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Can a previously defined relationship between sperm capacitation and the probability of a man generating pregnancy within three cycles, prospectively predict male fertility in diverse clinical settings? A second study asked, what is the prevalence of impaired sperm fertilizing ability in men questioning their fertility (MQF), and does this relate to traditional semen analysis metrics?In the multicentric, prospective observational study, data (n = 128; six clinics) were analysed to test a published relationship between the percentage of fertilization-competent, capacitated spermatozoa (Cap-Score) and probability of generating pregnancy (PGP) within three cycles of intrauterine insemination. Logistic regression of total pregnancy outcomes (n = 252) assessed fit. In the cohort comparison, Cap-Scores of MQF (n = 2155; 22 clinics) were compared with those of 76 fertile men.New outcomes (n = 128) were rank-ordered by Cap-Score and divided into quintiles (25-26 per group); chi-squared testing revealed no difference between predicted and observed pregnancies (P = 0.809). Total outcomes (n = 252; 128 new + 124 previous) were pooled and the model recalculated, yielding an improved fit (P0.001). Applying the Akaike information criterion found that the optimal model used Cap-Score alone. Cap-Scores were performed on 2155 men (with semen analysis data available for 1948). To compare fertilizing ability, men were binned by PGP (≤19%, 20-29%, 30-39%, 40-49%, 50-59%, ≥60%). Distributions of PGP and the corresponding Cap-Scores were significantly lower in MQF versus fertile men (P0.001). Notably, 64% of MQF with normal volume, concentration and motility (757/1183) had PGP of 39% or less (Cap-Scores ≤31), versus 25% of fertile men.Sperm capacitation prospectively predicted male fertility. Impaired capacitation affects many MQF with normal semen analysis results, informing diagnosis versus idiopathic infertility.

Semen analysis (SA) poorly predicts male fertility, because it does not assess sperm fertilizing ability. The percentage of capacitated sperm determined by GM1 localization ("Cap-Score™"), differs between cohorts of fertile and potentially infertile men, and retrospectively, between men conceiving or failing to conceive by intrauterine insemination (IUI). Here, we prospectively tested whether Cap-Score can predict male fertility with the outcome being clinical pregnancy within ≤3 IUI cycles. Cap-Score and SA were performed (n = 208) with outcomes initially available for 91 men. Men were predicted to have either low (n = 47) or high (n = 44) chance of generating pregnancy using previously-defined Cap-Score reference ranges. Absolute and cumulative pregnancy rates were reduced in men predicted to have low pregnancy rates versus high ([absolute: 10.6% vs. 29.5%; p = 0.04]; [cumulative: 4.3% vs. 18.2%, 9.9% vs. 29.1%, and 14.0% vs. 32.8% for cycles 1-3; n = 91, 64, and 41; p = 0.02]). Only Cap-Score, not male/female age or SA results, differed significantly between outcome groups. Logistic regression evaluated Cap-Score and SA results relative to the probability of generating pregnancy (PGP) for men who were successful in, or completed, three IUI cycles (n = 57). Cap-Score was significantly related to PGP (p = 0.01). The model fit was then tested with 67 additional patients (n = 124; five clinics); the equation changed minimally, but fit improved (p < 0.001; margin of error: 4%). The Akaike Information Criterion found the best model used Cap-Score as the only predictor. These data show that Cap-Score provides a practical, predictive assessment of male fertility, with applications in assisted reproduction and treatment of male infertility.

Sperm must mature functionally in the process of capacitation to become able to fertilize. Capacitation depends on membrane lipid changes, and can be quantitatively assessed by redistribution of the ganglioside GM1 , the basis of the Cap-Score™ sperm function test. Here, differences in Cap-Score were compared among and within men at two time points. Ejaculates were liquefied, washed, and incubated for 3 hr under capacitating (Cap) conditions, then fixed and analyzed immediately (Day0); after being incubated 3 hr under Cap conditions then maintained 22-24 hr in fix (Day1-fix); or after 22-24 hr incubation under Cap conditions prior to fixation (Day1). In all cases, a light fixative previously shown to allow membrane lipid movements was used. Day1-fix and Day1 Cap-Scores were greater than Day0 (p < 0.001; n = 25), whereas Day1-fix and Day1 Cap-Scores were equivalent (p = 0.43; n = 25). In 123 samples from 52 fertile men, Cap-Score increased more than 1SD (7.7; calculated previously from a fertile cohort) from Day0 to Day1-fix in 44% (54/123) of the samples. To test whether timing of capacitation was consistent within an individual, 52 samples from 11 fertile men were classified into either "early" or "late" capacitation groups. The average capacitation group concordance within a donor was 81%. Median absolute deviation (MAD; in Cap-Score units) was used to assess the tightness of clustering of the difference from Day0 to Day1-fix within individuals. The average (2.21) and median (1.98) MAD confirmed consistency within individuals. Together, these data show that the timing of capacitation differed among men and was consistent within men.

Semen analysis lacks a functional component and best identifies extreme cases of infertility. The ganglioside GM1 is known to have functional roles during capacitation and acrosome exocytosis. Here, we assessed whether GM1 localization patterns (Cap-Score™) correspond with male fertility in different settings: Study 1 involved couples pursuing assisted reproduction in a tertiary care fertility clinic, while Study 2 involved men with known fertility versus those questioning their fertility at a local urology center. In Study 1, we examined various thresholds versus clinical history for 42 patients; 13 had Cap-Scores ≥39.5%, with 12 of these (92.3%) achieving clinical pregnancy by natural conception or ≤3 intrauterine insemination cycles. Of the 29 patients scoring

The use of microsurgical techniques (vasovasostomy and epididymovasostomy) for vasectomy reversal has now enabled surgeons to perform both procedures with certainly acceptable success rates. However, these operations are technically demanding and require special training in microsurgery.Purpose: A new method of performing these procedures using laser tissue soldering is described and results are evaluated. Laser tissue soldering is different from laser welding in that it involves the laser activation of a protein solder with a dye specific for the specific wavelength of laser light; therefore, surrounding tissue is not affected by the laser.Materials and Methods: Ten rats underwent bilateral vasovasostomy and eleven underwent bilateral epididymovasostomy. In each rat, a sutured anastomosis was performed on one side while laser tissue soldering was performed on the other. Animals were sacrificed after one month and anastomoses were evaluated for patency and presence of sperm granulomas. Histologic ...

We assessed the frequency of bone metastases, their association with serum alkaline phosphatase (AP), and prognostic capabilities of AP in patients with renal cell carcinoma (RCC), using bone scan as the reference standard for diagnosis.We conducted a retrospective review of patients with metastatic RCC treated with either autologous ex vivo activated T-lymphocytes and cimetidine (ALT) or cimetidine alone.Twenty-eight of 90 patients (31%) had evidence of bone metastases by bone scan. With 100 mg/ dL as the upper limit of normal, 11 of 28 (39%) patients with bone metastases had normal AP levels. Of these 11 patients, 8 had bone pain. Of the 3 asymptomatic patients with bone metastasis and normal AP levels, only 1 had bone as the only site of metastasis and would have been incorrectly staged without the scan. Patients with bone metastases had a significantly shorter median survival than those without bone metastases (13.8 versus 25.3 months; P0.05). Among patients without bone metastases who had elevated AP levels, those treated with ALT had significantly longer median survivals than those treated with cimetidine alone (27.6 versus 14.5 months; P0.05). Overall, patients treated with ALT had a significantly longer median survival than the ones treated only with cimetidine (21 versus 8.5 months; P0.05). Overall, the median survival for patients with elevated AP levels (10 months) was not significantly different from that of those with normal AP levels (13 months).In a high-risk group of patients with metastatic RCC, 31% had bone metastases. Elevated AP levels, the presence of bone pain, or the presence of other metastases correctly predicted bone metastasis in all but 1 patient. A bone scan may safely be omitted in patients with RCC, normal AP levels, and no bone pain. However, AP elevation itself had little prognostic capability in these patients.

Objective . To examine the efficacy of prostate-specific antigen (PSA) density (PSAD; serum PSA/prostate volume) as a predictor of clinical outcome of patients undergoing radical retropubic prostatectomy for clinically confined prostate cancer, and its ability to determine the presence of micrometastatic disease. Methods. A retrospective analysis of patient outcome as reflected by surgical stage and postoperative PSA was performed with respect to PSAD as determined by preoperative PSA and pathologic prostate gland volume. The findings for 107 consecutive patients who underwent radical prostatectomy are reported. Results. PSAD at low values was found to be 90 percent accurate in predicting operative success or absence of micrometastatic disease. PSAD at high values was shown to be 70 percent accurate in predicting failure. Conclusions. PSAD appears to be useful in selecting patients for radical prostatectomy and may be capable of identifying patients with micrometastatic disease.

Purpose: Several different methods to construct a bladder substitute after cystectomy have been described. We evaluated our experience with the Studer ileal ureter neobladder during the last 5 years.Materials and Methods: We reviewed retrospectively the results in 32 patients who underwent construction of a slightly modified ileal neobladder from that originally described. Mean followup was 25 months (range 6 to 68).Results: Patients experienced few complications and only 1 required reoperation. Daytime and nighttime continence rates were 94 and 74 percent, respectively. One patient sustained a ureteral stricture resulting in hydronephrosis (1 of 64 renal units).Conclusions: The results reveal the ileal neobladder to be an easily constructed pouch with a low complication rate, and a high success rate in regard to continence and the establishment of adequate capacity at low pressure. Within the study period upper tract preservation was excellent. However, a 10 to 15-year followup is indicated to co...

This paper reviews the application of laser technology (CO2 laser technique neodymium:yttrium aluminum garnet laser technique laser tissue soldering) to vasectomy reversal surgery. Modern methods of vasectomy reversal that utilize microsurgical techniques have produced high success rates but these procedures are also technically demanding. Due to the demands of conventional sutured microsurgical vasovasostomy new techniques have been reported in laser tissue-welding employing both carbon dioxide and neodymium:yttrium aluminum garnet (Nd:YAG) lasers to assist in the performance of microsurgical vasovasostomy. With laser technology the reanastomosis of the vas deferens after a vasectomy can be a simple procedure performed in a shorter operative time with possibly even better results. In conclusion it appears that the application of laser technology in vasovasostomy for vasectomy is still in its early stage of development. Moreover laser technology application if proven in appropriate clinical experiments offers the promise of providing a method for shorter and less technically demanding procedure for the surgeon. In addition laser tissue soldering may theoretically create less devascularization because tissue absorption of laser energy is minimal.

Objective To assess the accuracy of the Hemacytometer (Hausser Scientific, Horsham, PA), Makler (Sefi-Medical Instrument, Haifa, Israel), Cell-VU (Millennium Sciences Inc., New York, NY), and Micro-Cell chambers (Conception Technologies, San Diego, CA) counting chambers. Design A solution containing a known concentration of latex beads was used as the standard to perform counts on the four different counting chambers. Main Outcome Measures Bead counts for the four different chambers were compared with the bead counts of the standard solution. Variability within chambers also was determined. Results Mean bead concentrations for both the Cell-VU and Micro-Cell chambers were consistently similar to the bead concentration of the standard solution. Both the hemacytometer and the Makler chambers overestimated the actual bead concentration of the standard solution by as much as 50% and revealed significant interchamber variability. Conclusions Our data revealed marked differences in the accuracy and reliability of the different counting chambers tested and emphasized the need for standardization and quality control of laboratory procedures.

Objectives Incontinence after radical retropubic prostatectomy remains a common problem. This study determines the efficacy of a tubularized bladder neck reconstruction for improving the time to continence and also the total rate of continence following radical retropubic prostatectomy. Methods Tubularized bladder neck reconstruction was performed in 29 patients by creating a trapezoidalshaped anterior bladder flap and performing tubularization over a 30 F red rubber catheter prior to urethrovesical anastomosis. This flap measured approximately 5 cm at its base and 3 cm at its apex. Continence rates of these patients were compared to results of 30 randomly selected patients in whom a bladder flap was not used. Results Seven of 29 (24%) patients with tubularized bladder neck reconstruction were fully continent within 24 hours of catheter removal and 27 of 29 (93%) were fully continent by 3 months follow-up. An additional patient was continent at 6 months for a total continence rate of 28 of 29 (97%). These continence rates were significantly higher at all follow-up times than for patients in whom an anterior bladder flap was not used. One patient developed a bladder neck contracture and was successfully managed with visual urethrotomy. He is fully continent. Conclusions Tubularized bladder neck reconstruction following radical prostatectomy may both increase the successful achievement of postoperative continence and decrease the time needed to achieve full continence without increasing morbidity.

The metastatic pattern of renal cell carcinoma has been well established. Studies have revealed a relatively high incidence of spread to lung, liver, bone and brain. A retrospective review of the records of ninety patients with metastatic renal cell carcinoma showed seven to have evidence of brain metastases. Six of the seven were asymptomatic at time of diagnosis. This study shows a significant incidence of asymptomatic brain metastases in patients with metastatic renal cell carcinoma. Subsequent to our chart review, an additional two patients have presented to our institution with asymptomatic brain lesions from metastatic renal cell carcinoma.

Continent urinary diversions have gained popularity during recent years in the treatment of patients who require cystectomy. The formation of urinary stones remains a possible late complication of urinary diversion. We report the successful use of a percutaneous approach to remove stones from an Indiana pouch after other methods failed.

A testicular tumor presenting as torsion is reported in a fifty-two-year-old man. This is the first reported case in a patient more than twenty-eight years old.

An incidentally discovered 1.5 cm renal mass was followed by serial CT scans for a period of 2 years. The mass showed no signs of growth or change during this period. The patient underwent radical nephrectomy with pathology positive for renal cell carcinoma. The evaluation of small renal masses is reviewed.

To the Editor. —Even though the recent Clinical Crossroads article by Dr Collins was entitled "A Couple With Infertility," 1 the article ignores the evaluation of an essential part of that couple, namely, the male partner. Although the clinical scenario includes a normal semen analysis (which is never defined) and postcoital test as proof of a normal male factor, this limited evaluation of the male partner is inadequate; unfortunately, more and more couples encounter this type of approach. Medical students are taught that 90% of diagnoses are made from the history and physical examination. Did the male in this couple have history of orchitis, epididymitis, previous inguinal surgery, or other risk factors for development of antisperm antibodies? It is possible to have a normal semen analysis and yet have antisperm antibodies interfere with fertilization at the site of sperm-zona pellucida interaction. It is also possible that the male in this