Assessment of seminal granulysin in infertile men with varicocele

Varicocele has a common association with male infertility, but its exact role is still debated. Apoptosis has been suggested as one of the mechanisms of varicocele‐associated infertility. Granulysin is a molecule that plays a role in apoptosis with no previous study about its role in male infertility. This case‐controlled study aimed to assess seminal plasma granulysin level in infertile patients with varicocele. This study involved 90 men that were allocated into fertile normozoospermic men (n = 20), infertile men without varicocele (n = 30) and infertile men with varicocele (n = 40). These men were subjected to history taking, clinical examination, semen analysis and estimation of seminal granulysin. In general, seminal granulysin level was significantly elevated in infertile men compared with fertile men. Infertile men with varicocele showed significantly higher seminal granulysin compared with infertile men without varicocele, in bilateral varicocele cases and in grade III varicocele. Seminal granulysin level was negatively correlated with sperm concentration, sperm motility, sperm normal forms percentage and testicular volumes. It is concluded that increased seminal granulysin has a negative impact on spermatogenesis in infertile men in general and in infertile men associated with varicocele in particular.     

Assessment of seminal YKL-40 in infertile men with varicocele

Several studies attempted to explain the negative impact of varicocele on spermatogenesis and fertilisation processes. YKL-40 is a novel glycoprotein biomarker that had been associated with several diseases. This quasi-interventional study aimed to assess the seminal levels of YKL-40 in infertile men with varicocele before and after varicocelectomy. Overall, 50 men were included in this study divided into 20 healthy fertile men and 30 infertile oligoasthenoteratozoospermic (OAT) men with varicocele that underwent varicocelectomy. All participants were subjected to history taking, clinical examination and scrotal Doppler. Also, semen analysis and seminal YKL-40 assessment were carried out in the start and 6 months after varicocele surgical repair. The results showed a significant increase in the mean seminal YKL-40 level in infertile OAT men with varicocele compared with the healthy fertile men. Six months post-varicocelectomy, the mean seminal KYL-40 level exhibited significant decreases correlated with improved sperm parameters. Overall, seminal levels of YKL-40 showed significant negative correlations with sperm concentration, total sperm motility and sperm normal morphology. It could be concluded that seminal YKL-40 is elevated in infertile OAT men with varicocele where varicocelectomy induces decreased seminal YKL-40 levels correlated with improved semen parameters.     

Assessment of seminal mast cells in infertile men with varicocele after surgical repair

This study aimed to assess seminal mast cells in infertile men associated with varicocele (Vx) pre‐ and post‐surgical repair. Forty‐five infertile men associated with Vx were subjected to history taking and clinical examination. In addition, semen parameters and seminal mast cells stained with 1% toluidine blue were estimated pre‐varicocelectomy and three months post‐varicocelectomy. Vx surgical repair revealed a significant improvement in the mean sperm concentration, progressive sperm motility, total sperm motility and sperm abnormal morphology and a significant decrement in seminal mast cells (mean ± SD, 3.56 ± 2.23 cells per high‐power field (HPF) vs. 2.22 ± 1.06 cells per HPF, p = .01). The pre‐operative mean mast cell count demonstrated significant increases in cases with Vx grade III compared with other Vx grades and in cases with bilateral Vx compared with unilateral Vx cases. Seminal mast cells demonstrated a significant correlation with sperm concentration, progressive sperm motility and total sperm motility and a nonsignificant correlation with age and sperm abnormal morphology. It is concluded that seminal mast cells decrease significantly in infertile men with Vx after surgical repair showing a significant negative correlation with sperm concentration, progressive sperm motility and total sperm motility.     

Varicocelectomy reduces reactive oxygen species levels and increases antioxidant activity of seminal plasma from infertile men with varicocele

Several theories have been advanced to explain the mechanisms by which varicocele impairs male fertility. These theories include scrotal hyperthermia, retrograde flow of adrenal or renal metabolites, Leydig cell dysfunction and hypoxia. Varicocele is reported to be associated with elevated reactive oxygen species (ROS) production in spermatozoa and diminished seminal plasma antioxidant activity. The aim of this study was to investigate whether surgical correction of varicocele might reduce ROS or increase the antioxidant capacity of seminal plasma from infertile patients with varicocele. The study group consisted of 68 infertile males, selected from patients scheduled for varicocelectomy at Cairo University Hospital during the year 1999. Seminal plasma levels of two ROS [malondialdehyde (MDA), hydrogen peroxide (H2O2)] and one ROS radical [nitric oxide (NO)] were estimated as well as six antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), vitamin C (Vit C), vitamin E (Vit E), albumin) on the day prior to varicocelectomy. For comparison, the same parameters were measured again 3 and 6 months post-operatively. A statistically significant reduction in the 3 month post-operative levels of MDA, H2O2 and NO was observed when compared with the pre-operative values. A further significant reduction took place during the following 3 months. Four of the six antioxidants tested (SOD, CAT, GPx, and Vit C) showed a significant increase in seminal levels when comparing 3-month post-operative with pre-operative values. A further significant increase of the four antioxidant levels took place during the following 3 months. No significant change in the level of seminal plasma albumen took place during the first 3 months after varicocelectomy, however, a significant increase was noted during the next 3 months. In contrast to other antioxidants, seminal plasma levels of Vit E showed a significant decrease when comparing 3-month post-operative with pre-operative values. A further significant decrease took place during the following 3 months. It is concluded that varicocelectomy reduces ROS levels and increases antioxidant activity of seminal plasma from infertile men with varicocele.     

Relationship between seminal ascorbic acid and sperm DNA integrity in infertile men

Ascorbic acid has recently been reported to protect sperm DNA from the damage induced by exogenous oxidative stress in vitro. But, there is no report on seminal ascorbic acid and sperm DNA fragmentation in infertile men. In this study, we asked whether sperm DNA damage correlates with seminal ascorbic acid levels. Sperm DNA fragmentation index (DFI) was analysed in 75 men by flow cytometry after acridine orange staining. We also measured the levels of seminal plasma ascorbic acid and total antioxidant capacity. Abnormal sperm DNA integrity (DFI >or= 30%) was observed in 12% of the patients with normal semen parameters and in 52% of the patients with abnormal semen parameters. There were significant correlations between the level of DFI and conventional semen parameters including sperm count, motility and morphology (r = -0.29, -0.55 and -0.53 respectively; p < 0.05). Seminal ascorbic acid level was significantly lower in the patients with leucospermia than the patient with normal semen parameters. Interestingly, a significantly greater percentage of men with abnormal DFI were observed in the patients with low levels of seminal ascorbic acid compared with those with normal or high levels of ascorbic acid (59% vs. 33%, p < 0.05). Men with insufficient seminal ascorbic acid frequently have sperm DNA damage.     

Seminal cyclooxygenase relationship with oxidative stress in infertile oligoasthenoteratozoospermic men with varicocele

This study aimed to assess the relation of seminal cyclooxygenase COX‐1, COX‐2 with oxidative stress in infertile oligoasthenoteratozoospermic (OAT) men with varicocele (Vx). In all, 128 men were allocated into fertile men, fertile men with Vx, infertile OAT men without Vx and infertile OAT men with Vx. They were subjected to history taking, clinical examination and semen analysis. Also, seminal COX‐1, COX‐2, malondialdehyde (MDA) and glutathione peroxidase (GPx) were estimated. Mean levels of seminal COX‐1, COX‐2 were over‐expressed, the mean level of seminal MDA was significantly increased, and the mean level of seminal GPx was significantly decreased in infertile OAT men with Vx compared with other groups. Seminal COX‐1 and COX‐2 were over‐expressed in cases with Vx grade III compared with Vx grades I, II cases and in cases with bilateral Vx compared with unilateral Vx. There was significant negative correlation between seminal COX‐1 and COX‐2 with sperm concentration, sperm motility, sperm normal morphology, seminal GPx and significant positive correlation with seminal MDA. It is concluded that seminal COX‐1 and COX‐2 are over‐expressed in infertile OAT men with Vx compared with fertile men with/without and infertile OAT men without Vx being associated with oxidative stress, Vx grade and Vx laterality.     

精索静脉曲张不育患者的精浆生化分析

目的 探讨精索静脉曲张不育患者精浆中酸性磷酸酶、果糖、锌和α-糖苷酶水平的变化.方法 分别检测120例精索静脉曲张不育患者、180例非精索静脉曲张不育患者和36例正常男性的精浆中酸性磷酸酶、果糖、锌和α-糖苷酶含量.结果 精索静脉曲张不育组和非精索静脉曲张不育组精浆中酸性磷酸酶含量均显著低于正常对照组（P＜0.01）,但精索静脉曲张不育组和非精索静脉曲张不育组之间的差异无显著性意义（P＞0.05）;各组精浆果糖活性无显著性差异（P＞0.05）;精浆中锌和α-糖苷酶含量随精索静脉曲张程度的增加而降低,且明显低于正常对照组（P＜0.05）,但与非精索静脉曲张不育组之间的差异无显著性意义（P＞0.05）.结论 精索静脉曲张可通过某些因素引起精浆中酸性磷酸酶、锌和α-糖苷酶含量降低,从而造成男性不育.     

Significance of malondialdehyde concentration in seminal plasma of infertile men

Objective: To determine the concentration of malondialdehyde (MDA), product of lipid peroxidation, in seminal plasma and evalu ate its significance. Methods: Ninety-three cases of infertile pa tients were divided into the obstructive azoospermic (12 cases), the non-obstructive azoospermic (15 cases), the oligozoospermic (21 cases), the asthenozoospermic (19 cases), the oligoastheno zoospermic (16 cases) and the oligoasthenoteratozoospermic (10) groups. Eighteen fertile males served as the controls. MDA con centration was assessed by high-performance liquid chromatogra phy (HPLC). Results: With the exception of the obstructive azoospermic group, the MDA concentration in the seminal plasma was significantly different between the control group and the infer tile groups (P<0.01) as well as between the different infertile groups. Conclusion: Determination of MDA concentration in the seminal plasma is helpful to the diagnosis of male infertility induced by overproduction of reactive oxygen species.     

低位显微外科与腹腔镜两种精索静脉结扎术治疗精索静脉曲张性不育疗效比较

目的 比较低位显微外科与腹腔镜精索静脉结扎术治疗精索静脉曲张性不育患者的疗效.方法 40例精索静脉曲张性不育患者,随机分为两组,低位显微外科精索静脉结扎术组(A组,20例)和腹腔镜精索静脉结扎术组(B组,20例),比较术前、术后第1、6、12月的精液质量,并且追踪术后2年内配偶临床妊娠结果.结果 两组术后精子密度、精子总数和(a+b)级精子数均较术前有显著提高(P<0.05),但组内术后第1、6、12月的精液质量各主要参数间对比,无统计学差异(P>0.05).组间术前、术后第1、6、12月精液质量各主要参数进行对比,无统计学差异(P>0.05).术后随访2年配偶临床妊娠A组为13例(65%),B组为12例(60%).结论 低位显微外科精索静脉结扎术对精索静脉曲张(VC)伴有男性不育患者是一种经济、简单、有效、便于推广的手术治疗方式.     

Prediction of reproductive function recovery after microsurgical varicocelectomy in men from infertile couples: Clinical and laboratory predictors

The objective was to reveal predictors for fertility recovery after varicocelectomy in subfertile men. This retrospective study recruited 93 men with clinical varicocele and pathozoospermia who underwent microsurgical varicocelectomy. Stepwise discriminant analysis was performed to identify predictors of spontaneous pregnancy (SP) after surgery. ‘Clinically significant improvement’ (CSI) following varicocelectomy was defined as an increase in total progressively motile sperm count (TPMSC) by at least 12.5 million (calculated from WHO-2010 reference values). 52% of patients showed CSI, and 28% reported SP after surgery. Patients who reported SP (group II), compared to that remained infertile (group I), were younger (27.3 ± 2.9 versus 30.2 ± 4.2 years; p < .01), had less infertility period (24.1 ± 14.0 versus 44.4 ± 32.9 months; p < .05) and had initially higher TPMSC (median (25% −75%) = 34 (11–67) versus 9.5 (0–33) mln; p < .05). The stepwise discriminant analysis showed that male age (coefficient value = −0.157), total sperm motility (0.024) and postoperative increase in TPMSC (0.010) were the significant predictors of SP. The predictive ability, sensitivity and specificity of the discriminant function were 84%, 87%, 76% respectively. This algorithm can be recommended after varicocelectomy in decision-making on natural conception or the ART protocols usage.     

Seminal SIRT1-oxidative stress relationship in infertile oligoasthenoteratozoospermic men with varicocele after its surgical repair

This work assessed seminal SIRT1-oxidative stress (OS) relationship in infertile oligoasthenoteratozoospermic (OAT) men after varicocele repair. Overall, thirty OAT men with varicocele were investigated. Inclusion criteria were infertile males (males who were unable to initiate a pregnancy within 1 year of regular unprotected intercourse), confirmed OAT and normal female factor. These cases were subjected to history taking, clinical checkup and semen analysis. In their semen, seminal SIRT1, malondialdehyde (MDA) and glutathione peroxidase (GPx) levels were assessed. These men were subjected to varicocele surgical repair and were followed up for 3 months. Post-operatively, the mean seminal SIRT1, GPx levels showed significant increases and the mean MDA level showed significant decrease compared to the pre-operative levels linked to improved sperm parameters. The mean seminal SIRT1, GPx, MDA levels showed more significant improvement in grade III varicocele cases compared to grade II cases after surgical repair. Seminal SIRT1 levels showed significant positive correlations with sperm concentration, sperm motility, sperm normal morphology, seminal GPx levels and a significant negative correlation with seminal MDA levels. It could be concluded that seminal SIRT1 is significantly decreased in infertile OAT men with varicocele after its surgical repair linked to improved sperm parameters as well as seminal OS.     

Clomiphene citrate versus varicocelectomy in treatment of subclinical varicocele: A prospective randomized study

BACKGROUND: The purpose of the study was to compare the effect of varicocelectomy with that of clomiphene citrate on seminal improvement and pregnancy rates in patients with subclinical varicocele. METHODS: A total of 42 infertile men with left subclinical varicocele were randomized to group I (21 patients, surgery) and group II (21 patients, medical therapy). The patients in group I were treated with varicocelectomy and those in group II with clomiphene citrate, 50 mg/day, orally. Sperm parameters (sperm density, motility and morphology) were recorded before and 6 months after beginning the treatment and pregnancy rates were estimated. In statistical analysis, paired and independent-samples t-tests, Kaplan-Meier and Log rank tests and Fisher's exact test were used. RESULTS: Mean +/- SD age of the series was 32.7 +/- 6.1 years, that of group I was 32.2 +/- 5.5 years and that of group II was 33.1 +/- 6.7 years (P = 0.680). All seminal parameters increased after both surgical and medical treatment, but only increases in sperm density and motility following varicocelectomy were statistically significant. Changes in seminal parameters between groups I and II were statistically insignificant. Pregnancy was seen in two cases in group I and in one in group II (P = 0.500). The cumulative pregnancy rates were 12.5% in group I and 6.7% in group II (P = 0.589). CONCLUSIONS: Clomiphene citrate did not increase sperm density and motility as effectively as subclinical varicocelectomy, but there was no statistically significant difference between surgical and medical therapy methods in terms of seminal improvement and pregnancy rate.     

Proteomic profile of seminal plasma in adolescents and adults with treated and untreated varicocele

Varicocele, the most important treatable cause of male infertility, is present in 15% of adult males, 35% of men with primary infertility, and 80% of men with secondary infertility. On the other hand, 80% of these men will not present infertility. Therefore, there is a need to differentiate a varicocele that is exerting a deleterious effect that is treatable from a “silent” varicocele. Despite the growing evidence of the cellular effects of varicocele, its underlying molecular mechanisms are still eluding. Proteomics has become a promising area to determine the reproductive biology of semen as well as to improve diagnosis of male infertility. This review aims to discuss the state-of-art in seminal plasma proteomics in patients with varicocele to discuss the challenges in undertaking these studies, as well as the future outlook derived from the growing body of evidence on the seminal proteome.     

Seminal plasma oxytocin and oxidative stress levels in infertile men with varicocele

This study aimed to assess seminal plasma oxytocin (OT) and oxidative stress (OS) levels in infertile men with varicocele (Vx). A total of 131 men were divided into fertile men (n = 20), fertile men with Vx (n = 17), infertile men without Vx (n = 40) and infertile men with Vx (n = 54). OT, malondialdehyde (MDA) and glutathione peroxidase (GPx) were estimated in seminal plasma. Mean levels of seminal OT, MDA were significantly decreased, and the mean level of GPx was significantly increased in fertile men with/without Vx compared with infertile men with/without Vx. Mean levels of OT, MDA were increased, and mean level of GPx was significantly decreased in Vx grade III cases compared with Vx grades I, II cases and in bilateral Vx cases compared with unilateral Vx. There was significant negative correlation between seminal OT with sperm count, sperm motility, seminal GPx and significant positive correlation with sperm abnormal forms, seminal MDA. It is concluded that seminal OT is significantly decreased in fertile men with/without Vx compared with infertile men with/without Vx. Seminal OT demonstrated significant negative correlation with sperm count, sperm motility, seminal GPx and significant positive correlation with sperm abnormal forms, seminal MDA. Seminal OT is associated with Vx grade and its bilaterality.     

Bilateral is superior to unilateral varicocelectomy in infertile men with bilateral varicocele: Systematic review and meta‐analysis

To investigate whether bilateral surgery can bring more benefits to infertile patients with bilateral varicocele than unilateral surgery. A search of PubMed, Web of Science, EMBASE and the Cochrane Library on 13 January 2019 was conducted to identify studies published in English that used varicocelectomy. The protocol of the present meta‐analysis was pre‐published on PROSPERO (registration number CRD42019093894). Primary outcomes were spontaneous pregnancy rates. A total of eleven articles were finally enrolled in, with a total of 1,743 patients. Spontaneous pregnancy rate was higher in patient with bilateral varicocelectomy than unilateral varicocelectomy with an odds ratio (OR) of 1.89 (95% CI 1.52–2.35; I² = 0%; p < .00001). The results indicated bilateral is superior than unilateral varicocelectomy concerning sperm concentration (SMD: 2.88 × 10⁶/ml; 95% CI: 1.06, 4.70; I² = 93%), sperm motility (SMD: 5.08; 95% CI: 2.65, 7.50; I² = 0%), progression of sperm motility (SMD: 6.48; 95% CI: 5.16, 7.81; I² = 0%) and sperm morphology (SMD: 2.38%; 95% CI: 0.72, 4.03; I² = 94%) between bilateral and unilateral varicocelectomy. Bilateral varicocelectomy may be superior to unilateral in regard to spontaneous pregnancy rate and sperm motility for infertile male with bilateral varicocele (both left clinical and right subclinical varicocele and bilateral clinical varicocele).     

Coenzyme Q10 supplementation in infertile men with low‐grade varicocele: an open,uncontrolled pilot study

Many conditions associated with male infertility are inducers of oxidative stress, including varicocele. Antioxidants, such as coenzyme Q10, may be useful in this case. To evaluate the antioxidant capacity of seminal plasma of infertile men with varicocele before and after an oral supplementation with coenzyme Q₁₀, 38 patients were recruited from a pilot clinical trial. A standard semen analysis was also performed at baseline and 3 months after an oral supplementation with exogenous coenzyme Q₁₀ 100 mg per die. Seminal plasma antioxidant capacity was measured using a spectroscopic method. Coenzyme Q₁₀ therapy improved semen parameters and antioxidant status. This study highlights the importance of oxidative stress in the pathogenesis of male infertility, namely in varicocele, and strengthens the possibility of the usefulness of the antioxidant therapy.     

Oxidative stress markers in seminal plasma of idiopathic infertile men may be associated with glutathione S-transferase M1 and T1 null genotypes

This study aimed to investigate the association between glutathione S-transferase (GST) M1 and T1 null genotypes and thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC) and nitric oxide (NO) levels in male infertility. For this purpose, semen samples were collected from fertile and infertile subjects, and then they were genotyped for GSTT1 and GSTM1 genes using multiplex-PCR. The TBARS, TAC and NO levels in seminal plasma were then measured via the ferric-reducing ability of plasma (FRAP). A significant association was observed between GSTT1 null genotype and oligozoospermia, asthenozoospermia and teratozoospermia. But, the GSTM1 null genotype was merely associated with teratozoospermia. Moreover, the GSTT1−/GSTM1+ combined genotype was associated with all subgroups of male infertility. Besides, an association was observed between GSTT1−/GSTM1− genotype and asthenozoospermia and teratozoospermia. Further analysis showed that the GSTT1 null genotype was associated with increased NO in asthenozoospermia. Also, the GSTT1 null genotype was associated with increased TBARS in oligozoospermia and asthenozoospermia. As well, GSTM1 null genotype was associated with decreased TAC and increased NO in asthenozoospermia respectively. As a preliminary conclusion, the GSTM1 and GSTT1 null genotypes could be considered as genetic risk factors for male infertility, interfering with some oxidative stress markers in infertile men.     

Five mm laparoscopic varicocelectomy versus conventional varicocele ligation in young men with symptomatic varicocele: A randomized clinical study

ObjectivesTo compare the therapeutic success, morbidity and the costs of 5 mm laparoscopic varicocele ligation (LV) compared to inguinal varicocelectomy (IV).Patients and methodsEighty patients with idiopathic symptomatic varicocele of grades I–III diagnosed by clinical examination and Doppler ultrasonography were randomly assigned to LV or IV (40 patients in each group). The mean patient age was 25.2 ± 1.4 (range 18–40) years. Of the 80 patients treated 21.3% had a left-sided varicocele, 70% had bilateral varicoceles and 8.8% a right-sided varicocele. Of 136 varicoceles, 37 (27.2%) were grade III, 51 (37.5%) grade II and 48 (35.3%) were grade I. The indications for varicocele ligation were: abnormal spermiogram in 47 patients (58.7%), scrotal pain in 19 (23.8%) and cosmetic impairment in 14 (17.5%). A total of 136 varicocele ligations were performed (67 IV and 69 LV). All patients were followed up for 4–8 months to assess early complications, testicular size, late complications and persistence or recurrence of the varicocele.ResultsLV was associated with shorter operative time, shorter hospital stay and lower cost compared to IV. The overall incidence of postoperative complications including hydrocele, epididymitis and local pain was significantly higher among patients undergoing IV compared with LV (17.5% vs 5%). The incidence of persistent varicoceles was not significantly different between the 2 groups, but the varicocele recurrence rate was significantly lower in the LV compared to the IV group (5% vs. 17.5%, p ≤ 0.02).ConclusionsLV is a less invasive treatment than IV for managing male varicoceles. It is also associated with lower costs and better outcomes and should therefore be the preferred method of treatment for male varicoceles.     

Inflammatory and anti‐inflammatory cytokines in the seminal plasma of infertile men suffering from varicocele

Varicocele is one of causes of the declined sperm quality and low sperm production, which can lead to infertility in males. There are several experimental and epidemiological findings which support the idea that inflammatory mechanisms play an essential role in varicocele pathogenesis. Besides, in this pathological state, interleukin‐37 (IL‐37) as an anti‐inflammatory cytokine is able to bind interleukin‐18‐binding protein (IL‐18BP), and subsequently binds IL‐18 receptor β, inhibiting the pro‐inflammatory activity of IL‐18. To explore the interaction between IL‐37 and IL‐18 in infertility, we measured the amount of these cytokines in the seminal fluid of infertile men affected by varicocele. The seminal plasma levels of IL‐37 and IL‐18 were measured in 75 infertile men with varicocele and 75 healthy fertile controls (age range, 30–48 years) using enzyme‐linked immunosorbent assay. The seminal levels of IL‐37 and IL‐18 were significantly increased in infertile men with varicocele when compared to fertile controls (p < .0001). Because of the essential role(s) of cytokines in inflammatory response of cell systems, it could be possible that sperm motility is reduced following increased IL‐18, activated neutrophils and reactive oxygen species in semen of infertile patients with varicocele. Moreover, the results of this study indicated that interaction between IL‐37 and IL‐18Rβ can lead to reduced inflammatory responses. It seems that IL‐37 might be a potential biomarker and therapeutic target for male infertility.     

Evaluation of sperm DNA fragmentation index,Zinc concentration and seminal parameters from infertile men with varicocele

The aim of this study was to investigate the effect of varicocele on DNA fragmentation index (DFI), zinc concentration and seminal parameters in infertile patients. In this prospective study, 179 men with at least 1‐year history of infertility and varicocele were examined for semen quality at Hanoi Medical University Hospital (HMUH), Hanoi, Vietnam. In addition, an inverse correlation between zinc concentration and the degree of sperm DNA fragmentation in patients with clinical varicocele was found. The difference in mean values of sperm DNA fragmentation index in patients with various grades of varicoceles can be neglected, whereas most patients with varicocele of grades II and III had DFI >30%. Varicocele is associated with high levels of DNA damage in spermatozoa and reduced zinc levels that correlate with different grades of disease. Therefore, DNA fragmentation index and zinc concentration can be used as essential additional diagnostic test for patients with clinical varicocele. A study should be conducted to evaluate the benefits of zinc supplementation to improve seminal parameters in patients with varicocele.