Testicular function in varicocele

Testicular testosterone concentration serum testosterone, LH and FSH, sperm count and testicular histology were evaluated in 17 patients with varicocele. Testicular testosterone was either normal or high (mean 906 +/- 723 ng/g of tissue), and serum testosterone was within the normal range in most patients. Serum LH was elevated in half of the patients. The degree of testicular damage observed was extremely variable and correlated with sperm analysis. Testicular testosterone tended to be higher in patients with severe microscopic lesions of the testis. It is concluded that even though Leydig cell function is partially altered, this deficiency is compensated by LH stimulation and therefore, failure of spermatogenesis is not secondary to low testosterone levels.     

Testicular volume assessment in the adolescent with a varicocele.

Testicular growth arrest is the main criterion for performing varicocele ligation in the adolescent population. Previous assessments concerning significant size discrepancy range from 0.5 to 5 cm.3, a 10-fold difference. We prospectively assessed testicular size in 22 male adolescents (ages 9 to 19 years) with varicoceles, and compared testicular volume as measured by ultrasound and Prader orchidometer in 19 of these patients. The accuracy of ultrasound for this purpose was evaluated by blinded ultrasonic measurements of models of known volume and a standard deviation of +/- 1.6 cm.3 was found. Using a size discrepancy of greater than 2 cm.3 as the criterion for growth arrest, 4 of 17 patients (24%) with growth arrest would have been missed with the Prader orchidometer alone. Testicular volumetric assessment by ultrasound accurately measured volumetric differences of greater than 2 cm.3 and can be used to determine growth arrest in the male adolescent with a varicocele.     

Testicular tumors in men with human immunodeficiency virus.

During a 2-year period 5 men positive for the human immunodeficiency virus (HIV) presented with 6 testis tumors among a total of 3,015 men seen at our hospital acquired immunodeficiency syndrome (AIDS) clinic. This testis tumor incidence of 0.2% is 57 times that of the United States average of 3.5 cases per 100,000 men. Two patients were only HIV positive and 3 others already had AIDS-related complex for 2 to 15 months at the time of tumor diagnosis. Tumor histology was mixed germ cell tumor in 4 patients, pure seminoma in 1 and Burkitt's lymphoma in 1. Patients underwent routine staging evaluations. Three patients had low stage mixed germ cell tumor (clinical stage 1 or 2A) and underwent retroperitoneal lymphadenectomy, which revealed pathological stage 1 or 2A disease in 1 and 2, respectively. These patients did not receive adjuvant chemotherapy. Two patients had advanced mixed germ cell tumor (clinical stage 2C) or Burkitt's lymphoma (clinical stage 4) and received combination chemotherapy from the onset. Outcome was evaluated with regard to progression of HIV disease and tumor status. The 2 patients who were only HIV positive remained so for 9 and 48 months. The 3 patients with AIDS-related complex had progression to AIDS within 1 to 9 months and 2 of these patients died 1 1/2 and 7 months after tumor diagnosis. All 3 patients with resected low stage disease had tumor recurrence within 1 to 9 months and were begun on platinum-based combination chemotherapy. The risk of false low clinical staging and early tumor progression may be higher in HIV positive men than in other testis tumor patients. Patient ability to tolerate chemotherapy and to obtain a satisfactory tumor response appeared to be primarily related to lack of progression of HIV disease to frank AIDS.     

Testicular biopsies in 101 cases of varicocele

Testicular biopsies were done on 101 patients who underwent ligation of the internal spermatic vein as primary treatment for infertility. Retrospective analysis included evaluation of tubular thickening, Leydig cell hyperplasia, premature sloughing, maturation arrest and decreased spermatogenesis. A comparison was made of biopsy profiles, sperm counts and pregnancies in an attempt to determine further the value of testicular biopsy in the subfertile man. The pregnancy rate was 40 per cent over-all, with 32 per cent of the patients with tubular thickening reporting pregnancies. There was only 1 pregnancy in patients with Leydig cell hyperplasia. The controversial finding of premature sloughing had no consistent relationship to results.     

Testicular oxidative stress. Effects of experimental varicocele in adolescent rats

OBJECTIVE: This present study was undertaken to determine the levels of malondialdehyde (MDA), nitric oxide (NO) and total antioxidant status (TAS) in testes of adolescent rats with experimental bilateral varicocele and to determine the effects of oxidative stress on testis produced by varicocele. METHODS: 6-week-old, male Wistar rats, weighing 146-334 g (228.37 +/- 41.34 g), were randomly allocated into two groups. The first group underwent selective and bilateral partial ligation of the spermatic vein (n = 28), and the second group underwent a sham operation and served as the controls (n = 15). Animals were sacrificed 12 weeks after surgery and dilatation of the spermatic veins was observed in the first study group. Bilateral orchiectomy was performed in all rats, and MDA, NO and TAS levels were measured. RESULTS: In the study group, the mean MDA (SEM) level was 15.58 +/- 6.07 micromol/g protein, and in the control group, it was 11.59 +/- 3.86 micromol/g protein, respectively; this difference was statistically significant (p < 0.05). The mean NO level was 82.73 +/- 77.84 nmol/g protein in the study group, whereas 28.65 +/- 20.18 nmol/g protein in the control group, this difference was also statistically significant (p < 0.005). The mean TAS levels of the study and control groups were 0.91 +/- 0.32 and 1.78 +/- 0.46 nmol/g tissue, respectively, and this difference was also statistically significant (p < 0.001). But there was no correlation between these three parameters (MDA<-->TAS: r = -0.103, p > 0.05; MDA<-->NO: r = -0.104, p > 0.05; NO<-->TAS: r = -0.123, p > 0.05). CONCLUSION: These findings suggest that varicocele may change the testicular oxidative status and may play a role in testicular dysfunction that causes infertility.     

Histological lesions in the testis of infertile men with varicocele.

Varicocele frequently causes male infertility and histological lesions at the contralateral testis. The most frequent lesions found in this study included maturation arrest in the spermatidic phase, cellular and acellular thickening of the tubular wall, and degeneration of the Leydig cells. These lesions were typical of varicocele and their simultaneous presence suggests that scrotal temperature and modified endocrine secretion of the interstitial testis play a role in the pathogenesis of this type of infertility.     

Testicular arterial perfusion in varicocele: the role of rapid sequence scintigraphy with technetium in varicocele evaluation

Rapid sequence scintigraphy was used to study testicular arterial perfusion and venous stasis in 53 patients with varicocele-associated infertility, 17 with idiopathic testicular failure and 9 treated for varicocele. Arterial blood supply to the diseased testicle was decreased in 63 per cent of the patients with subclinical or low grade varicocele compared to 18 per cent with idiopathic testicular failure. In the majority of cases the disturbance of perfusion disappeared immediately after interruption of retrograde blood flow in the internal spermatic vein by transcatheter embolization, whereas persistently impaired perfusion was found in a few cases with no improvement of semen quality after treatment. Venous stasis was found in only 18 per cent of the patients with low grade varicocele compared to 88 per cent with large varicoceles. It is suggested that impaired arterial blood supply rather than venous stasis is the pathogenic factor in epididymo-testicular dysfunction associated with low grade varicocele.     

Testicular hypotrophy does not correlate with grade of adolescent varicocele

PURPOSE: Testicular hypotrophy is the most widely accepted indication for correcting adolescent varicocele. Previous studies in adolescents have shown a relationship between increasing grade of varicocele and the likelihood of testicular hypotrophy. As this relationship has significant clinical implications, we studied the correlation between grade and testicular volume disproportion in our adolescent varicocele population. MATERIALS AND METHODS: We reviewed the adolescent varicocele database at our institution. A total of 168 patients 8 to 21 years old were studied. We routinely calculated testis volumes using scrotal ultrasound. Testicular disproportion was calculated using the equation [(size of unaffected testis) - (size of affected testis)]/(size of unaffected testis) x 100%. Disproportion was categorized as less than 10%, 10% to 20% and more than 20%. Varicoceles were graded by an attending urologist with the patient standing, using the system of Dubin and Amelar. Analysis of variance and Pearson chi-square indicated no significant differences in volume differential between varicocele grades. RESULTS: Mean +/- SD volume differential was 18% +/- 15% for grade I, 25% +/- 20% for grade II and 19% +/- 14% for grade III. ANOVA revealed no significant difference in mean volume differential between the 3 varicocele grades (p = 0.10). When categorizing patients into 3 levels of volume differential (less than 10%, 10% to 20%, more than 20%) no significant correlation was observed between varicocele and volume differential (p = 0.48, chi-square test). CONCLUSIONS: Grade of varicocele does not correlate with presence or severity of testicular disproportion in adolescent boys with varicocele as measured by scrotal ultrasound.     

Left spermatic vein cortisol in subfertile men with varicocele

Varicocele is one of a number of well-documented causes of male subfertility. In patients undergoing varicocelectomy high success rates are achieved postoperatively, with improved women quality and subsequent pregnancies. Why varicocele causes subfertility in some men is unknown. Recently, it has been hypothesized that the left spermatic vein might be rich in by-products of adrenal metabolism, thus leading to diminished spermatogenesis. This study does not support this hypothesis, finding no significant difference in plasma cortisol in the left spermatic vein than from distant peripheral circulation. Further investigation into the etiologic factors causing subfertility with varicocele is recommended.     

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.     

精索静脉曲张严重少精子症患者Y染色体微缺失分析

目的:探讨精索静脉曲张和Y染色体微缺失对生精障碍的影响。方法:对随机挑选的100例左侧精索静脉曲张严重少精子症患者(精子浓度<5×106/ml,组1),100例左侧精索静脉曲张轻度少精子症患者[精子浓度(10～20)×106/ml,组2],100例特发性严重少精子症患者(组3),100例特发性轻度少精子症患者(组4)和30例正常生育男性对照组(组5)采用聚合酶链反应(PCR)技术进行Y染色体微缺失检测,选取无精子因子(AZF)a、b和c区9个序列标签位点(STS)。结果:组1中有19例患者存在AZF微缺失(19%);组3中有11例患者存在AZF微缺失(11%),其余各组均未发现AZF微缺失;组1比组3有较高的缺失率。结论:在治疗精索静脉曲张严重生精障碍患者前应先进行Y染色体微缺失检测,避免不必要的治疗。     

Testicular growth and gonadotrophin response associated with varicocele repair in adolescent males

OBJECTIVE: To measure testicular volume and the gonadotrophin response to gonadotrophin-releasing hormone (GnRH) stimulation in adolescents undergoing left varicocelectomy. PATIENTS AND METHODS: Thirteen adolescents undergoing varicocelectomy had their testicular volume and endocrine function evaluated before and after surgery. RESULTS: The initial left testicular volume was consistently smaller than the right but after surgery both increased. Baseline follicle-stimulating hormone (FSH) levels and the FSH response to GnRH stimulation increased after surgery. There were no differences in luteinizing hormone and testosterone levels, and no changes in Tanner staging. CONCLUSIONS: Unilateral varicocelectomy with ipsilateral testicular atrophy results in bilateral testicular growth and increased FSH levels. In adolescent development, elevated FSH levels in conjunction with an increased response to the GnRH stimulation test represent a normal physiological response. The GnRH stimulation test cannot be used to determine which adolescent would benefit from surgical repair.     

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.     

Testicular gonadotropin receptors in men with hypogonadotropic hypogonadism

To investigate the reason(s) why human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) treatment is not always effective for men with hypogonadotropic hypogonadism (HH), we measured hCG and follicle-stimulating hormone (FSH) receptors in testicular tissues obtained by biopsy from 5 men with idiopathic HH and 2 men with secondary HH. The difference between these 7 men and age-matched controls in the numbers of testicular hCG and FSH receptors were not significant. Histologic examination of the testes also showed that Leydig and Sertoli cells had a normal appearance. Therefore, responsiveness to gonadotropins seems to be preserved in the testes of men with HH. Fro these results it could be concluded that combined hCG and hMG treatment may be used with good results for the treatment of HH.     

Testicular ultrastructure in infertile men

The review shows typical ultrastructural alterations of germ, Sertoli, and Leydig cells in infertile men. Regardless of the cause of infertility, the disruption of the spermatogenic process usually occurs in the pachytene stage of meiotic prophase and in the stages of early spermatid maturation. The disturbances affect the cytoplasm more than the nucleus, and the synaptonemal complexes have shown significant stability even in the severely injured testes. An acrosome formation is found to be open to injury in more advanced germ cells during spermatid maturation. The manner of reaction of the Sertoli cells under different pathological conditions depends on the presence and degree of maturation of the neighboring germ cells. The appearance of immature Sertoli cells is accompanied by the loss of germ cells more advanced in their differentiation. In most pathologically altered testes, mature Sertoli cells reveal a universal manner of reaction of cell organelles. Leydig cell ultrastructure fluctuates considerably, and the alterations predominantly affect the sites of steroid synthesis, in spite of disease specificity. It becomes clear that a complex estimation of a real testicular state requires the application of new techniques as well as recognition of local control mechanisms. This will provide evidence toward elucidation of male infertility.     

Testicular microlithiasis in Taiwanese men

Testicular microlithiasis (TM) is an unusual ultrasonographic manifestation in testicular parenchyma. Limited information is available about TM in Taiwanese men. We performed a retrospective analysis to investigate the characteristics of TM and its association with testicular cancer and infertility in Taiwan. Male patients who had received scrotal ultrasonography because of scrotal symptoms or infertility between January 2000 and December 2003 were recruited. The incidence of TM was 7.6%. Both testicular microlithiasis and testicular cancer occurred chiefly in the third decade. Patients with TM exhibit a higher chance of testicular cancer (6% vs. 0.9%). No local field effect between TM and testicular cancer was observed. Testicular microlithiasis severity is not positively correlated with sperm quality and sterility. Forty-eight patients (32%) were available at follow-up. No patient developed a testicular tumor or elevated tumor markers (AFP, beta-hCG) during follow-up. We suggest monthly self-examination, annual scrotal ultrasonography and tumor markers screening between the age of 20 and 30 years of patients with TM.     

Male varicocele. Analysis of the incidence of varicocele in a population of 18,800 young men

The authors evaluate the incidence of varicocele after having examined 18,800 healthy white men members of the Italian Army Corps born in 1966 and visited in 1985. They found a varicocele in 775 patients (4.12%), in 5 was present bilaterally, and in 770 in the left side. In 45 patients the surgical treatment was already done at the time of the examination and there were 3 recurrences. The patients with varicocele were divided according to the classification of Dubin-Amelar and were: grade I n. 175 (0.93%); grade II n. 515 (2.74%); grade III n. 35 (50.18%). In 566 (73.03%) the diagnosis was done at the moment of the examination, 152 (19.62%) discovered the varicocele at the self examination; in 57 (7.37%) the diagnosis was already done by the family doctor. Infertility is sometime associated to the varicocele and with the unrelieved local discomfort are the main indications for surgery. It should be also emphasized the need of education on the infertility problems during the high school that is a time of the life in which there is the highest incidence of varicocele.     

Varicocelectomy improves intrauterine insemination success rates in men with varicocele

PURPOSE: We determined whether varicocele treatment before intrauterine insemination significantly affects intrauterine insemination success rates. MATERIALS AND METHODS: A total of 58 infertile couples, of whom the women had normal evaluations and men had abnormal semen analyses and a history of varicocele, were included in this study. They were identified after reviewing the charts of all women undergoing intrauterine insemination for male factor infertility at our center. Of the men 24 participated in 63 intrauterine insemination cycles without varicocele treatment, while in the remaining 34 varicocele was treated before a total of 101 intrauterine insemination cycles. Variables associated with pregnancy or live birth were analyzed using repeat measures logistic regression with generalized estimating equation techniques. An initial stepwise generalized estimating equation was performed without including varicocele treatment status. Subsequently varicocele treatment status and the significant associated factors were included in analysis. The semen characteristics of untreated and treated varicocele groups were compared with repeat measures analysis of variance. RESULTS: On pre-wash semen analysis patients with untreated varicocele had significantly higher mean motility plus or minus standard error than patients whose varicoceles were treated (48.6% +/- 2.3% versus 38.1% +/- 1.8%, p = 0.02). However, no statistically significant difference was noted in the mean post-wash total motile sperm count in the treated and untreated groups (7.2 +/- 1.0 versus 14.8 +/- 2.6, p = 0.1). Despite these findings the pregnancy and live birth rates per cycle were significantly higher in patients in whom varicocele was treated than in those without varicocele treatment (11.8% versus 6.3%, p = 0.04 and 11.8% versus 1.6%, p = 0.007, respectively). CONCLUSIONS: Varicocele treatment may not improve semen characteristics in all men but it appears to improve pregnancy and live birth rates among couples undergoing intrauterine insemination for male factor infertility. A functional factor not measured on routine semen analysis may affect pregnancy rates in this setting. Men should be screened for varicocele before intrauterine insemination is initiated for male factor infertility.