Antegrade scrotal sclerotherapy of internal spermatic veins for varicocele treatment: technique,complications, and results

Varicocele repair is mainly indicated in young adult patients with clinical palpable varicocele and abnormal semen parameters. Varicocele treatment is associated with a significant improvement in sperm concentration, motility, morphology, and pregnancy rate. Antegrade scrotal sclerotherapy (ASS) represented one of the main alternatives to the traditional inguinal or suprainguinal surgical ligation. This article reviews the use of ASS for varicocele treatment. We provide a brief overview of the history of the procedure and present our methods used in ASS. In addition, we review complication and success of ASS, including our own retrospective data of treating 674 patients over the last 17 years. Herein, we analyzed step by step the ASS technique and described our results with an original modified technique with a long follow-up. Between December 1997 and December 2014, we performed 674 ASS. Mean operative time was 14 min (range 9 to 50 min). No significant intraoperative complications were reported. Within 90 days from the procedure, postoperative complications were recorded in overall 49 (7.2%) patients. No major complications were recorded. A persistent/recurrent varicocele was detected in 40 (5.9%) cases. In 32/40 (80%) cases, patients showed preoperative grade III varicoceles. In patients with a low sperm number before surgery, sperm count improved from 13 × 10⁶ to 21 × 10⁶ ml⁻¹ (P < 0.001). The median value of the percentage of progressive motile forms at 1 h improved from 25% to 45% (P < 0.001). Percentage of normal forms increased from 17% before surgery to 35% 1 year after the procedure (P < 0.001). In the subgroup of the 168 infertile patients, 52 (31%) fathered offspring at a 12-month-minimum follow-up. Therefore, ASS is an effective minimal invasive treatment for varicocele with low recurrence/persistence rate.     

Radiologically assessed testicular changes in infertile males with varicocele

The aim of this study was to assess vascular disturbances in the testis of infertile males associated with varicocele. In total, 124 consecutive male subjects were divided into the following groups: healthy fertile controls (n = 10), Gp1 (n = 28); infertile males with subclinical varicocele, Gp2 (n = 26); infertile males with grade I left varicocele, Gp3 (n = 28); infertile males with grade II left varicocele and Gp4 (n = 32); infertile males with grade III left varicocele. They were subjected to colour duplex for pampiniform plexus and scrotal scintigraphy. There was significant decrease in arterial blood velocity, testicular arterial diameters and testicular perfusion especially in high grade varicocele compared with healthy controls. The mean vein diameter demonstrated significant negative correlation with arterial diameter, arterial blood velocity, perfusion index, testicular size and significant positive correlation with perfusion index. The mean testicular size demonstrated significant positive correlation with arterial blood velocity, perfusion index and nonsignificant correlation with arterial diameter. It is concluded that there are significant decreases in testicular volume, testicular perfusion, blood velocity and testicular artery diameter in infertile males with varicocele.     

A rare cause of infertility: intratesticular varicocele associated with ipsilateral extratesticular varicocele

Intratesticular varicocele is an uncommon condition with variable sonographic appearence and identified as dilated intratesticular veins lying from the mediastinum through testicular parenchyma. We present a case of a 20‐year‐old male, married and unable to conceive for 2 years. Routine scrotal sonography disclosed extratesticular varicocele which was associated with ipsilateral intratesticular varicocele. Colour Doppler ultrasonography should be the first choice modality of imaging to confirm the diagnosis. Detection of intratesticular varicocele is essential because it is one of the most common recoverable reasons of male infertility.     

Age is a significant predictor of early and late improvement in semen parameters after microsurgical varicocele repair

Accumulating evidence indicates that varicocele repair improves sperm quality. However, longitudinal changes in sperm parameters and predictors of improved semen characteristics after surgery have not been fully investigated. We retrospectively reviewed data from 100 men who underwent microsurgical subinguinal varicocele repair at a single centre. Follow‐up semen examinations were carried out at 3, 6 and 12 months post‐operatively. Logistic regression was used to identify predictors of early (3 months) and late (≥6 months) improvement in semen parameters after varicocele repair. At 3 months post‐operatively, 76.1% of the patients had improved total motile sperm counts, which continued to improve significantly up to 12 months post‐operatively (p = .016). When comparing changes in semen parameters between younger (<37 years) and older (≥37 years) men, post‐operative improvements in sperm concentration and motility were greater among younger men. Multivariate analysis showed that younger age was associated with early (p = .043) and late (p = .010) post‐operative improvement in total motile sperm count. Our findings indicate that early varicocele repair improved semen parameters after surgery.     

Preserved testicular artery at varicocele repair

Whether or not varicocele causes infertility is a contentiously debated issue. This study aimed to compare semen parameters and pregnancy rate in infertile males who underwent varicocelectomy with preserved or accidentally ligated testicular artery. Ninety-five infertile oligoasthenozoospermic patients with left-sided varicocele were subjected to subinguinal varicocelectomy with trial of preserving testicular artery. According to absence or presence of testicular artery in the histological excised pedicle the cases were divided into two groups; group 1 ( n  = 60) with preserved testicular artery and group 2 ( n  = 35) where the artery was accidentally ligated being not defined or injured. Semen analysis was carried out after 4, 8 and 12 months and post-operative pregnancy rate was assessed after 1 year. Serum follicle-stimulating hormone (FSH), luteinising hormone (LH) and total testosterone (T) were estimated pre- and post-operatively. Semen parameters (total sperm count, sperm concentration and sperm motility) showed significant increase post-operatively compared with pre-operative parameters but were comparable in both groups with no significant difference. Serum FSH, LH, T hormones and pregnancy rate (23.3% versus 22.9%) 1 year post-operatively showed no significant difference. It is concluded that accidental ligation of testicular artery has no deleterious effect on semen parameters during primary varicocele repair if the testicular arterial supply was not compromised.     

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.     

ACP1 genetic polymorphism and spermatic parameters in men with varicocele

Platelet‐derived growth factor (PDGF) and its receptors (PDGFRs) play a key role in the regulation of the embryonic and postnatal development of male gonads. PDGF deficiency is associated with severe spermatogenic impairment. ACP₁ is a phosphoprotein tyrosine phosphatase that is able to dephosphorylate PDGFR, decreasing its activity as growth factor. The enzyme is polymorphic and shows strong differences in enzymatic activity among genotypes. At the Outpatient Department for Infertility, University of Rome La Sapienza, we investigated the effect of high‐activity ACP₁ genotype on spermatic parameters in 105 subjects referred to for varicocele. ACP₁ genotype was determined by DNA analysis. In ACP₁ *B/*C genotype, which shows the highest enzymatic activity, spermatic concentration is significantly lower and atypical spermatozoa are significantly more frequent as compared to other ACP₁ genotypes. It is concluded that subjects carrying *B/*C genotype who represent about 10% of the population have a severe impairment of spermatic parameters in the presence of varicocele.     

Sonographic quantitative evaluation of scrotal veins in healthy subjects: normative values and implications for the diagnosis of varicocele

OBJECTIVES: To define the normative values of scrotal vein diameters, investigate the eventual presence and characteristics of scrotal reflux in healthy subjects, and describe its implication for the diagnosis of scrotal varicocele. METHODS: Color-Doppler ultrasonography was performed on a population of 145 healthy, symptomless subjects, with clinical examinations and semen analyses within normal limits. RESULTS: The upper limit of the scrotal veins diameter (3.7-3.8mm) exceeds values presently employed for a diagnosis of varicocele. Furthermore, a high percentage of healthy subjects (53%) were found to have reflux in the scrotal veins, currently considered one of the criteria for diagnosing varicocele, especially in its subclinical form. CONCLUSIONS: To reduce the risk of misinterpretations between the various specialists involved in Color-Doppler ultrasonography and urologists, quantitative data of the scrotal veins (i.e., maximum diameter and the presence, velocity, and duration of reflux) should be described in reports of sonographic examinations performed for scrotal varicocele.     

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.     

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.     

Varicocele sclerotherapy improves serum inhibin B levels and seminal parameters

The usefulness of treating varicocele in order to improve fertility is still a matter of debate. The aim of this study was to evaluate variations in seminal parameters and inhibin B concentrations in a group of males affected by varicocele and treated by percutaneous retrograde sclerotherapy in comparison with a group of patients who did not undergo varicocele treatment. Thirty-eight patients with left varicocele underwent spermatic vein phlebography and percutaneous retrograde sclerotherapy with hydroxy-polyaethoxy-dodecanol. Serum inhibin B, follicle-stimulating hormone (FSH), testosterone levels and seminal parameters (sperm concentration, motility and morphology) were performed before and 6 months after sclerotherapy. Forty patients with left varicocele who did not undergo sclerotherapy were studied as controls. A significant increase (p < 0.01) in serum inhibin B levels and a significant decrease (p < 0.05) in FSH levels were observed 6 months after treatment. Semen analysis showed a significant improvement in sperm concentration (p < 0.05) and progressive motility (p < 0.01) after treatment. In control group no significant variations in hormonal and seminal parameters were observed 6 months after the basal examination. Six months after the basal evaluation, inhibin B levels were significantly higher in treated subjects than in controls (p < 0.05) whereas FSH levels were significantly lower (p < 0.05). Sperm concentration and progressive motility were significantly increased (p < 0.05 and p < 0.001, respectively) in treated subjects in comparison with controls. In conclusion, varicocele sclerotherapy improves inhibin B levels and seminal parameters, confirming the positive effect of this treatment on spermatogenesis and Sertoli cell function.     

Seminal reactive oxygen species‐antioxidant relationship in fertile males with and without varicocele

The aim of this study was to assess seminal reactive oxygen species (ROS)‐antioxidants relationship in fertile and infertile men with and without varicocele. One hundred and seventy six males were studied; fertile healthy volunteers (n = 45), fertile men with varicocele (n = 45), infertile oligoasthenozoospermia (OA, n = 44) without varicocele and infertile OA with varicocele (n = 42). In their seminal plasma, two ROS parameters (malondialdehyde, hydrogen peroxide) and five antioxidants (superoxide dismutase, catalase, glutathione peroxidase, vitaminE, vitaminC) were estimated. Compared with fertile healthy men, in all other studied groups, estimated seminal ROS were significantly higher and estimated antioxidants were significantly lower. Infertile men with varicocele showed the same relationship as infertile men without varicocele. Sperm concentration, total sperm motility as well as sperm normal forms were negatively correlated with seminal malondialdehyde and were positively correlated with vitaminC. It is concluded that varicocele has an oxidative stress (OS) in fertile normozoospermic bearing conditions. This may allow understanding that, within men with varicocele, there is a threshold value of OS over which male fertility may be impaired.     

Semen and reproductive hormone parameters in fertile men with and without varicocele

Although varicoceles are a widely accepted identifiable male factor in infertile couples, the benefit of varicocele repair in improving pregnancy and live birth rates remains uncertain. The Study for Future Families obtained semen and reproductive hormone samples from US men whose partners were currently pregnant. In our analysis cohort of 709 men, a varicocele was detected by clinical examination in 56 (8%) of men. Men with varicocele had smaller left testis, and lower total and total motile sperm counts than men without varicocele. Gonadotropin levels were higher as well in men with varicocele. Interestingly, testosterone levels were also slightly higher in men with varicocele. Despite these differences, there was no difference between the groups in the time to achieve the study pregnancy or percentage of men with a previous pregnancy. We conclude that even in fertile men, varicoceles are associated with some degree of testicular hypofunction. This would support current recommendations to consider varicocele repair in male partners in infertile couples who demonstrate both a varicocele and abnormal semen parameters and after evaluation for treatable female factors.     

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.     

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.     

转流术与断流术治疗精索静脉曲张症的疗效评价

目的　为评价精索静脉转流术与结扎术二种手术方法对治疗精索静脉曲张引起男性不育的疗效。方法　于术后一年中分别随访 82例病人 ,接受转流者 47例 ,结扎者 35例。结果　 (1)术后病人症状、精子质量均得到显著改善 ,但是 ,两组间无明显差异 (P >0 .0 5 )。 (2 ) 15例有症状者术后缓解 ,47例转流受术者无一复发 ,35例结扎受术者 2例复发 ,占 5 .7%。两者精子质量改善者共 47例 ,占 5 8.5 3% ,妊娠及分娩 2 5例 ,占 30 .5 %。 (3)术后 3月 ,精子活力提高明显好于精子质量的其它参数 ,而在术后半月中 ,精子活力的提高转流者 2 7例 ,结扎者仅 7例。结论　精索内静脉转流术仍是部分精索静脉曲张不育症者治疗的较好手段     

精索静脉曲张超声分型与手术前后精液质量变化对比研究

目的:探讨精索静脉曲张(VC)的超声分型对手术前后精液质量改善的影响。方法:经彩色多普勒超声(CDU)诊断为VC患者共129例,以蔓状静脉丛(PPV)反流程度、PPV最大内径、PPV最大内径和反流程度3种不同分级指标分为VCⅠ级、VCⅡ级、VCⅢ级,所有患者均行精索静脉高位结扎,术前及术后均行精液常规检查。结果:以PPV的最大内径为分级标准,术前术后精液质量VCⅠ级、VCⅡ级无明显改变(P>0.05),VCⅢ级较术前有显著改变(P<0.05),以PPV的反流程度或以PPV的最大内径和反流程度为分级标准,术前术后精液质量VCⅠ级无显著差异(P>0.05),VCⅡ级有显著差异(P<0.05),VCⅢ级有极显著差异(P<0.01)。精子的畸形率各级组间均无显著差异(P>0.05)。结论:不同的分级标准对手术前后精液质量改善的评价有一定的影响,以PPV的反流程度或以PPV的最大内径和反流程度为分级标准更为合理、可靠。不同曲张等级VC手术效果不同,CDU诊断为VCⅠ级患者是否必要行手术治疗有待进一步探讨。     

Heme oxygenase enzyme activity in seminal plasma of oligoasthenoteratozoospermic males with varicocele

This work aimed to assess seminal plasma heme oxygenase (HO) enzyme activity in oligoasthenoteratozoospermia (OAT) males with varicocele. Ninety‐three men were divided according to their sperm count and clinical examination into: healthy fertile controls (n = 34), OAT without varicocele (n = 37) and OAT associated with varicocele (n = 22). They were subjected to semen analysis and estimation of seminal plasma HO enzyme activity in the form of bilirubin concentration. Seminal plasma HO enzyme activity decreased significantly in OAT cases compared with controls. Seminal plasma HO in OAT cases associated with varicocele decreased significantly compared with OAT cases without varicocele and healthy controls (mean ± SD; 109.2 ± 29.5, 283.6 ± 88.4, 669.5 ± 236.1 nMol bilirubin/mg ptn/min, P < 0.001). There was positive correlation between seminal plasma HO enzyme activity and sperm concentration, per cent of motile spermatozoa, number of motile spermatozoas ml^?1 and significant negative correlation with sperm abnormal forms per cent. It is concluded that varicocele has a negative impact on seminal HO enzyme activity. Therefore, improved seminal picture after correcting varicocele repair might be related, in part, to improved HO action(s).     

Comparison between thermography and venous scintigraphy of the scrotum in the diagnosis of varicocele

Fifty-one consecutive infertile men were examined for the presence of (sub)clinical varicocele with both scrotal thermography and venous radionuclide scintigraphy. Venous scintigraphy with 99^mTC yielded false negative results in about half of the patients suspected of varicocele because of clinical findings and/or abnormal scrotal thermography. Venous scintigraphy cannot serve as an alternative for scrotal thermography for the detection of spermatic venous reflux in varicocele.     

Obstruction of the tubuli recti and ductuli efferentes by dilated veins in the testes of men with varicocele and its possible role in causing atrophy of the seminiferous tubules

Hormone measurements, spermiograms and testicular biopsies studies were performed in young with varicocele. In addition, the testes and epididymides of 27 adults with varicocele were obtained from autopsies. Light and electron microscopic examination of biopsy and autopsy specimens revealed two types of lesions in testes with varicocele: 1) a diffuse lesion consisting of abnormal spermatozoa and spermatid morphology and sloughing of immature spermatozoa and spermatid; 2) focal lesion, distributed irregularly throughout the testicular parenchyma, affecting several small groups of seminiferous tubules. Each of these groups corresponded to a testicular lobule and showed different degrees of tubular atrophy, so that the focal lesions were distributed in a mosaic pattern. The testicular interstitium showed dilated veins and venules, and progressive collagenization. Some testes showed dilated veins in the rete testis, which compressed several tubuli recti and caused tubular atrophy in the seminiferous tubules opening into these tubuli recti. Other testes showed dilated young veins among the ductuli efferentes, and the rete testis channels appeared to be dilated. Among the different etiological mechanisms which have been suggested to for testicular lesions in varicocele, tubular obstruction at the level of either the tubuli recti or the ductuli efferentes might be responsible for lesions leading to testicular atrophy.