Male subfertility: diagnostic and therapeutic advances.
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Adult↗
Biomedical subjects
E D Kim
Publications and source records attributed to E D Kim.
Image analysis assessment of the abnormal testis biopsy in male infertility.
PURPOSE: We previously demonstrated that testis biopsy image analysis is an effective method for quantifying intratubular spermatogenic cells in the obstructed testis with normal spermatogenesis. As an extension of the initial report, we describe using the quantitative ploidy and morphological characteristics of cells counted with image analysis in abnormal testis biopsies obtained for a male infertility evaluation. MATERIALS AND METHODS: Image analysis using a specifically designed filter was performed on Feulgen stained 5 microns, sections of paraffin embedded testicular tissue. Archival testicular tissue had been obtained using standard biopsy techniques from patients with azoospermia or severe oligospermia. Qualitative classification was based on standard evaluation of hematoxylin and eosin processed tissue. RESULTS: There were 62 biopsies performed in 58 men. Significant differences in the intratubular content of haploid (spermatozoa and spermatids), diploid and tetraploid cells were found among the 5 categories of abnormalities: the Sertoli-cell-only syndrome, spermatocyte arrest, spermatid arrest, hypospermatogenesis and normal spermatogenesis. Moderate variability was found in the proportion of cell types in spermatid arrest and hypospermatogenesis. CONCLUSIONS: Testis biopsy image analysis provides a quantitative method for categorizing abnormalities of intratubular cell content present in male infertility states by using deoxyribonucleic acid content and morphology characteristics. The limitations of the present qualitative analysis system are emphasized by the moderate variability evident within the current categories of spermatid arrest and hypo-spermatogenesis states.
Adult↗
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.
Adult↗
Testis biopsy image analysis effectively quantifies spermatogenic cell types.
PURPOSE: Evaluation of the testis biopsy specimen in male infertility has been hampered by the qualitative rather than quantitative nature of routine histological techniques and interpretation. Although useful, flow cytometry has demonstrated significant limitations due to its inability to differentiate among haploid cell types, spermatozoa and spermatids. Thus, deoxyribonucleic acid image analysis was performed on testis biopsy specimens to combine the advantages of quantitative ploidy and morphological characteristics to develop a more effective quantitative system. MATERIALS AND METHODS: Image analysis using a specifically designed filter was performed on Feulgen stained 5 microns. sections of paraffin embedded testicular tissue. The archival testicular tissue had been obtained using standard biopsy techniques from patients with azoospermia and normal spermatogenesis on routine hematoxylin and eosin processed tissue. RESULTS: The overall findings (mean plus or minus standard deviation) in 20 biopsies from 18 men are haploid 54.2 +/- 5.6, diploid 31.2 +/- 5.2 and tetraploid 15.0 +/- 4.6%. Spermatozoa and spermatids contributed 23.2 +/- 5.7 and 30.9 +/- 7.6% to the total cell content, respectively. A mean of 2,462 +/- 254 cells were counted per case. CONCLUSIONS: We used image analysis to evaluate testicular biopsies. This technique can quantitatively determine the percentages of various cell types within the seminiferous tubules. Furthermore, it can differentiate between spermatozoa and spermatids based on morphological characteristics. This technique, which combines ploidy and cell morphology characteristics, represents a significant advancement in the interpretation of the testicular biopsy, and has implications for redefining the presently used system of qualitative interpretative assessment.
Adult↗
Results of laser tissue soldering in vasovasostomy and epididymovasostomy: experience in the rat animal model.
UNLABELLED: 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 analysis was also performed. RESULTS: Patency rates were 8/10 (80%) for sutured vasovasostomy versus 9/10 (90%) for the laser technique. Epididymovasostomy patency rates were 8/11 (73%) for sutured versus 9/11 (82%) for the laser technique. Mean operative times were significantly shorter for lasered anastomoses when compared to controls. The frequency of granuloma formation did not significantly differ between laser and control groups. CONCLUSIONS: Laser tissue soldering resulted in similar patency when compared to a conventional 2 layered sutured anastomosis while decreasing operative time. In addition, since fewer sutures are placed, the laser method is less technically demanding.
Animals↗
Intracytoplasmic sperm injection for treatment of the infertile male.
Intracytoplasmic sperm injection (ICSI) with in vitro fertilization represents one of the most significant advances in fertility technology. In this relatively new procedure, a single viable sperm is microinjected into an oocyte that has been extracted transvaginally. After fertilization occurs, the embryo is transferred into the uterus. This procedure now affords men who were previously thought to be irreversibly infertile the chance to initiate their own biologic pregnancy. However, because of the procedure's significant costs and its potential risk to the mother, careful selection of couples following a thorough male factor evaluation is mandatory.
Congenital Abnormalities↗
The epidermal growth factor receptor couples transforming growth factor-alpha, heparin-binding epidermal growth factor-like factor, and amphiregulin to Neu, ErbB-3, and ErbB-4.
The epidermal growth factor (EGF) family hormones amphiregulin (AR), transforming growth factor-alpha (TGF-alpha), and heparin-binding EGF-like growth factor (HB-EGF) are thought to play significant roles in the genesis or progression of a number of human malignancies. However, the ability of these ligands to activate all four erbB family receptors has not been evaluated. Therefore, we have assessed the stimulation of erbB family receptor tyrosine phosphorylation by these hormones in a panel of mouse Ba/F3 cell lines expressing the four erbB family receptors, singly and in pairwise combinations. We also measured the stimulation of interleukin-3-independent survival or proliferation in this panel of Ba/F3 cell lines to compare the patterns of erbB family receptor coupling to physiologic responses induced by these peptides. EGF, TGF-alpha, AR, and HB-EGF all stimulated qualitatively similar patterns of erbB family receptor tyrosine phosphorylation and coupling to physiologic responses. Therefore, EGF, TGF-alpha, AR, and HB-EGF are functionally identical in this model system and behave differently from the EGF family hormones betacellulin and neuregulins.
Amphiregulin↗
Evaluation of the infertile couple.
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Female↗
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.
Ejaculatory Ducts↗
Testicular touch preparation cytology.
PURPOSE: The applications, technique and limitations of testicular touch preparation cytology in evaluation of the infertile man are described. MATERIALS AND METHODS: The technique and histological results of testicular touch preparation cytology for normal specimens and various pathological conditions of male infertility are described in detail. RESULTS: Testicular touch preparation cytology is able to differentiate between late spermatids and mature spermatozoa, as well as to identify other spermatogenic elements. CONCLUSIONS: Touch preparation cytology has 2 important purposes: 1) distinguishing between maturation arrest at the late spermatid stage and normal spermatogenesis, and 2) determining whether obstruction is the cause of azoospermia. While testis biopsy is the gold standard, touch preparation cytology is an extremely important adjunct because of its ability to define whole sperm. The urologist and pathologist are better able to make a diagnosis when routine biopsy and touch preparation cytology are performed.
Cytological Techniques↗
A surgical approach to penoscrotal lymphedema.
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Adult↗
Papaverine topical gel for treatment of erectile dysfunction.
Intracavernous injection of vasoactive substances has been shown to be an effective means of treatment of organic erectile dysfunction. However, up to 50% of men eventually discontinue treatment often because of lack of spontaneity and needle phobia. This study was done as a phase I, placebo controlled, nonblinded investigation of the safety and efficacy of a topical papaverine gel in the treatment of erectile dysfunction. Of 20 men with organic impotence 17 completed the trial and 13 of these patients had spinal cord injuries. After application of a 15% and 20% papaverine base gel to the scrotum, perineum and penis, cavernous artery diameter was significantly increased (36%, p < 0.001) as assessed by color flow Doppler ultrasound. Peak systolic flow velocity increased 26%. Only 3 of 14 patients achieved an increase in cavernous artery diameter of 75% or more and 2 of 14 had a peak systolic flow velocity of 25 cm. per second or more after application of a topical base gel. Similar findings were present when only the patients with spinal cord injury were analyzed. The effect of a papaverine base in producing flow alterations to the penis is dose-dependent. A diminution in blood pressure was present at 15 and 30 minutes after application to the forearm, and the heart rate diminished from 68 to 62 beats per minute after application to the genitalia. No patient was symptomatic. Serum papaverine levels were not elevated over pre-application values. No hepatotoxic effects were demonstrated. Full clinical erections (mean duration 38.7 minutes) were present in 3 patients but were also present with the placebo preparation (mean duration 8.0 minutes). In conclusion, topical papaverine gel appears to be safe and well tolerated after application to the genitalia, and increases blood flow to the penis with a 15% and 20% base preparation. Minimal systemic absorption occurs and, thus, effects are probably from local absorption. Topical therapy appears to augment reflex erections in the spinal cord injury patient and may be especially beneficial in this population. Further investigation is warranted at higher concentrations or in combination with different skin absorption enhancers.
Administration, Cutaneous↗
Long-term results with penile vein ligation for venogenic impotence.
Penile vein ligation for venogenic impotence was performed on 15 patients between 1989 and 1992. Preoperative evaluation included color flow Doppler ultrasound, and dynamic infusion cavernosogram and cavernosometry with vasoactive substance injection. All operations were performed by 1 surgeon via an inguinoscrotal incision by excising the deep dorsal, cavernous and, if necessary, crural veins. All patients were interviewed using a structured telephone questionnaire from 19 to 45 months (mean 29) postoperatively. Postoperative potency was defined as erections sufficient for unaided coitus on more than 75% of attempts and was present in 9 patients (60%). The 2 failures had temporary improvement within the first 6 months. The only significant preoperative variable in assessing postoperative potency was the duration of erectile dysfunction before penile vein ligation: median 60 months (range 48 to 120) in the impotent group and median 24 months (range 12 to 168) in the potent group (p < 0.05, Mann-Whitney test). No correlation was found with systolic and diastolic arterial flow or resistive index as assessed by color flow Doppler evaluation, sites of leakage or patient age at operation. Similarly, no correlation was found with preoperative dynamic infusion cavernosometry maintenance rates. The most common complication was contracture of the penis in 6 patients (40%), although only 1 complained of a functional disturbance. We demonstrated favorable long-term results with an extensive venous ligation. While preoperative assessment with color flow Doppler ultrasound, dynamic infusion cavernosography and cavernosometry, and vasoactive substance injection establishes a diagnosis of corporeal veno-occlusive dysfunction, this evaluation provides no predictive indicators for successful outcomes in penile vein ligation.
Adult↗
Prostate specific antigen in the expressed prostatic fluid of men with benign prostatic hyperplasia and prostate carcinoma.
PURPOSE: We tested the hypothesis that the histochemically demonstrated prostate specific antigen (PSA) content of prostate carcinoma cells does not necessarily reflect PSA production and secretion by evaluating expressed prostatic fluid. MATERIALS AND METHODS: Expressed prostatic fluid and serum from 152 men with clinical benign prostatic hypertrophy (BPH), 132 with histologically proved BPH and 46 with prostate carcinoma were analyzed with the Hybritech PSA assay. RESULTS: Expressed prostatic fluid PSA levels from carcinoma patients (median 1.70 mg./ml., mean 2.25) were significantly higher than in the histologically proved BPH group (median 1.28 mg./ml., mean 1.42, p < 0.05). CONCLUSIONS: PSA concentration is increased in the expressed prostatic fluid of prostates of men with carcinoma compared to those with histological BPH. This finding may be a functional manifestation of a field change or paracrine effects within the prostate.
Aged↗
Topical prostaglandin-E1 for the treatment of erectile dysfunction.
This study was undertaken as a phase I, placebo controlled, nonblinded investigation of the safety and efficacy of topical prostaglandin-E1 for the treatment of erectile dysfunction. Nine men with erectile dysfunction secondary to spinal cord injury and 1 man with mild arterial insufficiency were enrolled in the trial and underwent color flow Doppler ultrasound of the penis after application of topical prostaglandin-E1 to the penis, scrotum and perineum. Eight men completed all phases of the study. Mean cavernous artery diameter increased from 0.09 to 0.11 cm. (p < 0.05) and mean peak systolic flow velocity increased from 15.4 to 22.8 cm. per second (p < 0.05) using color flow Doppler ultrasound. Peak systolic flow velocity increased in both cavernous arteries in 7 of 10 patients. Clinical erections were observed in 2 patients but they were not present with placebo application. Diastolic blood pressure and heart rate varied after application of prostaglandin-E1 to the genitalia. No patient was symptomatic and no adverse skin effects were observed in the 8 patients completing all phases of the study. In conclusion, topical prostaglandin-E1 appears to be safe and well tolerated after application to the genitalia, and significantly increases blood flow to the penis. Further investigation is being pursued.
Administration, Cutaneous↗
Long-term followup of treatment of Peyronie's disease with plaque incision, carbon dioxide laser plaque ablation and placement of a deep dorsal vein patch graft.
Numerous surgical therapies have been used for Peyronie's disease in patients who maintain potency. We report on incision and carbon dioxide laser ablation of Peyronie's plaque combined with a deep dorsal vein patch graft in the treatment of 6 men (mean age 57 years). The chief indication for surgery was curvature interfering with intromission, with voiding difficulty being a secondary indication as well. Long-term followup (mean 31 months) was available in 6 men, each of whom was potent preoperatively. Potency was preserved in all men, and 5 described significant improvement in penetration and curvature. In 1 patient the curvature returned to preoperative levels. Each patient reported a subjective shortening of the penis from one-quarter to 1 inch but no case was functionally debilitating. We describe this technique, which to our knowledge has been reported previously by only 1 group with 18 patients, and conclude that it may be used with successful preservation of potency and restoration of intercourse in the treatment of Peyronie's plaques.
Aged↗
Post-radical prostatectomy penile blood flow: assessment with color flow Doppler ultrasound.
Cadaveric dissections have revealed that accessory blood vessels to the penis often arise near or through the apex of the prostate. These accessory vessels may be easily injured during radical prostatectomy. Increasing attention since the 1980s has focused on preserving potency after radical prostatectomy with a nerve sparing technique. However, many patients are impotent even after a nerve sparing procedure. An arterial, venous or psychological mechanism may be involved. A prospective study was designed to assess cavernous artery diameter, peak systolic flow velocity, penile blood flow, end diastolic flow velocity and resistance index preoperatively and postoperatively in patients undergoing radical prostatectomy. Ten patients with a mean age of 60 years were evaluated, of whom 8 underwent a unilateral nerve sparing procedure, 1 bilateral nerve sparing procedure and 1 bilateral nonnerve sparing procedure. Mean penile blood flow as calculated by the formula penile blood flow = peak systolic flow velocity x pi (diameter/2)2 increased 0.33 ml. per second (+26%) on the nerve spared side, while diminishing 0.68 ml. per second (-41%) on the nonspared side. Overall penile blood flow was diminished. End diastolic flow velocity increased on spared and nonspared sides after surgery. The resistance index for all radical prostatectomy patients diminished 7% from 0.83 preoperatively to 0.77 postoperatively (p = 0.16). While these findings were not statistically significant, they suggest that arterial insufficiency and corporeal venous occlusive dysfunction may be involved in sexual dysfunction after nerve sparing radical prostatectomy.
Adenocarcinoma↗
Basal cell carcinoma of the penis: case report and review of the literature.
Basal cell carcinoma of the skin is the most common tumor in humans but occurrence in the penis is extremely rare. We report the sixteenth case of basal cell carcinoma of the penis. This lesion was successfully treated with simple local excision. A review of the literature revealed that most such tumors present in the fifth through seventh decades of life on the shaft of the penis. Natural history is that of a slowly growing tumor with little propensity to metastasize. Universal success has been achieved with simple local excision.
Adult↗