[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.

[The use of a complex of natural antimicrobial peptides and cytokines for treatment of male infertility and chronic prostatitis].

INTRODUCTION: Chronic prostatitis (CP) has long been considered one of the common causes of male infertility. The influence of therapy for CP on spermatogenesis is well studied. However, recently, especially in the era of the new coronavirus infection (COVID-19), much attention has been paid to the effects of cytokines on the pathogenesis of the inflammatory process, and their impact on male fertility. AIM: To study the effect of a complex of natural antimicrobial peptides and cytokines (Superlymph) on ejaculate, MAR test, oxidative stress (OS), and sperm DNA fragmentation (SDF) in men with infertility and a history of CP. In some patients, the level of cytokines before and after treatment was determined. MATERIALS AND METHODS: A total of 583 infertile men with a history of CP, aged 18-75 years, were screened according to the inclusion/ exclusion criteria. In group I, patients received antioxidant stimulation of spermatogenesis (triovit, trental, mexidol) in combination with a complex of natural antimicrobial peptides and cytokines (Superlymph) one suppository 25 IU at night for 20 days for 1-3 weeks and for 6-8 weeks for 2 months. In group II, antioxidant stimulation of spermatogenesis was prescribed along with suppositories for the prevention of CP for 2 months. The evaluated criteria included sperm analysis, MAR test, oxidative stress in spermatozoa (reactive oxygen species (ROS)) and SDF. The levels of seminal plasma cytokines were also measured before and after treatment in 32 patients using the Bio-Plex Pro panel for the simultaneous determination of 17 human cytokines, the Human Cytokine 17-plex Assay. Statistica-10 software was used for statistical analysis (p<0.05). RESULTS: Of 135 eligible patients, results were collected from 125 men (mean age 31.7 +/- 13.4 years). In group I, there was a more pronounced increase in motility by 42.3%, a decrease in the MAR-test level by 64.7%, oxidative stress in spermatozoa by 56.1%, and SDF by 25.6%, compared to group II (30.4 %, 10.5%, 45.7%, 21.9%), respectively. All these changes were significant with the exception of a decrease in the level of SDF. In group I, there was a predominant increase in the activity of anti-inflammatory cytokines (IL-4, 10, 13), a decrease in the level of pro-inflammatory cytokines ((IL-2, 12). In group II, there was a significant decrease in both pro-inflammatory (IL-2, 6, 8), and anti-inflammatory cytokines (IL-4). The remaining changes were insignificant. Among mild side effects, there were a change in the color of the sclera in 4 (3.2%), anal pain in 3 (2.4%), a decrease in libido in 2 (1.6%) patients. No differences between groups in the frequency of side effects were recorded (p>0.05). CONCLUSION: Antioxidant stimulation of spermatogenesis in infertile men and CP is an effective and safe. The addition of a complex of natural antimicrobial peptides and cytokines (Superlymph) leads to a more profound increase in sperm motility, a decrease in the MAR-test, oxidative stress in sperm cells, which potentiates the effects of therapy. The use of Superlymph is accompanied by a more pronounced positive effect on pathospermia, an increase in anti-inflammatory and a decrease in pro-inflammatory cytokines. In the contrary, in control group, where patients received antioxidant stimulation of spermatogenesis, only a decrease in the level of main cytokines was observed. The effect of a complex of natural antimicrobial peptides and cytokines (Superlymph) on the level of SDF, as well as the relationship with fertility and childbirth rates, requires further study.

[Double-blind, randomized placebo-controlled study of efficiency and safety of complex acetyl-L-carnitine, L-carnitine fumarate and alpha-lipoic acid (Spermactin Forte) for treatment of male infertility].

INTRODUCTION: Oxidative stress of sperm is a common pathologic condition, which can be detected in 30-80% infertile men. It is established that dietary consumption of antioxidants and microelements contributes to an increase of conception probability in subfertile couples, and also reduces the risk of reproductive losses. Drug complexes influencing various factors of spermatogenesis disturbance (oligo-, astheno-, teratozoospermia), oxidative stress and the level of sperm DNA fragmentation are of greatest and reasonable interest. AIM: To study the effects of complex acetyl-l-carnitine, l-carnitine fumarate and alpha-lipoic acid (SpermActin Forte) on oxidative stress, ejaculate quality and sperm DNA fragmentation in men with infertility. MATERIALS AND METHODS: A total of 80 infertile men aged 25-40 years with increased level of sperm DNA fragmentation and oxidative stress were included in open-label, prospective, randomized study. In Group A (n=20) patients received a placebo for 180 days, and in Group B patients were prescribed to SpermActin Forte, 1 sachet of 10 g once a day. The criteria for the efficiency of therapy included sperm analysis, the level of sperm DNA fragmentation, the level of sperm oxidative stress, as well as information about achievement of pregnancy, obtained by interviewing all participants. RESULTS: In patients taking antioxidant complex SpermActin Forte there were significant positive changes in the main parameters of sperm analysis, including sperm mobility and morphology starting from the third month of therapy. The level of free oxygen radicals (as indicator of oxidative stress) in Group B also significantly decreased (by 86%). A more profound decrease in DNA fragmentation was seen in Group B compared to Group A (21.5% vs. 3.6%). Pregnancy was achieved in 1 and 13 cases in Group A and B, respectively. CONCLUSION: The use of the SpermActin Forte antioxidant complex allowed to improve sperm analysis in most patients, and these changes were significant starting from the third month of therapy. Stimulation of spermatogenesis using the antioxidant complex SpermActin Forte is an effective and safe method of treating male infertility.

[Erectile function after corporoplasty in patients with peyronies disease].

PURPOSE: To evaluate erectile function in patients with Peyronies disease (PD) who underwent corporoplasty. MATERIALS AND METHODS: A total of 374 patients who underwent corporoplasty by a single surgeon during 1996-2016 were analyzed. In all cases IIEF questionnaire was evaluated pre- and postoperatively. Intracavernous injection test and penile doppler ultrasonography were performed if required. Median follow-up was 9.5 years. Analysis of risk factors for erectile dysfunction (ED) before and after corporoplasty was performed. RESULTS: Prevalence of risk factors for ED in our sample has greatly increased during follow-up. At the last follow-up visit 285 patients were sexually active. Evaluation of patient satisfaction with the quality of erections has shown that 139 patients were fully satisfied (48.8%), 84 patients were somewhat satisfied (29.5%) and 62 patients were not satisfied with their erectile function (21.7%). According to IIEF questionnaire, 105 patients (36.8%) had no ED (> 26 points); 74 patients (26%) had mild ED; 67 patients (23.5%) had mild-to-moderate ED; 21 patients (7.4%) had moderate ED; and 18 patients (6.3%) had severe ED. However, a causal relationship between ED and treatment of Peyronie's disease was found not in all cases. Seven patients had infrequent sexual intercourse (1-2 per month) and 50 patients had no sexual activity. DISCUSSION: At long term after corporoplasty some patients experience ED, though causality between ED and PD treatment couldnt be confirmed in all such cases. It should be noted that we have found an increase in prevalence of independent risk factors for ED during follow-up period. These patients could possibly benefit in terms of quality of life if they underwent penile prosthesis placement during primary surgical treatment for PD. However, some patients had no sexual activity due to causes unrelated to ED. CONCLUSION: Not all patients with PD are satisfied with their sexual functioning after corporoplasty. However, ED after surgical management of PD is not always a consequence of surgery itself.

[Docosahexaenoic acid in the treatment of idiopathic male infertility].

AIM: docosahexaenoic acid is one of the most common fatty acids in the cell membranes of sperm. This substance is a structural component of cell membranes, and is responsible for such properties as plasticity and fluidity which are necessary for the implementation of the process of capacitation and acrosome reaction. In addition, docosahexaenoic acid has antioxidant properties. Aim of our study was to assess the effect of dietary supplement docosahexaenoic acid (Brudi PLUS) on such markers of male fertility as the sperm DNA integrity, standard indicators of semen analysis and cryotolerance in infertile men. MATERIALS AND METHODS: a randomized, multicenter, double-blind, placebo-controlled study was conducted. A total of 109 infertile men were recruited to participate in the study. All patients underwent different analyzes, including semen analysis, sperm DNA fragmentation, MAR-test, test of cryotolerance and electron microscopy analysis of spermatozoa. In active treatment group patients were prescribed to drug containing 350 mg of docosahexaenoic acid 3 times a day for 90 days. In the control group, patients were administered to a placebo with a similar scheme. All analyzes were repeatedly performed after 3-months of therapy. RESULTS: An increase in the progressive mobility and sperm viability was determined after the test of cryotolerance in the active treatment group. According to electron microscopy analysis of spermatozoa, positive changes were observed in the number of heads of the normal form with the normal structure of chromatin and acrosome, as well as a decrease in the number of spermatozoa with insufficiently condensed chromatin. CONCLUSIONS: the therapy with drug Brudi PLUS in patients with male infertility allows to increase in cryotolerance of sperms as well as decrease in number of sperm ultrastructure defects.

[Antioxidant therapy improves the results of -test in infertile men during a preparation for assisted reproductive technology (IVF/ICSI)].

INTRODUCTION: Male infertility accounts for 45-50% of all barren marriages, and in up to 40% of cases an idiopathic male infertility is diagnosed. The introduction of ART programs into clinical practice allowed to restore the childbearing function in various diseases, both in women and men, which were previously considered absolutely unpromising for treatment. AIM: to study an influence of the antioxidant complex (Androdoz) on the results of HBA-test in infertile men during a preparation for assisted reproductive technology (IVF/ICSI). MATERIALS AND METHODS: A total of 80 men aged from 25 to 45 years planning an ART program were included in a comparative, randomized, prospective, controlled study. Sixty men in a main group received an antioxidant complex (Androdoz) for 3 months, while 20 men were allocated to control group. The criterion of efficiency of the treatment was an improvement of HBA-test as well as pregnancy rate in the couples determined by interviewing patients participating in the study. RESULTS: After 3 months of therapy an increase in the number of morphologically normal spermatozoa in the ejaculate was shown in the main group, while in the control group negative changes were noted. There was a decrease in the proportion of spermatozoa with a progressive movement (+) in comparison with the control group. A positive influence of antioxidant complex (Androdoz) on the functional properties of sperm was proven by the increase in HBA-test by 13.8%, whereas there were no positive changes in the control group. A pregnancy rate after the first cycle of ART in the main group was 45% compared to 25% in the control group. CONCLUSION: The use of the antioxidant complex (Androdoz) for the treatment of male infertility in those patients who considers ART program is perspective method which allows to improve the main criteria of sperm analysis and functional tests (HBA-test), and also contributes to an increase in positive outcomes of ART program.

[The role of drug therapy in the management of varicocele].

Varicocele-related infertility is traditionally considered an indication for surgery. At the same time in some specific clinical settings, especially with subclinical varicocele, conservative therapy using hormonal or antioxidant drugs is also possible. The potential role of drug therapy in this patient category remains controversial. The article discusses the options and treatment regimens for men with varicocele-related infertility. Given the difficulties in interpreting the results of studies and the heterogeneity of the data, it is not yet possible to recommend abandoning varicocelectomy in favor of drug therapy. The most promising option for drug therapy is adjuvant antioxidants after surgical treatment of varicocele.

[Adjuvant antioxidant therapy in varicocele infertility].

INTRODUCTION: Infertility affects an estimated 15% of couples globally. Male factor infertility accounts for about a half of infertility cases. About 40% of infertile men have varicocele. The aim of this study was to investigate the efficacy and safety of a complex of acetyl-L-carnitine, L-carnitine fumarate and alpha-lipoic acid (SpermActin-forte) (SA) for adjuvant antioxidant therapy after microsurgical varicocelectomy (MVE) in men with varicocele and assess its impact on the level of DNA fragmentation in sperm cells. MATERIALS AND METHODS: This is an open, prospective, randomized trial comprising 114 men aged 25-45 (mean 34.1+/-12.1) years who underwent MVE. The patients were allocated to receive either adjuvant SA (n=38), SA in combination with a vitamin complex (VC) (n=38) or no adjuvant therapy (n=38). The efficacy was assessed at 3 months by testing standard semen parameters and the level of sperm DNA fragmentation. RESULTS: MVE led to a 21.7% increase in the progressive sperm motility compared to the baseline level. In patients receiving SA, this was by 76.7% due to active sperm motility (category A) at 3 months. MVE with concurrent supplementation of SA resulted in a 22.3% decrease in the level of sperm DNA fragmentation at 3 months. When used in the postoperative period after MVE, SA and VC resulted in a 27% increase in the sperm concentration at 3 months. There were no side effects of pharmacotherapy. The statistical significance of the change in variables was calculated using the Wilcoxon test. Critical level =0.05 was established for all criteria. CONCLUSION: Using nutraceuticals (SA) after MVE is an effective and safe adjuvant antioxidant therapy of male infertility in patients with varicocele which leads to an improvement in the basic sperm parameters (sperm concentration and motility) and a decrease in the level of sperm DNA fragmentation in the short term. Adjuvant antioxidant therapy of varicocele infertility potentiates the effects of monotherapy (both medical and surgical), leads to an increase in its effectiveness and shortens the time to pregnancy. Further studies in this field are needed to assess long-term outcomes of the treatment.

[Results of urethral reconstruction in adults after multiple hypospadias repairs].

AIM: To improve treatment results in patients after multiple hypospadias repairs by optimizing the postoperative management. MATERIALS AND METHODS: Eighty-two patients (mean age 48.1+/-15.3 years) with urethral strictures secondary to failed hypospadias repairs underwent staged graft urethroplasty using oral mucosa (cheek, lip, tongue) as a grafting material. In 62 patients, at the end of surgery the bladder was drained with a standard Foley catheter. In twenty patients the bladder was drained with a modified silicone urethral catheter, which had an additional channel for delivering drugs and removing the urethral wound effluent, and a second additional channel for inflating a balloon fixed to the catheter tube at different parts of the catheter. RESULTS: The mean length of the stricture was 5.4+/-1.2 cm (from 1 to 16 cm). Twenty-eight patients had postoperative complications. Using the modified catheter resulted in statistically significantly (p<0.05) smaller percentage of complications (10% vs 41.9%) compared to standard Foley catheter. Urinalysis and sperm test on the follow up examination at 12 months showed that only 9 (10.9%) patients had signs of the inflammatory process. Seventy-five patients (91.5%) rated the appearance of the penis as "good"; only 5 (6.1%) and 2 (2.4%) patients considered the result as "satisfactory" and "unsatisfactory", respectively. Eighty patient (97.6%) regarded the treatment result as "good" for the quality of urination and only two (2.4%) considered it "satisfactory". When assessing the strength of urinary stream, 64 (78.1%), 13 (15.8%) and 5 (6.1%) patients rated it as "good", "satisfactory", and "unsatisfactory", respectively. CONCLUSION: The study findings shows that staged urethroplasty using the oral mucosa restores the urethral patency, reduces the severity of the inflammatory process, thus improving the quality of life of patients after failed hypospadias repair. The proposed modification of the catheter ensures the timely delivery of drugs to the surgical site, evacuation the wound effluent from the urethra and helps prevent strictures by periodically inflating the adjustable balloon-dilator.

[Phosphodiesterase type 5 inhibitors in the treatment of erectile dysfunction: past, present and future].

This review article describes the differences in efficacy and side effects between available phosphodiesterase type 5 (PDE-5) inhibitors used for treating erectile dysfunction. The most studied PDE-5 inhibitor is sildenafil.

[A man's role in recurrent miscarriage in a spouse].

In a review article based on the published literature and their own research, the authors examine the role of a man in recurrent miscarriage and reproductive losses in a spouse. Detailed description is presented of the negative impact of elevated levels of sperm DNA fragmentation on the course of pregnancy, especially during the first trimester, on the occurrence of recurrent miscarriage or missed abortion, on the effectiveness of assisted reproductive technology (ART) programs. The etiology and pathogenesis of damage to sperm DNA are described. Outlined are positive effects of correcting adverse lifestyle factors, the role of varicocelectomy and antioxidant therapy, and advances in ART. The review specifies the role of different male karyotype abnormalities (translocations) in the pathogenesis of pregnancy loss. The implications of urologic surgery, preimplantation genetic diagnosis in solving this problem are discussed. New treatment strategies using correction of male disorders for couples with recurrent miscarriage are offered.

[Sildenafil citrate in the treatment of men with erectile dysfunction].

Based on literature data and the results of own authors' research, the review article considers the efficacy and safety of sildenafil, including its long-term use. Application of this drug leads to an improvement of erectile function in patients of all ages, regardless of etiology, severity and duration of erectile dysfunction (ED). Drug has long-term efficacy. Sildenafil affects both arterial and venous blood flow to the penis, which makes it indicated in vasculogenic erectile dysfunction first. Treatment with sildenafil is accompanied by improvement of the cavernous electrical activity, which justifies its use in neurogenic form of the disease. According to results of IIEF questionnaire, sildenafil provides quick and lasting therapeutic effect. Efficacy and safety of sildenafil is rated as good. As for short-term and long-term use, sildenafil does not cause dependence and addiction.

[Optimization of an approach to solving the problem of a barren marriage in secretory azoospermic men].

AIM: To compare the efficiency of using different interventional procedures for a barren marriage in case of secretory azoospermia (SAS). SUBJECTS 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.

[Current approach to therapy for male infertility in patients with varicocele].

AIM: To improve the results of treatment for male infertility in patients with varicocele and to evaluate the efficiency of microsurgical varicocelectomy performed by the same surgeon in a large group of patients. SUBJECTS AND METHODS: 1127 infertile males aged 22 to 52 years (mean 29.6 +/- 9.2 years) with varicocele were examined. An analysis of the patients' presenting complaints, collection of history data, examinations, spermogram studies, mixed agglutination reaction (MAR) test, ultrasonography and Doppler study of the scrotum, estimation of blood hormone and inhibin B levels, and genetic studies (karyotype, azoospermia factor (AZF), cystic fibrosis gene) were done. The analysis excluded 193 patients with other causes of infertility. 728 patients underwent uni- and bilateral microsurgical subinguinal varicocelectomy according to the Marmar procedure modified by the authors, 107 had spermatogenesis stimulation (clomiphene citrate, vitamins A and E, selenium, L-carnitine, pentoxifylline, antioxidants) for 3-6 months; 56 patients were untreated. The follow-up period was 3-12 months depending on the efficiency of treatment. Control examination was made every 3 months. RESULTS: After microsurgical varicocelectomy, there were increases in the concentration of spermatozoa from 8.8 +/- 7.2 to 23.2 +/- 7.9 mln/ml and their active motility from 7.2 +/- 5.4 to 31.2 +/- 5.2% (category A); the proportion of abnormal sperm forms (Kruger morphology) reduced from 95.4 +/- 5 to 87.8 +/- 8.3%. The patients with azoospermia (n = 39), spermatozoa appeared in 46.2% of cases; 52.8% of the patients with complete teratozoospermia (n = 36) exhibited morphologically normal sperm postoperatively (unlike the results of treatment in the comparison groups). Higher sperm concentrations were observed after both microsurgical varicocele and empirical stimulation of spermatogenesis in 69.9 and 29.9% of the patients, respectively. Spontaneous conception occurred in the partners of 47.1% of the males after microsurgical varicocele, 21.5% of those after drug stimulation, and 3.6% of those untreated. CONCLUSION: Microsurgical varicocele is the most effective and safe treatment option for male infertility in patients with varicocele. Its effect far exceeds the results of drug stimulation of spermatogenesis and those of the follow-up. It lies in a rapid and significant improvement in spermatogenic parameters just 3-6 months after surgery and further continues to increase. This gives rise to spontaneous pregnancy in about 50% of the infertile couples within a year postsurgery. Microsurgical varicocele may be recommended not only as the gold standard surgical treatment for varicocele, but also for the therapy of male infertility in these patients. At the same time, prior to surgical treatment for varicocele, one should rule out all other causes of male infertility and female factor (particularly tubal one).

[Morphological characteristics of ovarian biopsy specimens in infertility].

The authors present the results of their studies and the data available in the literature on the morphological examination of ovarian biopsy specimens in fertility. They highlight the specific features of preparation of histologic specimens. The types of male infertility and impaired spermatogenesis are given and their morphological diagnostic criteria are indicated.

[Levitra (wardenafil) effects on endothelial function of brachial and cavernous arteries].

We studied effects of oral PDE-5 inhibitor wardenafil (levitra, Bayer & GlaxoSmithKline) on endothelial function of cavernous and brachial arteries in males with normal erectile function and in patients with erectile dysfunction (ED). Endothelial function of the brachial and cavernous arteries was studied in 75 males with ED and 20 healthy volunteers before and after wardenafil intake in a dose 20 mg using ultrasound examination of postcompression diameter changes. The results show that wardenafil improves endothelial function of cavernous and brachial arteries. The degree of the positive effect depends on baseline condition of the endothelial function of the vessels. The highest activity of the drug was seen in patients with arteriogenic ED who had significant decline of endothelial function of both cavernous and brachial arteries. The dependence of wardenafil effect on baseline condition of the endothelial function is confirmed by negative correlation between changes in postcompression artery dilatation after the drug intake and baseline values. This evidences for wardenafil ability to correct disturbed endothelial function of the arteries.

[Prediction of clinical efficacy of levitra (vardenafil) in patients with arteriogenic erectile dysfunction].

Oral inhibitors of phosphodiesterase of type 5 (PDE-5) are drugs of choice in therapy of erectile dysfunction (ED). However, 20-30% patients do not respond to them. We studied potentialities of ultrasonic investigation (UI) of postcompression increase in cavernous arteries diameter (PICAD) after intake of vardenafil (levitra, Bayer&GlaxoSmithKline) which is a PDE-5 inhibitor in prediction of clinical efficacy of this medicine. A total of 75 males with ED participated in the study. Significant correlations were found between PICAD after vardenafil administration and clinical efficacy of the drug in patients with arteriogenic ED. The highest response to the drug was observed at PICAD value > or = 50%. High sensitivity and specificity of the PICAD threshold value obtained indicate high potentialities of the method in decision making on treatment policy in patients with organic ED.

[Comparative assessment of the results of ultrasonic measurements of postocclusive alterations in the brachial and cavernous arteries].

We compared the results of functional endothelial tests of the cavernous penile arteries by the modified by us method with results of the study of endothelial function of the brachial artery. The analysis of the results of examination of 116 patients with endothelial dysfunction of various genesis and 14 men free of endothelial dysfunction has not found a correlation between the tests, but all the patients with postocclusive increase in the diameter of the cavernous artery by less than 50% indicating arteriogenic endothelial dysfunction had signs of endothelial dysfunctions in the study of brachial artery. This suggests the presence of systemic endothelial dysfunction in all the examinees with arteriogenic endothelial dysfunction supporting its role in pathogenesis of this form of endothelial dysfunction.

[Levitra-test in diagnosis of vasculogenic erectile dysfunction].

Dopplerography in artificial erection induced by intracavernous injection of drugs is now the most common method of diagnosis in examination of patients with erectile dysfunction (ED). We studied possibility of inducing erection by the novel potent and selective oral drug levitra (vordenafil) from the group of inhibitors of phosphodiesterase of the 5th type. The comparison of the dopplerographic results of two methods (erection induced by intracavernous injection of prostaglandin E and levitra) showed no statistical differences between the two methods. Thus, levitra-test is a highly informative technique in diagnostic examination of patients with erectile dysfunction with the same pharmacodopplerographic efficacy as intracavernous injection of vasoactive drugs.