Unilateral Varicocele Research Articles

Effects of Experimental Varicocele Require Neither Adrenal Contribution Nor Venous Reflux

Experimental left varicocele (ELV) is known to induce bilateral changes in the rat testis that, where comparisons are possible, are similar to the changes induced by unilateral varicocele in the human. In the present study, we have determined whether or not left adrenal products are important to the changes induced by ELV and whether or not reflux of left renal vein content occurs in the ELV rat. In the first study, testicular blood flow and temperature were studied in control animals and those with ELV, left adrenalectomy (LAX), or ELV + LAX. Control left and right testicular blood flow (33.6 ± 0.8 and 33.6 ± 1.5ml./min./100gm. tissue respectively) was significantly elevated by ELV (to 39.9 ± 0.9 and 41.2 ± 2.7ml./min./100gm. tissue, respectively) and the difference between abdominal and testicular temperatures (AT) was significantly reduced. Control ΔT’s for right and left testes were 3.2 ± 0.2C and 3.2 ± 0.2C, respectively, and right and left ΔT’s for ELV animals were 2.0 ± 0.3°C and 2.0 ± 0.3C, respectively. These blood flow and temperature changes also occurred when ELV animals were subjected to simultaneous LAX. Additionally, when 85Sr-labelled microspheres were infused into the left renal vein, they did not appear in either left or right testes of ELV animals. We conclude that there is no evidence for reflux down the spermatic vein in ELV in rats and adrenal products do not reach the testis via this route after being secreted into the renal vein. We raise the suggestion that the same may be true in the human. (J. Urol., 142: 1372–1375, 1989)

Luteinizing hormone secretion by male rat pituitary cells perifused in vitro: effect of experimental left varicocele and orchiectomy.

It has been shown previously that experimental left varicocele in the rat, results in a bilateral decrease in intratesticular testosterone. In the present work, pituitary responsiveness to GnRH as a possible mediator of this effect has been examined. Unilateral varicoceles were created in adult rats. A second group of animals underwent a sham operation and a third underwent bilateral orchiectomy. Thirty days after surgery, rats from all three groups were sacrificed and their pituitaries were removed. Dispersed pituitary cells were perifused in Bio-Gel columns with varying concentrations of GnRH. The concentration of LH in the collected eluent was determined by radioimmunoassay. The mean, overall GnRH-stimulated LH immunoreactive secretion rate (ng/min/10(7) cells) by pituitary cells from rats with varicocele (0.062 +/- 0.11) was no different from the overall release from the sham-operated controls (0.051 +/- 0.007). The dose-response curves for GnRH-stimulated release of LH by dispersed pituitary cells in the two groups also were not different. The overall GnRH-stimulated LH release by cells from the orchiectomized rats (0.171 +/- 0.032) was significantly greater than release by cells from the sham-operated and varicocele rats, and the concentration-response curve from the orchiectomy group was significantly elevated over those of the other two groups. These results indicate that GnRH-stimulated immunoreactive LH release is not altered in rats with experimental left varicocele and, thus, is not the source of an endocrinopathy that leads to decreased intratesticular testosterone concentrations in these animals.

Elevation of Intratesticular and Scrotal Skin Surface Temperature in Men with Varicocele

A possible mechanism of varicocele-induced infertility is believed to be elevation of testicular temperature. Sensitive needle thermistors were used to measure directly intratesticular and bilateral scrotal surface temperatures simultaneously in anesthetized infertile men with varicocele and control subjects. We found that intratesticular temperature is elevated significantly in humans with varicocele. In addition, we have shown that scrotal skin surface temperature is elevated in men with varicocele. Furthermore, we demonstrate that unilateral varicocele is associated with bilateral elevation of scrotal surface temperature. These findings confirm the results of animal studies revealing elevation of intratesticular temperature associated with varicocele and suggest bilateral elevation in unilateral varicocele.

Pathological and immunological effects of surgically induced varicocele in juvenile and adult rats.

The presence of a varicocele in adult men has been correlated with infertility. This study documents the effect of an experimentally induced unilateral varicocele in 21-day-old juvenile prepubertal and 51-day-old adult rats (n = 10 per group) on subsequent adult testicular function. Varicoceles were induced by partial occlusion of the spermatic vein. There were ten sham-operated and five nonoperated control rats in each age group. The rats were sacrificed 1 month after surgery. Intrascrotal temperatures were elevated in both groups with varicoceles. Histologically, the ipsilateral testes of rats in both age groups demonstrated a decrease in the numbers of functioning seminiferous tubules and germ cells, but the decrease was significantly greater in the juveniles than in the adult rats. No changes were seen in the contralateral testes. Significant titers of cytotoxic sperm antibodies were present in all animals with varicoceles, which is in contrast to controls. The juveniles had significantly lower antibody titers (mean log2 +/- SEM; 3.2 +/- 0.09 vs. 8.5 +/- 1.1, P less than 0.001) than the adults. The induction of a unilateral varicocele damaged spermatogenesis and testicular function to a greater extent in juveniles than in adult rats. This damage may be immune complex-mediated.

Adolescent Varicocele

To the Editor.— The recent article on testicular histology in the adolescent with a varicocele (Pediatrics 1987;79:996-998) pointed out the potential histologic testicular damage that can occur in the presence of this condition. The authors stated that, in some cases of unilateral varicocele, histologic abnormalities were found in the contralateral testis. They further commented that early ligation of varicoceles would seem reasonable if it could be shown that progressive histologic damage could be arrested by the procedure.

The effects of unilateral, experimental varicocele are not mediated through the ipsilateral testis.

Unilateral varicocele has been associated with diminished male fertility in humans and with bilateral physiologic and histologic changes in the testis of humans and laboratory animals. In particular, left varicocele in Sprague-Dawley rats results in bilateral increases in testicular temperature and blood flow. The mechanism by which unilateral varicocele can cause testicular changes is not known. The purpose of the present study was to determine whether or not the presence of either the ipsilateral or contralateral testicle is necessary for these effects of the varicocele to occur in the opposite testis. Varicoceles were created in adult, male rats by partial constriction of the left renal vein. Bilateral testicular blood flow was measured by a radiolabelled microsphere distribution technique and testicular temperature was taken with a needle probe thermometer. Right or left orchiectomies were performed on selected animals at the time of surgery to establish the unilateral left varicocele. Animals were studied 30 days after surgery. Mean testicular blood flow was significantly increased (P less than 0.01) in all animals having a left varicocele when compared with animals not having a varicocele regardless of whether a unilateral orchiectomy was performed. Likewise, the mean difference between intraabdominal temperature and intratesticular temperature (delta T) was significantly decreased in all groups of animals having varicoceles when compared with groups without varicoceles whether or not an orchiectomy had been performed. Thus, the studied bilateral effects of left-sided, experimental varicocele in the rat are not dependent upon the presence of a left testicle.

Varicocele: Temporal Considerations

The pathophysiology of the abnormal spermatogenesis seen in the presence of the varicocele has not been elucidated in spite of extensive study. Furthermore, no satisfactory explanation exists for the bilateral abnormal spermatogenesis seen in a process which is felt to be unilateral in the majority of cases. The present study was designed to determine if a surgically produced unilateral varicocele would lead to ipsilateral testicular changes prior to the onset of contralateral testicular alterations. Utilizing the rat model and microsurgical techniques, the effects of the varicocele on ipsilateral and contralateral spermatogenesis was studied at intervals over 49 days. Mean seminiferous tubular diameter measurements and flow cytometric analysis of testicular tissue were utilized to assess spermatogenesis. A statistically significant decrease in mean seminiferous tubular diameter was seen between day 1 and day 49 in the left testicle. The right testicle tended to demonstrate similar changes but these were not significant by the method of analysis used. Flow cytometric analysis of testis DNA content also revealed a statistically significant difference in the percentage of haploid, diploid and tetraploid cells in the left testis on day 1 as compared to day 49. The right testis again tended to demonstrate similar but not significant changes. Though primarily a unilateral process, bilateral spermatic vein abnormalities were also visualized in some animals. This observation may contribute to the bilateral effect observed.These studies demonstrate that a surgically created left varicocele will result in bilateral testicular alterations. Within the time frame of the study, the ipsilateral alterations progressed to a greater degree.

Radiological Anatomy of the Internal Spermatic Vein(s) in 200 Retrograde Venograms

The radiological anatomy of the internal spermatic vein(s) was studied in 200 retrograde venograms performed as part of presurgical evaluation in patients with variocele. A large range of anatomical variations was found at the left side. Bilateral reflux occurs in one out of four patients with unilateral varicocele at palpation. Bilateral treatment is therefore necessary in as much as one fourth of cases with ‘unilateral’ left side varicocele. In right side varicocele the spermatic vein generally enters the right renal vein. Varicocele ligation should be performed near the internal inguinal ring in order to interrupt reflux most securely. Non-surgical treatment of varicocele by means of sclerosis or embolization of the internal spermatic vein, will remain restricted to those cases in which reflux passes through only one spermatic vein. Insufficient knowledge of the anatomy of the internal spermatic vein(s), and the resulting incomplete interruption of reflux in this (or these) vessel(s) may be the cause of poor treatment results reported by some authors.

Radiological anatomy of the internal spermatic vein(s) in 200 retrograde venograms.

The radiological anatomy of the internal spermatic vein(s) was studied in 200 retrograde venograms performed as part of presurgical evaluation in patients with variocele. A large range of anatomical variations was found at the left side. Bilateral reflux occurs in one out of four patients with unilateral varicocele at palpation. Bilateral treatment is therefore necessary in as much as one fourth of cases with "unilateral' left side varicocele. In right side varicocele the spermatic vein generally enters the right renal vein. Varicocele ligation should be performed near the internal inguinal ring in order to interrupt reflux most securely. Non-surgical treatment of varicocele by means of sclerosis or embolization of the internal spermatic vein, will remain restricted to those cases in which reflux passes through only one spermatic vein. Insufficient knowledge of the anatomy of the internal spermatic vein(s), and the resulting incomplete interruption of reflux in this (or these) vessel(s) may be the cause of poor treatment results reported by some authors.

Seminological, hormonal and histological evaluations of unilateral varicocele in relation to fertilizing potential

Seminological, hormonal and histological evaluations of unilateral varicocele in relation to fertilizing potential

Pituitary-gonadal function in schoolboys with varicocele and indications of varicocelectomy.

Pituitary-gonadal functions were investigated by LH-RH test, HCG test and bilateral testicular biopsies in 5 boys with unilateral varicocele at various pubertal stages and the results were compared with those in the normal boys at puberty. The ages of the patients ranged from 12 to 18 years. With the progress of pubertal stage, both the basal value and response of serum FSH to LH-RH became higher as compared with normal boys. The basal value and response of serum LH showed no significant difference except for one case where higher values and no significant differences in the basal value and response of plasma testosterone to HCG stimulation were observed. The disturbance of spermatogenesis in the affected testis becomes prominent with the progress of puberty, while changes in the testis of opposite side were mild.

Detection of varicocele by radionuclide blood-pool scanning.

Varicocele is a common and treatable cause of male subfertility. The authors describe a new technique for varicocele detection using radionuclide blood-pool imaging of the scrotum. Of 83 patients studied, 29 had a clinically palpable varicocele of various sizes, and 26 of them were demonstrated by this technique. Two of the false negatives were bilateral varicoceles. In the 41 patients with no clinically detectable varicocele, there were 10 positive and 10 marginally asymmetric studies. The results indicate that this technique detects unilateral varicoceles with high sensitivity, including some which are subclinical. There may be significant implications for treatment of infertility.

A Possible Mechanism for the Detrimental Effect of Varicocele on Testicular Function in Man

Seminiferous epithelium histology, Leydig cell density, and in vitro testosterone synthesis were quantitated in bilateral testicular biopsies from men with varying degrees of unilateral or bilateral varicoceles. Results were correlated with plasma levels of gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and testosterone (T), as well as with semen quality. In patients with bilateral varicoceles, spermatogenesis, Leydig cell density, plasma T levels, and in vitro T synthesis were significantly lower than in patients with unilateral varicoceles. Varicoceles appeared to affect maximally the latest stages of spermatogenesis. A negative correlation between FSH and LH levels and spermatogenesis was observed; however, a dissociation between the two gonadotropins occurred when spermatogenesis declined. Plasma T levels were within the normal range in all patients. The T:LH ratio was significantly correlated with spermatogenesis and sperm motility. Leydig cell density was abnormally low in oligospermic patients, and it was significantly correlated with in vitro T synthesis, spermatogenesis, sperm motility, and semen volume. Sperm count and motility were significantly correlated in this group of patients, suggesting a common pathophysiology for the effect of varicocele on spermatogenesis and sperm motility. This common pathophysiology appears to be disturbed Leydig cell function resulting in decreased testicular androgen production, in turn causing inadequate spermatogenesis and epididymal function.