Subclinical Varicocele Research Articles

Surgery or embolization for varicoceles in subfertile men: summary of a Cochrane review

Treatment of varicoceles may improve fertility outcomes in subfertile couples where the male has a varicocele. This systematic review evaluates surgical or radiologic interventions for clinical or subclinical varicoceles.

The varicocele: the proper therapy for the proper patient

Varicocele is present in 15% to 20% of the general population, but in approximately 35% to 40% of males presenting for an evaluation of their infertility. Indeed it is well known that varicocele can cause testicular damage and infertility. No evidence indicates a varicocele treatment in infertile men who have normal semen analysis or in men with subclinical varicocele. In this situation, varicocelectomy cannot be recommended. Varicocele repair may be effective in men with subnormal semen analysis, a clinical varicocele and otherwise unexplained infertility, but we need further randomized studies to confirm that this subgroup of infertile couples will benefit from treatment. There is no doubt about the standard indications of varicocelectomy, but recent literature seems to go towards new indications of varicocele repair. The aim of this review is to give a look at the literature to analyze the proper indications to varicocelectomy for the proper patient.

Children and adults varicocele: diagnostic issues and therapeutical strategies.

Varicocele is defined as abnormally dilated scrotal veins. It is present in 15% of normal males and in 40% of males with infertility. This disorder is a challenge for the physicians involved in the diagnosis and treatment, as the pathophysiology of varicocele is not yet completely understood. For this reason, accurate diagnostic criteria and clear indications for treatment in asymptomatic adolescents or adults with clinical or subclinical varicocele are still not defined. Ultrasonography (US) is considered the best method for calculating the volume of the testicles, measuring vein diameter and monitoring the growth of the testis in adolescent patients. Color-Doppler US is the method of choice for detecting spermatic vein reflux and for classifying the grade of varicocele. Various classification systems have been published with recommendations on how to perform US imaging of the scrotum. Currently, color-Doppler US and spectral analysis are the most effective, non-invasive diagnostic procedures as they allow detection of subclinical varicocele associated with infertility. Various techniques are used in the treatment of varicocele including open surgery, laparoscopic procedures and interventional radiology. However, there is no consensus among physicians on which technique is the most effective in terms of outcome and complication rates. This review shows that color-Doppler US is currently the most widely employed diagnostic method for detection and classification of varicocele caused by venous reflux, as it is reliable and easily performed. The review also highlights the role of varicocelectomy in the management of adult male infertility.

Clinical and Subclinical Varicocele Incidence in Patients With Primary Varicose Veins Requiring Surgery

The purpose of this study was to analyze the incidence of clinical and subclinical varicocele in patients with primary varicose veins requiring surgery. A total of 100 patients with primary varicose veins requiring surgery were evaluated. Clinical varicocele was found in each patient through physical examination. Each patient was also evaluated with ultrasound because of evidence of subclinical varicocele. Among the patients with varicose veins, 28 had no clinical sign of varicocele, whereas the remaining 72 had varicocele with different clinical levels (72%). Doppler ultrasound revealed that 32 patients had no reflux flow, whereas the other 68 had different grades of reflux flow (68%). Clinical or subclinical varicocele may be highly present in patients with severe venous disease. However, these types of varicoceles do not cause infertility in most patients. Nevertheless, infertility may occur in subsequent years, especially in young patients who have venous disease and undergo surgery, and they should be aware of this condition.

The Role of Doppler Ultrasonography in Subfertile Patients With Left Subclinical Varicocele

The Role of Doppler Ultrasonography in Subfertile Patients With Left Subclinical Varicocele

765 COMPARATIVE IMPACT OF SEMINAL VESICAL INVASION VERSUS LYMPH NODE METASTASES ON SURVIVAL FOR PATIENTS FOLLOWING RADICAL PROSTATECTOMY

reproductive system were excluded. Mean age was 37 y and mean follow-up postoperatively 19,6 months. In 5 patients (14%) the varicocele was bilateral and they were subjected to bilateral varicelectomy. In the rest of the patients (n 30, 86%) the laparoscopic procedure was unilateral–29 on the left side (83%) and 1 on the right side (3%). The grade of varicocele was 3 in 17 patients (48.5%), 2 in another 17 (48.5%) and 1 in 1 patient (3%). The mean pre-op visual analogue score (VAS), was 2.39 in the scale of 0-5, and in all patients fertility was not an issue. All patients were followed up at 3 months and bi-annually thereafter. RESULTS: After the operation 32 patients (91%) had significant improvement in (VAS), two had partial improvement (6%), and one had no change (3%). In our cohort we haven’t observed post-op worsening of the symptoms. Mean VAS score post-op at 3 months was 0.4. During the follow-up period we observed 4 recurrences (12%) with 2 re-do procedures, performed by inguinal approach. In 3 of these recurrences (75%) the improvement in pain symptoms was significant, and in 1 (3%) it remained unchanged even after the re-do procedure. We have observed two cases of wound infection (6%). Post operatively three cases (9%) of de novo developed hydroceles were observed. CONCLUSIONS: Laparoscopic varicocelectomy is a highly successful option for surgical treatment of varicocele in our cohort, with significant improvement of symptoms in approximately 90% of the patients and minimal complications. We feel that this high success rate can be attributed to the careful selection of patients and by excluding those with sharp radiating scrotal pain. Another factor that possibly contributes to these results is the fact that our cohort doesn’t include small subclinical varicoceles, although this was not explicit excluding criteria.

Impact of Surgical Varicocele Repair on Pregnancy Rate in Subfertile Men With Clinical Varicocele and Impaired Semen Quality: A Meta-Analysis of Randomized Clinical Trials

PurposeTo elucidate the impact of surgical varicocele repair on the pregnancy rate through new meta-analyses of randomized clinical trials that compared surgical varicocele repair and observation.Materials and MethodsThe PubMed and Embase online databases were searched for studies released before December 2012. References were manually reviewed, and two researchers independently extracted the data. To assess the quality of the studies, the Cochrane risk of bias as a quality assessment tool for randomized controlled trials was applied.ResultsSeven randomized clinical trials were included in our meta-analyses, all of which compared pregnancy outcomes between surgical varicocele repair and control. There were differences in enrollment criteria among the studies. Four studies included patients with clinical varicocele, but three studies enrolled patients with subclinical varicocele. Meanwhile, four trials enrolled patients with impaired semen quality only, but the other three trials did not. In a meta-analysis of all seven trials, a forest plot using the random-effects model showed an odds ratio (OR) of 1.90 (95% confidence interval [CI], 0.77 to 4.66; p=0.1621). However, for subanalysis of three studies that included patients with clinical varicocele and abnormal semen parameters, the fixed-effects pooled OR was significant (OR, 4.15; 95% CI, 2.31 to 7.45; p<0.001), favoring varicocelectomy.ConclusionsVaricocelectomy for male subfertility is proven effective in men with clinical varicocele and impaired semen quality. Therefore, surgical repair should be offered as the first-line treatment of clinical varicocele in subfertile men.

Clinical and laboratory profiles of a large cohort of patients with varicocoele.

The prevalence of varicocele is 7% and 10–25% in pre pubertal and post pubertal males, respectively [1]. Varicoceles are found in 21–41% of men with primary infertility and 75–81% of those with secondary infertility. Physical examination of varicocele has a sensitivity and specificity of around 70%. The Color Doppler ultrasound (7MHz) has sensitivity of 50% and specificity of 90%. A pencil probe of 9 MHz is good in detecting subclinical varicocele. This has advantage when bilateral varicoceles are suspected [2]. The effect of varicocele on the testis is due to stasis of blood, increased testicular temperature, and reflux of toxic metabolites from the kidney and adrenal gland. This leads to oxidative stress, apoptosis, a deleterious effect on DNA integrity, and the OAT syndrome [3]. The indications for varicocele treatment are pain, arrest of testicular growth, and infertility. Varicoceles in early adolescence should be followed up and treated if there is persistent discrepancy of testicular size by >20% or >2 cm. However, this should be taken in to consideration together with the peak retrograde flow. A peak retrograde flow of 38cm/s or more may indicate that the arrest of testicular growth is likely to worsen [4]. Research by Goldstein's group in 2011 showed that men with varicoceles have lower testosterone than a comparison group (men without varicoceles presenting for reversal of vasectomy). There was a 70% improvement in testosterone levels of men who had varicocelectomy. The mean increase was 178 ng/dl [5]. Controversies have dominated research on varicocelectomy as a treatment for infertility in the last decade, but research in the last couple of years tends to favor treatment of varicoceles in the presence of abnormal semen parameters and infertility. A prospective randomized trial by Abdel Meguid et al. in which 150 men were randomized to either observation or a microscopic subinguinal varicocelectomy revealed an overall improvement in the odds of achieving pregnancy with varicocelectomy. After 12 mos. of follow–up, 13.9% of the observation group and 32.9% of the treatment group had achieved pregnancy (odds ratio [OR]: 3.04; 95% confidence interval [CI], 1.33–6.95). The authors found a number needed to treat of 5.27 (95% CI, 1.55–8.99), which suggests that 5.27 men need to undergo varicocelectomy to achieve one spontaneous pregnancy [6]. A meta–analysis of outcomes of varicocelectomy in the treatment of infertility in oligospermic men in 2011 by Bazeem and coexperts in the field revealed that combined odds ratio was 2.23 (95% CI, 0.86–5.78; p = 0.091), showing varicocelectomy is moderately superior to observation, but the effect is not statistically significant. They concluded that there is no evidence that a varicocele repair improves spontaneous pregnancy rates. They had observed that varicocelectomy improves sperm parameters (count, total, and progressive motility), reduces sperm DNA damage and seminal oxidative stress, and improves sperm ultramorphology [7]. An updated Cochrane systemic review in 2012 involving 894 men from 10 studies found out that the combined fixed–effect odds ratio (OR) of the 10 studies for the outcome of pregnancy was 1.47 (95% CI 1.05 to 2.05). The number needed to treat for an additional beneficial outcome was 17. A sub analysis of five studies in which patients had normal semen analysis, but were subfertile also favored treatment with a combined OR 2.39 (95% CI 1.56 to 3.66). The number needed to treat for an additional beneficial outcome was seven. The authors concluded that treatment of varicocele in men from couples with otherwise unexplained subfertility may improve a couple's chance of pregnancy. However, the findings are inconclusive as the quality of the available evidence is very low and more research is needed with live birth or pregnancy rate as the primary outcome [8]. Analyzing the different meta–analyses, the European Association of Urology guidelines recommended varicocele repair in cases of infertility with clinical varicocele and oligospermia, as well as in adolescents with progressive failure of testicular development (Grade B). It recommended against treatment of varicocele in infertile men with normal semen parameters and subclinical varicocele (Grade A) [9]. The current popular methods of varicocele treatment are microsurgical lymphatic and arterial sparing, subinguinal varicocelectomy, and radiological embolization. The authors, with over one thousand patients in their study, have added one of the largest series of clinical and laboratory profiles on men with varicoceles to the literature on the subject. Their finding of slightly higher level of testosterone in men with grade 3 varicocele compared to grade 1 and 2 has defied most studies as discussed above, but their explanation is plausible though more research is needed on it. However, it is a known fact that precision and standardization of testosterone assay is a challenge in itself [10].

Surgery or embolization for varicoceles in subfertile men

A varicocele is a meshwork of distended blood vessels in the scrotum, usually left-sided, due to dilatation of the spermatic vein. Although the concept that a varicocele causes male subfertility has been around for more than 50 years now, the mechanisms by which a varicocele would affect fertility have not yet been satisfactorily explained. Neither is there sufficient evidence to explain the mechanisms by which varicocelectomy would restore fertility. Furthermore, it has been questioned whether a causal relation exists at all between the distension of the pampiniform plexus (a network of many small veins found in the human male spermatic cord) and impairment of fertility. To evaluate the effect of varicocele treatment on live birth and pregnancy rate in subfertile couples where the male has a varicocele. We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (12 September 2003 to January 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 1, 2012), MEDLINE (January 1966 to January 2012), EMBASE (January 1985 to January 2012), PsycINFO (to Week 1 2012) and reference lists of articles. In addition, we handsearched specialist journals in the field from their first issue until 2012. We also checked cross-references, references from review articles and contacted researchers in the field. Randomised controlled trials (RCTs) were included if they were relevant to the clinical question posed. If they reported pregnancy rates or live birth rates as an outcome measure, and if they reported data in treated (surgical ligation or radiological embolization of the internal spermatic vein) compared to untreated or placebo groups. Two authors independently screened potentially relevant trials. Any differences of opinion were resolved by consensus (none occurred for this review). Ten studies met the inclusion criteria for the review. For one study we had only data from a published abstract. All ten studies only included men from couples with subfertility problems; one excluded men with sperm counts less than 5 million per mL and one excluded men with sperm counts less than 2 million per mL, with or without progressive motility of less than 10%. Two trials involving clinical varicoceles included some men with normal semen analysis. Three studies specifically addressed only men with subclinical varicoceles. Studies were excluded from meta-analysis if they made comparisons other than those specified above. The meta-analysis included 894 men. No studies reported live birth. The combined fixed-effect odds ratio (OR) of the 10 studies for the outcome of pregnancy was 1.47 (95% confidence interval (CI) 1.05 to 2.05, very low quality evidence), favouring the intervention. The number needed to treat for an additional beneficial outcome was 17, suggesting benefit of varicocele treatment over expectant management for pregnancy rate in subfertile couples in whom varicocele in the man was the only abnormal finding. Omission of the studies including men with normal semen analysis and subclinical varicocele, some of which had semen analysis improvement as the primary outcome rather than live birth or pregnancy rate, was the subject of a planned subgroup analysis. The outcome of the subgroup analysis (five studies) also favoured treatment, with a combined OR 2.39 (95% CI 1.56 to 3.66). The number needed to treat for an additional beneficial outcome was 7. The evidence was suggestive rather than conclusive, as the main analysis was subject to fairly high statistical heterogeneity (I(2) = 67%) and findings were no longer significant when a random-effects model was used or when analysis was restricted to higher quality studies. There is evidence suggesting that treatment of a varicocele in men from couples with otherwise unexplained subfertility may improve a couple's chance of pregnancy. However, findings are inconclusive as the quality of the available evidence is very low and more research is needed with live birth or pregnancy rate as the primary outcome.

A critical appraisal on the role of varicocele in male infertility.

Varicocele is a major cause of male infertility, as it may impair spermatogenesis through several distinct physiopathological mechanisms. With the recent advances in biomolecular techniques and the development of novel sperm functional tests, it has been possible to better understand the mechanisms involved in testicular damage provoked by varicocele and, therefore, propose optimized ways to prevent and/or reverse them. Up to now, there is still controversy involving the true benefit of varicocele repair in subfertile men as well as in certain specific situations such as concomitant contralateral subclinical varicocele or associated nonobstructive azoospermia. Also, with the continued development of assisted reproductive technology new issues and questions are emerging regarding the role of varicocelectomy in this context. This paper reviews the most recent data available on the pathogenesis, diagnosis, and management of varicocele with regard to male infertility.

UP-01.139 The Role of Surgical Ligation of the Left Internal Spermatic Vein for the Management of Infertile Men With Subclinical Left Varicocele

UP-01.139 The Role of Surgical Ligation of the Left Internal Spermatic Vein for the Management of Infertile Men With Subclinical Left Varicocele

Radiologically assessed testicular changes in infertile males with varicocele

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

Color Doppler ultrasound imaging in varicoceles: is the venous diameter sufficient for predicting clinical and subclinical varicocele?

Investigating the diagnostic value of color Doppler ultrasound for defining the varicocele grade according to WHO criteria. A total of 217 men (129 with clinical varicocele and 88 without clinical varicocele) were investigated by physical examination and color Doppler ultrasound and categorized according to WHO varicocele criteria (0, subclinical, I, II, and III). Diameter and reflux of the largest vein in the pampiniform plexus were measured bilaterally with the patient in the supine position in rest and during the Valsalva maneuver. To assess the possibility of differentiating varicocele grade by venous diameter, optimal cut-point values were determined by receiver-operator characteristic (ROC) analysis. With increased varicocele grade, a larger vein diameter was more significant in rest and during Valsalva (in all cases P < 0.05), except between grade I and grade II. Retrograde peak flow velocities were similar in every group (in all cases P > 0.1). Only grade III varicoceles demonstrated significantly increased peak flow values compared with all other grades (P < 0.001). There were no side-related differences when comparing identical varicocele grades (in all cases P > 0.1). Venous diameters above 2.45 mm in rest (sensitivity 84%, specificity 81%) or 2.95 mm during Valsalva (sensitivity 84%, specificity 84%) predicted the presence of a clinical varicocele. Our findings support the hypothesis that clinical varicoceles can be predicted with high accuracy based only on the diameter of testicular veins using cut-point values of >2.45 mm in rest or >2.95 mm during Valsalva maneuver in the supine position.

Reply

As explained in our article, 1 Scaramuzza A. Tavana R. Marchi A. Varicocele in young soccer players. Lancet. 1996; 348: 1180-1181 Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar all clinical examinations and Doppler scans were performed by a single clinician (N.Z.) to reduce bias. In this type of study, there may be 2 possible errors to be considered: errors occurred during Doppler scans, and errors correlated with the clinical diagnosis of varicocele. Diagnosis of subclinical varicocele is already 1 of the study inclusion criteria, so the only test to be standardized is Doppler velocimetry. In this type of test, bias can be represented by false-positive and false-negative results. If all study patients are examined by the same clinician (an expert in pediatric andrology and urology), the number of false-negative results is reduced, especially if physical examination is always performed in association with Doppler velocimetry. Therefore, the bias could be represented only by false-positive results. However, if patients are observed once a year for 3 years, the error can be amended the following year and the patient excluded from the study. Therefore, it is more important to observe the clinical onset of varicocele than to grade varicocele. In Italy, the costs for physical examinations to practice agonistic sport activities are paid by patients and include manual palpation of the genitals to exclude varicocele. Doppler velocimetry (with portable Doppler scanner) does not involve additional costs, so the suggestion to try to identify subclinical varicocele at this stage would not be expensive at all. Early diagnosis of subclinical varicocele is important to avoid the development of clinical varicocele in adulthood, possibly associated with hypofertility. It is also important to remember that most varicoceles are associated with hypofertility, and that most varicoceles are still diagnosed in adulthood. This is not the final purpose of preventive medicine. Editorial CommentUrologyVol. 77Issue 5PreviewThis is a prospective longitudinal observational study to determine whether the presence or absence of a subclinical varicocele and/or athletic activity put healthy, adolescent boys at greater risk of developing a clinical varicocele. Four populations were followed up for 3 years: (a) nonathletes without a subclinical varicocele, (b) athletes without a subclinical varicocele, (c) nonathletes with a subclinical varicocele, and (d) athletes with a subclinical varicocele. Of the athletes with a subclinical varicocele, 36% developed a clinical varicocele compared with 25% of nonathletes with a subclinical varicocele and 6% of athletes without a subclinical varicocele. Full-Text PDF

Varicocele: Management and the continuing controversies

Varicoceles have long been associated with infertility. Despite this long history, there remains much controversy regarding their aetiology and management. The aim of this review is to present the mostcurrent information on the management of varicoceles and to highlight some of the management controversies: Association of varicocele with male infertility; Management of varicocele in adolescent; safety and effectiveness of varicocele embolization and management of subclinical varicoceles. It is hoped that this review study will stimulate further research into this condition in order to find a more common ground regarding its management.

Subclinical Varicocele and Sports: A Longitudinal Study

To evaluate the influence of physical activity on the evolution of subclinical varicocele because subclinical and clinical varicoceles are common in adolescents. The study enrolled healthy male volunteers (athletes and nonathletes) and athletes with subclinical varicocele from October 2006 to March 2007. A fourth group of nonathletes with subclinical varicocele was created. Subclinical varicocele was defined as spermatic vein reflux detected with Doppler velocimetry only with the Valsalva maneuver. All patients were pubertal boys of 14-16 years old. Those practicing sports on a regular basis ≥3 times weekly for ≥2 consecutive hours were considered athletes. The boys were examined every year for 3 years from October 2006 to March 2010. At each examination, each patient underwent Doppler velocimetry and testicular volume measurements with a standard orchidometer. The rate of progression to a clinically palpable varicocele and its relationship to sport practice was also assessed. The follow-up compliance rate was 80%. The rate of progression to a clinically palpable varicocele was significantly greater in the athletes with a subclinical varicocele than in the healthy group (athletes and nonathletes) without a subclinical varicocele (36% vs 5%, respectively; P < .05). The probability of developing a subclinical varicocele for healthy athletes and healthy nonathletes was similar (23% vs 20%, respectively). Subclinical varicocele should be considered as the first stage of varicocele development. Although sports practice seemed to cause progression to a clinical varicocele, this finding was confirmed only in patients already affected by spermatic vein reflux (subclinical varicocele).

Protamine 1 to protamine 2 ratio correlates with dynamic aspects of DNA fragmentation in human sperm

To investigate the relationship between the protamine 1 to protamine 2 (P1/P2) ratio and the rate of sperm DNA fragmentation in sperm samples from human males with proven fertility and three different cohorts of male patients. P1/P2 ratio was analyzed using acid-urea polyacrylamide acid-urea gels electrophoresis (PAGE). Sperm DNA fragmentation using sperm chromatin dispersion methodology was analyzed after 0, 4, 8, and 24 hours of incubation at 37°C. University medical school and hospital. A total of 32 human males: six with proven fertility, seven carriers of chromosome reorganizations, nine clinical varicocele patients, and ten subclinical varicocele patients. None. P1/P2 ratio, sperm DNA fragmentation (SDF) and the rate of sperm DNA fragmentation (rSDF). P1/P2 ratio correlated with SDF and rSDF. Statistical differences were detected between fertile controls and patients for the three pathologies studied. rSDF yielded information that differed from baseline SDF. No differences were detected for P1/P2 ratio among patient groups, in reference to the three pathologies studied. SDF and rSDF correlates with P1/P2 ratio in human sperm, and statistical differences were detected when fertile controls were compared with three different cohorts of patients.

Effects of bioflavonoids in the management of subclinical varicocele

Subclinical varicocele is a relative rare condition. The aim of this study is to identify the role of bioflavonoids in the management of subclinical varicocele. We analyzed the medical charts of patients treated for subclinical varicocele with bioflavonoids between 1999 and 2004; inclusion criteria were created before treatment. Short and long-term results after treatment were studied and compared with untreated patients. One hundred and sixty-eight patients with left subclinical varicocele were included in the study. Long-term results showed a possible correlation between use of bioflavonoids and lesser rate of clinical progression to palpable varicocele (11 vs. 31%), higher rate of stable vein reflux (47 vs. 38%) and higher resolution rate (41 vs. 31%) (p > 0.05). Bioflavonoids did not show any protective factor against testicular growth arrest. Subclinical varicocele should be considered as the starting point of varicocele, and although the use of bioflavonoids in patients with subclinical varicocele could reduce the development of palpable varicocele, it cannot prevent the onset of testicular growth arrest.

Right subclinical varicocele: how to manage in infertile patients with clinical left varicocele?

Right subclinical varicocele: how to manage in infertile patients with clinical left varicocele?

UP-2.057: An Evaluation for Coincidence of Subclinical Varicocele (Detected by Doppler Venous Reflux) with Contralateral Grade III Varicocele and Effects of Subclinical Varicocelectomy on Sperm Parameters

UP-2.057: An Evaluation for Coincidence of Subclinical Varicocele (Detected by Doppler Venous Reflux) with Contralateral Grade III Varicocele and Effects of Subclinical Varicocelectomy on Sperm Parameters