprost for prevention of exacerbations of chronic abacterial prostatitis].

Active substance of vitaprost is a complex of water-soluble biologically active peptides isolated from bovine prostate. The prostatic extract has an organotropic action in relation to the prostate. As all peptide bioregulators, prostatic extract has antiaggregant and anticoagulant properties, enhances synthesis of antihistamine and antiserotonine antibodies, improves microcirculation in the prostatic gland. This accounts for its ability to reduce edema in prostatic inflammation. This clinical trial demonstrated that vitaprost tablets decreases twice probability of chronic prostatitis exacerbation, of development of secondary exacerbations. A prophylactic intake of vitaprost relieves symptoms of chronic prostatitis, first of all pain (discomfort), improvement of quality of life by NIH-CPSI, including exacerbation and significantly reduces size of the prostate. Vitaprost tablets can be effectively used prophylactively in chronic prostatitis for reducing probability of the disease exacerbations and their severity.

[Regeneration of testicular tissue and restoration of rat fertility in xenotransplantation of enriched fetal cell cultures in bilateral abdominal cryptorchism].

The study of cell cultures enriched with stem and progenitor cells in the treatment of experimental hypergonadotropic hypogonadism was made on 30 white non-inbred rats with experimental cryptorchism who have undergone xenotransplantation of human fetal enriched cell cultures. Spermatogenic epithelium on histological sections was studied on day 14 and 28 after xenotransplantation with calculation of the spermatogenesis index. The fertility index was estimated for each of the groups. Transplantation of enriched cell cultures enhances efficacy of restoration of adequate germinogenic and spermatogenic testicular function, accelerates recovery of spermatogenesis and fertility with high indices of spermatogenesis and fertility but effect of the above recovery after treatment with enriched cell cultures can be seen not earlier than 72 days after transplantation.

Effect of xenotransplantation of cell cultures enriched with stem and progenitor cells on hormonal profile of rats with abdominal cryptorchism.

We present the results of application of cell cultures enriched with stem and progenitor cells for the treatment of experimental abdominal cryptorchism in outbred albino rats. Xenotransplantation of human fetal enriched cell cultures was performed to animals with experimental cryptorchism during orchiolysis. Total testosterone, luteinizing and follicle-stimulating hormones were assayed by immunochemiluminescent method. It was found that xenotransplantation of cell cultures enriched with stem and progenitor cells normalized the level of total testosterone, decreased the concentrations of gonadotropic hormones, reduced hyperplasia of Leydig cells and the number of chromaffin granules, and restored normochromism of Leydig cells nuclei.

[Vitaprost forte in the therapy of patients with prostatic adenoma].

Active substance of the drug vitaprost is a complex of water-soluble biologically active peptides isolated from bovine prostatic gland. Prostatic extract has an organotropic effect in respect to the prostatic gland. It inhibits proliferative activity of cells and, therefore, development of prostatic adenoma, reduces edema and inflammation activity in prostatic diseases. Our study has shown that rectal suppositories vitaprost forte, as monotherapy of prostatic adenoma, produces a statistically significant moderate decrease of prostate size. The resultant infravesical obstruction also diminished this manifesting with increased maximal and mean volumetric urine flow rate and low volume of residual urine. A decline in obstructive and irritative symptoms due to vitaprost forte was confirmed by IPSS scores showing deterioration of quality of life. Rectal suppositories vitaprost forte can be used as monotherapy of prostatic adenoma in patients with moderate infravesical obstruction irrespective of age and concurrent diseases.

[Use of oral vitaprost in the treatment of chronic abacterial prostatitis].

An open trial performed in 2001 by the Research Institute of Urology has demonstrated good efficacy and safety of rectal suppositoria Vitaprost, the active substance of which is a complex of water-soluble biologically active peptides isolated from bovine prostate, in combined treatment of chronic bacterial and abacterial prostatitis in patients of all ages including those with concomitant adenoma. Current comparative clinical trial has shown that Vitaprost tablets in combination with nonsteroid anti-inflammatory drugs effectively treat prostatic inflammation in patients with chronic abacterial prostatitis, produce more potent and stable effect than monotherapy with ketonal. The absence of side effects and negative alterations in clinical and biochemical blood and urine parameters evidences for good tolerance and safety of Vitaprost tablets. Vitaprost tablets can be used in therapy of chronic abacterial prostatitis for raising efficacy of the standard treatment in patients of different ages and having associated diseases.

[Impase in the treatment of erectile dysfunction].

The authors review epidemiology, classification, etiology and pathogenesis of erectile dysfunction (ED), its diagnosis and treatment with a focus on mechanisms of action and efficacy of the drug impase. Impase is the drug of superlow doses of affinitively purified potentiated antibodies to human endothelial NO-synthase. The drug regulates NO synthesis in the cavernous bodies, enhances an NO relaxing action on their smooth muscles and blood flow in the penis under sexual stimulation. The drug demonstrated its high efficacy and safety in many clinical trials. Impase trial performed in the Research Institute of Urology in 2004 has found that impase is more effective in long-term administration, most of the examinees exhibited a clinical response only after one month of regular intake. The drug can be used both as the first-line monotherapy of ED and combined treatment of this disease. Clinical recommendations for practitioners on administration of impase are provided.