Edward D. Kim

Sildenafil citrate after radical retropubic prostatectomy

PURPOSE Erectile dysfunction continues to be a significant problem for men after radical retropubic prostatectomy despite nerve sparing techniques. Sildenafil citrate (Viagra) has proved effective for erectile dysfunction in many men. We determine the efficacy of sildenafil in men with erectile dysfunction after radical retropubic prostatectomy and examine variables that may impact the response to treatment. MATERIALS AND METHODS A total of 84 men were prescribed sildenafil after radical retropubic prostatectomy and asked to complete a series of questionnaires, including the International Index of Erectile Function (IIEF), on erectile function before and after sildenafil administration. The importance of factors, such as patient age, time since surgery, degree of cavernous nerve sparing, preoperative prostate specific antigen, Gleason score, clinical and pathological stage, and baseline postoperative erectile function, was examined. RESULTS Of the 84 patients 45 (53%) had improved erections and 34 (40%) had improved ability for intercourse while taking sildenafil. Mean IIEF score for the erectile function domain increased from 9 to 14 (p <0.001). Orgasmic function (p = 0.004) and intercourse satisfaction (p = 0.009) also significantly improved. The degree of nerve sparing and baseline postoperative erectile dysfunction had a significant impact on the ability of sildenafil to improve erectile function (p = 0.010 and p <0.001, respectively) and total IIEF questionnaire responses (p = 0.031 and p <0.001, respectively). Age and pathological stage also appeared to have a significant effect. CONCLUSIONS Sildenafil improved erectile function and the ability to have intercourse in more than half of men after radical retropubic prostatectomy. Baseline postoperative erectile function, which is dependent on the degree of nerve sparing technique, significantly impacts the likelihood that patients will respond to sildenafil.

Side-effect profile of sildenafil citrate (Viagra) in clinical practice

OBJECTIVES Sildenafil citrate (Viagra) has been shown to be an effective treatment for erectile dysfunction. Initial studies reported a high tolerability and low incidence of certain characteristic adverse reactions. We sought to evaluate the incidence of side effects of sildenafil citrate, independent of industry support and constraints, utilizing a heterogeneous cohort of patients from a university-based practice. METHODS A prospective, open-label, flexible-dose study of 256 patients treated with sildenafil citrate for erectile dysfunction was performed at a single institution. The patients were questioned explicitly about the occurrence of headache, flushing, dyspepsia, nasal congestion, visual changes, and other side effects. RESULTS The adverse reactions most commonly observed were flushing (30.8%), headache (25. 4%), nasal congestion (18.7%), and heartburn (10.5%). All events were short lived and mild in nature. In the present study, 31.6% of patients experienced one or more adverse events. However, no one withdrew from the study because of the severity of these events. There was a significant association between higher doses and the occurrence of side effects. CONCLUSIONS The incidence of adverse events attributable to sildenafil citrate may be higher than initially reported, but an explanation may be the methodology of data collection and the industry-independent nature of this study. The side-effect profile is dose related and mild. Sildenafil citrate remains a safe and well-tolerated treatment for erectile dysfunction.

Unilateral testicular injury from external trauma: evaluation of semen quality and endocrine parameters.

PURPOSE Because few studies have described the impact of unilateral testicular trauma on fertility parameters, we review the experience at the Ben Taub General Hospital during a 16-year period. Semen and endocrine profiles were analyzed to evaluate the influence on the outcomes of orchiectomy versus testicular salvage. MATERIALS AND METHODS From 1979 to 1995, 67 patients were identified who sustained unilateral testicular trauma. Of these patients 12 were located and 10 agreed to be evaluated. Injuries included gunshot wounds, stab wounds and blunt trauma, and treatment consisted of unilateral orchiectomy or testicular repair. The study protocol comprised a history and physical examination, routine semen analysis, determination of semen and serum antisperm antibody titers (Immunobead* assay) and a modified gonadotropin stimulation test. Results were compared with a group of semen donors with proved fertility. RESULTS In the 7 patients who underwent unilateral orchiectomy mean sperm density was normal but significantly decreased compared with that of the fertile controls (81.6 versus 132.6 x 10(6)/ml., p = 0.04). Sperm motility was not significantly affected. Baseline follicle-stimulating hormone (FSH) and luteinizing hormone (LH), and post-stimulation LH were significantly increased in this group compared with controls (p < 0.01). In the group that underwent testicular repair sperm density, motility, and baseline and post-stimulation FSH and LH levels were not significantly different from controls. In all patients in both groups testosterone levels and contralateral testicular size were normal. Only 1 patient in the repair group had an elevated serum and semen antisperm titer. CONCLUSIONS While the testicular salvage group had no significant seminal or endocrine abnormality, the orchiectomy group had a significant decrease in sperm density and elevation of baseline FSH and LH. These preliminary data suggest that testicular salvage is more protective of overall testicular function than orchiectomy.

Testis Biopsies Frequently Demonstrate Sperm in Men With Azoospermia and Significantly Elevated Follicle-Stimulating Hormone Levels

PURPOSE Men with azoospermia, markedly elevated serum follicle-stimulating hormone levels and testicular atrophy were previously considered irreversibly infertile. Thus, testicular biopsy in this patient population was considered unnecessary. However, presently men with even the most severe infertility disorders are potentially able to initiate a pregnancy with intracytoplasmic sperm injection provided sperm can be recovered in even relatively few numbers directly from the testicular tissue. For these reasons we sought to reevaluate the findings from testicular biopsies in these men in the era of advanced micromanipulation techniques. MATERIALS AND METHODS Chart review identified men with azoospermia, confirmed on a pelleted specimen, and a serum follicle-stimulating hormone level of 3 or more times normal. Mature sperm in the touch preparation cytology and testis biopsy specimen were confirmed. RESULTS A total of 57 men, most with testicular atrophy, underwent a testicular biopsy and in 17 (30%) mature sperm were identified. The most common diagnosis in these men was severe hypospermatogenesis. Men without sperm most commonly had a pure Sertoli-cell-only pattern. CONCLUSIONS Men with azoospermia and testicular atrophy with significantly elevated follicle-stimulating hormone levels should undergo testicular biopsy if in vitro fertilization with intracytoplasmic sperm injection is an acceptable approach for the couple.

APOPTOTIC FREQUENCY IS INCREASED IN SPERMATOGENIC MATURATION ARREST AND HYPOSPERMATOGENIC STATES

PURPOSE Increased testicular apoptosis has been observed in maturation arrest and hyposper-matogenesis states in rodent models, but this process has not yet been characterized in humans. We hypothesized that increased cell death present with accelerated apoptosis is significant in pathophysiology of many male infertility states associated with abnormal spermatogenesis. We examined frequency of apoptotic bodies in human testis biopsy specimens from infertile men using morphometric analysis of hematoxylin and eosin stained paraffin sections. MATERIALS AND METHODS Testis biopsy specimens were obtained for routine clinical purposes from azoospermic and severely oligozoospermic men and were stained with hematoxylin and eosin. Apoptotic bodies were identified using established morphometric criteria. Apoptotic indexes, defined as apoptotic bodies per total number of cells and per Sertoli cells, were calculated after counting all intratubular spermatogenic cells and Sertoli cells in 20 tubules. RESULTS A total of 51 biopsies was performed in 50 men. Significantly increased apoptotic body per total cell and apoptotic body per Sertoli cell ratios were observed in maturation arrest and hypospermatogenesis states in comparison to Sertoli cell only and normal spermatogenesis (p < 0.05, Mann-Whitney test). CONCLUSIONS Increased apoptosis in maturation arrest and hypospermatogenesis states compared to normal but obstructed spermatogenesis and Sertoli cell only were observed, indicating a prominent role for this form of programmed cell death in human male infertility.

SPERM PELLET ANALYSIS: A TECHNIQUE TO DETECT THE PRESENCE OF SPERM IN MEN CONSIDERED TO HAVE AZOOSPERMIA BY ROUTINE SEMEN ANALYSIS

PURPOSE In men considered to have azoospermia by routine semen analyses sperm may be identified after centrifuging the semen. Because these sperm may be used for intracytoplasmic sperm injection, we describe our technique and findings of sperm pelleting. MATERIALS AND METHODS Semen centrifugation for sperm pellet analysis was performed in 140 consecutive men in whom no sperm was identified on routine semen analysis and who were categorized as having obstructive or nonobstructive azoospermia. Obstructive azoospermia was defined as failed vasectomy reversal, failed reconstruction for congenital vasal or epididymal occlusion, or an acquired obstruction unrelated to ejaculatory duct obstruction. Patients with congenital absence of the vas deferens or who had undergone vasectomy were not included in the study. Nonobstructive azoospermia was defined as moderate to severe testicular atrophy with markedly elevated serum follicle-stimulating hormone (greater than 3 times normal), or a testicular biopsy that revealed maturational arrest, severe hypospermatogenesis or the Sertoli-cell-only pattern. Obstructive and nonobstructive azoospermia were present in 70 men who provided 109 samples and 70 who provided 103, respectively. RESULTS Motile and nonmotile sperm was identified in 13 of the 70 patients (18.6%) with obstructive and in 16 of the 70 (22.8%) with nonobstructive azoospermia. Pellet variability, that is the absence of sperm in 1 specimen and its presence in another from the same patient, was noted in 7 of the 17 men (41.2%) with obstructive and 2 of the 17 (11.8%) with nonobstructive azoospermia (not statistically significant). Motile sperm was present in the pellets of 6 of the 70 men (8.6%) with obstructive and 15 of the 70 (21.4%) with nonobstructive azoospermia. The median number of motile sperm was lower in the obstructive than in the nonobstructive group (0 sperm in 17 samples versus 5 sperm in 41 samples, p <0.001). The median value of 0 in the obstructive azoospermia group reflects the finding that 9 of the 17 samples did not contain motile sperm. Similarly the median number of nonmotile sperm was lower in the obstructive than in the nonobstructive group (5 versus 8 sperm). CONCLUSIONS We demonstrated the presence of motile and nonmotile sperm in a significant number of men considered to have azoospermia by routine semen analysis. Semen centrifugation (sperm pelleting) should be performed in all men considered to have this condition by routine semen analysis, especially those with testicular failure and those in whom intracytoplasmic sperm injection is possible.

COMPARISON OF TUNICA ALBUGINEA SUBSTITUTES FOR THE TREATMENT OF PEYRONIE'S DISEASE

PURPOSE Peyronies disease is a connective tissue disorder resulting in fibrotic plaque formation on the tunica albuginea of the penis. One approach to repair consists of plaque excision and patching with one of many potential patch materials. Because the optimal patch material for covering the resultant defect has not been determined, this study compares histological and cavernosometric changes in the penis as a result of the placement of three different types of patch grafts used in surgery for Peyronies disease. MATERIALS AND METHODS Eleven mongrel dogs were divided into three groups, each receiving a different patch material (superficial dorsal penile vein, silicone fabric, and dermabraded preputial flap). Each dog had dynamic infusion cavernosometry (DIC) performed prior to placement of the patch over a 6 x 3 mm. defect surgically created in the tunica albuginea. Three months later, DIC was repeated prior to sacrifice. Histology of the penis was examined using Massons trichrome, and hematoxylin and eosin stains. RESULTS The only difference among the cavernosometric parameters (preop versus postop) was a higher initial pressure in the dermabraded preputial flap group postoperatively. The dogs undergoing vein patch had moderate fibrosis with apparent reformation of the tunica albuginea over the patch site. The normal venous architecture of the graft was no longer recognizable. Those dogs receiving a silicone patch had moderate fibrosis with a fibrous sheath of compressed histiocytes and fibroblasts enveloping the graft site. Finally, the dermabraded preputial flap patch group had mild-moderate fibrosis with focal loss of the cavernosal space underlying the flap. CONCLUSIONS We feel that continued use of the vein patch for repair of Peyronies disease is warranted.

Treatment of infertility due to anejaculation in the male with electroejaculation and intracytoplasmic sperm injection.

PURPOSE We tested the hypothesis that spinal cord injury and/or anejaculation affects the outcome of intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS From November 1993 to October 1998 we obtained and prospectively reviewed data on 34 ICSI cycles using electroejaculated sperm, 620 male factor infertility ICSI cycles using normal ejaculated sperm and 120 cases of obstructive azoospermia, in which microsurgical epididymal aspiration and testicular sperm extraction-ICSI were done in 93 and 27, respectively. RESULTS A total of 34 ICSI cycles were performed in 17 couples with male infertility due to anejaculation secondary to spinal cord injury in 10 patients and retroperitoneal lymph node dissection in 5, and idiopathic in 2. In all 17 couples at least 3 previous intrauterine insemination cycles had failed. After electroejaculation 11 men had oligozoospermia and 6 normal sperm density. Median sperm retrieval volume plus or minus standard deviation was 1.9 +/- 1.9 ml., median sperm concentration 70.7 +/- 60.2 x 106 sperm per ml., median motility 10.7% +/- 10.8% and median forward progression 2.3 +/- 0.5 (scale 1 to 4). In the anejaculation group ICSI resulted in a median fertilization of 60% +/- 28%, 15% pregnancies per cycle and 29% pregnancies per couple. In the control group of 620 ICSI cycles from ejaculated specimens obtained from male patients with infertility median fertilization was 58% +/- 26%, and there were 39% pregnancies per cycle and 47% pregnancies per couple. The rate of pregnancies per embryo transfer and per couple was higher in the control than in the electroejaculation-ICSI group (p <0.05). However, there was no statistically significant difference in the fertilization rate. CONCLUSIONS ICSI or in vitro fertilization is a viable alternative for patients with anejaculation in whom intrauterine insemination failed. While the fertilization rate is similar in these couples, the pregnancy rate is significantly lower than that achieved with ejaculated specimens from patients with severe male factor infertility. ICSI is a viable alternative for a patient with anejaculation in whom intrauterine insemination or in vitro fertilization failed.

Role of ultrasound in the assessment of male infertility

The use of ultrasonography has become an important component in the evaluation and treatment of male reproductive tract disorders. From the use of color flow Doppler ultrasonography for the assessment of varicoceles to transrectal ultrasonography combined with seminal vesiculography for the evaluation of ejaculatory duct obstruction, ultrasonography has practical clinical applications. In this article, the authors review the indications and use of ultrasonography in the assessment and treatment of the infertile male. The recent advances in diagnostic transrectal ultrasonography for ejaculatory duct obstruction, in particular, are emphasized.

VARICOCELECTOMY IMPROVES SPERM STRICT MORPHOLOGY AND MOTILITY

PURPOSE We prospectively examined the effect of varicocelectomy on standard semen parameters and Kruger strict morphology, including site of specific sperm defect. MATERIALS AND METHODS Kruger strict morphology and routine semen analysis were performed in a blinded fashion before and a minimum of 4 months after varicocelectomy in 61 subfertile men with a primary diagnosis of varicocele. RESULTS Sperm motility, total number of motile sperm, and percentage and total number of sperm with normal strict morphology were significantly increased after varicocele repair. Average density was also increased, while volume and forward progression were unchanged. The percentage of normal head strict morphology was significantly improved, whereas tail and neck morphology did not reflect similar changes. CONCLUSIONS Varicocele repair in subfertile men improves Kruger strict morphology. In addition, motility and total motile sperm are significantly improved after repair. Since the stoichiometry of the sperm head is crucial to egg and sperm interaction, this decrease in head defects may be partially responsible for the increase in pregnancy rates after varicocele repair.