Percutaneous treatment of varicocele

Varicocele is a common finding in adolescents and adult men. Its association with male infertility has been well documented: varicoceles are reported to be present in 20-40% of infertile men. It has been demonstrated that varicocele correction leads to an improvement in the quality of semen in most cases. Percutaneous sclerotherapy is an established treatment method for varicocele performed on an outpatient basis. In our report we review our experience with venographic study and transcatheter sclerotherapy based on 560 cases of infertile patients with varicocele. Our study confirms that percutaneous therapy of varicocele may lead to improved spermatogenesis in the majority of patients.     

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.     

Spermatozoa protein alterations in infertile men with bilateral varicocele

Among infertile men, a diagnosis of unilateral varicocele is made in 90% of varicocele cases and bilateral in the remaining varicocele cases. However, there are reports of under-diagnosis of bilateral varicocele among infertile men and that its prevalence is greater than 10%. In this prospective study, we aimed to examine the differentially expressed proteins (DEP) extracted from spermatozoa cells of patients with bilateral varicocele and fertile donors. Subjects consisted of 17 men diagnosed with bilateral varicocele and 10 proven fertile men as healthy controls. Using the LTQ-orbitrap elite hybrid mass spectrometry system, proteomic analysis was done on pooled samples from 3 patients with bilateral varicocele and 5 fertile men. From these samples, 73 DEP were identified of which 58 proteins were differentially expressed, with 7 proteins unique to the bilateral varicocele group and 8 proteins to the fertile control group. Majority of the DEPs were observed to be associated with metabolic processes, stress responses, oxidoreductase activity, enzyme regulation, and immune system processes. Seven DEP were involved in sperm function such as capacitation, motility, and sperm-zona binding. Proteins TEKT3 and TCP11 were validated by Western blot analysis and may serve as potential biomarkers for bilateral varicocele. In this study, we have demonstrated for the first time the presence of DEP and identified proteins with distinct reproductive functions which are altered in infertile men with bilateral varicocele. Functional proteomic profiling provides insight into the mechanistic implications of bilateral varicocele-associated male infertility.     

Chromosomal abnormalities and y chromosome microdeletions in infertile men with varicocele and idiopathic infertility of South Indian origin

Various factors cause spermatogenesis arrest in men and, in a large number of cases, the underlying reason still remains unknown. Little attention is paid to determining the genetic defects of varicocele-related infertility. The objective of our present study was to investigate the chromosomal abnormalities and Y chromosome microdeletions in infertile men of South Indian origin with varicocele and idiopathic infertility. Metaphase chromosomes of 251 infertile men with varicocele and unexplained infertility were analyzed using Giemsa-Trypsin-Giemsa (GTG) banding and fluorescence in situ hybridization (FISH). The microdeletions in 6 genes and 18 sequence-tagged-sites (STS) in the Yq region were screened using polymerase chain reaction (PCR) techniques. Out of 251 infertile men, 57 (22.7%) men were with varicocele, of which 8.77% were azoospermic, 26.31% were severely oligozoospermic, 21.05% were mildly oligozoospermic, and 43.85% were oligoasthenoteratozoospermic (OAT), and 194 (77.29%), with idiopathic infertility, of which 51% were azoospermic, 13.40% were severely oligozoospermic, 19.07% were mildly oligozoospermic, and 16.4% were with OAT. Genetic defects were observed in 38 (15.13%) infertile individuals, including 14 (24.56%) men with varicocele and 24 (12.37%) men with idiopathic infertility. The frequencies of chromosomal defects in varicocele and idiopathic infertility were 19.3% and 8.76%, respectively, whereas Y chromosome microdeletions were 5.26% and 3.60%, respectively. Overall rate of incidence of chromosomal anomalies and microdeletions in 251 infertile men were 11.5% and 3.98%, respectively, indicating a very significant higher association of genetic defects with varicocele than idiopathic male infertility. Our data also demonstrate that, among infertile men with varicocele, severely oligozoospermic and OAT men with varicocele have higher incidences of genetic defects than mildly oligozoospermic and azoospermic men.     

Effect of varicocele on chromatin condensation and DNA integrity of ejaculated spermatozoa using cytochemical tests

Varicocele occurs in approximately 15% to 20% of the general male population and it is the most common cause of poor semen production and decreased semen quality. It has been demonstrated that patients with varicocele have a significantly higher DNA fragmentation index (DFI) and spermatozoa with nuclear anomalies than healthy fertile men. Therefore, the aim of this study was to evaluate sperm chromatin integrity in these patients. Sixty men referring to the andrology laboratory were categorised into three different groups: 20 infertile men with varicocele, 20 infertile men with abnormal semen parameters and 20 fertile men who had normal spermatogram were considered as control group. Semen analysis was performed according to WHO criteria. To evaluate sperm chromatin quality and DNA integrity, after fixation of sperm smears, aniline blue, toluidine blue, chromomycin A₃ and acridine orange staining were applied in three groups. The slides were analysed by light and fluorescent microscopy and to determine the percentage of mature or immature spermatozoa, 200 spermatozoa were counted in each slide. The results showed that the rates of aniline blue-reacted spermatozoa were significantly higher in infertile and varicocele patients than in the normal group ( P  < 0.001). In addition, with regard to chromomycin A₃, acridine orange and toluidine blue staining, there was a significant difference between the three groups ( P  < 0.001). The results showed that the varicocele samples contain a higher proportion of spermatozoa with abnormal DNA and immature chromatin than those from fertile men as well as infertile men without varicocele. Therefore, varicocele results in the production of spermatozoa with less condensed chromatin and this is one of the possible causes of infertility due to varicocele.     

Does treatment of varicocele improve male fertility? Results of the ‘Deutsche Varikozelenstudie’, a multicentre study of 14 collaborating centres

Treatment of varicocele is suggested in infertile men if sperm parameter values are abnormal. The effectiveness of the treatment with respect to fertility remains to be clarified. A multicentre, prospective randomized study on varicocele treatment in infertile men to demonstrate the superiority of sclerotization of the varicocele in preventing persistence, was started in 1995 with the collaboration of 15 German andrological centres. The primary endpoint was the incidence of pregnancy 1 year after randomisation. The number of cases needed to achieve the goal of the study was calculated at 460. However, three years after starting the study, only 67 patients had been randomized. Different reasons contributed to the poor recruitment. There was no significant increase in pregnancy rate in the treated group, compared to the controls, the confidence interval being 20.8% to 15.7%. The authors would like to encourage further collaborative study groups to start another prospective, randomized study with the aim of avoiding the costs and risks of varicocele treatment when its success remains unclear.     

VARICOCELE IS ASSOCIATED WITH ELEVATED SPERMATOZOAL REACTIVE OXYGEN SPECIES PRODUCTION AND DIMINISHED SEMINAL PLASMA ANTIOXIDANT CAPACITY

PURPOSE: Because varicocele is seen often in infertile men and oxidative stress has been implicated in sperm dysfunction, we assessed spermatozoal reactive oxygen species and seminal total antioxidant capacity in men with and without varicocele. MATERIALS AND METHODS: Levels of reactive oxygen species and total antioxidant capacity were measured in the semen of 21 infertile men with varicocele, 15 men with incidential varicocele and 17 normal donors without varicocele (controls). Men with leukocytospermia (more than 1 x 10(6) white blood cells per ml.) were excluded from study. Reactive oxygen species were measured in washed spermatozoa with a luminol dependent chemiluminescence assay. Total seminal antioxidant capacity was measured with an enhanced chemiluminescence assay, and the results were expressed as trolox equivalents. Sperm characteristics were assessed with a computer assisted semen analyzer, and sperm morphology was assessed using World Health Organization and Kruger's strict criteria. RESULTS: Patients with varicocele had significantly higher reactive oxygen species levels than controls (p = 0.02). Reactive oxygen species levels did not differ significantly between infertile and men with incidental varicocele. Total antioxidant levels were significantly lower among men with varicocele (p = 0.02) and those with incidental varicocele compared to controls (p = 0.05). Reactive oxygen species and total antioxidant capacity levels did not correlate in any group. CONCLUSIONS: Our results suggest that elevated reactive oxygen species and depressed total antioxidant capacity levels are associated with varicocele. These changes may be related to functional sperm abnormalities and infertility seen commonly in these patients. These findings support a possible rationale for controlled clinical trials of antioxidant supplementation in infertile men with varicocele.     

Antispermatozoal antibody values after varicocelectomy

Although there are many causes of the production of antispermatozoal antibodies, there are still unknown aetiological factors. Antispermatozoal antibodies were investigated in the postoperative period in 25 infertile men with varicocele whose antispermatozoal antibody tests were negative in the preoperative period. Antispermatozoal antibodies were found in the serum in 4 of the 25 (16%) infertile men after varicocele operation. Postoperative genital infections were detected in 6 patients and antispermatozoal antibodies were present in only 2 of them. The correlation between these antibodies and varicocele has been demonstrated but there is no report on the association of antibodies with varicocelectomy in the literature to date.     

Y chromosome microdeletions and varicocele as aetiological factors of male infertility: A cross‐sectional study

The pathogenic mechanisms by which varicocele disrupt spermatogenesis are not clearly understood. Over 30% of male infertility cases resulting from spermatogenic problems are associated with genetic abnormalities, and Y chromosome microdeletions are the second most frequent genetic cause. Here, we aimed to evaluate the frequency of Y chromosome microdeletion in infertile men with varicocele. A cross‐sectional study comprising 51 infertile men with varicocele presenting spermatogenesis failures was performed. Y chromosome microdeletion research was made using polymerase chain reaction. Of the 51 men with infertility and varicocele, 35.3% (18/51) had nonobstructive azoospermia and 64.7% had severe oligozoospermia. Y chromosome microdeletion was found in two cases (3.9%): one patient had nonobstructive azoospermia and complete microdeletion of the AZFb and AZFc regions, and another patient had severe oligozoospermia and complete microdeletion of the AZFc region. Although in recent years, a genetic aetiology related to Y chromosome microdeletions has become a major cause of infertility in males with spermatogenesis failures, in this study, the varicocele was the clinical cause of seminal abnormalities that could lead to infertility, suggesting that both varicocele and Y chromosome microdeletion aetiologies can present, alone or combined, as factors of male infertility.     

生殖道支原体感染与精索静脉曲张不育关系的探讨

为研究精索静脉曲张男性不育症中生殖道感染因素，对５９０例患精索静脉曲张（曲张组）和３３５例无精索静脉曲张（对照组）的男性不育患者进行了精液解脲支原体（ＵＵ）的培养研究。结果表明：ＵＵ总感染率为４８．２２％。曲张组中生殖道ＵＵ感染率高达５５．７６％，而对照组ＵＵ感染率为３４．９３％，两组间有高度显著性差异（Ｐ〈０．００５）。曲张组精子活力低下者明显增多，而精液分析正常者明显减少。认为精索静脉曲张的存     

Scrotal ultrasound in the infertile man: detection of subclinical unilateral and bilateral varicoceles

Clinical and laboratory studies have provided convincing evidence that varicoceles are detrimental to spermatogenesis and that this effect is unrelated to their size. Thus, physicians have used diagnostic techniques other than physical examination to find these small but clinically significant varicoceles. Because scrotal sonography has proved to be invaluable to detect many intrascrotal abnormalities, and has the unique ability to visualize the testicle and surrounding structures, we used it to evaluate 50 infertile men. Of our 50 patients 22 had a clinically palpable left varicocele and 3 additional patients had bilateral varicoceles. All clinical varicoceles were confirmed by sonography. However, sonography also demonstrated a left varicocele in an additional 12 patients (34 of 50 or 68 per cent) and a right varicocele in 21 (a total of 24 or 48 per cent). Reflux on the right side always occurred in conjunction with that on the left side. Thus, among our 50 infertile men 24 of 34 (70 per cent) had bilateral varicoceles as detected by sonography, and 12 of 50 (24 per cent) had a subclinical varicocele on the left side. The high percentage of bilateral varicoceles detected by sonography may explain the pathophysiological mechanism by which what formerly was considered a unilateral anatomical abnormality may produce bilateral testicular dysfunction. It also may challenge us to change our present unilateral surgical approach to the patient with a clinically evident left varicocele.     

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.     

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.     

精子染色质扩散实验检测精索静脉曲张及不明原因不育患者精子DNA碎片

目的了解精索静脉曲张(VC)及不明原因不育患者精子DNA碎片的发生比例。方法改进的精子染色质扩散(SCD)实验分析精子DNA碎片。检测VC不育患者39例,不明原因不育患者57例。以生育健康成年男性32例为对照组。结果VC不育患者SCD小光晕和无光晕精子(精子DNA碎片)比值平均为(36.6±18.9)%,VC不育组明显高于对照组(12.1±5.2)%(P<0.001),而大光晕和中光晕精子比值VC不育组明显低于对照组(P<0.01);不明原因不育患者精子DNA碎片比值平均为(26.8±10.2)%,与对照组[(12.1±5.2)%]比较有显著性差异(P<0.001)。结论SCD实验表明,VC及不明原因不育患者精子DNA碎片比值增高。     

Decrease of topoisomerase I activity in the testes of infertile men with varicocele

Topoisomerase I, which is involved in DNA metabolism, was measured in the testes of 37 infertile men with varicocele, using a minute amount of testicular biopsy specimen. In 38% of infertile men topoisomerase I activity was lower than that of normal men. Forty-six percent of patients with high grade varicocele (grade III) showed reduced topoisomerase I activity, while only 26% of patients with low grade varicocele (grades I and II) showed reduced levels of topoisomerase I. Johnsen's score of the patients with low topoisomerase I activity was lower than that of patients with normal levels of topoisomerase I. The decrease of topoisomerase I activity may be correlated with at least some fraction of hypospermatogenesis associated with varicocele.     

Soluble Fibrinogen-like protein 2 plays a role in varicocele induced male infertility

Varicocele is the most common cause of male infertility. Several theories have been proposed to explain how varicocele induces infertility. The role of epididymis in male infertility is not fully well established. Fibrinogen-like protein 2 is one of serine proteases and is a potent coagulant in membranous form and immune-modulator in soluble form (sFGL-2) and expressed in the epididymis. There are no previous reports about its possible role in varicocele. This case-controlled study aimed to evaluate the seminal level of sFGL-2 in infertile men with varicocele and in men with idiopathic infertility. This study included 85 participants divided into three groups; 25 normal fertile men, 30 infertile men with varicocele and 30 infertile men of idiopathic cause. Clinical examination, Doppler ultrasound, semen analysis and measurement of seminal level of sFGL-2 were done to all participants. Seminal level of sFGL-2 was significantly elevated in infertile than normal fertile men. Seminal level of sFGL-2 showed negative correlations with sperm concentration, motility and normal morphology. Seminal level of sFGL-2 had a positive correlation with seminal liquefaction time. This study concluded that seminal level of sFGL-2 is increased in infertile men with idiopathic cause and with varicocele induced infertility and affects seminal liquefaction.     

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.     

Thiol–disulphide homoeostasis as an oxidative stress marker in men with varicocele

Oxidative stress is the most common factor leading to infertility in men with varicocele. Reactive oxygen species and other markers of oxidative stress are measured to predict the extent of oxidative stress. Thiol groups are important antioxidants and essential molecules protecting organism against the harmful effects of reactive oxygen species. Thiol–disulphide homoeostasis is a unique, easy and new method to demonstrate oxidative stress. The aim of this study was to determine thiol–disulphide homoeostasis as an oxidative stress marker in infertile men with varicocele. The hormonal profile and parameters of thiol–disulphide homoeostasis were studied in 46 infertile men with varicocele, 70 fertile men with varicocele and 37 fertile controls. Infertile men with varicocele had significantly higher disulphide concentrations and disulphide/native thiol, disulphide/total thiol and native/total thiol ratios than those of fertile men with varicocele and fertile controls. According to these results, the blood plasma of patients with varicocele contains excessive oxidative stress, even in men with normospermia, and therefore, thiol–disulphide homoeostasis may be useful as an oxidative stress marker in men with varicocele.     

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.     

精索静脉曲张不育与微量元素锌和镉关系的研究

本研究应用原子吸收光谱法 (AAS)测定 18例精索静脉曲张 (VC)不育患者和 14例正常生育的斜疝和或鞘膜积液患者外周静脉血、精索静脉血、精浆中的锌 (Zn)和镉 (Cd)的含量。结果表明 :精索静脉曲张不育患者精静脉血和精浆中Cd含量较对照组明显增高 (P <0 .0 1)、而精浆中的Zn含量较对照组明显减低 (P <0 .0 1)。此外 ,其精索静脉血和精浆中Cd/Zn比值与对照组也有显著性差异 (P <0 .0 1)。提示Cd的增高可能是导致精索静脉曲张不育的原因之一