Association between promoter methylation of MLH1 and MSH2 and reactive oxygen species in oligozoospermic men-A pilot study.

MLH1 and MSH2 are important genes for DNA mismatch repair and crossing over during meiosis and are implicated in male infertility. Therefore, the methylation patterns of the DNA mismatch repair genes MLH1 and MSH2 in oligozoospermic males were investigated. Ten oligozoospermic patients and 29 normozoospermic donors were analysed. Methylation profiles of the MLH1 and MSH2 promotors were analysed. In addition, sperm motility and seminal reactive oxygen species (ROS) were recorded. Receiver operating characteristic (ROC) analysis was conducted to determine the accuracy of the DNA methylation status of MLH1 and MSH2 to distinguish between oligozoospermic and normozoospermic men. In oligozoospermic men, MLH1 was significantly (p = .0013) more methylated compared to normozoospermic men. Additionally, there was a significant positive association (r = .384; p = .0159) between seminal ROS levels and MLH1 methylation. Contrary, no association between MSH2 methylation and oligozoospermia was found. ROC curve analysis for methylation status of MLH1 was significant (p = .0275) with an area under the curve of 61.1%, a sensitivity of 22.2% and a specificity of 100.0%. This pilot study indicates oligozoospermic patients have more methylation of MLH1 than normozoospermic patients. Whether hypermethylation of the MLH1 promoter plays a role in repairing relevant mismatches of sperm DNA strands in idiopathic oligozoospermia warrants further investigation.

Significant medical pathology discovered during a male infertility evaluation.

PURPOSE: Because a pregnancy can be achieved without a male infertility evaluation, some have questioned its usefulness. However, by bypassing a urological evaluation the man might not learn the cause of infertility and not be offered specific corrective therapy. In addition, men with subfertility may have a serious underlying medical or genetic problem that could also be overlooked. We determine the incidence of significant medical pathology discovered during a male infertility evaluation at 2 academic infertility practices. MATERIALS AND METHODS: All men examined for either primary or secondary infertility were included in our study, while men seen for vasectomy reversal were not. All patients underwent evaluation, consisting of a complete history, physical examination, semen analysis, hormone testing, urinalysis and genetic testing when appropriate. RESULTS: Significant medical pathology was discovered in 33 of 536 (6%) patients. A total of 27 patients had genetic abnormalities, including cystic fibrosis mutations in 24 and karyotypic abnormalities in 3. Of the remaining 6 patients 1 had testis cancer, 1 prostate cancer, 3 diabetes mellitus and 1 hypothyroidism. CONCLUSIONS: Significant medical pathology can be detected by a male infertility evaluation. In addition to identifying the cause of infertility, the evaluation may uncover conditions that threaten the health of the male partner or any potential offspring.

Repeat vasectomy reversal after initial failure: overall results and predictors for success.

PURPOSE: We review the treatment outcomes for microsurgical reconstruction following failed vasectomy reversal and identify predictors for success. MATERIALS AND METHODS: We performed a retrospective review of our experience with microsurgical reconstruction in 41 men who underwent 1 or more prior unsuccessful vasectomy reversal procedures. Of these patients 20 underwent bilateral (16) or unilateral (4) vasoepididymostomy, 11 underwent bilateral (7) or unilateral (4) vasovasostomy and 10 underwent unilateral vasoepididymostomy with contralateral vasovasostomy. Postoperative followup consisted of serial semen analyses and telephone interviews. RESULTS: Patency and pregnancy followup data were available in 33 and 31 patients, respectively. Five couples had ongoing uncorrected female factor infertility problems and were not included in pregnancy rate calculations. Mean obstructive interval was 10.6 years. Overall patency and pregnancy rates were 79 and 31%, respectively. Mean total motile sperm count for patients demonstrating patency at followup was 38.0 million. History of conception with the current partner was predictive of future conception with 4 of 5 nonremarried couples (80%) initiating a pregnancy versus 3 of 18 remarried couples (17%) (p = 0.006). Other factors, including smoking history and obstructive interval, did not correlate with postoperative success. Reconstruction with vasovasostomy on at least 1 side trended toward improved patency (p = 0.17) and pregnancy rates (p = 0.15), although they did not assume statistical significance. CONCLUSIONS: Microsurgical reconstruction following failed vasectomy reversal is associated with high patency and moderate pregnancy rates at short-term followup. In our series previous conception with the current partner was predictive of future conception after reconstruction. Urologists performing repeat vasectomy reversal must be familiar with microsurgical techniques, since almost three-quarters of patients will require at least unilateral vasoepididymostomy.

PIP: This paper reviews treatment outcomes for microsurgical reconstruction following failed vasectomy reversal. Additionally, the report also examines a variety of factors, including smoking history, time since vasectomy, prior conception with current partner, as well as type of repair, in an attempt to identify predictors of successful surgical outcome. A total of 41 men, who underwent one or more prior unsuccessful vasectomy reversal procedure, participated in the study. Of these patients, 20 underwent bilateral (16) or unilateral (4) vasoepididymostomy; 11 underwent bilateral (7) or unilateral (4) vasovasostomy; and 10 underwent unilateral vasoepididymostomy with contralateral vasovasostomy. Patency and pregnancy follow-up data were available in 33 and 31 patients, respectively. Due to the ongoing severe female factor fertility problems, 5 couples were not included from pregnancy rate calculations. The total patency and pregnancy rates were 79% and 31%, respectively. Mean total motile sperm count for patients demonstrating patency at follow-up was 38 million. The history of conception with the current partner was predictive of future conception with 4 or 5 nonremarried couples (80%) initiating pregnancy versus 3 of 18 remarried couples (17%) (p = 0.006). Reconstruction with vasovasostomy on at least one side trended toward improved patency (p = 0.17) and pregnancy rates (p = 0.15) although they did not assume statistical significance. The study concludes that microsurgical reconstruction following failed vasectomy reversal is associated with high patency and moderate pregnancy rates at short-term follow-up.

Adult pseudosarcoma of the bladder.

Pseudosarcomatous tumor of the urinary bladder is an unusual benign proliferative lesion that poses a diagnostic dilemma for both the urologist and pathologist. Its clinical and histologic features mimic a malignant neoplasm, although simple excision is curative. Although similar lesions have been reported in multiple extravesicle locations, most commonly the lung, bladder lesions have only recently been reported. We describe 2 cases of pseudosarcomatous bladder tumors presenting in patients with no known risk factors. We review clinical, histologic, and management issues in these patients. By recognizing the existence of this lesion, possible extensive and inappropriate surgery may be avoided.

Intermittent azoospermia associated with epididymal sarcoidosis.

OBJECTIVE: To report an unusual case of intermittent azoospermia associated with epididymal sarcoidosis. DESIGN: Retrospective case analysis. SETTING: Wilford Hall Medical Center. PATIENT(S): A 36-year-old male with secondary infertility and epididymal sarcoidosis. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): An analysis of sperm count in relation to steroid courses. RESULTS(S): Epididymalgia, and to a lesser extent, sperm counts were noted to fluctuate temporally around steroid courses given for pulmonary flares of sarcoidosis. Epididymal sarcoidosis can be associated with intermittent azoospermia. Presumably, epididymal granulomas undergo exacerbations and remissions and cause intermittent ductal obstruction. CONCLUSIONS(S): Because of the unpredictable effect of sarcoidosis on the male genital tract, all patients interested in paternity should obtain a semen analysis at the time of disease diagnosis. If oligospermia is noted or if there is clinical evidence of epididymal involvement, the patient should be offered sperm banking for possible future assisted reproductive techniques.

The effect of parenteral testosterone replacement on prostate specific antigen in hypogonadal men with erectile dysfunction.

PURPOSE: Parenteral testosterone supplementation is a common treatment for erectile dysfunction in hypogonadal men. Despite its frequent use, the effect of testosterone on prostate specific antigen (PSA) in these patients has not been documented previously. In this study we determined the effect of parenteral testosterone replacement on PSA and PSA velocity in a group of men being treated for erectile dysfunction. MATERIALS AND METHODS: A retrospective analysis of 48 patients (mean age 65.9) was performed and 2 study groups were identified. Group 1 consisted of 27 patients with a serum PSA level before and after initiating testosterone replacement therapy, and group 2 consisted of 27 men with a minimum of 3 PSA measurements (intervals of 6 months or greater) while on testosterone replacement. Each man had erectile dysfunction, a normal digital rectal examination and a low or low-normal total serum testosterone level before initiating therapy. Testosterone replacement was discontinued if no subjective improvement in erectile function was obtained, or if prostate adenocarcinoma was suggested by digital rectal examination or PSA. RESULTS: The mean increase in PSA after initiating testosterone replacement was 0.29 ng./ml. representing a mean change of 37% from baseline (mean interval 12.8 months). The mean PSA velocity was 0.05 ng./ml. per year. Pretreatment testosterone level, age and testosterone dose did not independently alter the PSA during testosterone replacement. Eleven men required prostate biopsies during treatment. Biopsies were indicated for abnormal digital rectal examination in 10 men and an elevated PSA in 1. All biopsies were benign. CONCLUSIONS: Parenteral testosterone replacement in hypogonadal men with normal pretreatment digital rectal examination and serum PSA levels does not alter PSA or PSA velocity beyond established nontreatment norms. Thus, any significant increase in PSA or PSA velocity should not be attributed to testosterone replacement therapy and should be evaluated.

Fibrin-glue assisted vasoepididymostomy: a comparison to standard end-to-side microsurgical vasoepididymostomy in the rat model.

PURPOSE: The use of fibrin glue for vasovasostomy has produced high patency rates in animal models. Vasoepididymostomy is a microsurgical technique that might be made easier if fibrin glue could substitute for microsutures. We evaluated the efficacy of a new vasoepididymostomy technique using fibrin glue. MATERIALS AND METHODS: Bilateral vasoepididymostomies were performed in 24 male Sprague-Dawley rats using a conventional microsurgical technique on one side and a fibrin-glue assisted technique on the other. The rats were sacrificed 30 days after surgery and anastomotic patency was assessed by examining the vasal fluid for sperm, injecting methylene blue dye into the vas deferens and observing backflow into the epididymis by gross inspection and histological studies. Additionally, the incidence of granuloma formation was compared between the two techniques. RESULTS: Fibrin-glue anastomoses showed a patency rate of 79% (n = 19), compared with 63% (n = 15) for the conventional suture anastomoses (p = 0.29). Among the patent anastomoses, the incidence of sperm granuloma formation between the sutured (12, 50%) and the fibrin glue anastomoses (16, 67%) did not differ significantly (p = 0.36). Morphological tissue changes were similar for the two techniques. The time required for anastomosis using fibrin glue was significantly shorter than the conventional suture technique (p < 0.001). CONCLUSIONS: Conventional suturing techniques for vasoepididymostomy require advanced microsurgical skills. The use of fibrin glue simplifies this procedure and provides patency rates comparable to microsutured, end-to-side anastomoses.

Excessive testosterone production in a patient with Nelson syndrome and bilateral testicular tumors.

Bilateral primary testicular tumors are rare and usually consist of either interstitial cells or hypertrophic testicular adrenal remnant tissue. Their differentiation on clinical presentation and histologic examination remains difficult but is essential because of the different therapeutic approaches. We report a rare case of excessive testosterone production by bilateral testicular tumors in a patient with Nelson syndrome (ACTH-secreting pituitary adenoma after bilateral adrenalectomy in patients with Cushing's disease). Increased ACTH stimulation in this patient supports the thesis of pluripotent cells within the testis which can undergo differentiation to cells which are not only morphologically similar to Leydig cells but also have the functional property of these cells. Our clinical findings support the diagnosis of hyperplasia of adrenal remnant or pluripotent cells rather than a true Leydig cell tumor. We emphasize the need for hormonal evaluations which should be assessed in the context of the size of these nodular tumors prior to therapeutic decisions. In cases with elevated serum ACTH and small nodular hyperplasia, we would favor a 'wait-and-see' strategy with appropriate hormonal therapy. In large tumors with clinical signs of hormonal activity, patient noncompliance with steroid replacement regimens or with local symptoms, scrotal exploration and tumor enucleation are indicated.

Diagnostic tunica vaginoscopy in a rodent model of testicular torsion.

OBJECTIVES: To evaluate the effectiveness of percutaneous endoscopy of the tunica vaginalis for identifying testicular torsion in a rodent model. METHODS: One testis was randomly selected in 10 Wistar rats weighing 500 to 600 g. Following 2 hours of 720 degree torsion, bilateral percutaneous endoscopy of the tunica vaginalis was performed by a blinded investigator utilizing a 70 degree cystoscope lens through a single midline 3 to 4 mm scrotal cutdown incision. RESULTS: Using this technique, the blinded investigator was able to identify the torsed testis rapidly in every case, which was distinguished by its cyanotic color and by the size and color of the testicular surface vessels. CONCLUSIONS: Tunica vaginoscopy is a simple, accurate, rapidly performed, minimally invasive, diagnostic technique in this experimental model of testicular torsion.

Effectiveness of crossover transseptal vasoepididymostomy in treating complex obstructive azoospermia.

OBJECTIVE: To review the indications, surgical technique, and results of crossover transseptal vasoepididymostomies for treatment of complex obstructive azoospermia and oligospermia. DESIGN: Retrospective review of our experience with crossover transseptal end-to-side vasoepididymostomies in 10 men. INTERVENTIONS: Ten men underwent crossover transseptal end-to-side vasoepididymostomies. Nine men had primary and one had secondary infertility. Seven men were azoospermic, and the remaining 3 had severe oligospermia (sperm density < 1 x 10(6)/mL). All had a combination of irreparable ipsilateral ductal obstruction or agenesis with a normal testis and a poorly functional or absent contralateral testis. Contralateral testicular atrophy was associated with a prior hernia repair in 3 men, varicocele-induced atrophy in 2, and severe orchitis in 2. Cryptorchidism, testicular torsion, and one unknown cause were reported for three others. Congenital absence of the vas deferens caused the ipsilateral ductal pathology in 5 men. Three men had a vas injury from pediatric inguinal surgery, and 2 had an idiopathic vas obstruction. RESULTS: Twelve microsurgical crossover transseptal vasoepididymostomies were performed (2 men had repeat procedures). Anastomosis was performed to the caput in five men, the corpus in two, and the cauda in three men. Eight of nine men followed for 6 months or more had sperm in their ejaculate. Two of seven couples have established pregnancies. Total sperm counts ranged from 18 to 201 x 10(6) (mean, 98.1 x 10(6)) with motility of 5% to 37% (mean, 13%). Men with congenital absence of the vas deferens had significantly lower postoperative total sperm counts than men with all other causes of ductal pathology: 37.8 x 10(6) versus 135 x 10(6). No other characteristics (type of infertility, preop semen analysis, cause of testicular pathology, site of epididymal anastomosis) were useful predictors of postoperative sperm counts. CONCLUSIONS: If there is a solitary functioning testis with irreparable excurrent ductal obstruction or agenesis, a crossover transseptal vasoepididymostomy can restore patency in most men.

Modified resectoscope loop for transurethral resection of the ejaculatory duct.

We report the design of a modified resectoscope loop for transurethral resection of the ejaculatory ducts. The loop is a modification of a standard 24 F resectoscope loop. Cutting dimensions are 2.5 mm in width and 3 mm in depth for the modified loop versus 6 mm in width and 5 mm in depth for the conventional loop. This modification allows precise resection of obstructed ejaculatory ducts with minimal trauma to the prostatic fossa, reducing the potential for troublesome bleeding.

Transcatheter embolization of large idiopathic renal arteriovenous fistula.

Renal arteriovenous fistulas are unusual lesions with a variety of clinical manifestations. Congenital and acquired forms have been treated successfully with transcatheter embolization for 2 decades. In the case of large aneurysmal lesions the risk of inadvertent pulmonary embolism has traditionally precluded this approach and necessitated open surgery. However, with refinements in angiographic equipment and technique, such an approach is now feasible and desirable.

Cavernous adrenal hemangioma.

Cavernous hemangiomas are unusual tumors with a propensity for skin and liver involvement and rarely involving genitourinary organs. We report an unusual case of adrenal hemangioma which was successfully treated surgically. In addition, we review the salient clinical, radiographic, and pathologic features of this disease.