Right varicocele and hypoxia, crucial factors in male infertility: fluid mechanics analysis of the impaired testicular drainage system.

Varicocele is considered a predominantly unilateral left-sided disease. However, since male fertility is preserved with only one healthy testis, infertility perforce represents bilateral testicular dysfunction. It was hypothesized that: (i) right varicocele cannot be diagnosed by palpation and therefore has not been treated in the past by the traditional treatment, and (ii) right varicocele causes impaired oxygen supply in the right testicular microcirculation, leading to germ cell degeneration. This study performed venographies of both right and left internal spermatic veins during the treatment of 840 infertile men with varicocele and analysed the results using tools of fluid mechanics. Histopathology of the right testis revealed stagnation of blood flow and degenerative changes attributed to lack of adequate oxygenation in all testicular cell types. Right varicocele was found in the vast majority of the patients. We found that due to the destruction of one-way valves, pathologic hydrostatic pressure is produced in the testicular venous microcirculatory system about five times higher than normal, exceeding arteriolar pressure. The pressure gradient between the arterioles and venules in the testicular tissue is therefore reversed, leading to persistent hypoxia. Right varicocele, although undetected, is prevalent in infertile men with varicocele, hence only bilateral occlusion of the internal spermatic veins, including the associated bypasses, eliminating the pathologic hydrostatic pressure will lead to resumption of arterial blood flow in the testicular microcirculation.

A proposed anatomic typing of the right internal spermatic vein: importance for percutaneous sclerotherapy of varicocele.

PURPOSE: To classify the anatomic types of the right internal spermatic vein (ISV). METHODS: We evaluated venograms obtained in 150 consecutive patients with idiopathic varicocele referred for transfemoral sclerotherapy. RESULTS: Six anatomic types of the right internal spermatic vein (ISV) were recognized. These were classified by the location of their orifices and the tributary venous patterns. In roughly half the patients (53%), the ISV appeared as a simple vein with no remarkable retroperitoneal interconnections. In the remainder, complex retroperitoneal anastomoses were encountered. CONCLUSION: By understanding these anatomic variations, the angiographer can approach treatment of right-sided varicocele with foreknowledge of the nature of these types and the presence of valves and collaterals.

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.

Induction of spermatogenesis in azoospermic men after internal spermatic vein embolization for the treatment of varicocele.

BACKGROUND: To evaluate the improvement in semen quality and pregnancy rate after internal spermatic vein (ISV) embolization in men with nonobstructive azoospermia virtual azoospermia, or extremely severe oligoteratoasthenoazoospermia (OTA). METHODS: A prospective cohort of 101 azoospermic or severe oligoteratoasthenospermic men of mean (+/-SD) age 34.1+/-7.7 years who underwent ISV between September 1998 and June 2003 were evaluated for semen characteristics, endocrinology profile, and conception rate. RESULTS: Significant improvement was noted in mean sperm concentration, motility, and morphology in 83 men (82%). Mean sperm concentration increased from 0.22+/-0.30 x 10(6)/ml total sperm in the ejaculate to 9.28+/-1.2 x 10(6)/ml after embolization (P < 0.001); mean sperm motility rose from 8.78+/-1.59 to 29.56+/-2.0% (P < 0.001), and mean sperm morphology rose from 3.79+/-0.74 to 13.72+/-1.37% (P < 0.005). Pregnancy was achieved in 34 cases (34%), 20 (20%) unassisted and 14 (14%) assisted. CONCLUSIONS: Based on our findings, the following statements can be made: (i) Varicocele may cause any variation of severity in OTA, including azoospermia. (ii) Since male fertility is preserved with only one testis, OTA, azoospermia or virtual azoospermia represent bilateral testicular dysfunction. (iii) Treatment of bilateral varicocele may reverse testicular dysfunction and improve spermatognesis and testosterone production in men with extremely severe OTA and induce sperm production in men with azoospermia and virtual azoospermia. (iv) If azoospermia is not too long-standing, the treatment of varicocele may significantly improve spermatogenesis and renew sperm production. (v) Adequate treatment may spare in > 50% of azoospermic patients the need for testicular sperm extraction as preparation for ICSI. (vi) Since achievement of pregnancy in IVF units is higher when spermatogenesis is better, the treatment of varicocele (bilateral) is an effective medical adjunct for the IVF units prior to the treatment. We recommend that infertile men with azoospermia or virtual azoospermia or extremely severe OTA be evaluated for varicocele, with special attention to its bilateral nature.

Elevation of serum testosterone and free testosterone after embolization of the internal spermatic vein for the treatment of varicocele in infertile men.

BACKGROUND: To evaluate the effect of internal spermatic vein (ISV) embolization on levels of serum testosterone and free testosterone and on spermatogenesis. METHODS: The files of 83 infertile men treated for varicocele were reviewed for changes in serum testosterone, free testosterone and spermatogenesis after ISV embolization. RESULTS: Mean serum testosterone concentration rose after embolization by 43%, from 12.07 +/- 6.07 nmol/l to 17.22 +/- 8.43 nmol/l (P<0.001). Mean serum free testosterone concentration rose by 72%, from 5.93 +/- 2.44 nmol/l to 10.21 +/- 7.69 nmol/l (P<0.001). Mean sperm concentration increased from 7.49 +/- 1.73 x 10(6)/ml to 18.14 +/- 2.36 x 10(6)/ml (P<0.001); mean sperm motility increased from 21.74 +/- 2.47 to 34.47 +/- 2.27% (P<0.001); and mean sperm morphology increased from 6.63 +/- 1.07 to 13.08 +/- 1.44% (P<0.001). CONCLUSIONS: ISV embolization apparently induces an increase in both serum testosterone and free testosterone concentrations and in sperm parameters in infertile patient with varicocele, regardless of the size of the varicocele.

Non-resectable slow-growing meningiomas treated by hydroxyurea.

PURPOSE: To test the benefit of hydroxyurea in the treatment of recurrent and non-resectable slow-growing meningiomas. METHODS: Twelve patients with regrowing non-malignant meningiomas, were enrolled for a protocol of 2 years with continuous chemotherapy with hydroxyurea, 20 mg/kg/day. Response to treatment was evaluated both clinically and by diagnostic imaging using computed tomography (CT) and 201-Thallium single photon emission CT. One minimal response was documented by CT, accompanied by clinical stabilization. Nine patients showed progressive disease, at least by one imaging procedure, with a median time to progression of 13 months (range 4-24). Two other patients were not available for response due to early removal from the study, following abrupt manifestation of grades 3-4 hematological toxicity. CONCLUSION: In this series hydroxyurea has not shown effectiveness in the treatment of non-resectable slow-growing meningiomas: neither for achieving response, nor for arresting disease progression.

Varicocele: a bilateral disease.

OBJECTIVE: To evaluate the prevalence of varicocele in the left and right spermatic veins in infertile men by several methods of examination. DESIGN: Prospective study. SETTING: Andrology unit of a department of obstetrics and gynecology, and interventional radiology unit of the radiology department at a tertiary care facility. PATIENT(S): Two hundred eighty-six infertile men evaluated for varicocele. INTERVENTION(S): Patients underwent evaluation for infertility. Physical examination was followed by contact thermography, Doppler sonography, and venography of both testes. MAIN OUTCOME MEASURE(S): We measured the prevalence of varicocele in the left and right spermatic veins in infertile men, and the response of semen parameters after embolization of internal spermatic vein. RESULT(S): Varicocele was detected by one of the noninvasive methods and confirmed by venography in 255 patients (89.2%): the left site in 45 (17.6%), the right side in 4 (1.5%), and bilaterally in 206 (80.8%). All patients were treated by embolization. Mean sperm concentration increased from 6.12 +/- 1.02 to 21.3 +/- 1.69 million/mL; mean sperm motility from 16.81 +/- 1.51 to 35.90 +/- 1.41%; and mean sperm morphology from 9.75 +/- 0.85 to 16.92 +/- 1.17%. Pregnancy rate was 43.5%. CONCLUSION(S): The present study finds that what was traditionally considered a predominantly unilateral anatomical abnormality apparently has a strikingly high bilateral prevalence (80.7%). This may suggest that we should consider varicocele a bilateral disease. The second finding is the high rate of varicocele detected by venography, thermography, and sonography when compared with physical examination results. Our study may have important implications for treatment, indicating that patients with clinical evidence of unilateral left varicocele should be carefully evaluated for bilateral varicocele.

Adolescent varicocele: is it a unilateral disease?

OBJECTIVES: To evaluate the incidence of left and right varicocele in adolescents. METHODS: The study group consisted of 28 adolescents who underwent evaluation for varicocele at our clinic. In 19 patients, varicocele was detected on routine physical examination, and 9 patients presented with scrotal pain or discomfort. All patients were evaluated by three methods. Physical examination was followed in all cases by contact thermography and venography studies of both testes. RESULTS: The rate of left and right retrograde flow in the spermatic veins by the three methods used was as follows: physical examination 92.8% and 10.7%; contact thermography 100% and 89%; and venography 100% and 85.7%, respectively. Varicocele was not detected by physical examination in 2 (7.2%) of the 28 patients on the left side and in 21 (87.5%) of 24 on the right side. CONCLUSIONS: The main finding of this study was that varicocele is a bilateral disease in 85.7% of adolescents. The high percentage of bilateral varicocele in our sample may explain the pathophysiologic mechanism whereby what has traditionally been considered a unilateral disease can produce bilateral testicular dysfunction. The high incidence of subclinical bilateral varicocele may indicate that we should consider varicocele a bilateral disease. The second finding was that only 10% of patients with right varicocele were diagnosed by physical examination and more than 85% were diagnosed by thermography, with confirmation by venography. Therefore, we suggest that thermography and venography should play a major role in the diagnosis of varicocele.