The utility of sildenafil citrate for infertile men with sexual dysfunction: a pilot study.

OBJECTIVE: To investigate the use the sildenafil citrate, recognized as a first-line therapy for men with erectile dysfunction (ED), and which is safe and effective in men with various causes and severity of ED, including psychogenic ED, in a population of infertile men with sexual dysfunction. PATIENTS AND METHODS: Infertility is a major source of life stress and might be associated with sexual dysfunction through the erosion of self-esteem and self-confidence, and in stimulating discord in a relationship. Men presenting for evaluation of fertility who on questioning by the physician reported the recent onset of sexual dysfunction, had a history taken, a physical examination, hormonal profile, and completed the International Index of Erectile Function (IIEF), a validated inventory for assessing sexual dysfunction. Thirty men with a score of <26 on the erectile function domain of the IIEF, or who complained of new onset rapid or delayed ejaculation, were treated with sildenafil with no randomization or placebo control. The evaluation was repeated and the IIEF completed again > or =3 months after starting treatment. RESULTS: For men complaining of ED, subjective erectile rigidity, duration of erection, and the percentage of successful penetration attempts significantly improved with sildenafil. The mean (sd) IIEF domain scores for erection and satisfaction, at 18 (4) vs 27 (3), and 12 (2) vs 16 (3) (both P = 0.01), and orgasm, at 4 (1) vs 6 (3) (P = 0.001), respectively, significantly improved after treatment. In patients with ejaculatory dysfunction, the function improved in 64% after sildenafil therapy. CONCLUSIONS: We identified the nature of sexual dysfunction associated with male-factor infertility, and showed the efficacy of sildenafil therapy in men with this condition.

Defining the clinical characteristics of Peyronie's disease in young men.

INTRODUCTION: Peyronie's disease (PD) is usually seen in men in their fifth decade of life. AIM: In this study, we investigated the characteristics of the disease in young men. MAIN OUTCOME MEASURES: The demographics, clinical features, and associated comorbidities of the patients with PD were retrospectively reviewed. METHODS: The findings were compared between men with the disease who were under 40 years of age with those over 40 years. Statistical analyses were conducted to define differentiating features between these two groups. RESULTS: Of the 296 patients, 32 were under the age of 40 years and 264 over 40 years. The mean duration of the disease was 2 +/- 4 and 6 +/- 8 months in the respective age groups. Fifty-six percent of the patients under the age of 40 years and 75% of the patients over this age presented with curvature (P < 0.01). Thirty-seven percent under 40 years and 12% men over 40 years had more than one plaque at presentation (P < 0.01). Dupuytren's contracture was seen only in patients over 40 years of age. Pain at presentation was found in 75% under the age of 40 years and in 65% over 40 years (P = 0.03). Trauma history was found in 18% under 40 years and in 5% over this age (P < 0.01). Statistical significant differences were found between the groups under and over the age of 40 years for hypertension (P < 0.01) and dyslipidemia (P < 0.01). Diabetes was noted in 50% of the patients under the age of 40 years and in 18% of the patients over this age (P < 0.001). Multivariate analysis of conditions associated in men with PD under 40 years of age showed statistical significant differences for diabetes (P = 0.015), presentation within 6 months (P = 0.004), and having multiple plaques (P = 0.008). CONCLUSIONS: Young men with PD are more likely to present at an earlier stage of the disease, to have diabetes, and to have more than one plaque at the time of presentation.

Microsurgical reconstruction of iatrogenic injuries to the epididymis from hydrocelectomy.

PURPOSE: We determined the feasibility and outcome of microsurgical reconstruction of the excurrent ductal tract in men with obstruction secondary to iatrogenic injury to the epididymis from hydrocelectomy. MATERIALS AND METHODS: A retrospective chart review was done to identify men with iatrogenic injury to the epididymis or scrotal vas deferens and a history of hydrocelectomy. The outcome of microsurgical reconstruction was assessed by postoperative semen analysis. Pregnancy data were noted in patients actively attempting to conceive at a followup of 6 months or greater. RESULTS: Eight men were found to have iatrogenic injury to the epididymides (6) or scrotal vas deferens (2) due to previous hydrocelectomy. Injury was bilateral in 4 men and unilateral in 4 with contralateral testicular absence, dysfunction or obstruction resulting from different etiologies, rendering all patients azoospermic. The mean obstructive interval was 16 years (range 6 to 32). Bilateral and unilateral vasoepididymostomy was performed in 4 and 2 men each, and crossed vasovasostomy was performed in 2. Postoperative semen analysis data were available on 6 men. A patent microsurgical anastomosis was observed in 5 of 6 cases (83%). Four of the 5 men with patency had a followup of greater than 6 months, of whom 3 actively pursued conception. One pregnancy was achieved naturally and 1 was achieved by in vitro fertilization with intracytoplasmic sperm injection. CONCLUSIONS: Hydrocelectomy may result in inadvertent injury to the excurrent ductal tract, causing obstruction and infertility. Microsurgical reconstruction results in the restoration of spermatozoa to the ejaculate in 83% of cases. The return of spermatozoa to the ejaculate may provide the couple with an opportunity to conceive naturally or through assisted reproduction.

Recombination in men with Klinefelter syndrome.

Klinefelter syndrome (KS: 47,XXY), occurs in one in 1000 male births. Men with KS are infertile and have higher rates of aneuploidies in sperm compared with normal fertile men. In the course of analyzing recombination in a population of infertile men, we observed that four men in our study presented with KS. We examined whether these men differed in recombination parameters among themselves and relative to normal men. Even though the number of men with KS analyzed was small, we observed remarkable variation in spermatogenesis. In spite of the fact that the men had the same genetic cause for infertility, two of four KS patients had few or no spermatogenic cells that progressed through meiosis to the pachytene stage, whereas the other two men produced abundant pachytene cells that had recombination frequencies comparable with those of fertile men, although one had a significant reduction in fidelity of synapsis. Moreover, regardless of histological appearance, examination of outcomes of assisted reproduction indicated that sperm were extracted from testis biopsies in all four cases, and when used in assisted reproductive practices chromosomally normal babies were born. These results reinforce that: (i) men with the same underlying genetic cause for infertility do not present with uniform pathology, (ii) the checkpoint machinery that might arrest spermatogenesis in the face of chromosomal abnormalities does not prevent pockets of complete spermatogenesis in men with KS, and (iii) aneuploidy, in some cases, is compatible with birth of a chromosomally normal child, suggesting that sperm produced from a background of aneuploidy can be normal in men with KS.

Defective recombination in infertile men.

Two percent of men are infertile owing to defects in sperm production. In 10-15% of cases, Y chromosome deletions that encompass critical spermatogenesis genes are detected; in the remaining cases, the cause of infertility is unknown. In model organisms, defects in recombination genes cause infertility, germ cell aneuploidy and subsequent development of inviable or abnormal progeny. Several studies have also linked infertility and higher rates of germ cell aneuploidy in men and women. Thus, we reasoned that defective recombination may be a major cause of infertility in men with poor or no sperm production and we performed the first comparison of recombination parameters within populations of single spermatocytes from infertile and fertile men who reported for assisted reproduction. We observed that 10% of non-obstructive azoospermic men had significantly lower recombination frequencies than men with normal spermatogenesis. Furthermore, when we focused our analysis only on those men who had a pathological diagnosis of 'maturation arrest' due to arrest during sperm development, about half had detectable defects in recombination. In contrast, none of the men with normal spermatogenesis had defects in recombination. Thus, this study provides direct evidence that defects in recombination are linked to poor sperm production in a significant percentage of infertile men. Implications of this observation for the use of assisted reproductive technologies are especially relevant to consider, given that recombination is required to both introduce genetic variation and insure proper chromosome separation during meiosis.

Intraoperative varicocele anatomy: a microscopic study of the inguinal versus subinguinal approach.

PURPOSE: The groin approach to varicocelectomy is performed by an inguinal (aponeurosis of external oblique opened) or subinguinal (external oblique aponeurosis intact) technique. We describe the number and relationship of internal and external spermatic arteries, veins and lymphatics within the subinguinal portion of the spermatic cord in infertile men undergoing microscopic varicocelectomy and compare these findings to the microanatomy observed with the inguinal approach. MATERIALS AND METHODS: A total of 48 consecutive patients underwent 84 microsurgical subinguinal varicocelectomies during which the detailed intraoperative microanatomy of the spermatic cord and gubernacula was recorded. These observations were compared with a previously reported group of 83 consecutive patients that underwent 115 inguinal varicocelectomies. Subinguinal microscopic findings were also evaluated relative to clinical varicocele grade. RESULTS: The spermatic cord in the subinguinal dissection was characterized by a smaller number of large (greater than 5 mm) internal spermatic veins and a greater number of small (less than 2 mm) internal spermatic veins than the cord in the inguinal dissection (mean 0.4 vs 1.9 large veins and mean 7.9 vs 4.7 small veins, respectively). The subinguinal dissection was also characterized by a significantly greater percentage of external spermatic veins greater than 2 mm than that observed during inguinal dissection (93% vs 74%, respectively, p <0.05). Multiple spermatic arteries were identified in 75% of subinguinal dissections and in only 31% of inguinal dissections (p <0.03). Internal spermatic arteries were surrounded by a dense complex of adherent veins in 95% of cases using the subinguinal approach, whereas this finding was true in only 30% of cases with the inguinal approach (p <0.001). The clinical grade of a varicocele was significantly associated with the number of internal spermatic veins greater than 2 mm found intraoperatively (p <0.001) but not with the maximum internal spermatic vein diameter. CONCLUSIONS: Although the subinguinal approach to microsurgical varicocelectomy obviates the need to open the aponeurosis of the external oblique, it is associated with a greater number of internal spermatic veins and arteries compared with the inguinal approach. The primary branch point for the testicular artery occurs most commonly during its course through the inguinal canal. Internal spermatic arteries at the subinguinal level are more than 3 times as likely to be surrounded by a dense network of adherent veins than when they are identified at the inguinal level. Taken together, these data suggest that microscopic dissection is more difficult with a subinguinal incision.

Preservation of renal function in children with myelomeningocele managed with basic newborn evaluation and close followup.

PURPOSE: Children with myelomeningocele who leak with high intravesical pressures are at risk for upper urinary tract deterioration. Urodynamic study shortly after birth and routinely thereafter has been advocated to predict which newborns are at risk for upper tract deterioration. We hypothesize an approach that excludes routine application of urodynamic evaluation in neonates, reserving this study for use only when clinically indicated, is a safe and effective management option. MATERIALS AND METHODS: Of 188 patients seen in the myelomeningocele clinic 84 underwent initial evaluation at age 6 months or less and comprise the study group. Initial evaluation consisted of a history, physical examination, urine culture and renal ultrasound. Infants with hydronephrosis or evidence of retention were placed into a high risk group and all others were placed into a low risk group. High risk patients underwent prompt urodynamic evaluation. High and low risk patients were followed closely at 2 to 4-month intervals with serial physical examination, upper tract imaging and urine culture. Conversion from low to high risk occurred with new onset hydronephrosis, febrile urinary tract infection, urinary retention or incidental finding of vesicoureteral reflux at the time of evaluation for continence. These findings warranted urodynamic evaluation and appropriate intervention. Upper tract deterioration, defined as new onset hydronephrosis, was distinguished from renal deterioration, defined as cortical thinning or scarring, failure of renal growth or decreased renal function on renal scan. RESULTS: A total of 18 infants were placed into the high risk group at initial evaluation, including 12 for retention and 6 for hydronephrosis. The majority of patients were treated with clean intermittent catheterization or vesicostomy. Of the 65 infants placed into the low risk group 29 were converted to high risk at a mean age of 3.1 years, most commonly for febrile urinary tract infection (45%), and appropriate intervention was instituted. Mean followup is 10.4 years (range 0.25 to 26.5). Despite the occurrence of upper tract deterioration, renal deterioration occurred in only 2 of the 162 total renal units (1.2%). CONCLUSIONS: Basic evaluation of the newborn with myelomeningocele along with careful followup and intervention when indicated results in an excellent rate of renal preservation and represents a safe method of management.

Ultrasound guided needle localization and microsurgical exploration for incidental nonpalpable testicular tumors.

PURPOSE: We describe a technique by which incidental, nonpalpable intratesticular tumors are excised using intraoperative ultrasonography and the operating microscope. MATERIALS AND METHODS: Men with impalpable intratesticular tumors incidentally detected by ultrasonography underwent intraoperative ultrasound guided needle localization and microsurgical exploration of the mass. The testis was delivered through an inguinal incision and placed on ice to minimize warm ischemia. Two rubber shod vascular clamps were placed across the spermatic cord. The tumor was identified by ultrasound and localized with a 30 gauge needle, which was placed adjacent to the tumor. An operating microscope providing 6x to 25x magnification was used to excise the lesion with a 2 to 5 mm. margin. Tissue diagnosis was obtained by frozen section. Multiple random biopsies of the remaining parenchyma were done to confirm absent malignancy. RESULTS: Ultrasound showed incidental, nonpalpable testis tumors in 4 of the 65 men who underwent infertility evaluation and were entered into the microsurgical testis biopsy database between January 1995 and December 2001. All lesions were hypoechoic. Frozen section analysis of the lesions revealed 2 Leydig cell tumors, 1 mass with an inconclusive pathological diagnosis and 1 inflammatory mass. On permanent section the latter 2 lesions were seminoma. The seminomas were 1.6 and 0.9 cm. in the greatest diameter, and the Leydig cell tumors were 0.35 and 0.2 cm., respectively. Random biopsies were positive for seminoma and intratubular germ cell neoplasia in both testes with seminoma. These 2 patients subsequently opted to undergo radical orchiectomy. No residual tumor was detected in either radical orchiectomy specimen. CONCLUSIONS: Intraoperative ultrasound guided needle localization with microsurgical exploration is a safe and effective approach to even small impalpable testicular masses. This technique provides the opportunity to identify and remove benign and malignant lesions, and preserve the testis when the lesion is benign. In cases of a solitary testis or bilateral synchronous lesions the technique allows a potentially testis sparing operation for small malignancies.

The diagnosis and treatment of the azoospermic patient in the age of intracytoplasmic sperm injection.

Microsurgical reconstruction remains the treatment of choice for men with reconstructable obstructive azoospermia. Sperm retrieval techniques performed with ICSI are highly effective for men in whom reconstruction is not feasible. In men with nonobstructive azoospermia, the optimization of spermatogenesis with hormonal therapy and, when appropriate, microsurgical varicocelectomy can result in the appearance of adequate sperm in the ejaculate for ICSI. In men with persistent nonobstructive azoospermia, TESE with ICSI has provided encouraging results. Caution must be used when this ART is applied in couples in whom genetic aberrations are detected given certain inheritance of these anomalies, as the genetic consequences of this procedure have not been thoroughly elucidated. Just as the possibility of ICSI was thought to be inconceivable several decades ago, the advent of future sentinel discoveries will present the possibility for realization of achievements that now seem incredulous.