Development and use of surgical procedures to bypass selected regions of the mammalian epididymis: effects on sperm maturation.

Microsurgical procedures have been used to examine the function of selected regions of the epididymis. Vasoepididymostomy in the rabbit and rat confirmed that spermatozoa require some exposure to the epididymal environment for normal development of motility and fertilizing ability. In both of these species surgical redirection of spermatozoa from a region just distal to the initial segment into the vas deferens resulted in a significant reduction in sperm viability, motility and fertility compared with untreated animals. Surgical bypass of the distal cauda epididymidis in the rabbit did not significantly reduce the number of spermatozoa in ejaculates or the total sperm output accumulated during exhaustive ejaculations. The capacity of these bypass animals to store spermatozoa may be explained by the post-surgical formation of convolutions in the normally straight segment of the rabbit vas deferens. Vas autografts in the rabbit and rat were used to bypass selected epididymal segments. In rabbits, vascularized grafts were used as bridges to bypass the distal caput and proximal corpus epididymidis. Despite high rates of graft survival and patency in this species, the motility and viability of ejaculated spermatozoa were similar to those observed following high level vasoepididymostomy. In rats, non-vascularized vas grafts also showed a high survival and patency rate. There was a transitory reduction in sperm viability and motility 2 weeks after surgery which was associated with structural changes, especially in the epithelium, in vas bridge autografts during revascularization. Longer term observations (3 and 6 months) showed recovery of epithelial morphology and by three months after surgery, no difference was observed in sperm motility, sperm viability or fertility between experimental groups and controls. Similar results were obtained when epididymoepididymostomy was used as the surgical procedure to bypass the same regions of the epididymis. The evidence considered in this review clearly shows that the proximity of vasoepididymal bypass to the testis is inversely related to the state of maturity of ejaculated spermatozoa. More surprisingly, perhaps, it reveals that exposure of spermatozoa to the distal caput and proximal corpus regions of the epididymis in the rat is not obligatory for spermatozoa to develop a level of maturation in the remaining regions of the epididymis sufficient to ascend the female tract and fertilize ova. This finding suggests that the epididymis is more flexible in its functions than had been considered previously and that sperm maturation may not be as dependent on specific regional functions of the epididymis as had been previously proposed.

The role of the epididymis in human infertility.

This review describes the role of the epididymis in human infertility, by analysing the results of epididymovasostomies which confirm that the more distal the site of obstruction the greater the chance of fertility. The use of epididymal spermatozoa for in vitro fertilization (IVF) yielded poor results in contrast to intracytoplasmic sperm injection using either epididymal or testicular spermatozoa. The nature of the pathology causing obstructive azoospermia is examined reviewing in particular the possible role of mercury toxicity in Young's syndrome. This review describes the results of studies that show that the level of obstruction within the epididymis is correlated with the presence of sperm antibodies and distal obstructions are associated with the presence of sperm antibodies. The demonstration that necrozoospermia decreases with increased sperm transport through the epididymis, when combined with the observation of normal testicular sperm morphology, represents the basis for the disorder termed epididymal necrozoospermia. However, to date the nature of the epididymal pathology causing this disorder remains obscure.

Frozen-thawed epididymal spermatozoa for intracytoplasmic sperm injection.

OBJECTIVE: To report the fertilization rate and pregnancy results for intracytoplasmic sperm injection (ICSI) cycles using frozen-thawed epididymal spermatozoa. DESIGN: Retrospective analysis of consecutive ICSI cycles. SETTING: Tertiary referral center for infertility. PATIENT(S): Infertile couples in whom 39 patients (59 ICSI cycles) required the use of frozen-thawed epididymal spermatozoa. As no cycles were performed using fresh epididymal spermatozoa, outcomes were compared with those of 130 couples (170 ICSI cycles) using fresh ejaculated spermatozoa for severe oligoasthenozoospermia-teratozoospermia, in which < 200,000 motile spermatozoa were retrieved after Percoll density gradient centrifugation. INTERVENTION(S): Epididymal sperm aspiration during microsurgery, followed by ICSI. MAIN OUTCOME MEASURE(S): Fertilization, embryo cleavage, ET, and clinical pregnancy rates (PRs). RESULT(S): A total of 484 metaphase II oocytes were injected with frozen-thawed epididymal spermatozoa, resulting in a two-pronuclear fertilization rate per injected metaphase II oocyte of 47%, significantly lower than in cycles using fresh ejaculated spermatozoa (73%). Embryo implantation rates (12.0% versus 13.3%) and clinical PRs per transfer (18.4% versus 27.0%) were not different. When the prefreeze vitality was > 20%, compared with lower vitality, both the fertilization (56% versus 22%) and embryo cleavage (91% versus 57%) rates were significantly greater. CONCLUSION(S): The routine collection and cryopreservation of epididymal spermatozoa at microsurgery allows multiple ICSI treatment cycles with success rates similar to those of ejaculated spermatozoa. However, when the vitality of aspirated spermatozoa is < 20%, the poor fertilization rates indicate the need to consider an alternative source of viable spermatozoa.

Screening Young syndrome patients for CFTR mutations.

Young syndrome is characterized by obstructive azoospermia associated with chronic sinobronchial disease of an infectious nature, but normal sweat-gland and pancreatic function as well as normal nasal potential differences. Congenital bilateral absence of the vas deferens (CBAVD) in some patients arises from mutations within the cystic fibrosis (CF) transmembrane regulator (CFTR) gene. Because of some similarities between Young syndrome, CF, and CBAVD, we evaluated 13 patients with Young syndrome, including screening for more than 30 different mutations within the CFTR gene. The mean age of the patients was 43 yr (range, 32 to 50 yr), and all were of northern European extraction. The sweat chloride concentration was normal in all patients (mean = 29 mEq/L; range, 8 to 43 mEq/L). Most had intermittent bronchial and sinus infections, but none was chronically colonized with Staphylococcus aureus or Pseudomonas aeruginosa. The FEV1 was normal or only mildly reduced in most patients (mean = 74%; range, 48 to 100% predicted). Of 26 Young syndrome chromosomes, we identified one with the recognized CF mutation delta F508. The incidence of CFTR mutations (1 in 26) did not differ significantly from the expected carrier frequency in this population. In summary, it is unlikely that the typical Young syndrome patient has a clinical disease associated with CFTR mutation on both alleles.

Pregnancies after microsurgical correction of partial epididymal and vasal obstruction.

A group of 16 infertile patients suspected of having a partial epididymal obstruction on the basis of severe oligozoospermia, normal-sized testes and a normal serum follicle-stimulating hormone, underwent scrotal exploration. Evidence of partial obstruction of the epididymis was found in 13 cases and of the vas deferens in one case, and was supported by finding normal spermatogenesis on testicular biopsy. Vasoepididymostomy or vasovasostomy were performed, resulting in a significant improvement of semen analysis in 50% of cases and in six pregnancies in two patients. The diagnosis of partial epididymal obstruction should be considered when the above criteria are met. If pregnancies do not result when intracytoplasmic sperm injection (ICSI) is used with the ejaculated spermatozoa, a testicular biopsy followed by a microsurgical by-pass procedure should be considered whenever normal spermatogenesis is diagnosed. In all cases, the epididymal spermatozoa should be aspirated during the operation and either used immediately for insemination or stored frozen. The remarkable results of the new artificial reproduction technologies and in particular ICSI, question the indication for microsurgical correction in cases of partial epididymal obstruction.

Fertility in cases of hypergonadotropic azoospermia.

OBJECTIVE: To review the outcome of reconstructive microsurgery in men with hypergonadotropic azoospermia. DESIGN: A retrospective study on patients with hypergonadotropic azoospermia who underwent scrotal exploration and bypass microsurgery. SETTING: Male infertility microsurgery clinic affiliated with a tertiary university hospital. PATIENTS: Thirty-one hypergonadotropic azoospermic men with evidence of spermatogenesis on testicular biopsy. INTERVENTIONS: Microsurgical exploration of the testes, operative sperm aspiration, and bypass procedures: vasoepididymostomy or vasovasostomy. MAIN OUTCOME MEASURES: Intraoperative aspirated sperm, postoperative ejaculated sperm, proof of fertilizing ability (fertilizations), and pregnancies. RESULTS: Sperm were aspirated intraoperatively in all cases and were detected in postoperative ejaculations in 87%. Of the 14 patients with long-term follow-up data, 6 achieved pregnancies (8 children), and 3 more demonstrated the capacity for fertilization at IVF. CONCLUSIONS: The observation of a high serum FSH in men with azoospermia does not rule out the possibility of obstruction and the capacity for fertility. Caution should be exercised particularly if unilateral testicular atrophy is present. A testicular biopsy should be performed to detect possible spermatogenesis and, if present, then a microsurgical bypass can lead to a successful pregnancy.

Animal models for epididymoepididymostomy. Development of an alternative microsurgical procedure for vasoepididymostomy.

The present success rate for high level microsurgical vasoepididymostomy in patients with obstructive azoospermia is generally poor in comparison with more distal vasoepididymal bypasses, suggesting that the development of a high level bypass method which preserves the distal maturation and storage functions of the epididymis might increase the fertility success rate. To achieve this we have developed a segmental bypass of the distal caput-proximal corpus regions of the epididymis (epididymoepididymostomy) using the rat and rabbit as animal models. In this procedure the epididymides of 11 adult male Sprague-Dawley rats were exposed through a scrotal incision and a convolution of the duct in the proximal corpus region was attached to an opened convolution in the mid-caput epididymides using a standard microsurgical technique. Each male was rested for at least 3 months after the microsurgical bypass operation to allow the preoperative sperm contents of the caudal storage region to be replaced by post-bypass spermatozoa. Six of the 11 rats were proven fertile after surgery by siring litters from mating trials up to 11 months later. The patency of anastomoses was confirmed in 3 animals by laparotomy and recovery of large numbers of sperm with normal motility from the cauda epididymidis distal to the anastomosis site and also from the vas. Similar unilateral surgery in 2 adult male rabbits resulted in normal post-operative semen profiles in 1 and an in vivo fertilisation rate of 100% from 1 mating trial 8 months after surgery. The successful development of a reliable animal model for epididymoepididymostomy provides an experimental tool for studying the function of the epididymis. This technique may also have clinical application as an alternative to high level vasoepididymostomy in selected patients with obstructive azoospermia.

Pregnancy following intra-fallopian insemination of spermatozoa from a male with obstructive azoospermia.

A pregnancy obtained after intratubal insemination with epididymal spermatozoa recovered from a patient with obstructive azoospermia is reported. The successful outcome of the case emphasizes the beneficial nature of the intra-Fallopian environment.

Young's syndrome (obstructive azoospermia and chronic sinobronchial infection): a quantitative study of axonemal ultrastructure and function.

The ultrastructure and function of nasal cilia and sperm tails were examined in 23 men with Young's syndrome and compared with data previously collected from 10 normal subjects. Quantitative electron microscopic assessment showed that sperm tails from patients with Young's syndrome contained significantly fewer central pair microtubules, radial spokes, and inner dynein arms, and their cilia contained less inner dynein arms than normal subjects. The Young's syndrome patients had normal in vitro ciliary beat frequency (11.4 +/- 0.9 Hz), and 12 of the 23 had normal nasal mucociliary clearance (15.0 +/- 5.0 minutes). However, the remaining 11 had markedly abnormal nasal mucociliary clearance in vivo. In these patients, the deficiency of ciliary inner dynein arms did not appear to affect ciliary function in vitro but may under mucus loading lead to abnormal in vivo ciliary function. The consistent abnormalities shown in cilia and sperm tails, though apparently minor, constitute a common factor in both the reproductive and respiratory tracts which may, in combination with abnormalities in the in vivo environment, lead to the features of Young's syndrome.

Fibroma of tendon sheath with bone involvement.

The case is reported of a 62-year-old man presenting with a fibroma of tendon sheath of the left little finger with bone involvement. This is only the third such case reported. A brief discussion of this benign soft tissue tumour follows.

Epididymal microsurgery: current techniques and new horizons.

Surgical treatment for obstructive azoospermia was introduced about 30 years ago with the development of Bayle's vasoepididymal fistula technique (Bayle: Enc Med Chir 41:435, 1966). More recently this has been replaced by single tubule end-to-end microvasoepididymal bypass procedures with improved success rates. We describe the use of animal models in the development and application of a modified end-to-end microanastomosis technique in which the vas deferens is attached to a single surface convolution of the ductus epididymidis. In comparison with other microvasoepididymostomy (micro-VE) procedures, this technique results in less postoperative scarring and allows for easier access to the epididymis in those patients requiring subsequent epididymal surgery. With this procedure 60% of patients produced spermatozoa after operation, and 10% of 102 patients have so far achieved pregnancies. For patients, such as those with congenital absence of the vasa deferentia, whose infertility cannot be corrected by microvasoepididymal surgery, we describe a microaspiration procedure that can be used to collect spermatozoa from the epididymis for use in in vitro fertilization (IVF). This procedure has a low success rate at present, with an 18% fertilization and 3% pregnancy rate per cycle. Improvements in treatment procedures for aspirated sperm samples, such as the use of motility stimulators and in vitro maturation by coculture with epididymal tubule segments before IVF, may enhance the success for this technique. Microinjection of sperm collected by epididymal microaspiration into oocytes may be an alternative method of treatment for these patients in the future. Two procedures (microepididymoepididymostomy and the vas bridge bypass) that are currently being modelled in the rabbit may provide new directions for epididymal microsurgery and for examining epididymal function. Although the two methods are technically more difficult than standard micro-VE procedures, preliminary studies are encouraging and suggest a future role for these techniques in treating obstructive azoospermia. Such techniques make use of the epididymis distal to the obstruction site and may be particularly important in improving the success of surgery for obstructive azoospermic patients with high-level obstructions in whom sperm quality following micro-VE surgery is often poor.

Patterns of human epididymal fluid proteins on polyacrylamide gel electrophoresis.

Proteins were analysed by sodium dodecylsulphate polyacrylamide gel electrophoresis in fluid taken from six epididymal regions in 10 men undergoing microsurgery to bypass epididymal obstructions resulting from various disorders. Some major proteins common to most samples were identified with apparent molecular weights of 95, 67, 56, and 44 kilodaltons. A degree of regional specificity in the synthesis and secretion of epididymal proteins was indicated. There appeared to be no correlation between protein pattern or the abundance of individual proteins and the cause of obstruction, although methodological constraints may have partially obscured any such relationship.

Comparison of the short-term effects of vasoligation and open-ended vasectomy on the reproductive tract of the male rat.

Comparison was made between the short term effects of vasoligation and open-ended vasectomy in the rat at 2, 4 and 8 weeks after surgery. Epididymal granulomata were observed in 2/5 and 1/5 rats respectively 2 and 4 weeks after vasoligation. No epididymal granulomata were observed following open-ended vasectomy, providing some support for the suggestion that this procedure may be beneficial in reducing early post operative complications in the epididymis. An unexpected observation in the 2 week open-ended vasectomy group was the finding that in 2 of 5 animals the proximal end of the vas had been temporarily obstructed by overgrowth of a fibromuscular cap. Increased distal cauda epididymidis tubule diameter in these animals suggested an increased intratubular pressure. No sustained differences were seen in the incidence of granulomata or in the response of the testis or epididymis to either vasectomy procedure by 8 weeks. The results suggest, because of the high incidence of granulomata formation following vasoligation in the rat, that by 8 weeks after surgery both vasectomy procedures are equally effective in preventing further damage in the epididymis caused by elevated intraluminal pressures.

Human pregnancy by in vitro fertilization (IVF) using sperm aspirated from the epididymis.

Spermatozoa were collected by microaspiration from the corpus epididymidis of a 42-year-old man with secondary obstructive azoospermia and used for in vitro fertilization. At insemination 61% of the spermatozoa were motile, with a motility index of 157. One of five eggs was fertilized and this was subsequently transferred to the patient's wife at the two-cell stage. Ultrasound examination and changing hormone levels confirmed an on-going pregnancy, which is currently at 30 weeks of gestation. This technique will provide a useful alternative for the management of some infertile men with obstructive azoospermia.

Squamous cell carcinoma in dominant type epidermolysis bullosa dystrophica.

The unusual genetic disorder epidermolysis bullosa dystrophica has been reported in several patients in whom the chronic cutaneous scars led to the development of cutaneous squamous cell carcinoma. However, only one of these previously reported cases involved the autosomal dominant form of the disease; the remainder occurred in its recessive counterpart. We report the second and third patients with squamous cell carcinoma associated with the dominant form of epidermolysis bullosa dystrophica. In addition, we not only observed the previous electron microscopic findings of decreased numbers of anchoring fibrils beneath the basal lamina but have also noted marked disruption of the basal lamina itself.

The basal cell nevus syndrome: disasters occurring among a series of 36 patients.

We have reviewed a series of 36 patients with the basal cell nevus syndrome seen at Roswell Park Memorial Institute from 1950 to 1978. Among these patients a number of disastrous complications occurred. These include extensive uncontrolled basal cell epithelioma of the face resulting in one death from direct cerebral invasion via the orbit, one facial nerve palsy, two bilateral and two unilateral eye enucleations, and several severe facial mutilations in young patients. There were three patients who developed severe bradycardia and hypotension during induction of general anesthesia required postponement of the intended operation, and one patient with congenital hemiparesis who on investigation was found to have an absent internal carotid artery. A review of the syndrome complex is presented with a plan for recognition and management.

Solitary multinodular giant cell tumor of tendon sheath.

We present a 74 year old man with a solitary multinodular tumor of the right thumb and an adenocarcinoma of the prostate. Histologic examination of the hand tumor revealed a giant cell tumor of tendon sheath.

Arsenically associated cutaneous squamous cell carcinoma with hypercalcemia.

Squamous cell carcinoma of the skin complicated by hypercalcemia is very rare. This report is of a patient with long-term exposure to medicinal oral arsenic who developed an extensive squamous cell carcinoma complicated by hypercalcemia.