Sex chromosome micromosaicism in infertile men with normal karyotypes.

OBJECTIVE: To define the prevalence of low-level sex chromosome mosaicism in a cohort of infertile men. DESIGN: Prospective cohort study of infertile men. SETTING: Tertiary university infertility center. PATIENT(S): One hundred one consecutive men who presented with primary infertility for evaluation. INTERVENTION(S): Fluorescent in situ hybridization for X and Y was performed on 200 cells, and if an aberrant sex chromosome complement was noted, 400 cells were counted. For this study, any abnormality in sex chromosome complement was defined as micromosaicism. MAIN OUTCOME MEASURE(S): Low-level sex chromosome mosaicism. RESULT(S): Sixty-seven of these men (67%) had no mosaicism, and 34 men (34%) had micromosaicism. The median percentage of abnormal chromosomes in these men was 2%. The mean age of the men without micromosaicism was lower than for men with micromosaicism (31.1 years vs. 35.2 years). A trend toward higher FSH levels in men with low-level mosaicism was seen. Median sperm density and percent motility were higher in normal men. Percent normal morphology was identical between groups. CONCLUSION(S): We found low-level sex chromosome mosaicism in 34% of infertile men who presented for evaluation. Men with low-level mosaicism were significantly older. Low-level mosaicism may emerge with advancing age and may therefore help to explain the decline in fertility potential seen in older men.

The morphology of extracted testicular sperm correlates with fertilization but not pregnancy rates.

OBJECTIVE: To investigate sperm morphology on the day of fresh testicular sperm extraction (TESE) with intracytoplasmic sperm injection (ICSI), and its effect on fertilization and pregnancy rates, as TESE in conjunction with ICSI results in high fertilization and pregnancy rates in most patients, but to our knowledge only one small study has assessed the morphology of retrieved sperm and found no correlation with the success of fertilization. PATIENTS AND METHODS: In a retrospective database analysis in a large academic centre, 68 men had 75 cycles of TESE combined with ICSI from January 2004 until April 2006. Sperm obtained by TESE was morphologically analysed at high (x 400-600) magnification and used for ICSI on the day of tissue retrieval. Sperm were classified as being either normal, having an amorphous head, having a mid-piece defect or having multiple defects. The calculated percentage of abnormal sperm injected was compared with the normal fertilization rate using Pearson's correlation coefficient, and pregnancy rates between groups were compared using chi-square analysis. RESULTS: Fifteen cycles had all morphologically normal sperm; 21 cycles had 50-99% normal forms and 39 cycles had <50% normal sperm. There was a highly significant correlation between the percentage of normal sperm used for ICSI and fertilization rates (P = 0.007). Overall, 43 clinical pregnancies resulted in this series, i.e. three among the group with all normal sperm injected, 12 in the group with 50-99% normal sperm and 28 in the group with <50% normal forms. There were also 11 pregnancies in cycles that used no normal forms. Pregnancy rates did not differ significantly among the groups (P = 0.08). CONCLUSIONS: TESE with ICSI frequently results in successful pregnancy; normal morphology was highly and significantly associated with successful fertilization, but importantly there were still 10 clinical pregnancies in cycles where only abnormal sperm were used. Sperm morphology after TESE should be assessed at the time of the procedure, and whenever possible, morphologically normal sperm chosen for injection. However, it is reassuring that acceptable fertilization and pregnancy rates are still achievable in cases with no morphologically normal sperm available.

Medical and surgical management male infertility.

Male infertility is the result of a variety of highly treatable conditions. The critical step in treating male infertility is to evaluate properly every male partner of an infertile couple and to generate the proper treatment strategy. There are many medical and surgical options that can help most couples overcome male factor infertility. Male infertility can most easily be broken down into problems of sperm production (testicular dysfunction) and problems of sperm transport (obstruction). When applicable, medical therapies are used as an initial strategy to improve sperm production or as a preliminary therapy to boost production transiently in anticipation of a surgical sperm retrieval attempt. A range of surgical options is available to correct varicoceles, reconstruct the obstructed system, or retrieve sperm for assisted reproduction.

Early use of a phosphodiesterase inhibitor after brachytherapy restores and preserves erectile function.

OBJECTIVE: To investigate whether the early use of phosphodiesterase inhibitors (PDEIs) after brachytherapy (BT) is associated with better erectile function, as of men potent before BT 38-70% have erectile dysfunction afterward. PATIENTS AND METHODS: We evaluated a prospectively created database of 2500 patients who had had BT at our institution since 1992. We measured baseline age, cancer stage, Gleason grade, prostate specific antigen (PSA) level at diagnosis, implant type, use of neoadjuvant and adjuvant hormonal suppression therapy, use of external beam radiotherapy in conjunction with interstitial therapy, and follow-up PSA levels. Men were stratified by their use of PDEIs at <1 year (early group) or >1 year after implantation (late group). We excluded all men who did not have baseline Sexual Health Inventory for Men (SHIM) scores and at least one follow-up SHIM score; the latter were obtained at 6-month intervals after BT. Data were analysed using the Mann-Whitney U-test. RESULTS: In all, 210 men met the inclusion criteria; 85 began using PDEIs within a year of BT, and 125 started after a year. The mean time to PDEI use was 191 days in the early and 595 days in the late group. The median age was 62 years in the early and 63 years in the late group (P = 0.02). Baseline Gleason scores did not differ, nor did PSA levels between the groups. Of men in the early group, 48% received neoadjuvant and/or adjuvant hormonal suppression therapy, vs half of men in the late group. Baseline SHIM scores were not significantly different, nor were scores at the first two follow-up assessments, but the scores at 18-36 months after BT were significantly different. CONCLUSION: The early use of PDEIs after BT is associated with a significant improvement in and maintenance of erectile function compared with late use. Men undergoing BT should be encouraged to use PDEIs early after implantation, to preserve erectile function.

Correlation of ultrasound-measured venous size and reversal of flow with Valsalva with improvement in semen-analysis parameters after varicocelectomy.

We studied 68 men with varicoceles to determine preoperative parameters that are associated with improvements in semen analysis after varicocelectomy. Ultrasound-measured venous diameter and reversal of flow were found to correlate with successful outcome.

Ion channel gene therapy for smooth muscle disorders: relaxing smooth muscles to treat erectile dysfunction.

The promise of gene therapy to treat diseases remains largely unfulfilled. Past setbacks and the complexity of the delivery systems used, in terms of both targeting the appropriate cells and inducing expression of products at therapeutic levels, thus far have prevented significant success for gene therapy. Smooth muscle disorders represent a unique target for gene therapy. In many cases, smooth muscle is readily accessible and, to induce a therapeutic effect, will not require very high levels of gene product expression. This allows a lower efficiency of gene transfer to be successful. With these important features in mind, we believe that naked DNA transfer of potassium ion channels represents a novel and successful way to treat smooth muscle disorders. Herein, we present a rationale for treating erectile dysfunction, a smooth muscle disorder of the cavernosal bodies of the penis, with naked DNA gene transfer therapy. By inserting the hSlo gene, which codes for Maxipotassium channels, into smooth muscle cells, we can improve smooth muscle relaxation in the corporal bodies and thus improve erectile function. This method of gene transfer has proven to be safe and effective for erectile dysfunction, and human trials are ongoing.

Success of testicular sperm extraction [corrected] and intracytoplasmic sperm injection in men with Klinefelter syndrome.

PURPOSE: The aim of this study was to report the successful fertility treatment of men with Klinefelter syndrome using testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). METHODS: A total of 42 men with Klinefelter syndrome who underwent 54 TESE procedures were identified. Before TESE, patients with serum testosterone levels less than 15.6 nmol/liter were treated with an aromatase inhibitor. Sperm retrieval rates and results of ICSI, including fertilization and clinical pregnancy, were collected. RESULTS: Mean pretreatment FSH and testosterone levels were 33.2 IU/liter and 9.8 nmol/liter. During medical therapy, the mean testosterone level rose to 17.0 nmol/liter (P < 0.01). Spermatozoa were found during 39 microdissection TESE procedures, on the day before, or day of oocyte retrieval during a programmed in vitro fertilization cycle. The sperm retrieval rate was 72% (39 of 54) per TESE attempt, and 29 of the 42 different men (69%) had adequate sperm found for ICSI. Thirty-three in vitro fertilization cycles yielded embryos for transfer in the 39 (85%) cycles with sperm retrieved. Eighteen clinical pregnancies have resulted in 21 live births [18 of 39 (46%)]. All children had a normal karyotype. CONCLUSION: TESE/ICSI is a successful intervention for the majority of patients with azoospermia and Klinefelter syndrome. Sperm retrieval and ICSI success in men with Klinefelter syndrome are comparable with other men with nonobstructive azoospermia treated at our center.

Laparoscopic vs open partial nephrectomy in consecutive patients: the Cornell experience.

OBJECTIVE: To compare a contemporary series of laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN) at one institution, to evaluate the size and types of tumour in each group and the early outcome after each procedure, as LPN is replacing open radical nephrectomy as the standard of care for uncomplicated renal tumours but partial nephrectomy remains significantly more difficult laparoscopically, especially if the goal is to duplicate the open surgical technique. PATIENTS AND METHODS: We retrospectively analysed the records of all patients who underwent partial nephrectomy at our institution from January 2000 to April 2004, identifying 66 who had LPN and compared them with 59 who had OPN (mean age at LPN and OPN, 62.1 and 64.2 years, respectively; 70% men in each group). Variables analysed included operative time, blood loss, creatinine levels before and after partial nephrectomy, time to resuming clear liquids and regular diet, length of stay, tumour size, tumour pathological type and complications. Groups were compared using Student's t-test, with P < 0.05 taken to indicate significance. RESULTS: Of those having LPN, 59% had right-sided tumours, vs 53% in the OPN group; the respective mean tumour size was 2.2 and 3.4 cm, the mean operative duration 144 and 239 min (both P < 0.001), and the mean estimated blood loss 236 and 363 mL (P = 0.09). Seven patients in the OPN group had obligatory partial nephrectomy for either a solitary kidney (two) or azotaemia (five). No patient in the LPN group required an obligatory partial nephrectomy. Serum creatinine levels were measured before and 1 and 2 days after surgery, and were 88, 88 and 97 micromol/L for the LPN group, and 97, 106 and 106 micromol/L for the OPN group. Clear fluids were started a mean of 41 h after surgery, a regular diet resumed 76 h after and discharge was 129 h after surgery in the OPN group; the respective values for the LPN group were 24 h (P = 0.01), 49 h (P = 0.2) and 82 h (P < 0.001). Complications were similar in both groups but the pathological subtypes differed. CONCLUSIONS: LPN offers early functional advantages over OPN in terms of earlier resumption of diet and slightly earlier discharge. However, the two groups of patients were clearly not evenly matched for size nor pathological subtypes, with larger, malignant subtypes more predominant in the OPN group. These results suggest that while LPN is a safe, effective treatment for small renal tumours, obligatory partial nephrectomy or large tumours continue to be performed using open techniques with good results.

Neuroprotective strategies in radical prostatectomy.

In this section, authors from New York give their views on the various neuroprotective strategies for patients having a radical prostatectomy, such as the use of nerve grafts and other approaches. A joint study from Korea, the USA, Canada and the UK is presented in a paper on the importance of patient perception in the clinical assessment and management of BPH. There is also a review of robotic urological surgery. Finally, authors from New York give a review on the life of Isaac Newton. This is a new historical review in the journal, but one that will be of general interest.

Laparoscopic adrenalectomy for pheochromocytoma.

Laparoscopic adrenalectomy has become the standard technique for the surgical removal of the adrenal gland for functional adrenal tumors including aldosteronoma, glucocorticoid, and androgen/estrogen-producing adenomas. Many laparoscopic surgeons also think that for small to moderately sized pheochromocytomas, the laparoscopic approach is as safe and effective as the open technique. Several physiologic considerations specific to pheochromocytoma must be addressed before and during surgery regardless of the operative approach. The advantages of laparoscopic adrenalectomy over open adrenalectomy remain the same for pheochromocytomas as for other pathologic conditions of the adrenal gland. These include a shorter length of stay, a decrease in postoperative pain, a shorter time to return to preoperative activity level, and improved cosmesis.

Rapid disappearance of spermatozoa after vasal occlusion in the dog.

The reproductive system of the male dog is unusual in that the seminal vesicles and bulbourethral glands are absent. Therefore, we chose the dog as a model to evaluate the effect of seminal vesicles on clearance of spermatozoa from the male reproductive tract after vasal occlusion. Thirty adult male beagle dogs with ejaculates containing at least 500 x 10(6) sperm with greater than 90% motility were used for this study. The dogs' vasa were occluded percutaneously using a Vasocclude clip-applying device through a small scrotal puncture site. Dogs were ejaculated and semen analysis was performed before and after vas occlusion. The first 24 dogs were completely azoospermic 1 week following vas occlusion. In order to explain these unanticipated results, an additional 6 dogs were evaluated to determine the specific time course of sperm disappearance from the ejaculate at 1, 3, 5, and 7 days after vas occlusion. The results revealed that spermatozoa were almost completely absent within 1 day after vas occlusion (99.9% reduction, X = 1.0 + 1.1 x 10(6) sperm per milliliter at 1 day, P <.0005 vs prevas occlusion). The rapid elimination of spermatozoa after vas occlusion indicates that sperm transit rapidly through the vas deferens in dogs. Therefore, the delayed clearance of spermatozoa from the ejaculate in humans may be due to sperm storage in the seminal vesicles.

Henoch-Schonlein purpura involving the glans penis.

Henoch-Schonlein purpura is a systemic vasculitis syndrome characterized by palpable purpura, glomerulonephritis, arthralgias, and gastrointestinal signs and symptoms. This syndrome typically presents in children between the ages of 4 and 7 years. Renal involvement can be progressive, irreversible, and fatal. Although skin lesions are frequently found on the scrotum and have been described on the penile shaft, no cases of glandular involvement have been previously reported. We describe the presentation of a 4-year-old boy with extensive involvement of painless purpuric lesions on his penile shaft, scrotum, and glans penis.

Pulmonary embolus related to PC-SPES use in a patient with PSA recurrence after radical prostatectomy.

Patients diagnosed with a rising prostate-specific antigen level after radical prostatectomy represent a therapeutic dilemma. Herbal therapies including PC-SPES have gained popularity as alternatives to conventional hormonal ablation in such patients as a result of the perceived benefits of using natural products and proven clinical response in decreasing prostate-specific antigen levels. PC-SPES is one of the most popular herbs with known estrogenic activity in vitro and in vivo. Estrogenic compounds increase the risk of thromboembolic events. However, no specific guidelines are available with regard to the risk of thromboembolic events for patients using PC-SPES. We report a case of a patient treated with PC-SPES for prostate-specific antigen recurrence after radical prostatectomy who presented with pulmonary embolus and a right common femoral deep venous thrombus.