Association between varicocele and hypogonadism, or erectile dysfunction: A systematic review and meta-analysis.

OBJECTIVE: To assess the association between varicocele and hypogonadism, or erectile dysfunction. METHODS: We searched MEDLINE, EMBASE, LILACS, CENTRAL, and other sources. We included cohort, case-control, and cross-sectional studies. The primary outcome was the association between varicocele and hypogonadism, or erectile dysfunction, and the secondary outcome included semen analysis. We assessed the risk of bias with the Newcastle-Ottawa Scale. We performed statistical analysis in Review Manager 5.3 and reported information about the Odds Ratio (OR) with a 95% confidence interval. We produced a forest plot for the primary outcome. RESULTS: We included ten studies in qualitative analysis and six studies in quantitative analysis. Most of the cross-sectional studies showed a low risk of bias, not so for the two case-control studies, which represented a high risk of bias. Most of the reports described a correlation between having varicocele and presenting low testosterone levels: the meta-analysis showed that there is a significant association between varicocele and hypogonadism (OR 3.27 95% CI 1.23 to 8.68). Regarding varicocele and erectile, only one study showed a significant difference in erectile function in comparison to varicocele patients and men without varicocele. CONCLUSION: There is an association between varicocele presence and hypogonadism, although more studies are needed. Besides, not much is reported about an association between varicocele and erectile dysfunction, but impairment can occur through hormone disturbances.

Prevalencia de patología urogenital en la consulta ambulatoria de varones adolescentes. Estudio descriptivo transversal / Prevalence of urogenital disease in male adolescent outpatient visits. A descriptive, cross-sectional study

Introducción. El examen genital en varones es una evaluación clínica simple y rápida para detectar patología urogenital. Los datos sobre prevalencia de patología urogenital en varones adolescentes son limitados. Nuestro objetivo fue describir la prevalencia de patología urogenital en varones adolescentes. Población y métodos. Estudio descriptivo transversal en el Servicio de Adolescencia de un hospital público de la Ciudad de Buenos Aires. Se evaluaron retrospectivamente las historias clínicas (HC) de varones de 9 a 20 años atendidos entre 2008 y 2018; se incluyeron las que tenían examen genital. Se recabaron datos de edad, estadio puberal, orquidometría, patología urogenital antes de la adolescencia y al momento de la consulta. La prevalencia se expresó en porcentaje e intervalo de confianza del 95 % (IC95%). Se estimó necesario incluir 1167 HC como muestra poblacional. Resultados. Se evaluaron 2129 HC; se incluyeron 1429. En 686 casos no se hizo el examen genital. La población tuvo una mediana de edad de 12 años (rango intercuartílico 11-14 años). En 72 varones (5,7 %; IC95% 4,5-7,2), se halló una enfermedad genitourinaria antes de la adolescencia. Se detectó al menos una patología urogenital en 272 adolescentes (14,8 %; IC95% 13,1-16,7); las más frecuentes fueron adherencia balanoprepucial 5,3 % (IC95% 4,2-6,6), varicocele 2,7 % (IC95% 2-3,7) y fimosis 1,8 % (IC95% 1,2-2,6). Conclusiones. El examen genital permitió detectar que el 14,8 % de los varones adolescentes atendidos presentó alguna patología urogenital. Las entidades más frecuentes fueron adherencia balanoprepucial, varicocele y fimosis.

Introduction. The male genital exam is a simple and quick assessment to look for urogenital disease. Data on the prevalence of urogenital disease in male adolescents are limited. Our objective was to describe the prevalence of urogenital disease in male adolescents. Population and methods. Descriptive, cross-sectional study conducted at the Department of Adolescenceof a public hospital in the City of Buenos Aires. The medical records of male patients aged 9 to 20 years seen between 2008 and 2018 were retrospectively reviewed; all those with a genital exam were included. Data on age, pubertal stage, orchidometry, and urogenital disease before adolescence and at the time of consultation were recorded. The prevalence was described as percentage and 95% confidence interval (CI).As per estimations, 1167 medical records had to be included to establish the population sample. Results. A total of 2129 medical records were assessed and 1429 were included. No genital exam had been conducted in 686 cases. The median age of the population was 12 years (interquartile range: 11­14 years). Urogenital disease before adolescence was detected in 72 boys (5.7%; 95% CI: 4.5­7.2). Urogenital disease was found in 272 adolescents (14.8%; 95% CI: 13.1­16.7); the most common conditions were balanopreputial adhesions in 5.3% (95% CI: 4.2­6.6), varicocele in 2.7% (95% CI: 2­3.7), and phimosis in 1.8% (95% CI: 1.2­2.6). Conclusions. A genital exam allowed to detect that 14.8% of adolescent boys had a urogenital diseaseThe most common conditions were balanopreputial adhesions, varicocele, and phimosis.

Comparison of SPAG11A gene expression in infertile men with grade 1 and 2 varicocele before and after treatment.

OBJECTIVE: Sperm Associated Antigen 11A (SPAG11A) protein is a family of the epididymis-specific secretory proteins implicated in sperm maturation and function. Varicocele might cause pathophysiological difficulties in the testis and epididymis, with a harmful effect on the environment for spermatogenesis and sperm maturation. The aim of this study was to evaluate the expression level of the SPAG11A gene and sperm parameters in infertile men with grade 1 and 2 varicocele before and after treatment. METHODS: Semen specimens were collected from 20 infertile men with varicocele pre-and post-treatment and 10 healthy volunteers. Semen analysis was conducted according to world health organization guidelines. Real time PCR (qRT-PCR) reaction was applied for determination of SPAG11A mRNA expression. RESULTS: The results showed that there was a significant difference between the concentration and normal morphology between pre- and post-treatment groups and the controls. There were significant differences between pre-treatment and control groups in terms of progressive and non-progressive mobility. SPAG11A mRNA levels were significantly lower in the pre-treatment group than in healthy control subjects (p=0.007). There was no statistically significant difference in the expression of SPAG11A as well as semen parameters in the post-treatment group compared to the pre-treatment group. CONCLUSIONS: SPAG11A gene expression and semen parameters may be affected by varicocele. Whether varicocele treatment is an effective approach to reduce the adverse effect of this disease on SPAG11A expression and semen parameters needs further investigation.

Relationship between semen parameters, serum InhB, and INSL-3 levels, and the degree of varicocele.

BACKGROUND: Varicocele is an abnormal expansion of the pampininias venous plexus in the scrotum, resulting in impaired sperm production and reduced sperm quality. The exact pathophysiological mechanism leading to varicocele-related infertility has not been fully elucidated. Although treatable, varicocele may lead to male infertility. OBJECTIVE: To investigate the relationship between semen parameters, serum InhB and INSL-3 levels, and the degree of varicocele in male patients. METHODS: Serum InhB and INSL-3 were detected. To evaluate the relationship between semen parameters and serum InhB and INSL-3 levels. To evaluate the value of semen parameters and serum InhB and INSL-3 levels in distinguishing disease severity in patients with varicocele. RESULTS: Serum INSL-3 in patients with varicocele decreased with the severity of the disease. Serum INSL-3 was positively correlated with total sperm count and frequency of normal sperm morphology. There was a weak correlation between serum InhB and semen volume, concentration, and total sperm. Patients with different disease severity were similar within the groups, with partial overlap or similarity between varicocele Grade I and Grade II, and significant differences between Grade III and Grade I and II. Semen volume, concentration, total sperm, normal sperm morphology, and serum InhB and INSL-3 levels could distinguish the degree of varicocele. CONCLUSION: Semen parameters and the combination of serum InhB and INSL-3 levels in patients with varicocele are closely related to the severity of the disease. Serum INSL-3 is expected to be a potential biomarker for early clinical intervention.

Prevalence of urogenital disease in male adolescent outpatient visits. A descriptive, cross-sectional study. / Prevalencia de patología urogenital en la consulta ambulatoria de varones adolescentes. Estudio descriptivo transversal.

Introduction. The male genital exam is a simple and quick assessment to look for urogenital disease. Data on the prevalence of urogenital disease in male adolescents are limited. Our objective was to describe the prevalence of urogenital disease in male adolescents. Population and methods. Descriptive, cross-sectional study conducted at the Department of Adolescence of a public hospital in the City of Buenos Aires. The medical records of male patients aged 9 to 20 years seen between 2008 and 2018 were retrospectively reviewed; all those with a genital exam were included. Data on age, pubertal stage, orchidometry, and urogenital disease before adolescence and at the time of consultation were recorded. The prevalence was described as percentage and 95% confidence interval (CI). As per estimations, 1167 medical records had to be included to establish the population sample. Results. A total of 2129 medical records were assessed and 1429 were included. No genital exam had been conducted in 686 cases. The median age of the population was 12 years (interquartile range: 11-14 years). Urogenital disease before adolescence was detected in 72 boys (5.7%; 95% CI: 4.5- 7.2). Urogenital disease was found in 272 adolescents (14.8%; 95% CI: 13.1-16.7); the most common conditions were balanopreputial adhesions in 5.3% (95% CI: 4.2-6.6), varicocele in 2.7% (95% CI: 2-3.7), and phimosis in 1.8% (95% CI: 1.2-2.6). Conclusions. A genital exam allowed to detect that 14.8% of adolescent boys had a urogenital disease. The most common conditions were balanopreputial adhesions, varicocele, and phimosis.

Introducción. El examen genital en varones es una evaluación clínica simple y rápida para detectar patología urogenital. Los datos sobre prevalencia de patología urogenital en varones adolescentes son limitados. Nuestro objetivo fue describir la prevalencia de patología urogenital en varones adolescentes. Población y métodos. Estudio descriptivo transversal en el Servicio de Adolescencia de un hospital público de la Ciudad de Buenos Aires. Se evaluaron retrospectivamente las historias clínicas (HC) de varones de 9 a 20 años atendidos entre 2008 y 2018; se incluyeron las que tenían examen genital. Se recabaron datos de edad, estadio puberal, orquidometría, patología urogenital antes de la adolescencia y al momento de la consulta. La prevalencia se expresó en porcentaje e intervalo de confianza del 95 % (IC95%). Se estimó necesario incluir 1167 HC como muestra poblacional. Resultados. Se evaluaron 2129 HC; se incluyeron 1429. En 686 casos no se hizo el examen genital. La población tuvo una mediana de edad de 12 años (rango intercuartílico 11-14 años). En 72 varones (5,7 %; IC95% 4,5-7,2), se halló una enfermedad genitourinaria antes de la adolescencia. Se detectó al menos una patología urogenital en 272 adolescentes (14,8 %; IC95% 13,1-16,7); las más frecuentes fueron adherencia balanoprepucial 5,3 % (IC95% 4,2-6,6), varicocele 2,7 % (IC95% 2-3,7) y fimosis 1,8 % (IC95% 1,2-2,6). Conclusiones. El examen genital permitió detectar que el 14,8 % de los varones adolescentes atendidos presentó alguna patología urogenital. Las entidades más frecuentes fueron adherencia balanoprepucial, varicocele y fimosis.

From pathophysiology to practice: addressing oxidative stress and sperm DNA fragmentation in Varicocele-affected subfertile men

ABSTRACT Varicocele can reduce male fertility potential through various oxidative stress mechanisms. Excessive production of reactive oxygen species may overwhelm the sperm's defenses against oxidative stress, damaging the sperm chromatin. Sperm DNA fragmentation, in the form of DNA strand breaks, is recognized as a consequence of the oxidative stress cascade and is commonly found in the ejaculates of men with varicocele and fertility issues. This paper reviews the current knowledge regarding the association between varicocele, oxidative stress, sperm DNA fragmentation, and male infertility, and examines the role of varicocele repair in alleviating oxidative-sperm DNA fragmentation in these patients. Additionally, we highlight areas for further research to address knowledge gaps relevant to clinical practice.

Relationship between semen parameters, serum InhB, and INSL-3 levels, and the degree of varicocele

Abstract Background Varicocele is an abnormal expansion of the pampininias venous plexus in the scrotum, resulting in impaired sperm production and reduced sperm quality. The exact pathophysiological mechanism leading to varicocele-related infertility has not been fully elucidated. Although treatable, varicocele may lead to male infertility. Objective To investigate the relationship between semen parameters, serum InhB and INSL-3 levels, and the degree of varicocele in male patients. Methods Serum InhB and INSL-3 were detected. To evaluate the relationship between semen parameters and serum InhB and INSL-3 levels. To evaluate the value of semen parameters and serum InhB and INSL-3 levels in distinguishing disease severity in patients with varicocele. Results Serum INSL-3 in patients with varicocele decreased with the severity of the disease. Serum INSL-3 was positively correlated with total sperm count and frequency of normal sperm morphology. There was a weak correlation between serum InhB and semen volume, concentration, and total sperm. Patients with different disease severity were similar within the groups, with partial overlap or similarity between varicocele Grade I and Grade II, and significant differences between Grade III and Grade I and II. Semen volume, concentration, total sperm, normal sperm morphology, and serum InhB and INSL-3 levels could distinguish the degree of varicocele. Conclusion Semen parameters and the combination of serum InhB and INSL-3 levels in patients with varicocele are closely related to the severity of the disease. Serum INSL-3 is expected to be a potential biomarker for early clinical intervention.

Varicocele and testicular cord torsion: immune testicular microenvironment imbalance.

The main functions of the testis, steroidogenesis and spermatogenesis, depend on the endocrine axis and systemic and local tolerance mechanisms. Infectious or non-infectious diseases may disturb testicular immune regulation causing infertility. Literature has illustrated that bacterial and viral infections lead to autoimmune infertility: either sperm antibodies or autoimmune epidydimo-orchitis. However, little is known about the association between non-infectious testicular pathologic diseases and autoimmunity. Here we review the novel aspect of varicocele and testicular cord torsion pathology linked to inflammation and discuss how immune factors could contribute to or modulate autoimmunity in ipsi- and contralateral testis.

Insight into inflammation involvement in varicocele: A narrative review.

BACKGROUND: Varicocele is one of the main causes of male infertility. Although the pathophysiology mechanism of varicocele is very well described and understood, there are some unanswered questions that remains unknown. Some studies have previously described the state of testicular inflammation and sperm in animal models, especially the mouse model, and the seminal plasma of men with varicocele, with or without changes in semen parameters. METHODS OF STUDY: This review intended to verify the role of inflammatory mechanism in varicocele, using clinical studies as well as animal model studies on the effect of inflammation caused by varicocele on the function of testicular somatic and germ cells. RESULTS: In-vivo studies confirmed whether anti-inflammatory molecules could treat the semen of men with varicocele and rats with varicocele. The use of different anti-inflammatory agents in mouse model studies provided a new perspective for future clinical studies to investigate the effect of concurrent treatment with surgery to improve surgical outcomes. CONCLUSION: Similar to animal model studies, previously conducted clinical trials have demonstrated the effectiveness of anti-inflammatory therapy in varicocele patients. However, clinical trials using anti-inflammatory are needed to be conducted agents to evaluate different aspects of this therapeutical approach in varicocele patients.

Insight toward inflammasome complex contribution to male infertility.

During the last decades, a wide range of factors involved in the physiopathology of male infertility disease have been discussed. The inflammation role in some of the main infertility-related diseases has been studied, such as varicocele, spinal cord injury and obesity. Inflammation is the main response of the immune system to infection or cell damage, leading to intense inflammatory cytokine release during the loss of homeostasis. One of the first steps toward pro-inflammatory cytokines release is the recognition of dangerous signals by the immune cells, including pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). These molecules can activate an important multiprotein complex, called inflammasome. Although these complexes have been studied during the last decades, their participation in male infertility has gained attention recently. Considering the inflammasome complex's high potential to be targeted for drug therapy, this review tries to shed light on current literature. Therefore, in the current review paper, we aimed to discuss the inflammasome complex activation, involvement in different male infertility conditions, and localization in the male reproductive tract.

Understanding the impact of varicocele on sperm capacitation.

OBJECTIVE: To study the relationship between the seminal sample quality of men with varicocele and sperm capacitation. DESIGN: Cross-sectional observational study. SETTING: Academic hospital. PATIENT(S): Seventy-six men (19 control and 57 with varicocele) were analyzed. INTERVENTION(S): Semen samples were submitted to a discontinuous density gradient for sperm selection. Sperm capacitation was induced using a human tubal fluid medium supplemented with bovine serum albumin. MAIN OUTCOME MEASURE(S): After capacitation induction, the sperm were assessed by capacitation state, computer-assisted sperm motility, mitochondrial activity, membrane integrity, acrosome reaction, and intracellular oxidative stress. RESULT(S): The capacitation period increased sperm motility, showing an increase in the average path velocity and a decrease in the straightness compared with sperm before capacitation (paired analysis). After capacitation, the rate of capacitated sperm, motility, and mitochondrial activity showed differences between groups (control and varicocele). The varicocele group showed lower mitochondrial activity and capacitation than the control group. On the other hand, no significant differences were observed in the other variables evaluated. CONCLUSION(S): Varicocele men showed less viable sperm and mitochondrial activity than control men after capacitation sperm. The induction of capacitation altered motility by increasing path velocity and decreasing straightness in all of the studied groups, evidencing the occurrence of hyperactivation.

Oxidative Stress and Cell Cycle Arrest in Seminiferous Tubules Nearby Varicose Vessels: New Perspectives from Experimental Varicocele.

Varicocele (VCL) has been shown to induce severe oxidative stress in the testicular tissue resulting in 35% of males with primary infertility. To compare the exacerbating impacts of varicose on oxidative DNA damage and homeostatic antioxidant reactions in the seminiferous tubules (ST), enclosed and far from varicose vessels. Thirty mature Wistar rats were divided into control and VCL-induced groups. To approve VCL, the testicular diameters, volume, and blood circulation were measured using B-mode and Doppler ultrasonography. Next, to confirm oxidative stress (OS), the global homeostatic antioxidant biomarkers were evaluated. Moreover, the OS-induced oxidative DNA damage and homeostatic antioxidant reactions were compared between STs nearby and far from varicose vessels. Finally, to clarify the DNA damage-induced impact on the cell cycle progression, the global and local expressions of Cyclin D1, Cdk4, and p21 were examined. The VCL-induced group exhibited diminished global antioxidant status (marked with TAC, GPX, SOD, and CAT) and UNG and MPG expression levels. Moreover, the cross-sections of the VCL group represented a prominent reduction in the UNG, MPG, Cyclin D1, and cdk4, and upregulation in the p21 expression levels, more prominently in the STs nearby varicose vessels. Concerning severe oxidative DNA damage and intensive molecular changes in the STs nearby the varicose vessels, they can be considered the main cause of oxidative DNA damage in enclosed tubules. Thus, the varicose-mediated oxidative DNA damage negatively impacts the cell cycle progression in the tubules more intensively in the subcapsular area.

Do YouTube videos on microscopic varicocelectomy provide reliable information?

SUMMARY OBJECTIVE: This study aimed to assess the quality of YouTube videos about microscopic varicocelectomy. METHODS: On November 20, 2022, a YouTube search for "Microscopic Varicocelectomy" was conducted. Non-English videos uploaded by producers for commercial purposes that lacked audio and subtitles were excluded from the study. A total of 50 videos were evaluated using the Journal of the American Medical Association Benchmark Score and the Global Quality Score, both of which are recognized internationally. Additionally, the researcher developed the Microscopic Varicocelectomy Score to evaluate the videos' technical content. The upload source, video length, number of views, likes, dislikes, and video power indexes were evaluated. RESULTS: The Global Quality Score, Journal of the American Medical Association Benchmark Score, and Microscopic Varicocelectomy Score of the academically prepared videos were significantly higher than those of the physician-prepared videos (p<0.05). The Global Quality Score, Journal of the American Medical Association Benchmark Score, and Microscopic Varicocelectomy Score of uploaded videos with audio, audio, and subtitles were significantly higher than those with only subtitles (p<0.05). The video duration was positively correlated with Journal of the American Medical Association Benchmark Score, Global Quality Score, and Microscopic Varicocelectomy Score. The video power index had a strong positive correlation with the number of likes. Moreover, a strong positive correlation was observed, indicating that the Global Quality Score and Journal of the American Medical Association Benchmark Score increased as the Microscopic Varicocelectomy Score increased. CONCLUSION: YouTube videos regarding microscopic varicocelectomy were of notably low quality. If the video content created by specialist physicians and academic centers is more meticulously organized, more accurate data can be transmitted. Consequently, viewing video content may not be advised based on the available data.

The learning curve of bilateral laparoscopic varicocelectomy: a prospective study / A curva de aprendizado da varicocelectomia laparoscópica bilateral: um estudo prospectivo

ABSTRACT Varicocele occurs in 15% of general male population and in 35% of infertile men. Since 1992, surgical correction with laparoscopic varicocelectomy is the gold standard for treatment of symptomatic patients or patients with abnormal seminal analysis. The learning curve for this frequently performed procedure has not yet been described. In the present study, we investigated the learning curve of a single urologist in training performing his first 21 laparoscopic varicocelectomies using qualitative and quantitative tools to evaluate his performance during the process. Our results show that 14 bilateral laparoscopic varicocelectomies are enough to achieve the plateau of the learning curve.

RESUMO Varicocele ocorre em 15% dos homens e em 35% dos homens inférteis. Desde 1992, a correção cirúrgica com varicocelectomia laparoscópica é o padrão ouro para o tratamento de pacientes sintomáticos ou com análise seminal anormal. A curva de aprendizado para esse procedimento frequentemente realizado ainda não foi descrita. No presente estudo, investigamos a curva de aprendizado de um único urologista em treinamento realizando suas primeiras 21 varicocelectomias laparoscópicas usando ferramentas qualitativas e quantitativas para avaliar seu desempenho durante o processo. Nossos resultados mostram que 14 varicocelectomias laparoscópicas bilaterais são suficientes para atingir o platô da curva de aprendizado.

Bilateral inguinal transabdominal pre-peritoneal laparoscopic hernioplasty associated to bilateral laparoscopic varicocelectomy in the same intervention: a feasibility study / Hernioplastia inguinal pré-peritoneal transabdominal bilateral e varicocelectomia laparoscópica bilateral na mesma intervenção: um estudo de viabilidade

ABSTRACT Introduction: Inguinal hernia and varicocele are common conditions in male population. Laparoscopy brings the opportunity to treat them simultaneously, through the same incision. However, there are different opinions about the risks for testicular perfusion of multiple procedures in the inguinal region. In this study, we assessed the feasibility of simultaneous laparoscopic procedures by studying clinical and surgical outcomes of patients undergoing bilateral inguinal hernioplasty using the transabdominal preperitoneal (TAPP) technique with and without concomitant bilateral laparoscopic varicocelectomy (VLB). Methods: a sample of 20 patients from the University Hospital of USP-SP with indirect inguinal hernia and varicocele with indication for surgical correction was selected. Patients were randomized into two groups, 10 undergoing TAPP (Group I) and 10 undergoing simultaneous TAPP and VLB (Group II). Data regarding total operative time, complications and postoperative pain was gathered and analyzed. Results: there was no statistical difference between groups regarding total operative time and postoperative pain. Only one complication (spermatic cord hematoma) was observed in Group I and no complications were observed in Group II. Conclusions: simultaneous TAPP and VLB in was shown to be effective and safe, which provides a basis for conducting studies on larger scales.

RESUMO Introdução: hérnia inguinal e varicocele são doenças comuns na população masculina. O advento da laparoscopia traz a oportunidade de tratá-las simultaneamente, pelo mesmo acesso. Entretanto, existem divergências sobre os riscos para a perfusão testicular de múltiplos procedimentos na região inguinal. Neste estudo, avaliamos a viabilidade de procedimentos laparoscópicos simultâneos estudando resultados clínicos e cirúrgicos de pacientes submetidos à hernioplastia inguinal bilateral pela técnica transabdominal préperitoneal (TAPP) com e sem varicocelectomia laparoscópica bilateral (VLB) concomitante. Métodos: uma amostra de 20 pacientes do Hospital Universitário da USP-SP com hérnia inguinal indireta e varicocele com indicação de correção cirúrgica foi selecionada. Os pacientes foram randomizados em dois grupos, sendo 10 submetidos à TAPP (Grupo I) e 10 submetidos à TAPP e VLB simultâneas (Grupo II). O tempo operatório total, complicações e dor pós-operatória foram coletados e analisados. Resultados: não houve diferença estatística entre os grupos com relação ao tempo operatório total e à dor pós-operatória. Apenas uma complicação (hematoma do cordão espermático) foi observada no Grupo I e não foram observadas complicações no Grupo II. Conclusões: no mesmo procedimento, submeter pacientes à TAPP e à VLB no mesmo procedimento se mostrou eficaz e seguro, o que fornece embasamento para a realização de estudos em maiores escalas.

Varicocele at High Altitude; Venous Outflow Restriction by Hypobaric Hypoxia.

BACKGROUND: Testicular aches have been reported to occur on exposure to high altitude (HA). As a painful expression of venous congestion at the pampiniform plexus, varicocele (VC) might be a consequence of cardiovascular adjustments at HA. Chile's National Social Security Regulatory Body (SUSESO) emphasized evaluating this condition in the running follow-up study "Health effects of exposure to chronic intermittent hypoxia in Chilean mining workers." OBJECTIVES: This study aimed at investigating the prevalence of VC in a population usually shifting between sea level and HA, thereby intermittently being exposed to hypobaric hypoxia. METHODOLOGY: Miners (n=492) agreed to be examined at their working place by a physician, in the context of a general health survey, for the presence of palpable VC, either visible or not. Among them was a group exposed to low altitude (LA) <2,400 m; n=123; another one exposed to moderate high altitude (MHA) working 3,050 m; n=70, and a third one exposed to very high altitude (VHA) >3,900 m, n=165. The Chi2 test and Kruskal-Wallis test were used for the descriptive analyses, and logistic regression was applied to evaluate the association of VC with exposure to HA. The Ethics Committee for Research in Human Beings, Faculty of Medicine, University of Chile, approved this project. RESULTS: VC prevalence (grades 2 and 3) was found to be 10% at LA, 4.1% at MHA, and 16.7% at VHA (p≤0.05). Hemoglobin oxygen saturation (SaO2) was lower, and hemoglobin concentrations were higher in workers with high-grade VC at VHA compared to LA and MHA (Wilcoxon tests, p<0.001). Odds ratios (OR) for the association of VC with HA were 3.7 (95%CI: 1.26 to 12.3) and 4.06 (95%CI: 1.73 to 11.2) for MHA and VHA, respectively. CONCLUSION: Association of VC with HA, a clinically relevant finding, may be related to blood volume centralization mediated by hypobaric hypoxia.

Resveratrol benefits on sperm DNA, chromatin structure and reproductive outcomes of varicocelized rats.

In varicocele, the main cause of sperm DNA damage is oxidative stress (OS). Resveratrol, a polyphenol with antioxidant properties, can protect cells from injuries caused by OS. We investigated the benefits of resveratrol against reproductive damage caused by experimental varicocele induced from peripuberty. Eighty peripubertal male rats were distributed into 4 groups: sham-control (S), varicocele (V), resveratrol (R) and varicocele treated with resveratrol (VR). Varicocele was induced through the partial ligature of the left renal vein. Resveratrol was given in a daily dose of 300 mg/kg body weight (gavage). Sperm samples were collected at 100 days of age for vitality, DNA fragmentation and chromatin protamination evaluations. OS analyses were carried out. Rats from all groups were mated with healthy primiparous females for evaluation of reproductive capacity and embryonic quality. The V group showed reduction of sperm vitality, altered chromatin protamination and sperm DNA integrity and high levels of OS. The VR group showed an improvement of oxidative status, sperm vitality, DNA integrity and chromatin structure, and an enhancement in the gestational index and embryonic quality. Therefore, we showed in this experimental model that resveratrol is a promising nutraceutical adjuvant and should be deeply studied to mitigate subfertility in varicocele.

Characterization of varicocele-induced animal models: Potential role of inflammasome complex in the varicocele pathophysiology.

Varicocele mechanisms and its impact in testicular dysfunction has been studied in order to understand the pathophysiology involved in this disease. However, study designs using testicular tissues from varicocele patients are restricted due to ethical limitations. Therefore, the use of animal models, mainly rats, that mimics varicocele and its effects is an option to develop new approaches. The surgical technique, that induces the varicocele in rats, is based on the partial obstruction of the left renal vein, leading to a dilation in the left spermatic vein and consequently to the pampiniform plexus, resulting in varicocele-induced condition. Thus, the study of the cellular and molecular mechanisms involved in varicocele development can be addressed in depth. Besides the animal model goal to uncover the exact varicocele pathophysiology, varicocele induced models are the best options to develop new non-surgical and less invasive therapies. Various animal model studies designed and investigated antioxidant and anti-inflammatory agents to face varicocele conditions. Minding this fact, we tried to discuss a newly uncovered complex in varicocele condition, known as inflammasome complex. Taking into consideration the possible inflammatory state present in varicocele, the inflammasome complex has been proposed to be involved in the pathophysiology of this disease.

Improvement of semen parameters after coil embolization of varicoceles: a systematic review.

This systematic review was conducted in accordance with the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, including clinical studies in which one of the outcomes was semen parameter improvement after varicocele embolization using coils only. The objective of the review was to assess the evidence on the role of embolization using coils alone for semen parameter improvement in men with varicocele, since embolization using coils is the most cost-effective method of varicocele repair. Study quality was assessed using the methodological index for non-randomized studies (MINORS). Out of six retrospective and two prospective observational or comparative clinical studies involving 701 patients, semen concentration improved significantly in all five studies that assessed this parameter. Mean semen motility improved significantly in seven studies. The impact of embolization on semen density could not be analyzed.

Trata-se de uma revisão sistemática conduzida de acordo com o PRISMA 2009 (Principais Itens para Relatar Revisões Sistemáticas e Metanálises) que incluiu estudos em que a melhora dos parâmetros seminais tenha sido um dos desfechos. Esta revisão foi realizada com o objetivo de avaliar as evidências sobre o papel da embolização com uso apenas de molas na melhora de parâmetros seminais em homens com varicocele, uma vez que a embolização apenas com molas é o método com melhor custo-benefício para o reparo de varicoceles. A qualidade dos estudos foi analisada com o índice MINORS. Em seis estudos clínicos retrospectivos e em outros dois prospectivos observacionais ou comparativos, a concentração seminal melhorou significativamente em todos os cinco estudos que avaliaram esse parâmetro. A motilidade seminal melhorou significativamente em sete estudos. Não foi possível analisar o impacto da embolização com molas na densidade seminal.

Effect of varicocelectomy on sperm deoxyribonucleic acid fragmentation rates in infertile men with clinical varicocele: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of varicocelectomy on sperm deoxyribonucleic acid fragmentation (SDF) rates in infertile men with clinical varicocele. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Infertile men with clinical varicocele subjected to varicocelectomy. INTERVENTION(S): Systematic search using PubMed/Medline, EMBASE, Cochrane's central database, Scielo, and Google Scholar to identify relevant studies published from inception until January 2021. We included studies comparing SDF rates before and after varicocelectomy in infertile men with clinical varicocele. MAIN OUTCOME MEASURE(S): The primary outcome was the difference between the SDF rates before and after varicocelectomy. A meta-analysis of weighted data using random-effects models was performed. Results were reported as weighted mean differences (WMD) with 95% confidence intervals (CIs). Subgroup analyses were performed on the basis of the SDF assay, varicocelectomy technique, preoperative SDF levels, varicocele grade, follow-up time, and study design. RESULT(S): Nineteen studies involving 1,070 patients provided SDF data. Varicocelectomy was associated with reduced postoperative SDF rates (WMD -7.23%; 95% CI: -8.86 to -5.59; I2 = 91%). The treatment effect size was moderate (Cohen's d = 0.68; 95% CI: 0.77 to 0.60). The pooled results were consistent for studies using sperm chromatin structure assay, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, sperm chromatin dispersion test, and microsurgical varicocele repair. Subgroup analyses showed that the treatment effect was more pronounced in men with elevated vs. normal preoperative SDF levels, but the impact of varicocele grade remained equivocal. Meta-regression analysis demonstrated that SDF decreased after varicocelectomy as a function of preoperative SDF levels (coefficient: 0.23; 95% CI: 0.07 to 0.39). CONCLUSION(S): We concluded that pooled results from studies including infertile men with clinical varicocele indicated that varicocelectomy reduced the SDF rates. The treatment effect was greater in men with elevated (vs. normal) preoperative SDF levels. Further research is required to determine the full clinical implications of SDF reduction for these men.