Antisperm autoantibody response is reduced by early repair of a severed vas deferens in the juvenile rat

OBJECTIVE: To determine whether antisperm autoantibody production after prepubertal vas injury is influenced by immediate repair of the vas compared to delay of the reanastomosis until sexual maturity. DESIGN: Animal study comparing early repair, late repair, and sham-operated groups. SETTING: Research laboratory in a medical school. PATIENT(S): Lewis rats. INTERVENTION(S): After division of the vas deferens in juvenile rats, animals in an early repair group had the vasa repaired immediately by using an absorbable intraluminal stent. Animals in a late repair group had vasa obstructed by ligation until after puberty, when they underwent microsurgical vasovasostomy (age 60 days). MAIN OUTCOME MEASURE(S): Antisperm antibodies were assayed by ELISA. The weights of reproductive organs were determined, and samples of testis were studied by light microscopy. RESULT(S): The antisperm antibody response was less when the vas was repaired immediately than if the repair was delayed until after puberty. There was a low incidence of testicular alteration in the repair groups and none in sham-operated animals. CONCLUSION(S): If the vas deferens is injured or obstructed prepubertally, there may be a benefit to considering immediate repair to reduce the likelihood of developing antisperm autoantibodies, which have been associated with reduced fertility.     

Low incidence of sperm antibodies in men with congenital absence of the vas deferens

The incidence of antisperm antibodies in serum and seminal fluid of 27 azoospermic men with congenital absence of the vas deferens is evaluated. The presence of antisperm antibodies was assessed using the immunobead test, the agglutination test, and immobilization test. Five patients with vasovasostomy or vasoepididymostomy attempts were included in the study and tested for the presence of antisperm antibodies. Contrary to a previous report, a low incidence (11%) of antisperm antibodies has been found in patients with congenital absence of the vas. In agreement with previous studies, in five patients who had failed vasoepididymostomy or vasovasostomy, a high incidence (71%) of antisperm antibodies was found.     

Vasectomy and vasovasostomy in rhesus monkeys: the effect of circulating antisperm antibodies on fertility.

Rhesus monkeys develop agglutinating and complement-dependent antisperm antibodies after vasectomy. In order to study whether these antibodies affect fertility after vasovasostomy, 15 animals were given vasectomies and 6 months later vasovasostomies. Subsequently, each was mated with females of proven fertility. Five controls were given sham operations and similarly treated. During this period, each aimal was bled for serum to monitor the humoral immune response, ejaculated for semen analyses, and palpated for granuloma or fistula development. All control animals had a transient decrease in sperm density after sham vasectomy and vasovasostomy operations. The surgical procedures of vasectomy and subsequent vasovasostomy resulted in more animals having sperm of poor motility and quality. All of vasovasostomies were surgically successful in that sperm were again present in the ejaculate of each animal. The amount of sperm in the ejaculate could not be correlated with the ease of surgical procedure, presence or absence of macrophages in the ejaculum, motility, or forward progression. Only animals that had been vasectomized developed circulating antisperm antibodies. Sustained, elevated levels of antisperm antibodies most commonly occurred in monkeys that had high initial total sperm counts. Six of the experimental animals retained high levels of sperm-immobilizing antibodies after vasovasostomy. Of these, two were found to be infertile and two were classed as subfertile. Of the nine experimental animals without sustained antisperm antibody production, only one was classed as subfertile. This suggests that antisperm antibodies may in some cases impair the restoration of fertility after vasovasostomy.     

Effect of vasovasostomy on contralateral testicular damage associated with unilateral vasectomy in mature and immature Lewis rats

OBJECTIVE: We sought to determine if laser-assisted vasovasostomy could reverse the contralateral histologic testicular changes associated with unilateral vasectomy. DESIGN: A prospective, randomized, blinded, controlled study. SETTING: Animal microsurgical laboratory, St. John's Mercy Medical Center, St. Louis, Missouri. PATIENT(S): Twenty mature and 20 immature male Lewis rats. INTERVENTION(S): Ten mature and 10 immature male Lewis rats underwent unilateral vasectomy. At 5 months, testicular biopsy and laser-assisted vasovasostomies were performed followed 2 months later by evaluation of vas patency and repeat testicular biopsy. Control animals consisted of 10 rats in each group, 5 that underwent sham operations and 5 that had halothane anesthesia alone. RESULT(S): In the immature and mature groups unilateral vasectomy resulted in marked contralateral testicular damage in 30% (3 of 10) and 50% (5 of 10), respectively. Vas patency determined 2 months after vasovasostomy was 80% (8 of 10) in the mature group and 89% (8 of 9) in the immature group. No animal that had contralateral testicular changes after vasectomy and a patent vas after vasovasostomy showed improvement in testicular histology. CONCLUSION(S): It appears that contralateral testicular damage associated with unilateral vasectomy is not improved 2 months after successful vasovasostomy in mature or immature Lewis rats.     

Open-ended vasectomy: an assessment

Leaving open the testicular end of vas at vasectomy could reduce symptoms of epididymal congestion and improve the success rate of vasovasostomy but might have the disadvantage of increasing the incidence of painful sperm granulomas and spontaneous recanalization. In 4330 open-ended vasectomies the rate of epididymal congestion was significantly less than in 3867 standard vasectomies. The rate of painful sperm granulomas was not increased: it was significantly reduced. Spontaneous recanalization was rare in both groups. Whether or not open-ended vasectomy improves the success rate of vasovasostomy, it represents an improvement in technique because it reduces the rate of complications after vasectomy. Closure of the sheath over the prostatic end of vas is essential if recanalization is to be prevented.     

输精管结扎术后抗精子抗体在非射出精子上的存在

４８例正常育龄男子和２４例要求作输精管吻合术者，用免疫珠结合试验（ＩＢＴ）和精子－宫颈粘液接触试验（ＳＣＭＣ）分别检测其近睾端输精管液中的精子（非射出的精子）表面抗精子抗体的情况。结果显示：正常育龄男子非射出的精子上没有抗体存在；而输精管结扎术后非射出的精子上有抗精子抗体存在（ＩｇＧ：７９．４％，ＩｇＡ：３８．２％，ＳＣＭＣ：３５．５％）。这些抗体在输精管结扎术后不到１年就可发现，并保持到结扎术后３年以上。吻合术后１～３个月内，其精液中射出的精子上仍发现抗体存在。结果还提示：输精管结扎术后，不能以非射出的精子上抗体的水平去预测吻合术后射出的精子上抗体的水平；吻合术前血清抗体水平与非射出的精子上抗体水平并不一致。     

Fertility rates with delayed fibrin glue: vasovasostomy in rats.

OBJECTIVE: To determine if fibrin glued vasovasostomy had comparable fertility rates to sutured vasovasostomy. DESIGN: Twenty adult male Sprague-Dawley rats underwent bilateral vasectomy. Two weeks after vasectomy, 10 rats had a bilateral sutured vasal anastomosis consisting of four mucosal and four seromuscular sutures with 10-0 nylon. The second group of 10 rats underwent bilateral fibrin glue vasal anastomosis consisting of two transmural sutures with 10-0 nylon followed by application of fibrin glue. One month after vasectomy reversal, each male rat was mated with a female rat for a period of 2 weeks. SETTING: Animal laboratory. PATIENTS PARTICIPANTS: Twenty male Sprague-Dawley rats. INTERVENTIONS: Bilateral vasectomies in 20 male Sprague-Dawley rats. Two weeks after vasectomy, 10 rats had bilateral sutured vasal anastomosis, and 10 rats had bilateral glued vasal anastomosis. MAIN OUTCOME MEASURES: Pregnancy after vasectomy reversal. RESULTS: Ten of 10 rats in the sutured group produced offspring for a fertility rate of 100%. Eight of 10 rats in the fibrin glue group produced offspring for a fertility rate of 80%. There was no statistically significant difference in the pregnancy rates between the two groups at the 95% confidence interval. CONCLUSION: Fibrin glue-delayed vasectomy reversal produces comparable fertility rates compared with conventional sutured vasectomy reversal in the rat.     

Relationship of epididymal sperm antibodies to their in vitro fertilization capacity in men with congenital absence of the vas deferens.

OBJECTIVES: To test, using the immunobead binding technique, for the presence of antisperm antibodies on epididymal sperm, in epididymal fluid, and in serum of men with congenital absence of the vas deferens. To evaluate the in vitro fertilization (IVF) capacity of human epididymal sperm in the presence of antisperm antibodies. DESIGN: Prospective. At the time of oocyte insemination, sperm from the proximal caput epididymis or vasa efferentia were tested by direct immunobinding technique. The epididymal fluid and serum were tested by indirect immunobinding technique. SETTING: Center for Reproductive Health, University of California-Irvine. PATIENTS: Forty-five patients with congenital absence of the vas deferens participating in the microsurgical epididymal sperm aspiration and IVF program. MAIN OUTCOME MEASURE: Incidence of antisperm antibodies to epididymal sperm and their relationship with IVF results. RESULTS: Sixteen men (35%) tested positively to the direct immunobead test on epididymal sperm; 7 (16%) were positive in epididymal fluid and 13 (29%) were positive in serum. Five pregnancies (31%) occurred in the positive group of which two were from patients who had sperm binding of 100% for immunoglobulin (Ig)G (all over sperm surface) and 90% (midpiece, tail) and 50% (tail, tiptail), respectively, for IgA. Five pregnancies (18%) were obtained in the negative group. No statistical difference was observed in the overall fertilization rate between the two groups. CONCLUSION: Human epididymal sperm and epididymal fluid retrieved from men with congenital absence of the vas deferens can react positively to immunobead test. However, the presence of antisperm antibodies do not seem to impair the IVF capacity of epididymal sperm.     

Clinical experience of epididymovasostomy and vasovasostomy for obstructive azoospermia]

14 patients with obstructive azoospermia were treated with microsurgical vasovasostomy or epididymovasostomy. A total of 11 patients underwent 2-layer vasovasostomy, 6 cases following bilateral vasectomy and 5 cases suffering from bilateral vasal disruption by inguinal herniorrhaphy. 3 patients underwent end-to-end epididymovasostomy with Silber's specific tubule technique following bilateral epididymitis. After the operation, fertility was restored in 6 of 14 cases. The recovered sperm density was greater than 20 x 10 6/ml and sperm motility exceeded 50%. Pregnancy was achieved in 1 case following inguinal herniorrhaphy. Preoperative testicular biopsies carried out in 11 cases disclosed slight deterioration of spermatogenesis. Johnsen's mean score was 8.20 +or- 0.38 (mean +or- S.D.). The mean scores of the biopsies obtained from the cases obstructed for more than 20 years were significantly lower than those with less than a 20-year time period. After inguinal herniorrhaphy, reanastomosis of the vas deferens was difficult in order to restore fertility. This was due to the presence of longterm obstruction, defects in the vas deferens, or the absence of sperm granuloma at the vasectomy site. Epididymovasostomy restored fertility in 67% of the cases. The specific tubule technique was the most effective in the management of such pathological conditions. (author's modified)     

Low fertility rate in vasovasostomized males and its possible immunologic mechanism.

Contradictory views have been expressed about the role of the various antisperm antibodies which develop after vasoligation. The present study was conducted in 50 normal fertile males, 50 vasectomized subjects and 25 subjects after recanalization of their vas deferens in order to investigate the development of various anti-sperm antibodies after vasectomy, along with their incidence, their persistence after successful relief of vaso-obstruction by vasovasostomy and their role in the causation of infertility in vasoanatomized normospermia males. Sperm agglutinating, immobilizing and haemagglutinating antibodies showed rises in titres with increase during the post-vasectomy period, indicating continuous antigenic stimulus. Age, post-operative complications and blood group did not seem to alter the results. 86% of subjects developed antisperm agglutinins, mostly tail-to-tail type (54.5%), 1-12 years after vasoligation, while only 2% of fertile men had circulating spermagglutinins. A lower incidence of positive sperm in the immobilization test than in the agglutination test suggests either that different antibodies are detected by these two tests or these tests have differing sensitivities. Of the 25 vasovasostomized subject, 13 (52%) cases became normospermic and 4 (16%) oligospermic while 8 (32%) remained azoospermics. Except for 3 oligospermic subjects, all had circulating spermagglutinins. Among the 13 normospermic vasovasostomized persons, a significant correlation was found between the titres of circulating antisperm agglutinins and autoagglutination of spermatozoa in their ejaculates; and also between the sperm immobilization values of their sera and the degree of their sperm motility. Three normospermic recanalized men, having low levels of sperm agglutinins and haemagglutinins with normal seminogram and no sperm immobilizing antibody, successfully impregnated their wives. Another 10 vasovasotomized infertile subjects had sperm agglutinins in significant titre; 5 showed positive sperm immobilization values, a similar number showed autoagglutination of sperm, while a decreased degree of motility of sperms was noted in 6 cases. Thus there was a significant correlation between the titres of anti-sperm antibodies and autoagglutination of spermatozoa, which might be an important cause of male infertility after successful anatomic relief of vasoobstruction. Histological studies of testicular biopsy showed normal spermatogenesis in azoospermic recanalized subjects, although they had high levels of antisperm antibodies. This suggests that these antibodies do not affect normal spermatogenesis, and sperm counts.     

Unilateral obstruction of the vas deferens caused by childhood inguinal herniorrhaphy in male infertility patients.

OBJECTIVE: To study the incidence, diagnosis, and treatment of unilateral obstruction of the vas deferens caused by inguinal herniorrhaphy (IH) during childhood. DESIGN: Retrospective. SETTING: Kyoto University Hospital. PATIENTS: Unilateral obstruction of the vas deferens after IH was diagnosed and treated in 10 of 724 subfertile patients. INTERVENTIONS: Reanastomosis of the vas deferens using a microsurgical two-layer technique. MAIN OUTCOME MEASURES: Follow-up seminal analysis of the patients and the occurrence of pregnancy in their wives. RESULTS: The incidence of unilateral vas deferens obstruction caused by IH was 26.7% for subfertile patients with a history of IH during childhood. Unilateral vas deferens obstruction was detected through palpation of the scrotal vas deferens in 7 of the 10 patients. After vasovasostomy, the semen quality improved in 5 patients, and pregnancy was achieved by 2 patients. CONCLUSIONS: The incidence of vas deferens obstruction was unexpectedly high in subfertile patients with a history of IH during childhood. Careful palpation of the scrotal content was a useful and noninvasive method to diagnose unilateral vas deferens obstruction, and microsurgical vasovasostomy was treatment of choice.     

Occurrence of serum antisperm antibodies in patients with cystic fibrosis

OBJECTIVE: To determine if acquired obstruction of the vas deferens in men with cystic fibrosis (CF) induced the development of antisperm antibodies with genital tract obstruction similar to other men. DESIGN: Serum antisperm antibodies were assayed by an indirect immunobead test and an indirect immunofluorescence assay. Both homologous (human sperm/human zona) and heterologous (human sperm/zona-free hamster ova) sperm/egg interactions were evaluated in the presence of serum antisperm antibodies from patients with CF. SETTING: Cystic Fibrosis Clinic at the University of Oklahoma Health Sciences Center, a tertiary care referral center. PATIENTS: Fifteen CF patients (10 male and 5 female), 3 non-CF antisperm antibody-positive infertile patients (2 male and 1 female), 20 fertile controls (7 males and 13 females), and 9 fertile sperm donors were used. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Serum antisperm antibody levels in patients with CF. In those patients with antisperm antibodies, determine effect of these sperm antibodies on sperm/egg interactions and complement-mediated events. RESULTS: Sera from 3 (30%) of 10 men with CF demonstrated immunoglobulin (Ig)G, IgA, and/or IgM antisperm antibodies, whereas sera from all 5 CF women and the 20 control sera were negative for antisperm antibodies. The maximal titers for IgG, IgA, and IgM antisperm antibody were 1:8, 192, 1:256, and 1:64, respectively. The immunobead binding, which was restricted to the sperm head and tail-tip or the midpiece and tail-tip, correlated with the indirect immunofluorescence pattern. Antisperm antibody-positive sera from men with CF impaired both the binding and penetration of human zonae and the penetration of hamster ova by human sperm. CONCLUSIONS: Similar to other men with congenital or acquired obstruction of their genital tract, antisperm antibodies may occur in some men with CF. Antisperm antibodies may contribute to immune sperm dysfunction in some men with CF by activated complement-mediated events and interfering with sperm/egg interactions.     

40例输精管道梗阻性无精子症诊疗策略分析

目的:探讨输精管道梗阻性无精子症(OA)的诊疗策略。方法:40例输精管道OA患者为研究对象。首先行输精管道探查,根据术中探查情况行输精管-输精管显微吻合术(VV)、输精管-附睾显微吻合术(VE)、交叉输精管-输精管吻合术、交叉输精管-附睾管显微吻合术或睾丸取精冻存术。结果:精道探查后,共行吻合手术26例,取精+冻精手术14例。40例患者中,共有3例患者失访(2例吻合患者,1例冻精患者)。随访到的24例吻合术患者术后复通率为58.3%(14/24),自然受孕率为29.1%(7/24)。随访到的13例取精+冻精患者中已有11例行ICSI/冻精助孕。结论:输精管道OA,可根据术前严格评估和术中探查行显微复通手术或取精术;复通术后可获得自然妊娠的机会,交叉显微吻合为输精管道复通的有效途径之一。     

Characterisation of a sperm coating auto-antigen reacting with antisperm antibodies of infertile males using monoclonal antibodies

Objective In a previous study a number of sperm-specific antigens were identified which reacted with antisperm antibodies from both infertile and vasovasostomised males. To investigate the localisation and distribution of these antigens and their role in male fertility, monoclonal antibodies were raised against them; immunoblotting techniques were used to select only those antibodies which competed with human antisperm antibodies for these human auto-antigens.
Design One antibody, NW21, reacted with an 18 kDa auto-antigen present on epididymal sperm but absent from testicular sperm. Immunohistochemical studies showed that the antigen is produced in small basal cells between the columnar epithelium of the corpus epididymis, passes up into the tubule and then coats sperm passing along the epididymis. Sperm stored in the cauda epididymis and ductus deferens stain strongly for this sperm coating glycoprotein.
Conclusions The localisation of this antigen supports the suggestion that auto-immune infertility may represent a response to epididymal rather than testicular sperm. Monoclonal antibodies raised to unique and immunologically accessible sperm coating proteins, produced in the epididymis rather than in the testis, would seem to present an excellent theoretical solution to male contraception.     

Identification of human sperm antigens reacting with antisperm antibodies from sera and genital tract secretions.

OBJECTIVE: To identify sperm antigens reacting with antisperm antibodies relevant in human infertility. DESIGN: The reactions of separated sperm antigens with antibodies present in sera and genital tract secretions from infertile and fertile females and males were examined by immunoblotting techniques. SETTING: The patients were followed in an outpatient setting of a hospital clinic. PATIENTS: One hundred consecutive infertile males and females, referred for determinations of antisperm antibodies, comprised the study group. Fifty hospital and faculty employees with proven fertility served as a control group. RESULTS: A high proportion of sera from fertile and infertile humans contained antibodies reacting with at least one sperm antigen. However, two discrete bands of antigenic proteins with molecular weights of 44 and 72 kd reacted significantly more frequently with serum antibodies from infertile females than from fertile females. No apparent correlation could be demonstrated between any particular antigen and serum antibodies from infertile males. Nevertheless, antigenic proteins of 62 kd were identified as the major sperm antigens reacting with antibodies present in seminal plasmas from infertile males. CONCLUSIONS: The major sperm antigens reacting with systemic antibodies differ from the antigens recognized by local antisperm antibodies. Sperm antigens exhibiting relative molecular weights of 62 kd are major antigens reactive with local antisperm antibodies from infertile humans.     

Clinical characteristics of subfertile men with antisperm antibodies

This study investigated the clinical features which could serve as markers to identify subfertile men with antisperm antibodies including age, duration of infertility, history of abdominal or perineal surgery and previous genital trauma. Of the 162 men studied, 43 had a positive test for antisperm antibodies. A significantly greater number of these patients had a history of genital trauma and appendicectomy. Whereas the aetiological role of genital trauma in spermatozoal autoimmunity is readily explicable, that of appendicectomy is not. It can only be postulated that inflammation of the appendix may sometimes affect the vas deferens or that there is some inadvertent injury to the vas deferens during appendicectomy.     

Clinical characteristics of subfertile men with antisperm antibodies

Summary. This study investigated the clinical features which could serve as markers to identify subfertile men with antisperm antibodies including age, duration of infertility, history of abdominal or perineal surgery and previous genital trauma. Of the 162 men studied, 43 had a positive test for antisperm antibodies. A significantly greater number of these patients had a history of genital trauma and appendicectomy. Whereas the aetiological role of genital trauma in spcrmatozoal autoimmunity is readily explicable, that of appendicectomy is not. It can only be postulated that inflammation of the appendix may sometimes affect the vas deferens or that there is some inadvertent injury to the vas deferens during appendicectomy.     

Reduced levels of T suppressor/cytotoxic lymphocytes in semen from vasovasostomized men: relationship to sperm autoantibodies

The regulation of lymphocyte populations in semen and their function remains unknown. Using monoclonal antibodies and immunohistochemical techniques we compared the levels of mononuclear cells in ejaculates obtained from 14 men with intact vas deferens and 13 men who had undergone both a vasectomy and a microsurgical vasovasostomy. The presence of antisperm antibodies was also assessed by the immunobead binding assay. Semen from both groups contained about 10(3) T and B lymphocytes and monocytes. In men with intact vasa, T suppressor/cytotoxic cells predominated. In contrast, in vasovasostomized men the levels of T suppressor/cytotoxic cells were significantly reduced (P less than 0.005) and T helper/inducer cells predominated in their semen. Concentrations of seminal T helper/inducer lymphocytes, B lymphocytes and monocytes were similar in both groups. Antisperm antibodies were detected on sperm, in seminal fluid and/or in serum of all the vasovasovasostomy patients but in none of the controls, T suppressor/cytotoxic cells may limit the immune response to sperm within the male reproductive tract. Chronic obstruction resulting in damage to the integrity of the excurrent ducts may induce alterations in T cell regulation leading to a decrease in T suppressor/cytotoxic cells and create conditions permissive for the formation of autoantibodies to sperm-specific antigens.     

Teratological evaluation of an injectable male antifertility agent, styrene maleic anhydride, in rats.

Polymer styrene Maleic anhydride (SMA) dissolved in dimethylsulphoxide (DMSO) was injected into the lumen in each vas deferens of male rats at dose levels of 0.25 mg, 0.50 mg, 1.0 mg, 2.5 mg, and 5.0 mg, while control rats (groups 1) received 0.03 mL DMSO in each vas deferens. After 4 weeks, the lumen was flushed with 0.1 mL DMSO and the animals were left for another 6 weeks to regain fertility. These rats were mated with virgin and coeval females. No anomaly was observed which could be related to teratogenic action of the polymer in pregnant mothers or fetuses.