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PubMed1986

Demonstration of antispermatozoal antibodies in varicocele-related infertility with an enzyme-linked immunosorbent assay (ELISA).

To assess the existence of a possible immunologic factor in varicocele-associated infertility, we searched for antispermatozoal antibodies in serum, seminal plasma, and bound to spermatozoa in 32 infertile men with varicocele and 22 infertile patients without palpable varicocele, with the use of an enzyme-linked immunosorbent assay. In addition, we performed morphologic and microbiologic analyses of the semen and urethral smears for isolation of Chlamydia trachomatis. Twenty-nine men from the varicocele group (90.6%) demonstrated antispermatozoal antibodies, compared with only 9 men (40.9%) in the control group. The antibodies in both groups, when present, were mainly serum and seminal plasma immunoglobulins IgA and IgM. A significant quantitative difference between the varicocele and control groups was also observed for serum IgA, seminal plasma IgA and IgM, and sperm-bound IgG, IgA, and IgM. Oligozoospermia and asthenozoospermia were significantly more prevalent in the varicocele men. An asymptomatic genital tract infection with C. trachomatis, Ureaplasma urealyticum, and Escherichia coli was traced in 40.6% of the varicocele men and in 45.5% of the control group. No interaction could be demonstrated between the infection and antispermatozoal antibody formation. These data suggest that an immunologic factor may play a role in varicocele-associated infertility; however, its impact on reproduction has yet to be assessed.

Antibodies↗

PubMed2002

Impact of varicocele on testicular volume in young men: significance of compensatory hypertrophy of contralateral testis.

PURPOSE: We examined the impact on ipsilateral testicular volume in young men with varicocele and determined whether compensatory hypertrophy exists. MATERIALS AND METHODS: Between April and November 2001, 2,700 men who were 20 years old and dwelling in the community were randomly selected at a 10% sampling fraction after a sampling process according to census district. A total of 2,080 men (77% response rate) agreed to participate in the study. All volunteers underwent standard evaluation, including medical history and physical examination. RESULTS: Testicular volume on the affected side in men with varicocele was significantly smaller than that of the contralateral side, while testicular volume on the contralateral side was significantly larger than that of the left side in normal men. In those with unilateral varicocele testicular volume on the affected side did not depend on varicocele grade but contralateral testicular volume in men with grade I varicocele was significantly smaller than in men with higher grades of the entity. The rate of testicular atrophy increased depending on varicocele grade. CONCLUSIONS: Varicocele negatively impacts testicular volume on the affected side in young men. Our findings suggest that men with higher grades of varicocele have a hypertrophied testis on the contralateral side.

Adult↗

PubMed1982

In vitro fertilization rates after varicocele repair.

Causal relationship of varicocele to infertility is controversial. Studies of hormonal milieu, semen and testicular tissue yield data of debatable significance. We herein assay the fertilizing ability of men with varicocele and monitor changes consequent to surgical correction of varicocele. Zona-free hamster ova were used to determine fertilizing ability. A fertilization rate of less than 10 per cent correlates with infertility. Between May 1978 and November 1979, 75 men with varicocele presenting for fertility evaluation and 23 men with painful varicocele were tested. Of the patients infertile clinically and by in vitro fertilization assay 42 elected ligation of the internal spermatic vein(s). Average fertilization rate of the painful varicocele group was 20.5 per cent and for the infertile group it was 1.2 per cent. Average fertilization rates postoperatively in the infertile group were 2.9 per cent (3 months), 7.7 per cent (6 months), 2.8 per cent (9 months), 7.8 per cent (12 months), 17.5 per cent (15 months) and 8.0 per cent (18 months). Pregnancies occurred only in partners of men whose fertilization rates were between 2.9 and 8.3 per cent preoperatively and who improved to greater than 10 per cent postoperatively. The in vitro fertilization assay may help select those individuals with varicocele and infertility most likely to benefit from varicocele repair.

Fertilization in Vitro↗

PubMed2000

Color Doppler ultrasound in subclinical varicocele: an attempt to determine new criteria.

OBJECTIVE: The aim of this study is to determine new criteria in the diagnosis of subclinical varicocele in infertile patients. METHODS: A total of 208 testes in 104 patients who were infertile and had no varicocele on physical examination were studied by color Doppler ultrasonography (CDUS) with classical and new criteria. Population proportion difference test was used to compare two methods. RESULTS: One hundred and fourteen testes were accepted as varicocele negative in the same testes units in both methods. Ninety-four testes were varicocele positive with new criteria while 88 of these 94 testes were diagnosed also varicocele positive with the classical criteria. The value of Z* with population proportion difference test was 0.59 which is less than 1.96, which means the proportion of varicocele detection in two methods did not differ. CONCLUSION: Because a gold standard that defines the presence of a subclinical varicocele has not yet been established, new criteria may be needed. However, our new criteria did not add new information to the diagnosis of subclinical varicocele in infertile patients.

Adult↗

PubMed1999

Histologic evaluation of spermatic veins in patients with varicocele.

BACKGROUND: Information concerning varicocele is limited in spite of its clinical importance. This study intends to clarify anatomical features of varicocele. METHODS: Spermatic veins were obtained from varicocele patients at surgery. Areas of two distinct portions (extracellular matrix and smooth muscle) were measured by a micro computer imaging device image analysis system on histologic slides with Masson trichrome stain. In addition, we evaluated the shape and arrangement of the smooth muscle fibers by a scanning electron microscope (SEM). RESULTS: Masson trichrome stain revealed that grade of varicocele partly correlated with thickness of the wall and with amount of the smooth muscle fibers. In the patients with grade 3 varicocele, SEM examination showed marked hypertrophy of longitudinal smooth muscle fibers, which were discriminated clearly from the inner circular fibers. CONCLUSIONS: This study indicated that morphological changes occurred in the muscle layers of varicoceles in the worst grade of varicocele. These structural changes which result from abnormal venous blood circulation may cause development of varicocele, resulting in male infertility.

Adolescent↗

PubMed2003

Medical therapy of oligoasthenospermia associated with left varicocele.

OBJECTIVE: To ascertain whether a nonsteroidal anti-inflammatory drug (cinnoxicam) or surgical varicocelectomy are suitable therapies for oligoasthenospermia associated with varicocele. PATIENTS AND METHODS: Patients who were oligoasthenospermic and had a varicocele were blindly randomized into three groups and the varicocele graded using echo-colour Doppler ultrasonography. In group 1, seven men had grade V, four grade IV and 30 grade III varicoceles; in group 2 eight had grade V, 10 grade IV and 43 grade III; in group 3 six had grade V, eight grade IV and 40 grade III. Group 1 underwent surgery, group 2 received cinnoxicam (one 30 mg suppository every 4 days for 12 months) and group 3 received a placebo (one glycerine suppository every 4 days for 12 months). Sperm was analysed at intervals to follow the response in the three groups, and any side-effects considered. RESULTS: Surgery significantly increased sperm values in men with grade III-V varicocele within 4 months, the highest values being obtained at 8 and 12 months. Cinnoxicam significantly improved sperm quality after 2 months in men with grade III varicocele, but the results were best at 4 months and stable at 12 months; stopping therapy caused a decline to the baseline values. Cinnoxicam did not change the sperm quality of men with grade IV or V varicocele. The placebo was inactive, and there were no side-effects of active treatment. CONCLUSIONS: Cinnoxicam is a safe and reliable therapeutic option for men with oligoasthenospermia associated with a grade III varicocele, but surgery is better for those with grade II, IV and V.

Adult↗

PubMed2006

Body size and weight as predisposing factors in varicocele.

OBJECTIVE: The literature regarding the constitutional type of children and adolescents with varicocele is inconsistent. The aim of this investigation was to examine a possible influence of weight, height and body mass index (BMI) on the formation of varicoceles during childhood and adolescence. MATERIAL AND METHODS: In a retrospective data analysis, 193 Caucasian children and adolescents aged 9-19 years (mean age 14.7 years) with left-sided varicocele grade 2-3 were studied. The weight, height and BMI of the subjects were compared with the age-correlated normal values currently accepted in Germany. Additionally, the familial disposition for varicocele and the occurrence of relevant concurrent diseases were considered. RESULTS: In the group of patients examined, the mean percentiles of weight (57th) and height (58th) were significantly above and the mean BMI percentile (42th) was significantly below the age-correlated 50th percentile for the normal population (p=0.019, 0.005 and 0.002). In our case material, 12.2% of all brothers of the patients had varicoceles. CONCLUSIONS: The results of this investigation suggest a correlation between physical appearance and the formation of a varicocele during childhood or adolescence. We were able to demonstrate that patients with varicocele were heavier and taller than an age-correlated normal population, but had a distinctly lower BMI. Further studies are needed to verify whether this rather athletic habitus, together with the postulated difference in muscle:fat ratio, represents an important etiologic factor for varicocele formation.

Adult↗

PubMed2004

Bilateral increased apoptosis and bilateral accumulation of cadmium in infertile men with left varicocele.

BACKGROUND: Varicoceles are associated with venous flux that may cause increased heat and interstitial pressure within the testes, but these effects are variable. Some men with varicocele have infertility, but others do not. We question whether other factors contribute to the infertility, and whether these other factors could be identified by specific molecular/genetic markers. Can such markers predict the outcome of varicocele repair? Can these markers be demonstrated bilaterally in unilateral left varicocele? METHODS: Limited bilateral testes biopsies were obtained by ultrasonically guided percutaneous aspiration at the time of varicocelectomy. In each specimen, cadmium levels were determined by atomic absorption and the percentage apoptosis within the seminiferous tubules was quantified. RESULTS: The percentage of apoptotic nuclei and cadmium levels were high in some men with varicocele. There was a concordance of these values in both testes despite the presence of left-sided varicocele only. These values were inversely related to an increase in sperm concentration after varicocelectomy. CONCLUSIONS: Cadmium, a metal ion inducer of apoptosis, may contribute to this form of male infertility. Apoptosis may deplete the sperm concentration among men with varicocele and infertility. Pre-operative measurements of apoptosis and cadmium content may predict the outcome of varicocele repair.

Actins↗

PubMed2005

Varicocele, hypoxia and male infertility. Fluid Mechanics analysis of the impaired testicular venous drainage system.

BACKGROUND: Varicocele is a bilateral vascular disease, involving a network of collaterals and small, retroperitoneal bypasses. The right and the left testicular venous drainage systems are complex and not identical to each other. It was considered a predominantly unilateral (left-sided) disease. Its pathophysiology has not been clearly delineated and the treatments offered do not seem to be effective. The medical literature is replete with articles demonstrating inconsistent and even contradictory results which have led clinicians to dissociate varicocele from male infertility. Since male fertility is preserved with only one healthy testis, male infertility perforce represents bilateral testicular dysfunction. This poses an enigma to clinicians: How can left-sided varicocele causes bilateral testicular dysfunction? METHODS: We investigated the internal spermatic veins by venography to understand testicular damage due to varicocele. A total of 740 venographies of the internal spermatic veins (ISVs) were performed, with sclerotherapy of the ISV as treatment for varicocele. Epon-embedded testicular tissue sections were used to identify blood stagnation in the testis. RESULTS: Varicocele is predominantly a bilateral disease in 84% of cases, associated with collaterals and retroperitoneal venous bypasses in 70% in the left side and 75% in the right side. Histopathology demonstrate stagnation in the testicular microcirculation and hypoxic-ischaemic degenerative changes in all cells' types in the sperms' production site. CONCLUSION: Based on our findings (i) varicocele is a bilateral disease; (ii) the disease is expressed earlier in the left side and is more intense because the blood column is longer in the left side than the right; (iii) partial treatment to the left side only and ignoring bypasses is not adequate to correct the problem; (iv) hypoxia leading to ischaemic damage to both testes is the effect of varicocele due to hydrostatic pressures in the impaired venous drainage system, which exceeds the pressures in the testicular arterial microcirculation due to blood columns produced in the disease; (v) hydrostatic pressure does not depend on vein diameter but on blood column height, only; and (vi) thermography alone or combined with ultrasonography with special attention to the bilaterality of the disease are the best non-invasive tools for its detection.

Adult↗

PubMedDate not supplied

The study of varicocele through the use of animal models.

The pathophysiology of the varicocele has received considerable study, both in humans and in animal models. Mechanistic information is difficult to obtain from human subjects because study designs must not be invasive and the subject population is variable in the status of the varicocele, patient age, fertility or other health-related issues. Because of these limitations, animal models of varicocele have been developed in several species, the most common being the rat. Surgery to establish the varicocele involves partial obstruction of the left renal vein, causing a varicosity of the left spermatic vein, including the pampiniform plexus. Studies using this model have shown that experimental left varicocele induces bilateral increases in testicular blood flow and temperature contemporaneous with decreases in intratesticular testosterone and testicular sperm output. Spermatic vein reflux is not related to the pathophysiological consequences of experimental varicocele. Many questions remain regarding the mechanism by which varicocele induces testicular dysfunction, chief among them being how the unilateral varicocele causes a bilateral testicular response in the first place.

Animals↗

PubMedDate not supplied

The pathophysiology of varicoceles in the light of current molecular and genetic information.

Varicoceles are a common cause of male infertility, but despite data being obtained from animal models and human studies the pathophysiology remains unclear. Recently, molecular and genetic information has been reported on men with varicoceles which may shed new light onto the causes of decreased semen parameters and poor sperm function. Here, a number of studies are reviewed in an attempt to develop a working hypothesis for the relationship of varicoceles and infertility. New studies on testicular tissue of men with varicoceles have demonstrated increased apoptosis among developing germ cells, which may be the cause of oligospermia. Other studies with semen have shown increased levels of reactive oxygen species (ROS) in association with poor sperm motility. Recent studies of morphologically abnormal spermatozoa have demonstrated disruption of the sperm head actin by cadmium, a cation reported to be present in high concentrations among some men with varicoceles. Finally, microdeletions of the alpha-1 subunit of the sperm calcium channels in a proportion of men with varicoceles suggests a genetic defect leading to abnormal acrosomal function. The intent of this review was to explain the pathophysiology of varicoceles, and the findings seem to support a 'co-factor' hypothesis. In order for varicoceles to be associated with infertility, they exist as 'co-factors' along with other molecular/genetic problems.

Acrosome Reaction↗

PubMed1988

Varicocele in youth. A therapeutic dilemma.

The need for treatment of asymptomatic varicocele in youth is controversial. In the current study testicular volume and seminal variables were evaluated in three groups: young varicocele patients with undetermined fertility potential, infertile varicocele patients, and a control group of young males. The testicular volume was determined by ultrasonographic measurements. The results revealed a significant loss of "testicular mass" in both varicocele groups compared with the control group. The seminal findings disclosed a severe disturbance of spermatogenesis in the older varicocele group, whereas in the younger varicocele patients only the total spermatic count was significantly depressed. This difference in severity of functional impairment between the younger and older varicocele groups possibly points towards progressiveness of damage to the testicles. A more decisive therapeutic approach to the young male with asymptomatic varicocele and unknown fertility status could be justified.

Adolescent↗

PubMed1999

Serum inhibin B levels and the response to gonadotropin stimulation test in pubertal boys with varicocele.

PURPOSE: The impact of varicoceles on gonadal function in adolescents has been evaluated using several parameters, including size of testes, hormonal levels and provocative endocrine testing. Inhibin B has been demonstrated to be decreased in men with testicular damage from conditions other than varicocele. We determine whether inhibin B levels are low in adolescent boys with varicocele, and if there is a relationship between inhibin B and an exaggerated response to gonadotropin-releasing hormone (Gn-RH) stimulation testing, testicular hypertrophy and/or varicocele bilaterality. MATERIALS AND METHODS: We studied 9 boys at Tanner stages III to V of pubertal development who had either left or bilateral varicoceles. Basal inhibin B, follicle-stimulating hormone, luteinizing hormone and testosterone were measured. Each patient underwent Gn-RH stimulation testing. RESULTS: All patients had essentially normal inhibin B levels for Tanner stage. Of the 9 boys 4 had an exaggerated response to Gn-RH stimulating testing. Inhibin B levels did not vary significantly either with the presence of bilateral or unilateral varicoceles or asymmetric testis. CONCLUSIONS: The lack of correlation between inhibin B levels and the aforementioned parameters failed to suggest that inhibin B has a significant role in the clinical assessment of testicular function in adolescents with varicocele. Further studies of larger populations may further elucidate the value of inhibin B levels and varicoceles.

Adolescent↗

PubMed2005

Increased prevalence of varicocele in patients with coronary artery ectasia.

BACKGROUND: Coronary artery ectasia (CAE) is defined as localized or diffuse non-obstructive lesions of the epicardial coronary arteries with a luminal dilation exceeding the 1.5-fold of normal adjacent segment or vessel diameter. Varicocele is the dilatation of the pampiniform plexus. Recently increased prevalence of peripheral varicose veins has been shown in patients with CAE. In this study we aimed to assess the prevalence of varicocele, which is dilatation of another venous system, in patients with CAE. MATERIALS AND METHODS: Thirty-five male consecutive patients with coronary artery ectasia in combination with or without coronary artery disease (CAD) and 63 male, age-matched patients with coronary artery disease were included in the study. All patients were evaluated for the presence of varicocele. RESULTS: Twenty-one patients with CAE were found to have varicocele (62% of group I patients). In patients with CAD, 24 patients (38%) were found to have varicocele. The difference between the two groups in respect to presence of varicocele was statistically significant (P=0.02; odds ratio=1.57; 95% confidence interval 1.05- 2.3). CONCLUSION: We have shown that patients with coronary artery ectasia have an increased prevalence of varicocele compared to those with coronary artery disease. The mechanism underlying coronary artery ectasia might further increase the prevalence of varicocele in susceptible patients.

Coronary Angiography↗

PubMed2003

Optimizing the operative treatment of boys with varicocele: sequential comparison of 4 techniques.

PURPOSE: We compared 4 techniques of varicocele ligation in boys and young adolescents to determine the optimal operative treatment that avoids varicocele recurrence and postoperative hydrocele formation. MATERIALS AND METHODS: In 10 years a total of 128 varicocelectomies were performed sequentially in 121 boys and young adolescents with a mean age of 12 years using the laparoscopic, inguinal testicular artery sparing, standard Palomo (high mass retroperitoneal ligation) and modified Palomo approaches. The modified Palomo approach involved suprainguinal and retroperitoneal ligation of the veins and artery, and microsurgical sparing of the blue stained lymphatic pathway of the testis. Patients were followed a mean of 52 months. RESULTS: In the 19 boys in the laparoscopy group varicocele persisted in 10% and hydrocele developed in 5%. In the 21 patients who underwent inguinal surgery with artery preservation recurrent varicoceles were identified in 14% and no hydroceles were observed. In the 32 patients who underwent the standard Palomo procedure there was no palpable varicocele persistence or recurrence, while hydroceles developed in 12%. Of the 56 patients in the modified Palomo group varicocele recurred in 1 (2%) and there were no hydroceles. No testicular atrophy developed in any patient. CONCLUSIONS: Comparison of all 4 groups revealed significant differences in varicocele recurrence (p = 0.038) and hydrocele formation (p = 0.023). Pairwise group comparison showed that the modified Palomo technique resulted in a significant decrease in the incidence of postoperative hydrocele formation compared with the standard Palomo method (p = 0.015). This procedure can be recommended as the optimal surgical technique for varicocele treatment in males of this young age.

Adolescent↗

PubMed1996

Relationship between grade of varicocele and the response to varicocelectomy.

BACKGROUND: Although several studies indicate that larger varicoceles are associated with greater impairment of spermatogenesis, others suggest that the response to surgery is independent of varicocele size. In order to elucidate these seeming contradictions, correlations between the preoperative evaluation of varicoceles and improvement in semen quality after varicocelectomy were investigated. METHODS: Forty men with left unilateral varicocele, followed for at least 6 months after varicocelectomy, were included in this study. The relationships between the grade of varicocele by palpation, Doppler examination, ultrasound, or scintigraphy were correlated with a postoperative improvement in sperm density or sperm motility. RESULTS: Greater improvement in sperm density was observed in the patients with a large varicocele graded by palpation or measured by ultrasound, and greater improvement in sperm motility was observed in the patients with high uptake of radioactivity in the left side by scrotal scintigraphy. CONCLUSION: An improvement in semen quality after varicocelectomy is greater in patients with a large varicocele than in the patients with a small one. The significance of surgical repair of a small varicocele should be reconsidered.

Angiography↗

PubMed1988

Pathology of varicocele in the ram.

A total of 40 mature or aged rams with spontaneous varicocele detected by scrotal palpation were subjected to detailed necropsy examination. Varicocele was bilateral in 22 rams or was located on the left or right sides only, in 8 and 10 rams, respectively. This distribution contrasted with varicocele in man in which the left side is involved in 70 to 100% of cases. Mean sizes of varicoceles in mm (length x diameter) were 117 x 46 and 104 x 45 for the left and right sides, respectively, and they were located high in the pampiniform plexus, approximately 100 mm from the dorsal pole of the corresponding testis. All varicoceles were thrombosed. Changes associated with large varicoceles included testicular mineralisation and occluding thrombosis of testicular vessels. Total testis weight-bodyweight ratio in rams with varicocele (5.8 to 6.4 x 10(-3] was significantly less (P less than 0.05) than in normal (control) rams from the same flocks (7.9 x 10(-3] suggesting that some degree of testicular atrophy resulted from presence of a varicocele.

Animals↗

PubMed1987

Stop-type and shunt-type varicoceles: venographic findings.

Forty-four patients with a left-sided idiopathic varicocele were examined with bidirectional Doppler ultrasound (US), physical examination, and percutaneous retrograde venography. On the basis of the Doppler findings, the varicoceles were classified as either stop type or shunt type. On venography, the stop-type varicoceles showed only retrograde blood flow (reflux) in the testicular (internal spermatic) vein, whereas each shunt-type varicocele showed both retrograde and orthograde (i.e., physiologic) venous blood flow: First, reflux appeared in the testicular vein, then orthograde flow occurred in the deferential vein, cremasteric vein, or both. The shunt-type varicocele therefore represented a kind of venous bypass. Thus, the existence of two hemodynamically different types of varicocele as suggested initially by Doppler US is confirmed by percutaneous retrograde venography. The shunting of venous blood appears to be a precondition for medium and large varicoceles and might have some prognostic significance for subfertility associated with varicoceles.

Humans↗