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INTRODUCTION: Varicocoele is commonly encountered in males with infertility. Studies have shown that varicocoele repair (surgery or embolisation) can improve the rate of subsequent pregnancy. In Australia, there have been no studies assessing the cost of varicocoele embolisation and current practice is based on international data. This study aimed to assess the cost of varicocoele embolisation and estimate the treatment cost per pregnancy. METHODS: Retrospective cost-outcome study of patients treated by embolisation between January 2018 and 2023. A bottom-up approach was used to calculate procedure costs whereas a top-down approach was used to calculate costs for all other patient services, including direct and indirect costs. To calculate cost per pregnancy, costs were adjusted according to existing published data on the rate of pregnancy after embolisation. RESULTS: Costing data from 18 patients were included, of median age 33.5 years (range 26-60) and median varicocoele grade 2.5 (range 1-3). All patients had unilateral treatment, most commonly via right internal jugular (16 patients, 89%) and using a 0.035″ system (17 patients, 94%). The median cost for the entire treatment including procedural, non-procedural, ward and peri-procedural costs was AUD$2208.10 (USD$1405 or EUR€1314), range AUD$1691-7051. The projected cost to the healthcare system per pregnancy was AUD$5387 (USD$3429 or EUR€3207). CONCLUSION: Total varicocoele embolisation cost and the cost per-pregnancy were lower than for both embolisation and surgical repair in existing international studies. Patients undergoing varicocoele treatment should have the option to access an interventional radiologist to realise the benefits of this low-cost pinhole procedure.

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BACKGROUND: Clinical palpable varicocoeles in conjunction with isolated teratozoospermia are rarely observed. Therefore, the effects of varicocoelectomy on sperm morphology are not clear. The aim of this meta-analysis is to compile studies that assess the effectiveness of varicocoelectomy in isolated teratozoospermia to reach a more consistent and reliable conclusion. MATERIAL-METHODS: The present meta-analysis was registered to PROSPERO (CRD42023467933). We utilized the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline to report the outcomes. Articles published before 1 October 2023 were included in the study. The search terms used were teratozoospermia, isolated teratozoospermia, varicocoelectomy for isolated teratozoospermia, and semen analysis after varicocoelectomy in isolated teratozoospermia. RESULTS: We identified 1,013 studies in full publications or abstracts using the methodology and the search terms. Five studies were included for systematic review, while four were included for meta-analysis. The five studies (10-14) included 348 patients aged 18-44 years. The pooled analysis revealed a significant improvement in sperm morphology in isolated teratozoospermia patients undergoing varicocoelectomy (Q = 199.42, p < 0.0001; I2  = 98.49%). The pooled analysis revealed no significant improvement in sperm concentration in isolated teratozoospermia patients undergoing varicocoelectomy (Q = 5.69, p = 0.058; I2  = 64.85%). Three of the examined studies provided information regarding pregnancy rate and it was high in all studies. According to the Newcastle-Ottowa scale (NOS) assessment, the total quality score of all studies was 7. The funnel plot test demonstrated a visible asymmetry, and Begg and Mazumdar's rank correlation test confirmed the publication bias (p = 0.04). DISCUSSION: Varicocoelectomy can be an effective and reliable treatment option in patients with isolated morphology abnormalities and clinically palpable varicocoele. CONCLUSION: This meta-analysis reported that varicocoelectomy may increase pregnancy rates by improving semen parameters in infertile men with isolated teratozoospermia, although this conclusion requires further evidence.

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BACKGROUND: Surgical is appropriate for 35-40% of varicocoele-induced infertility. This comparative observational study presents a comparative assessment of microscopic or laparoscopic varicocoelectomy (grade II varicocoele; n = 132 cases). METHODS: Sperm count, density, total motility, and forward motility rate (preoperative and postoperative 6 months), operation duration, pain at 1 month, testicular atrophy (by scrotal ultrasound at 3 months), recurrence (angiography at 6 months), and scrotal edema (at 12 months) were measured. RESULTS: The preoperative semen parameters were comparable between groups (P > 0.05), as were certain postoperative results (total sperm count [median 162 (range 100-242) compared with median 182 (range 84-253)]; sperm density [median 47 (range 38-83) compared with median 42 (range 27-88)]; forward motility (37.18 ± 4.14 compared with 34.13 ± 7.79); P > 0.05). However, sperm motility was higher in the microscope group (52.79 ± 8.21 compared with 46.64 ± 10.04; t = 2.304, P = 0.040). Within the microscope group, postoperative sperm density [median 47 (range 38-83)], total sperm motility (53.79 ± 8.25), and forward motility sperm rate (37.19 ± 4.14) demonstrated significant improvements compared with preoperative values (Z = -2.679, P = 0.005; t = -4.548, P < 0.001; t = -5.029, P < 0.001). In contrast, the postoperative forward motility sperm rate (34.13 ± 7.78) displayed substantial improvements compared with preoperative values (27.74 ± 14.42) within the laparoscopic group (t = -3.895, P = 0.001). Testicular atrophy occurred in neither group. CONCLUSIONS: Microscopic varicocoelectomy may be safer and more effective.

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BACKGROUND: Elevated intrascrotal temperature has been suggested as a risk factor for testicular cancer, which is the most common neoplasm among young men. Varicocoele was linked to increased intrascrotal temperature, but whether it is associated with testicular cancer is unclear. OBJECTIVE: To explore the possible association between varicocoele at adolescence and the incidence of testicular cancer at adulthood. DESIGN, SETTING, AND PARTICIPANTS: This nationwide, population-based, historical cohort study includes 1,521,661 Israeli male adolescents (mean age 17.5 ± 0.4 years), who were screened for varicocoele during the years 1967-2012, as part of their medical assessment prior to compulsory military service. The mean follow-up was 18 ± 4.2 years. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The diagnosis of testicular cancer was ascertained from linkage of records to the the Israeli National Cancer Registry. Survival analysis was applied. RESULTS: In total, 53,210 adolescents were diagnosed with varicocoele stages 2 and 3 prior to military service. Of 1988 (0.13% of the total cohort) men who were diagnosed with testicular cancer during follow-up, 54 (0.1%) had varicocoele prior to military service, while 1934 (99.9%) did not; p = 0.213. The age at cancer diagnosis and the distribution of seminomas versus non-seminomas did not differ significantly between those with and without varicocoele in adolescence. In a multivariable analysis controlling for sociodemographic factors, varicocoele was not associated with testicular cancer; odds ratio = 0.816 (CI: 0.615-1.083). CONCLUSIONS: Varicocoele in adolescents was not found to be associated with testicular cancer in young adults. PATIENT SUMMARY: In light of the theoretical association between varicocoele and testicular cancer, we conducted this large population study. We found no association between varicocoele in young adulthood and testicular cancer later in life.

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BACKGROUND: Varicocoele is a common risk factor associated with reduced male fertility potential. The current understanding of varicocoele pathophysiology does not completely explain the clinical manifestation of infertility. The present treatment options such as antioxidant supplementation and varicocoelectomy only help ≈35% of men to achieve spontaneous pregnancy. OBJECTIVE: This review aims to summarize the available knowledge on cellular and molecular alterations implicated to varicocoele-associated male infertility and also highlights the new knowledge generated by "omics" technologies. MATERIALS AND METHODS: PubMed, MEDLINE, Cochrane and Google Scholar databases are searched using different combinations of keywords (varicocoele, infertile/fertile men with varicocoele, cellular changes, molecular mechanisms, proteome, epigenome, transcriptome and metabolome). A total of 229 relevant human and animal studies published till 2021 were included in this review. RESULTS: Current understanding advocates oxidative stress (OS) as a major contributory factor to varicocoele-associated male infertility. Excessive OS causes alteration in testicular microenvironment and sperm DNA fragmentation, which further contributes to infertility. Molecular and omics studies have identified several promising biomarkers such as AAMP, SPINT1, MKI67 (genetic markers), sperm quality and function related protein markers, global sperm DNA methylation level (epigenetic marker), Hspa2, Protamine, Gadd7, Dynlt1 and Beclin1 (mRNA markers), PRDX2, HSPA, APOA2, YKL40 (seminal protein markers), total choline and PHGDH (metabolic markers). DISCUSSION: Mature spermatozoa harbours a plethora of molecular information in form of proteome, epigenome and transcriptome, which could provide very important clues regarding pathophysiology of varicocoele-associated infertility. Recent molecular and omics studies in infertile men with varicocoele have identified several promising biomarkers. Upon further validation with larger and well-defined studies, some of these biomarkers could aid in varicocoele management. CONCLUSION: The present evidences suggest that inclusion of OS and sperm DNA fragmentation tests could be useful to the diagnostic workup for men with varicocoele. Furthermore, including precise molecular markers may assist in diagnostics and prognostics of varicocoele-associated male infertility.

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BACKGROUND: Varicocoele is the most common correctable cause of male infertility; however, predicting varicocoelectomy outcomes is difficult. "Omics" techniques have been increasingly used to develop new diagnostic and prognostics tools for several male infertility causes, and could be applied to study varicocoele. OBJECTIVES: The objective is to create metabolomics models capable of segregating men who improved semen analysis (SA) parameters or achieved natural pregnancy after microsurgical varicocoelectomy (MV) from those who did not, using hydrogen-1 nuclear magnetic resonance (1 H NMR) spectra of seminal plasma of pre-operative samples. MATERIAL AND METHODS: We recruited 29 infertile men with palpable varicocoele. 1 H NMR spectra of seminal plasma were obtained from pre-operative samples and used to create metabonomics models. Improvement was defined as an increase in the total motile progressive sperm count (TMC) of the post-operative SA when compared to the baseline, and pregnancy was assessed for 24 months after MV. RESULTS: Using linear discriminant analysis (LDA), we created a model that discriminated the men who improved SA from those who did not with accuracy of 93.1%. Another model segregated men who achieved natural pregnancy from men who did not. We identified seven metabolites that were important for group segregation: caprylate, isoleucine, N-acetyltyrosine, carnitine, N-acetylcarnitine, creatine, and threonine. DISCUSSION: We described the use of metabonomics model to predict with high accuracy the outcomes of MV in infertile men with varicocoele. The most important metabolites for group segregation are involved in energy metabolism and oxidative stress response, highlighting the pivotal role of these mechanisms in the pathophysiology of varicocoele. CONCLUSIONS: 1 H NMR spectroscopy of seminal plasma can be used in conjunction with multivariate statistical tools to create metabonomics models useful to segregate men with varicocoele based on the reproductive outcomes of MV. These models may help counseling infertile men with varicocoele regarding their prognosis after surgery.

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OBJECTIVES: To investigate clinical outcomes, radiation exposure and procedural costs associated with percutaneous varicocoele embolization using coils and sclerosing agents (SAs) in a cohort of young-adult men. MATERIALS AND METHODS: Data from consecutive men treated with percutaneous varicocoele embolization using coils and SA between 2017 and 2021 were analyzed. The allocation was based on a change of policy occurred in June 2020 with the substitution of coils with SA (before and after study). Semen analysis values were based on 2010 WHO reference criteria. Anatomic variants of gonadal veins were categorized according to Jargiello et al. Intraoperative radiation dose and procedural costs were collected for each patient. Descriptive statistics and linear regression models were used to describe the association between clinical parameters with procedural costs and radiation exposure. RESULTS: One hundred sixteen men were included, of whom 76 (65.5%) received coils, and 40 (34.5%) received SA. Baseline characteristics of the two study groups did not differ. A type 3 Jargiello anatomic variation of left gonadal vein was found in 45.7% of cases. Radiation dose was lower in the SA group as compared to the coils one (13.2 [7-43] vs. 19.8 [12-57] Gy/cm2 ; p < 0.001). Similarly, procedural costs were lower for the SA group (169.6 [169-199] € vs. 642.5 [561-775] €; p < 0.001). At follow-up, pain and sperm variables significantly improved in both groups (p < 0.01), without differences among the embolic materials. Linear regression model revealed that coils use was associated with higher radiation exposure (beta 8.8, p = 0.02) than SA after accounting for anatomic variation of gonadal vein, body mass index, and vascular access. CONCLUSIONS: SA and coils for varicocoele embolization are equally safe and effective. The use of SA was associated with lower radiation exposure and procedural costs than coils. These results should be considered in terms of public health cost and patient's safety.

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OBJECTIVE: To evaluate the scientific impact of videos about varicocoele on YouTube. METHODS: A cross-sectional study was conducted at Turkey in September 2020, and comprised YouTube videos related to varicocoele. The videos were divided into 2 groups according to their reliability and accuracy using the European Association of Urology Sexual and Reproductive Guidelines 2020. A 5-point modified reliability (DISCERN) tool, Global Quality Score, and Journal of the American Medical Association scores of each video were calculated. The user's engagements by total views, video-related comments, and "likes" and "dislikes" to the videos were compared. Data was analysed using SPSS 23. Results: Of the 151 videos assessed, 73(48.34%) were included; 36(49.3%) reliable and 37(50.7%) unreliable. All scores were significantly higher for reliable videos (p<0.05). The mean number of views was 108448±90567 for reliable and 392626±895897 for unreliable videos (p=0.044). The rates of "likes" and "dislikes" were similar between the groups, whereas the comment rate was significantly higher for reliable videos (p<0.05). Most of the videos 40(54.8%) were uploaded by medical advertisements or for-profit companies, while those uploaded by universities or professional organisations were 19(26%). CONCLUSIONS: Nearly half of the varicocoele-related videos on YouTube were unreliable, and the reliability of videos was not directly related to their popularity.

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BACKGROUND: Ultrasonography is the gold standard imaging method for scrotal investigation. Colour Doppler ultrasonography, contrast-enhanced ultrasonography and sonoelastography allow sonographers to assess size, echotexture, vascular features and stiffness of the scrotal organs and abnormalities. Scrotal ultrasonography has been used to investigate male reproductive health, scrotal pain, masses and trauma. However, ultrasonography thresholds/classifications used to distinguish normal and pathologic features of the scrotal organs have changed over time, and have not yet been fully standardized. OBJECTIVES: To evaluate historical trends for the standards in scrotal ultrasonography: what was, what is and what will be normal. METHODS: An extensive Medline search was performed identifying the most relevant studies in the English language from inception to date. RESULTS: We provide here (i) a brief overview of the history of ultrasonography, (ii) current indications for scrotal ultrasonography and (iii) previous and current normal values, cut-offs and classifications of the main colour-Doppler ultrasonography parameters/characteristics of the scrotal organs, as derived from recent guidelines and evidence-based studies. In addition, we report recommendations and the clinical utility of contrast-enhanced ultrasonography and sonoelastography. Finally, we discuss critical issues needing further evidence and future directions to fill in the current gaps. DISCUSSION: Several studies on scrotal ultrasonography are available. However, guidelines/recommendations dealing with specific ultrasonography applications have been published only in recent years. More recently, the European Academy of Andrology published evidence-based scrotal colour-Doppler ultrasonography reference ranges/normative parameters derived from a cohort of healthy, fertile men. In addition, a standardization of the methodology to evaluate qualitative and quantitative colour-Doppler ultrasonography parameters was reported. Other international societies reported indications, methodological standards, clinical utility and limitations of contrast-enhanced ultrasonography and sonoelastography. CONCLUSIONS: To date, colour-Doppler ultrasonography normative values for the scrotal organs are available. However, a wide international consensus on assessment and classification of several ultrasonography parameters is still lacking. An alignment of the world societies on these issues is advocated.

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BACKGROUND: Varicocoele-associated stressors, such as hypoxia and heat, can damage cell function and viability, and some exosomal biomarkers released from impaired cells may reflect the cell status in testis. OBJECTIVES: To find if seminal exosomal microRNAs can reflect the Sertoli cell function in varicocoele. MATERIALS AND METHODS: Experimental left varicocoele rat model was established (n = 24), and patients with different grades of varicocoele (n = 104) were enrolled. Primary rat Sertoli cells were isolated with enzymatic hydrolysis. Exosomes were isolated from primary rat Sertoli cells, rat epididymis tissue, and human seminal plasma with polymer-based precipitation method. Exosomal microRNAs were quantified with qPCR. Inhibin-B was detected with enzyme immunoassay. The correlation analysis between microRNA and inhibin-B was evaluated with Spearman's correlation. RESULTS: We screened 12 previously reported hypoxia-responsive microRNAs in the primary rat Sertoli cells and found that 4 exosomal microRNAs increased significantly in response to in vitro hypoxia treatment (P < .05). Of the 4 microRNAs, only miR-210-3p was upregulated in the rats with experimental varicocoele (P < .01). In the patients with varicocoele, we found that seminal exosomal miR-210-3p significantly increased in patients with grade II and III varicocoele (P < .01), and miR-210-3p negatively correlated with sperm count (P < .01) and seminal inhibin-B expression (r = -0.39, P < .01). For the 30 patients with microsurgical varicocelectomy, the operation notably decreased miR-210-3p (P < .01). DISCUSSION AND CONCLUSION: Seminal exosomal miR-210-3p may be a novel, sensitive, and non-invasive biomarker of Sertoli cell damage in varicocoele.

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BACKGROUND: Varicocoele-induced male infertility potentially involves oxidative stress. Although varicocoelectomy is recommended for varicocoele patients presenting abnormal semen findings, no pharmacotherapeutic methods currently exist. We have recently developed a silicon-based agent that produces hydrogen by the reaction with water. OBJECTIVES: This study aimed to investigate the therapeutic effects of oral administration of a Si-based agent on varicocoele rat. MATERIALS AND METHODS: Twenty-one rats were divided into four groups: varicocoele + normal diet (n = 5), varicocoele + Si-based agent-supplemented diet (n = 6), sham + normal diet (n = 5), and sham + Si-based agent-supplemented diet (n = 5). All rats were euthanized four weeks after surgery. RESULTS: The mean left epididymal sperm motility was 74.4% in the sham group, 72.3% in the sham + Si group, 57.6% in the varicocoele group, and 66.9% in the varicocoele + Si group. Epididymal sperm motility was significantly lower in the varicocoele group, but was significantly higher upon Si-based agent ingestion (P < .01). The mean left testicular weight, Johnsen's score, and left epididymal sperm concentration did not differ significantly between groups. The 8-OHdG concentration and DNA fragmentation rate were significantly increased in the varicocoele group, but were significantly decreased in the Si-based agent intake group (P < .01). Additionally, the IVF rate was significantly lower in the varicocoele group (26.3%) compared with the sham group (73.4%; P < .01), and was significantly higher in the varicocoele + Si group (51.8%) compared with the varicocoele group (P < .05), indicating that the Si-based agent improves IVF rates. DISCUSSION AND CONCLUSION: Oral intake of the silicon-based agent improves epididymal sperm motility and in vitro fertilization rates through hydrogen production and subsequent reduction of oxidative stress. Considering the lack of effective noninvasive methods, this Si-based agent is potentially applicable for treating varicocoele-induced abnormal semen parameters.

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BACKGROUND: Trends of male factor causes of couples' infertility over time have been poorly investigated. OBJECTIVE: We investigated trends in the causes of pure male factor infertility (MFI) throughout the last 10 years in a tertiary-referral academic andrology center. MATERIAL AND METHODS: Baseline characteristics at first presentation from a cohort of 1647 consecutive male factor infertility patients belonging to primary infertile couples between 2008 and 2018 have been comprehensively collected over time. Seven major causes of male factor infertility were identified: varicocoele; history of cryptorchidism; hypogonadism (primary and secondary); obstructive azoospermia; genetic abnormalities; other causes (large group including the remnant conditions of known causes); and idiopathic infertility. Rates of different male factor infertility causes over the study period were analyzed. Multivariable logistic regression models tested the likelihood of male factor infertility causes over time. Estimated trends were explored graphically. RESULTS: Of all, varicocoele was found in 615 (37.3%), cryptorchidism in 124 (7.5%), genetic abnormalities in 61 (3.7%), hypogonadism in 165 (10%), obstructive conditions in 55 (3.3%), other causes in 129 (7.8%) patients, and idiopathic infertility in 498 (30.3%) patients, respectively. Over time, a reduction in the proportions of cryptorchidism and varicocoele (all P < 0.001) cases was observed, along with an increase in the proportions of hypogonadism, other causes of MFI and idiopathic cases (all P ≤ 0.01). Rates of genetic and obstructive cases remained stable. The observed trends were confirmed at logistic regression models. DISCUSSION AND CONCLUSIONS: A decreasing trend in the proportions of varicocoele and cryptorchidism at first presentation was observed over the last 10 years; conversely, the proportions of idiopathic cases, hypogonadal patients, and infertile men presenting with other male factor infertility causes significantly increased over the same time frame at a single tertiary-referral academic andrology center.

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BACKGROUND: Varicocoele (VCL), one of the main causes of male subfertility, negatively affects testicular function. Due to limited access to human testicular tissue, animal model studies have been used to evaluate molecular and, recently, epigenetic changes attributed to pathophysiology induced by VCL. OBJECTIVES: This review aims to provide an update on the latest findings regarding the link between VCL-induced biochemical stress and molecular changes in germ cells and spermatozoa. Endocrine and antioxidant status, testicular chaperone-specific hemostasis failure, altered testicular ion balance, metabolic disorders, and altered carbon cycling during spermatogenesis are among the many features that will be presented. DISCUSSION: Literature review coupled with our own findings suggests that ionic imbalance, hypoxia, hyperthermia, and altered blood flow could lead to severe chronic oxidative and nitrosative stress in patients with VCL leading to defective spermatogenesis and impairment of the integrity of all sperm cell components and compartments down to the epigenetic information they carry. CONCLUSION: Since oxidative stress is an important feature of the reproductive pathology of VCL, therapeutic strategies such as the administration of appropriate antioxidants could be undertaken as a complementary non-invasive treatment line.

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The pathophysiology of varicocele remains to be unknown. Several genetic factors have been implicated in varicocele etiopathogenesis. We studied the relationship between NOS3 c.894G>T, c.786T>C and 4b/a polymorphisms to varicocele risk and their prognostic value as regards improvement of the post-operative seminal parameters &/or seminal malonaldehyde levels. The three NOS3 polymorphisms were evaluated in 100 patients with varicocele and 100 healthy subjects by RT-PCR. Seminal plasma MDA level was measured pre-operatively and 3 months after varicocelectomy by the thiobarbituric acid method. The GT, TT, TC and bb genotypes of NOS3 polymorphism were more commonly observed in varicocele patients (30%, 9%, 28% and 70% respectively) compared to normal controls (12%, 0%, 10% and 50% respectively). The mean percentage of post-varicocelectomy seminal MDA reduction was highest with the GT genotype (p < .001). Genotypes GT+TT, TC and bb were associated with varicocele occurrence in our patients. The T (c.894G>T), C (c.786T>C) and b (NOS3 intron 4 VNTR) alleles were significantly associated with varicocele occurrence in our cohort of patients. We also report a better response regarding the reduction of seminal MDA after varicocelectomy with the GT and ba genotypes.

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BACKGROUND: Varicocoele is a swollen bulge of the pampiniform venous plexus inside the scrotum. It is also considered one of the causes of infertility in males. It has been demonstrated that hesperidin has remarkable pharmacological potentials, including antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic effects. OBJECTIVE: The present study aimed to evaluate the protective effect of hesperidin on varicocoele-induced testicular tissue damage and oxidative stress in the testicles of adult male rats. MATERIALS AND METHODS: Animals were assigned into the following groups: control group (Ctrl) or sham, varicocoele group (Vcl) which received no treatment, varicocoele group that was daily fed with hesperidin (Vcl+Hsp) at a dose of 50 mg/kg for eight weeks, and hesperidin group (Hsp) which received only hesperidin. At the end of the treatment period, the levels of oxidative stress markers were measured in plasma, and the expression of Bax and Bcl-2 was determined by immunocytochemistry and RT-qPCR methods. The index of apoptosis was assessed by the TUNEL assay. RESULTS: Johnsen's score, the epithelium thickness, and diameter of seminiferous tubules were improved in the Vcl+Hsp group as compared to the Vcl group. Treatment with hesperidin enhanced the serum levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) enzymes and decreased the heightened concentrations of malondialdehyde (MDA) in testicular tissue (p < 0.001). Moreover, our results demonstrated that hesperidin considerably diminished Bax and increased Bcl-2 expression (gene and protein) levels compared with the Vcl group (p < 0.05). It also markedly reduced the rate of programmed cell death in germ cells (p < 0.05). CONCLUSIONS: It seems that the treatment with hesperidin could mitigate testicular tissue damage in rats underwent varicocoele possibly through its antioxidant properties.

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Ultrasonography was used to capture a coronal-sagittal image of the veins of the pampiniform plexus (PP) and the testicular artery of 327 maternal-line boars at approximately 6 months of age at the University of Nebraska-Lincoln. Varicocoele was diagnosed by two methods. Method 1 diagnosed varicocoele when the average vessel area on one side of the scrotum was 1.5 times larger than the average vessel area on the other side of the scrotum. Method 2 diagnosed varicocoele when the average vessel area on one side of the scrotum of a boar was 1.5 times larger than the average vessel on the same side of the scrotum of the boar's cohorts (same population and year). Varicocoele was diagnosed in 23.17% and 15.1% of boars measured using method 1 and method 2, respectively. Ultrasonography showed to be an effective means to measure PP vessel size in boars and may even allow for earlier detection of varicocoele than by using palpation. Animal models were employed to estimate the heritability for: average area of right PP vessels (0.52), average area of the left PP vessels (0.46), varicocoele presence using method 1 (0.26) and varicocoele presence using method 2 (0.25). These heritability estimates suggest that vessel size and varicocoele could be selected against in breeding programmes to potentially improve boar semen quality.

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BACKGROUND: The existing classifications of varicocoeles have poor predictive value regarding the effects of surgery on sperm count. OBJECTIVE: To develop a new grading system for varicocoeles, useful as an indication for surgery. MATERIALS AND METHODS: This is a three-center prospective study which examined 173 men having clinically detectable left varicocoeles and oligo ± astheno ± terato-spermia. The patients underwent medical history collection, objective examination, duplex Doppler ultrasound scrotal examination, hormonal profiles, two semen analyses before surgery, and two semen analyses after surgery. Sperm concentration, motility, and morphology (standard semen parameters) were evaluated 6 months after surgery in function of the following preoperative variables: patient age, follicle-stimulating hormone, clinical grade of varicocoele, right and left testicular volume, extension of venous reflux, and semen parameters. The venous reflux was graded in two centers using duplex Doppler ultrasound: reflux visible only with Valsalva and continuous reflux. Spearman's rank semiquantitative analysis was used. All patients had their varicocoeles corrected according to the Colpi technique. RESULTS: The variables capable of determining an improvement in semen parameters after varicocoele correction were in order of decreasing importance: venous reflux extent assessed by scrotal duplex Doppler ultrasound examination, varicocoele clinical grade, basal semen parameters, and follicle-stimulating hormone. Male age did not influence postoperative semen quality. Only patients with continuous reflux had their standard semen parameters improved after surgery. DISCUSSION: Venous reflux extent is the most critical variable capable of predicting semen improvement after varicocoelectomy. CONCLUSIONS: A correct duplex Doppler assessment of venous reflux is mandatory for predicting postoperative improvement of the sperm count.

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BACKGROUND: Cysteine-rich secretory protein (CRISP-3), a protein involved in inflammatory response, is highly increased in seminal plasma of adolescents with varicocoele and altered semen analysis, but not in adolescents with varicocoele and normal semen. It is not known, however, whether this increased seminal concentration occurs as an acute marker during the initial stages of varicocoele or whether this persists as an altered protein pathway. OBJECTIVE: The purpose of this study, thus, was to test the hypothesis that this inflammatory state persists through adulthood and the correction of varicocoele could correct this state, by identifying the levels of CRISP-3 in seminal plasma. MATERIALS AND METHODS: This study was carried out in two substudies: (i) to verify the effect of varicocoele and (ii) to verify the effect of varicocelectomy on seminal plasma CRISP-3 levels. Seminal plasma CRISP-3 levels (29 and 31 kDa isoforms) were assessed for each provided sample using standard Western blotting. RESULTS: The varicocoele group presented higher seminal levels of CRISP-3 when compared to controls, with a 67.5-fold increase in the unglycosylated isoform (29 kDa) and a 5.2-fold increase in the glycosylated isoform (31 kDa). In contrast, CRISP-3 levels decreased following varicocelectomy, both in the unglycosylated (5.6-fold decrease) and in the glycosylated (4.3-fold decrease) isoforms. DISCUSSION: CRISP-3, a protein involved in inflammation, is increased in seminal plasma of men with varicocoele and this is partially reversed by varicocelectomy. Monitoring its seminal levels may be useful for assessing inflammation-related alterations to fertility in men with varicocoele. CONCLUSION: We conclude that, in the presence of varicocoele, there is a marked increase in seminal CRISP-3 levels. Surgical intervention (varicocelectomy) decreases CRISP-3 levels and improves semen quality.

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OBJECTIVES: To investigate whether micronutrients in support of the one-carbon cycle and glutathione synthesis are effective in improving sperm damage after surgical varicocoele induction in rats and whether any effect is achieved without a rebound reductive stress as seen with oral antioxidants. MATERIALS AND METHODS: Surgical varicocoele was induced in adult male Wistar rats and resulted in significant damage to the testis and sperm cells measured at 2 and 4 months after surgery. At 2 months after surgery, rats received a 2-month oral supplementation in support of the one-carbon cycle containing B vitamins (B2, B3, B6, folic acid and B12), N-acetyl-cysteine, zinc, small amounts of vitamin E, and a natural source of betalains and quercetine (Condensyl® ; Parthenogen SAGL, Lugano, Switzerland and Nurilia SARL, Lyon, France). RESULTS: One-carbon cycle supplementation, compared to untreated controls, significantly improved the morphometric characteristics of testis (P < 0.05), sperm concentration, motility and abnormal morphology (P < 0.001), sperm chromatin condensation (aniline blue staining, P < 0.05), sperm DNA damage (acridine orange staining, P < 0.05) and sperm lipid peroxidation (BODIPY C11, P < 0.001). The improvement in both nuclear condensation and DNA damage and the lack of excessive inhibition of lipid peroxidation confirmed that no reductive stress had occurred. CONCLUSIONS: Micronutrients in support of the one-carbon cycle are effective in the treatment of surgically induced varicocoele in rats, probably by activating natural antioxidant defences and epigenetics. These results support the idea that essential micronutrients including B vitamins may also have a positive influence in clinical varicocoele, which should be tested in prospective clinical trials.

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In a case-controlled study, we assessed the expressed seminal NAD-dependent protein deacetylase (SIRT1) expression in infertile oligoasthenoteratozoospermic (OAT) men associated with varicocoele. Our study involved 81 men, recruited from the University hospitals, after ethical approval and informed consent. They were allocated into fertile normozoospermic men (n = 23), infertile OAT men without varicocoele (n = 23) and infertile OAT men with varicocoele (n = 35). Inclusion criteria consisted of confirmation of abnormal semen parameters and normal female partners whereas exclusion criteria were leukocytospermia, tobacco smoking, hormonal therapy, immunological disorders, dyslipidemia, hypogonadism, cardiovascular disorders, morbid obesity, and hepatic or renal failures. All participants had an interview to assess clinical history, clinical examination, semen analysis, and estimation of seminal SIRT1 expression. Seminal SIRT1 expression was significantly lower in infertile OAT men than fertile men. Among infertile OAT men, seminal SIRT1 expression was significantly lower in those with varicocoele than in those without. Additionally, seminal SIRT1 expression was significantly lower in varicocoele grade III cases compared with other grades. Seminal SIRT1 expression was positively correlated with sperm concentration (r = 0.327, p = 0.001), total sperm motility (r = 0.532, p = 0.001), and sperm normal forms (r = 0.469, p = 0.001). Our results suggest that seminal SIRT1 expression has a role of male infertility being significantly decreased in infertile OAT men in general and in infertile OAT men associated with varicocoele in particular.

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