Stuart S. Howards

Best practice policies for male infertility

University of California, San Francisco, San Francisco, California; Johns Hopkins University School of Medicine, Baltimore, Maryland; University of Louisville School of Medicine, Louisville, Kentucky; Baylor College of Medicine, Houston, Texas; Brown University, Providence, Rhode Island; Cleveland Clinic Foundation, Cleveland, Ohio; New York Presbyterian Hospital-Cornell, New York, New York; University of Virginia School of Medicine, Charlottesville, Virginia; Mayo Medical School, Rochester, Minnesota; University of Pennsylvania School of Medicine, York, Pennsylvania; University of California, Davis, Davis, California; and SUNY Health Science Center at Brooklyn, Brooklyn, New York

Influence of surgically induced varicocele on testicular blood flow, temperature, and histology in adult rats and dogs.

Varicocele had been repeatedly implicated as a cause of infertility in selected men, although neither a causal relationship nor a mechanism has been documented. The purpose of this investigation was to create a varicocele model in animals and to study the subsequent alterations in testicular physiology. Secondary dilatation of the left internal spermatic vein was achieved either by partial ligation of the left renal vein in rats and dogs or by surgical destruction of the valve of the left testicular vein in a second group of dogs. 1 mo after partial ligation in the rats and 3 mo after partial ligation or valve destruction in the dogs, testicular blood flow was measured using Strontium 85 (SR-85)-labeled microspheres (15 +/- 1.1 micrometer). Intratesticular temperature was measured with a Bailey needle probe thermometer and biopsies were obtained for histologic sections. Mean testicular blood flow in milliliters per minute per 100 g was significantly greater in the partially ligated rats; right testis control 26 +/- 2, left testis control 24 +/- 2 compared to right testis experimental 35 +/- 3, left testis experimental 35 +/- 4 (p less than 0.02). Dogs undergoing either partial vein ligation or valve destruction showed similar increases in mean testicular blood flow; right testis control 8 +/- 1, left testis control 8 +/- 1 vs. right testis experimental 16 +/- 3, left testis experimental 18 +/- 4 (p less than 0.01). The mean difference between intratesticular and intraperitoneal temperature in control rats was significantly higher (4.02 +/- 0.25 degrees C right testis, 3.77 +/- 0.14 degrees C left testis), than rats who underwent partial vein ligation (right testis 2.14 +/- 0.09 degrees C, left testis 2.34 +/- 0.12 degrees C) (p less than 0.001). Control dogs also had a significantly higher mean difference between intratesticular and rectal temperatures; (right testis control 3.61 +/- 0.42 degrees C, left testis control 3.60 +/- 0.40 degrees C) than the partially ligated or valve destruction dogs (right testis 2.31 +/- 0.17 degrees C, left testis 2.67 +/- 0.32 degrees C) (p less than 0.05). In addition, histologic evaluation revealed abnormalities in spermatogenesis in some of the animals. Thus, venous dilatation secondary to partial vein ligation or testicular vein valve obliteration is followed by large bilateral increases in testicular blood flow in these two species. A consequence of this increased flow is an elevation in bilateral testicular temperature, which it is postulated, leads to impaired spermatogenesis in some of the animals. In selected men varicocele may impair spermatogenesis by a similar physiologic mechanism.

Depression of fractional sodium reabsorption by the proximal tubule of the dog without sodium diuresis

The effect of infusions of hyperoncotic solutions on fractional sodium reabsorption by the proximal tubule of the dog was studied by the recollection micropuncture method. Tubule fluid to plasma inulin concentration ratios were measured for identified proximal tubule segments before and after infusion of 25% albumin or dextran solutions. Results were compared with changes in fractional reabsorption during saline diuresis. Plasma volume increased 66% +/- SE 5.8 after infusion of albumin solution and 94% +/- SE 8.2 after infusion of dextran solution. Fractional sodium reabosorption by the proximal tubule was depressed after infusion of both of these hyperoncotic solutions. Nevertheless, changes in sodium excretion after infusion of albumin and dextran were small. In contrast, after infusions of isotonic sodium chloride solution, which increased plasma volume 61% +/- SE 5.8, a decrease in fractional reabsorption of 50.7% +/- SE 7.2 was associated with large changes in sodium excretion.

CHRONIC TREATMENT WITH FINASTERIDE DAILY DOES NOT AFFECT SPERMATOGENESIS OR SEMEN PRODUCTION IN YOUNG MEN

PURPOSE Finasteride, an oral type 2, 5alpha-reductase inhibitor, is used in 1 mg. daily doses for the treatment of male pattern hair loss. A dose of 5 mg. finasteride daily reduces ejaculate volume by approximately 25%, and reduces prostate volume by approximately 20% and serum prostate specific antigen (PSA) by approximately 50% in men with benign prostatic hyperplasia. To our knowledge no data exist on the effect of 1 mg. finasteride daily on ejaculate volume or other semen parameters, or on the prostate in young men. Therefore, we studied the potential effect and reversibility of effect of 1 mg. finasteride daily on spermatogenesis, semen production, the prostate and serum PSA in young men. MATERIALS AND METHODS In this double-blind, placebo controlled multicenter study 181 men 19 to 41 years old were randomized to receive 1 mg. finasteride or placebo for 48 weeks followed by a 60-week off-drug period. Of the 181 men 79 were included in a subset for the collection and analysis of sequential semen samples. RESULTS There were no significant effects of 1 mg. finasteride on sperm concentration, total sperm per ejaculate, sperm motility or morphology. Ejaculate volume in subjects on finasteride decreased 0.3 ml. (-11%) compared to a decrease of 0.2 ml. (-8%) for placebo, with a median between treatment group difference of -0.03 ml. (1%, 90% confidence interval -10.4 to 13.1, p = 0.915). There were significant but small decreases in prostate volume (-2.6%) and serum PSA (-0.2 ng./ml.) in the finasteride group, which reversed on discontinuation of the drug. CONCLUSIONS Treatment with 1 mg. finasteride daily for 48 weeks did not affect spermatogenesis or semen production in young men. The effects of 1 mg. finasteride daily on prostate volume and serum PSA in young men without benign prostatic hyperplasia were small and reversible on discontinuation of the drug.

Initial Experience with Extracorporeal Shock Wave Lithotripsy in Children

The clinical experience is presented of 4 United States centers at which extracorporeal shock wave lithotripsy was used for the treatment of renal calculi in 38 children 12 months to 16 years old. Patient characteristics, treatment specifics and followup data are detailed. Complete fragmentation of calculi was obtained in 97 per cent of those treated, with a 5 per cent complication rate. This experience demonstrates that with proper safeguards, extracorporeal shock wave lithotripsy can be performed safely and effectively in the pediatric population.

Distribution of leukocytes in the epithelium and interstitium of four regions of the Lewis rat epididymis.

Leukocytes expressing different surface markers were studied in four regions of the epididymis of Lewis rats. Cells resembling lymphocytes or monocytes had been described in the epididymis, but previous studies differed as to their nature and immunologic significance.

Transdermal Testosterone Treatment of Hypogonadal Men

Hypogonadism, either primary or secondary, results in diminished libido and/or impotence. Conventional treatment consists of periodic intramuscular injections (usually bimonthly) of a depot testosterone preparation or daily oral ingestion of methyl testosterone. These conventional treatments may be associated with side effects, such as gynecomastia, liver function abnormalities and edema. A new method of administering testosterone is by daily application of a transdermal therapeutic system. We studied the efficacy and safety of the transdermal therapeutic system in 4 hypogonadal men. Three patients were treated for 12 weeks and 1 for 7 weeks, and they were evaluated weekly. Of 4 patients 3 had improvement in erectile and/or sexual function. Mean plasma testosterone levels increased significantly compared to pre-treatment values during 7 of 12 treatment weeks. There were no adverse effects of the transdermal therapeutic system as indicated by serial physical examinations, daily reports, blood chemistry studies, liver function tests, urinalysis and hematological profiles. This preliminary report of transdermal testosterone delivery indicates that it may provide an effective alternative method of gonadal steroid replacement.

Effects of Granuloma Formation at Site of Vasovasostomy

Spermatic granulomas forming after vasectomy reversal have been thought to mechanically compromise the anastomosis. We have studied the physiologic effects of vasectomy and vasovasostomy in rats. Following delayed microsurgical vasovasostomy, fluid flow through the anastomosis and cauda epididymidal hydrostatic pressure are not significantly different in tracts that form, or do not form, sperm granulomas at the anastomosis. Given a properly performed microsurgical vasectomy reversal, a sperm granuloma arising from a small leak does not appear to mechanically compromise the anastomosis in the rat. Fertility after vasovasostomy is not significantly reduced in rats with granulomas.

Micropuncture and Microanalytic Studies of the Effect of Vasectomy on the Rat Testis and Epididymis

Micropuncture techniques adapted for in vivo use in the male reproductive tract were used to study the effect of vasectomy on the concentration and morphology of spermatozoa in the seminiferous tubules and ductus epididymidis of the rat. Regardless of surgical technique, 85% of all rats which had previously under vasectomy developed a speratic granuloma at the proximal end of the ligated vas deferens. Vasectomy did not affect the weights of the ipsilateral (vasectomized) testes. Vasectomy without granuloma formation resulted in an elevation in the weight of the ipsilateral epididymis and an increase in the concentration of spermatozoa in the ipsilateral cauda. Vasectomy complicated by granuloma formation caused a significant increase in the ratio of the spermatocrit in the seminiferous tubule to that in the caput. In the vasectomized rat without granuloma, significantly more abnormal spermatozoa were in the caput than in the cauda; in the normal rat, the concentrations of abnormal spermatozoa in the two regions were not significantly different. Vasectomies with and without granuloma formation are distinct phenomena and should be investigated separately.

Scrotal Ultrasound for Evaluation of Subacute Testicular Torsion: Sonographic Findings and Adverse Clinical Implications

There is an increased use of scrotal ultrasound in the clinicians office and emergency room for the investigation of scrotal pain. The use of real-time scrotal ultrasound for the diagnosis of testicular torsion has been described in the literature. A false-negative ultrasound examination can postpone the diagnosis of torsion and result in testicular loss. We examined 6 patients 1 day to 18 years old who had subacute testicular torsion with scrotal symptomatology (pain and/or swelling) for longer than 8 hours (range 12 hours to 6 days). Scrotal ultrasound was performed as 1 of the initial tests. A common sonographic pattern was an inhomogeneous testicle with hypoechoic areas alternating with hyperechoic areas and thickening of adjacent scrotal tissue. Another common finding was an edematous hyperechoic epididymis and a small hydrocele. In 4 of the 6 cases these nonspecific findings suggested a misleading diagnosis of tumor or epididymitis and resulted in delay of surgery and testicular loss. Treatment was not delayed in only 2 patients in whom the diagnosis of torsion was made initially by history and physical examination, and ultrasound was done for interest only. Misdiagnosis of intratesticular blood flow and some potential pitfalls of scrotal imaging by color Doppler ultrasound are discussed. We conclude that real-time scrotal sonography can be misleading in cases of subacute testicular torsion and, therefore, it should not be used in this clinical setting.