精索静脉曲张不育患者的精液常规、精子动态参数和精浆生化指标分析

目的观察精索静脉曲张（VC）伴不育患者的精液质量和精浆生化水平的变化。方法利用计算机辅助精液分析系统（CASA）及酶免法分别检测52例VC不育患者、85例非精索静脉曲张不育患者和21例正常生育男性的精液常规、精子动态参数以及精浆酸性磷酸酶、精浆锌（Zn）、果糖、α-糖苷酶的含量。结果与对照组相比,VC组患者A级精子率、（A＋B）级精子率、精子直线速度（VSL）、直线性（LIN）、侧摆幅度（ALH）、精浆锌含量、α-糖苷酶的含量与对照组相比显著下降（P〈0.05）。与非VC不育组相比,VC不育组（A＋B）级精子率、精子直线速度（VSL）、侧摆幅度（ALH）、精浆锌含量、α-糖苷酶的含量也明显降低（P〈0.05）。并且随着精索静脉曲张程度的增加,VC患者A级精子率、（A＋B）级精子率、精子曲线速度VCL、直线速度VSL、直线性LIN、平均路径速度VAP、前向性STR、侧摆幅度ALH、精浆中锌含量、α-糖苷酶的含量有下降趋势。结论 VC能够降低精子活动率、精子动态活动能力以及改变了精浆微环境,从而导致男性生育力下降。     

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.     

Effect of spermatic vein ligation on seminal total antioxidant capacity in terms of varicocele grading

We aimed to assess the effect of spermatic vein ligation on seminal total antioxidant capacity (TAC) in patients with varicocele. Twenty infertile male patients with varicocele and 20 normal fertile men (control group) were included in the study. All the male patients were diagnosed with primary infertility and varicocele. The patients with varicocele were divided into two groups as nonpalpable (GI) (eight patients) and palpable (GII-III) (12 patients) varicocele groups. All the patients underwent microsurgical spermatic vein ligation. Seminal TAC levels and sperm parameters were evaluated in all the patients. Preoperative sperm count, sperm motility, sperm morphology and seminal TAC levels with equivalent figures 3-6 months after spermatic vein ligation and the same values of the control group were compared. There was a statistically significant increase in the total seminal antioxidant capacity level after spermatic vein ligation, and there was a statistically significant increase in the sperm count, sperm motility and spermatozoa with normal morphology. However, evaluation of the patients for varicocele grade showed a statistically significant increase in the TAC level only in the GII-III varicocele group. Spermatic vein ligation can improve the total seminal antioxidant capacity levels especially in patients with middle and high grade varicocele.     

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.     

alpha-1,4-Glucosidase activity in infertile oligoasthenozoospermic men with and without varicocele

This work aimed to assess seminal alpha-1,4-glucosidase activity in infertile oligoasthenozoospermic men associated with and without scrotal varicocele. Eighty men were investigated. They were divided into three groups: group 1 (n = 20), fertile normozoospermic men; group 2 (n = 30), oligoasthenozoospermia with varicocele; and group 3 (n = 30), oligoasthenozoospermia without varicocele. The patients underwent medical history, clinical examination, conventional semen analysis and estimation of seminal plasma alpha-1,4-glucosidase activity by double-beam spectrophotometer method and serum testosterone by radioimmunoassay method. There was a significant decrease in the mean seminal alpha-1,4-glucosidase activity levels in infertile men versus controls (mean +/- SD; 7.66 +/- 0.433, 2.088 +/- 0.565, 5.384 +/- 0.85 mU ml(-1) respectively). Mean serum testosterone levels demonstrated nonsignificant differences between studied groups. Seminal alpha-1,4-glucosidase activity levels demonstrated significant correlation with sperm count, sperm motility percentage and serum testosterone in oligoasthenozoospermia with varicocele group and demonstrated nonsignificant correlation in other groups. It is concluded that varicocele-induced hypoxia is the adverse effect that causes both oligoasthenozoospermia and decreased seminal alpha-1,4-glucosidase levels.     

The assessment of oxidative stress in infertile patients with varicocele

OBJECTIVES

To assess oxidative stress markers, antioxidant capacity and cytokines in seminal plasma from infertile patients with varicocele, and to investigate seminal oxidative status and sperm DNA damage after varicocelectomy.

PATIENTS, SUBJECTS AND METHODS

The records were retrospectively evaluated for 28 azoospermic, 30 oligospermic (15 with varicocele and 15 without) and 30 patients with normal semen characteristics (15 with varicocele and 15 without). The mean (sd ) age of the men was 32.4 (5.6) years; all men with varicocele had a unilateral or bilateral microsurgical subinguinal varicocelectomy. The level of nitric oxide (NO), 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), hexanoyl‐lysine (HEL), superoxide dismutase (SOD) activity, interleukin (IL)‐6, IL‐8 and tumour necrosis factor‐α in seminal plasma were measured. In addition, sperm DNA fragmentation was analysed before and 6 months after varicocelectomy.

RESULTS

Azoospermic and oligospermic patients had a significantly higher HEL concentration and SOD activity in seminal plasma; those with varicocele had a significantly higher NO, HEL, and SOD activity in seminal plasma. There was a significant increase in sperm concentration and reduction in NO, HEL, 8‐OHdG level and SOD activity after varicocelectomy. Oligospermic patients with varicocele had a significantly higher IL‐6 level in seminal plasma, and there was a significant reduction after varicocelectomy. The percentage of apoptosis‐positive sperm decreased significantly after varicocelectomy.

CONCLUSIONS

This study indicates that the seminal plasma of patients with varicocele is under excessive oxidative stress, and partly even in patients with normospermia, and that varicocelectomy reduces oxidative stress in seminal plasma and ameliorates sperm DNA damage.     

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.     

Seminal Tumour necrosis factor‐related apoptosis‐inducing ligand and its relationship to infertility in Egyptian patients with varicocele

Germ cell apoptosis has been proposed as one of the mechanisms by which varicocele can influence fertility. The aim of this study was to investigate the relationship between seminal tumour necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) levels and male infertility in patients with varicocele. This study included 112 males: 30 fertile males with varicocele, 44 infertile males with varicocele and 38 healthy fertile control subjects without varicocele. Semen analysis was performed, and serum levels of reproductive hormones were measured. Seminal TRAIL levels in the infertile varicocele group were significantly higher than in the fertile varicocele and the control groups (P = 0.014). A significant negative correlation was found between seminal TRAIL and progressive (P < 0.001) and total motility scores (P < 0.001) in the infertile varicocele group. A significant negative correlation was also detected between seminal TRAIL levels and normal sperm morphology in the fertile varicocele (P = 0.007) and infertile varicocele patients (P = 0.047). Seminal TRAIL was significantly correlated with varicocele grade whether the patients were fertile (P = 0.001) or infertile (P = 0.035). Seminal TRAIL may thus have a potential role in varicocele‐associated male infertility through its negative effect on sperm motility and morphology.     

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.     

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.     

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.     

Morphology of spermatozoa in infertile men with and without varicocele

This study was carried out to evaluate the morphology of spermatozoa in infertile men with and without varicocele. A series of 285 ejaculates were fully evaluated for seminal volume, sperm count, motility, and morphology, and classified into fertile (165 subjects), infertile without varicocele (93 subjects) and infertile with varicocele (27 subjects). Sperm morphology was classified by multiple entry criteria and recorded as normal, abnormal with head, midpiece, or tail single anomaly or abnormal with simultaneous multiple abnormalities. Semen volume was almost identical in the three groups. Among the infertile men, sperm count was lower in those having a varicocele, but conversely those with varicocele had a higher percentage of motile spermatozoa, higher percentage of spermatozoa with forward movement and higher sperm velocity. There were higher proportions of spermatozoa with abnormal morphology, total number of anomalies, and multiple anomalies in infertile men, both with and without varicocele, than in fertile men. The percentage of abnormal spermatozoa was higher in infertile men with varicocele than in those without varicocele. The pattern of sperm morphology differed between the infertile and the fertile group, and with the presence or absence of varicocele. In the presence of varicocele, only the incidence of elongated (tapered) forms was significantly increased.     

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.     

Effect of low-dose androgen and zinc sulfate on sperm motility and seminal zinc levels in infertile men

Beneficial effects of zinc therapy in some infertile patients with low seminal zinc concentrations and decreased sperm motility have been reported recently. The effects of zinc therapy, low-dose (5-10 mg/day) androgen therapy, and combination therapy of both zinc and low-dose androgen, on sperm motility and seminal zinc concentration were studied in patients referred to the andrology clinic. Low-dose androgen therapy increased seminal zinc concentrations and sperm motility, only when pretreatment seminal zinc concentrations were low. Furthermore, patients with low seminal zinc concentrations and poor sperm motility showed greater improvement of sperm motility and seminal zinc levels in response to zinc sulfate with fluoxymesterone than did fluoxymesterone alone or zinc sulfate alone, possible due to a synergistic effect of zinc and androgen.     

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.     

The relationship between varicocele and semen nitric oxide concentrations

We investigated the relationship between seminal plasma nitric oxide (NO) concentrations and conventional semen parameters in patients with varicocele. Semen samples were obtained from infertile patients with varicocele (n=55) and from normal controls (n=48). The mean NO concentration in the seminal plasma of patients with varicocele was significantly higher than that of the controls (P < 0.01). A significant negative correlation was noted between NO and sperm motility (r=−0.29, P=0.003), NO and sperm concentration (r=−0.26, P=0.008) and NO and normal morphology (normal %) (r=−0.25, P=0.01). It was concluded that increased NO production may influence sperm production, motility and morphology in patients with varicocele. Received: 21 February 2000 / Accepted: 20 June 2000     

精索静脉曲张不育患者的精液质量和精子形态学观察

目的:观察不育伴精索静脉曲张(VC)患者的精液质量和精子形态学变化。方法:98例不育伴VC患者精液按WHO标准常规分析并对精子形态学进行评价。130例正常供精者精液检测结果作为对照。结果:VC患者正常形态精子和前向运动精子明显低于对照组(P<0.001),精子畸形的类型以梨形、锥形和不定型头部畸形为主。结论:VC可导致精子畸形率升高,后者可能是男性生育力受损的重要标志之一,经染色后的精子形态学分析是判定VC患者精子受损的一个敏感指标。     

The varicocele: New experimental and clinical data

Numerous reports have shown that serotonin (5-HT) has a detrimental effect on spermatogenesis and androgen synthesis. Serotonin has two mechanisms of action on the testicle: (1) vasoconstrictive changes possibly causing premature sloughing of spermatozoa, and (2) alteration of androgen metabolism. The data in our animals with the experimental varicocele clearly mimic the human situation. All seminal parameters except volume are decreased after the varicocele is created. In many infertile patients with a varicocele, serotonin may be the inciting factor which results in subfertile semen. This is corroborated by the presence of elevated serotonin levels in spermatic vein plasma of most patients with a varicocele who undergo surgery. More data, comparing the relationship between spermatic vein and peripheral blood serotonin levels in patients with and without a varicocele, are needed. This investigation is being pursued in patients undergoing inguinal surgery for other lesions.     

The taurine and hypotaurine content of human semen.

Taurine and hypotaurine levels were measured in human sperm and seminal fluid. Sperm taurine ranged from 17 nmol/mg DNA to 348 nmol/mg DNA, and hypotaurine from 0 nmol/mg DNA to 251 nmol/mg DNA. Seminal fluid contained 319 mumol/L to 1590 mumol/L of taurine, but no detectable hypotaurine. The coefficient of variation in multiple ejaculates from a single man for these components ranged from 12% for hypotaurine to 24% for seminal fluid taurine, indicating a relative constancy in their concentrations. Sperm hypotaurine content was significantly correlated with sperm morphology, sperm relative forward progression, the percentage of motile sperm, and the total number of sperm in the ejaculate. By contrast, sperm taurine content was negatively correlated with these parameters. The mean hypotaurine content of sperm from 8 fertile men was 149 +/- 92 nmol/mg DNA, four times higher than that of sperm from 9 infertile men, which was 35 +/- 19 nmol/mg DNA (P = 0.011). In contrast, the mean sperm taurine content of the fertile men was lower than that of the infertile men (83 +/- 33 nmol/mg DNA versus 168 +/- 119 nmol/mg DNA, respectively; P = 0.07). Seminal fluid taurine concentrations, however, were similar for both groups. Hypotaurine, an antioxidant, may play an important role in protecting sperm from reactive oxygen species. Higher concentrations of taurine in the sperm of infertile men suggest that accelerated oxidation of hypotaurine to taurine may accompany the observed decline in other sperm parameters.     

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.