Arteriovenous malformation of the bladder presenting as gross hematuria.

Arteriovenous malformation, in which direct communication is present between arterioles and venules, are reflected histologically by abrupt changes in the thickness of the medial and elastin layers of the vessels. Another result of the lack of the interposed capillary bed is abnormal dilation and, often, advanced small vessel disease, which is due to the increased intravascular pressures as well as to the basic defects in the blood vessel walls. The diversion of arterial flow and small vessel disease may lead to ischemia, which is postulated to stimulate proliferation of the vascular channels in these lesions. Hence, they tend to grow slowly with time. The ischemia, increased pressure, and small vessel disease predispose to ulceration and hemorrhage, which is a common mode of presentation for these lesions. Common sites for arteriovenous malformations are the intestine, central nervous system, lungs, and extremities. The lesion has not been reported in the urinary bladder. The present case of massive hematuria was found at autopsy to be due to an arteriovenous malformation of the bladder neck.

Cystic fibrosis and congenital agenesis of the vas deferens, antisperm antibodies and CF-genotype.

Antisperm antibodies are formed as a result of vasal and epididymal obstruction. Fourteen males of different ages (pre-, peri- and post-pubertal) with bilateral congenital vasal agenesis and epididymal obstruction secondary to cystic fibrosis (CF), and seven men with congenital bilateral aplasia of the vas deferens (CBAVD) were evaluated with regard to both the presence and levels of serum antisperm antibodies, and the CF-genotype. While IgA and IgG were not detected among pre- and peri-pubertal CF patients, 4 out of 10 (40%) exhibited IgM binding to sperm tail-tip. Post-pubertal CF patients showed high antisperm antibody (ASA) levels in 3 of the 4 males (75%) evaluated for the three isotypes assayed. ASA were found in 5 of 7 CBAVD patients (71%); IgG (n = 3) and IgM (n = 4) were found to be the predominant isotypes bound to sperm tail-tip. CF-genotype analysis revealed two pre-pubertal patients with the DeltaF508/DeltaF508 CF-genotype and a positive ASA response, thus suggesting an earlier or more severe blockage. In addition, the two CBAVD patients found to have a ?/? CF-genotype on the initial screening did not have ASA. The altered antigenicity of sperm associated with initiation of spermatogenesis appears to modify the antisperm antibody isotypes. Further studies on a larger number of patients may allow for a better understanding of the ASA response, as well as a better understanding of a possible phenotype/genotype association between the CF-genotype and the immunologic response.

Comparison of histologic and flow cytometric evaluation of cyclophosphamide-induced testicular damage.

This study evaluates the ability of DNA histograms obtained by flow cytometry to detect and quantify reversible alterations in spermatogenesis induced by cyclophosphamide, a known inhibitor of spermatogenesis. Evaluation of per cent of cells in each of the haploid (lc), diploid (2c), and tetraploid peaks (4c) as determined by flow cytometry in treated and control Balb/C mice over a six-week period, and comparison with routine histologic evaluation have led us to conclude that DNA histogram evaluation is a rapid and accurate means of identifying testicular damage and recovery. This technique may be useful in sequential monitoring of the effects of malignancy and/or treatments applied on spermatogenesis in young men.

Varicoceles: effect on testicular volume in prepubertal and pubertal males.

A total of 63 prepubertal and 17 pubertal males were examined to determine both testicular volumes and to correlate testicular volumes with the presence or absence of a varicocele. In the prepubertal group neither the left nor the right testicle predominated in size. In the pubertal group, the left testicle with an associated varicocele was smaller than the right.

Aspiration flow cytometry of the testes in the evaluation of spermatogenesis in the infertile male.

Deoxyribonucleic acid (DNA) flow cytometry of testicular tissue has been demonstrated to be a quantitative means of assessing spermatogenesis. This study evaluates testes aspirates and DNA flow cytometry in the evaluation of the infertile male. Testicular tissue obtained from 12 men who underwent bilateral orchiectomy for prostate cancer (group 1) were examined by both flow cytometry and standard histologic technique to assess the correlation between these two modalities. Thirteen men evaluated for infertility (group 2) and requiring histologic evaluation of spermatogenesis underwent both open biopsy and fine needle aspiration of their testes. Histology was independently examined and grouped according to standard nomenclature. Flow cytometric analysis revealed characteristic patterns in the relative numbers of haploid (1C), diploid (2C), and tetraploid (4C) cells. These patterns correlated reproducibly with the histologic diagnoses. DNA flow cytometry of testicular aspirates provides a rapid and reliable quantitative means of assessing spermatogenesis.

The cofactor effect: varicocele and infertility.

The varicocele may be a cofactor that, when potentiated by other cofactors (i.e., gonadotoxins), causes male infertility. This hypothesis could explain the unpredictable effects of the varicocele on fertility. Male rats with experimental varicoceles, sham surgery, or no surgery were treated for 30 days with the known gonadotoxins cyclophosphamide or nicotine. Spermatogenesis was assessed by flow cytometry. Cyclophosphamide alone caused gonadotoxicity, and its effect was accentuated by sham or varicocele surgery. Nicotine and the presence of a varicocele were more gonadotoxic than either the varicocele or nicotine by itself. This data would lend support to the cofactor hypothesis of the pathophysiology of the varicocele.

The effect of delta 1-testolactone on serum testosterone and estradiol in the adult male rat.

delta 1-Testolactone, an androgen derivative without intrinsic hormonal action, is known to block the aromatization of androgens to estrogens. This study was designed to assess its effect upon serum testosterone (T) and estradiol (E2) in the adult male rat. By itself, testolactone (TL) did not affect T/E2 levels in the dosages utilized. Daily injections of human chorionic gonadotropin (hCG) for 15 days caused a tenfold rise in serum T, although there was no increase in serum E2. When given along with hCG, TL did not alter the Leydig cell response. However, pretreatment of animals with TL increased the testicular response to hCG over that of saline-treated animals. Studies were also carried out to delineate the sources of estrogen in the adult male rat. These experiments demonstrate that (1) the majority of E2 is not testicular in origin but is derived from the adrenal; (2) the conversion of androgen precursors to E2 in the rat is not affected by TL; and (3) in spite of no demonstrable inhibition of E2 production, TL causes an increased Leydig cell responsiveness to hCG.

Testicular torsion: temporal considerations.

Unilateral testicular torsion may result in contralateral testicular alterations which appear immunologically mediated and avoidable by immunosuppression or orchiectomy of the twisted testicle within 24 hours. This study was instituted to assess three temporal aspects of these observations: (1) The effect of prepubertal torsion was studied. It was found that after prepubertal torsion, the contralateral testicle underwent normal development. (2) The duration of torsion necessary to result in contralateral testicular alterations in adult rats was studied. Deoxyribonucleic acid (DNA) histograms were utilized to assess disturbed spermatogenesis. After greater than 8 hours of torsion, detorsion offered no protection to the contralateral testicle. Marked alterations occurred in DNA histograms of 60% to 80% of the animals. (3) The duration and significance of these alterations were assessed. The alterations persisted in the contralateral testis 6 months, and the fertility rates were significantly lower than for control animals.

Development of a new alloplastic spermatocele demonstrating successful sperm retrieval in an animal model.

OBJECTIVE: To create an alloplastic spermatocele capable of repeated sperm aspiration. The alloplastic spermatocele has long been a theoretical solution to infertility for those patients with congenital absence of the vas deferens or irreversible obstruction of the male reproductive ductal system. Recent studies have suggested that sperm from efferent ducts are capable of fertilization. Clinical use of alloplastic spermatoceles for collection of epididymal sperm has resulted in unacceptably low pregnancy rates. Improvement in spermatocele function may occur if a microsurgical anastomosis is performed to the epididymis. DESIGN: A newly designed alloplastic spermatocele was implanted in 17 mature male rabbits. The faceplate of the device had a 0.7-mm orifice, allowing direct precise microsurgical anastomosis to a specific loop of the epididymal tubule. RESULTS: Sperm retrieval was possible in 16/17 (94%) animals. Repeated successful aspirations (total of 73) were performed in all but one animal. The total number of sperm collected per spermatocele averaged 115 x 10(6) (range 0 to 734 x 10(6)). The sperm motility varied widely between animals and specimens, with a maximum average of 21.6% motile sperm/aspirate per animal. All spermatoceles eventually occluded (mean time of occlusion 14 days; range 3 to 30 days). The prostheses with the attached epididymides were examined histologically. CONCLUSIONS: This prototype alloplastic spermatocele allows repeated high density sperm retrieval over a short period of time. Low sperm motility may be less problematic clinically as new techniques of IVF become available.

Analysis of factors contributing to success in a program of micromanipulation-assisted fertilization.

OBJECTIVE: To determine factors important to clinical success in micromanipulation-assisted in vitro fertilization (IVF). DESIGN: Procedures invoked in two separate series of micromanipulation-assisted IVF cycles, one unsuccessful (series I) and the other successful (series II), were compared in an effort to identify changes that led to clinical success. SETTING: University-based IVF clinic. PATIENTS: In both IVF series involving micromanipulation, patients consisted of infertile couples who fit any of five categories of male-factor related infertility. The female patients underwent controlled hyperstimulation for oocyte retrieval and the oocytes were inseminated normally or were subjected either to partial zona dissection or subzonal sperm insertion to assist fertilization. Results in all groups were compared between the two patient series. RESULTS: In the successful series II, a noticeable improvement in fertilization rate and embryo quality was observed compared with series I. A significant increase in the percentage of patients reaching embryo transfer, the pregnancy rate per transfer, and the pregnancy rate per retrieval were noted in series II; a 25% ongoing pregnancy rate per retrieval was observed overall in this successful group, with "ongoing" defined as manifestation of at least a fetal sac on ultrasound with no detectable problems. Patients with a mixed transfer of embryos derived from manipulated and normally inseminated oocytes had a 75% rate of pregnancy per transfer in series II. Differences between the two series could not be attributed to patient selection or biases in selection of oocytes relegated to micromanipulation. However, oocyte handling, micromanipulation, and culture protocols differed significantly between the two series in that temperature and pH of oocytes was better controlled, and micromanipulation time was minimized in series II. CONCLUSION: Success in micromanipulation depends on maintenance of the oocyte in a stable and supportive environment throughout the micromanipulation procedure. It is also important to minimize trauma to the eggs by performing micromanipulation rapidly and with minimal distortion of the egg. Patients with a poor fertilization rate in standard IVF may experience a substantial increase in the likelihood of pregnancy when micromanipulation-assisted fertilization is performed on some eggs.

Testicular biopsy and vasography in the evaluation of male infertility.

Testicular biopsy is performed mainly to differentiate primary testicular failure from obstructive ductal lesions (usually occurring in the epididymis in azoospermic patients who have normal serum gonadotropins). Testicular biopsy may be performed easily on an outpatient basis with excision of a small piece of seminiferous tissue using a "no-touch" technique. Needle core biopsy and needle aspiration biopsy may become more widely used in the future. The role of flow cytometry for purposes of interpreting testicular specimens may be expanded in the future. Vasography should be performed only at the time of planned definitive correction of obstructive lesions of the genital duct system. Various techniques of performing vasography are discussed. Emphasis is placed on deferring vasography until the time that definitive surgery is performed to correct the patient's ductal obstruction. In that regard, vasography therefore generally is not performed as an isolated outpatient procedure.

Specific nonsurgical therapy in male infertility.

Although the objective of this article was to discuss the specific medically treatable causes of male infertility, the reader will be impressed by the fact that many of the treatments seem less than "specific." The need to treat infections to improve fertility is ill defined. The utilization of a scrotal cooling device as "specific" nonsurgical treatment for varicocele is yet to be defined. Immunologic suppression is indeed a specific form of therapy for a measurable phenomenon; unfortunately, the significance of that phenomenon as well as the best means and location of its assessment are undergoing significant reevaluation. An exciting frontier is the prospect of preventing infertility in the patient undergoing therapy for cancer, thus obviating the need for treatment of the ensuing infertility. Before specific therapies can be anticipated to have a predictable beneficial effect, these areas require active investigation to define the problem more clearly.

Treatment outcome after varicocelectomy. A critical analysis.

After extensively reviewing the literature that addresses the efficacy of varicocelectomy, it is apparent that the extent data are flawed because of inappropriate study design and reporting. These difficulties are compounded by an inadequate understanding of the pathophysiology of the varicocele and the complexities intrinsic to the study of reproduction. Varicocelectomy does, indeed, appear to have a beneficial effect on sperm density. This effect seems more pronounced when initial semen densities are greater than 10 million/mL. Conversely, a "ceiling effect" or less of a response may occur when preoperative sperm densities are greater than 40 million/mL. Although anecdotal reports suggest that varicocelectomy may be of benefit even to the azoospermic individual, we do not ascribe to this approach. Motility and morphology may improve significantly after varicocelectomy when an associated rise in density has occurred. Isolated improvements in either of these parameters have also been observed. Simultaneous improvements in density and morphology, however, have not been reported unless a concurrent significant improvement in semen density occurs. In spite of the occasional study which indicates that varicocelectomy does not improve fertility, the preponderance of the literature does in fact support a favorable effect. After carefully analyzing the design and outcome of the studies reviewed, it is clear that a definitive statement concerning the efficacy of varicocelectomy cannot be made. This therapeutic dilemma can be resolved only by a well-designed prospective, randomized, controlled study that examines the impact of varicocelectomy on seminal parameters, sperm function tests, and the pregnancy rates in couples evaluated by stringent protocols. Patients should be stratified according to seminal parameters and age. We conclude as we began: Varicocelectomy remains an important treatment of male factor infertility.

Testicular hemodynamic changes after the surgical creation of a varicocele in the rat. Intravital microscopic observations.

The present study investigated the effect of a surgically induced varicocele on the dynamics of testicular blood flow. The surface vasculature of the normal and the varicocele-affected testis was examined utilizing intravital epi-illumination microscopy. Application of this technique to the study of the varicocele is new. Blood flow characteristics in surface veins were studied as the surface temperature of the testis was varied. Periodic, reproducible stoppages in blood flow, determined by direct observation of the red blood cells, were seen in seven of eight sham animals at the lower temperatures. These stoppages were abolished and blood flow increased at higher temperatures; stoppages reappeared at lower temperatures. The periodic stoppages were present in only one of eight rats with a proven varicocele (P less than 0.025) at any temperature studied. This loss of blood flow regulation may be the result of a loss of testicular arteriolar tone and may explain the increase in testicular blood flow and temperature elevation observed in association with a varicocele. These findings may provide new insights into the pathophysiology of the varicocele and highlight the need to study the microvascular sequelae of this vascular abnormality.

Treatment of congenital penile curvature with penile torsion: a new twist.

Congenital penile curvature secondary to asymmetry of corpora cavernosal length is an uncommon cause of penile deformity. Although the deformity generally is not severe enough to preclude sexual intercourse it can be a source of great concern to the patient and may cause him to avoid all sexual contact. The Nesbit procedure is a simple, effective surgical technique to correct lateral or ventral curvature. Rarely penile deviation is accompanied by penile torsion. This unique problem requires a novel surgical approach to create a straight, nontwisted erection. We report 2 cases of congenital lateral penile curvature with accompanying penile torsion and describe a simple modification of the Nesbit procedure for surgical correction.

Ultrasound and infertility: diagnostic and therapeutic uses.

Ultrasound has become essential in the diagnosis and management of the infertile male. Scrotal ultrasonography provides a detailed examination of the testes and assesses the presence or absence of varicoceles and can identify other abnormalities of the scrotal contents and the spermatic cord. Transrectal ultrasonography can "visualize" the excurrent ejaculatory ductal system, including the ejaculatory ducts, seminal vesicles, and vas deferens. The expansion of these ultrasonographic techniques has provided the urologist with non- or minimally invasive techniques with which to evaluate the infertile male. These advancements consequently have led to innovative surgical and radiologic treatments.

Cystic fibrosis presenting in a 45-year-old man with infertility.

Cystic fibrosis commonly is regarded as a disease of childhood associated with severe pulmonary and pancreatic pathological conditions. We report on a previously healthy 45-year-old man who was diagnosed as having cystic fibrosis after presentation with primary azoospermia. The literature is reviewed. Although references are made to late presentations of cystic fibrosis none was found in which the initial complaint was infertility. Primary azoospermia may be the presenting manifestation of cystic fibrosis in the absence of major respiratory symptoms.

Long-term functional results of urinary tract reconstruction in childhood.

When reviewing the important long-term parameters of urinary tract reconstruction in childhood, one must consider the protection of renal function, maintenance of social continence and freedom from urinary tract infection as paramount. The 3-year assessment of 25 patients who underwent urinary tract reconstruction for a variety of underlying conditions is presented in terms of renal function, social continence and urinary tract sterility. The underlying pathological condition in our patients was weighted toward children with obstructive uropathy rather than neurogenic vesical dysfunction, and the most common form of diversion was an ileal conduit. Maintenance of renal function was achieved in 21 of our 25 patients (84 per cent). All 8 children (100 per cent) who underwent reconstruction for neurogenic vesical dysfunction have maintained preoperative renal function, while only 12 of the 17 children originally diverted for obstructive uropathy (75 per cent) have done well with reconstruction. Social continence with or without intermittent catheterization has been achieved in 23 of the 25 patients (92 per cent) and sterile urine has been maintained in 22 of the 25 patients (88 per cent). Factors involved in the success or failure of reconstruction are discussed, and observations toward future selection are made from this data base.