Immunological consequences of vasectomy and vasovasostomy in rhesus monkeys

The effects of circulating antibodies on fertility after vasovasostomy was studied in rhesus monkeys. After vasectomy there was rapid rise in antibody levels against spermatozoa; these reached a peak after 2 weeks, rather more rapidly than has been reported in man. Antibody levels declined after this period. Monkeys with high antibodies were also more likely to have granulomas and fistulas. After vasovasostomy several monkeys became fertile again with sperm counts in ejaculate reaching a high level at 3 months, although levels were lower than before vasectomy. Some males retained a high and sustained level of sperm immobilizing antibodies in plasma, sometimes for 18 months or more. These males produced fewer spermatozoa and were more likely to be subfertile or infertile after vasectomy. Almost all the monkeys without antibodies were fertile. Presence of antibodies at vasovasostomy was not a definite indication of subsequent infertility but did provide an indication of likelihood of continuing sterility. These are similar to observations of men undergoing vasectomy and vasosostomy.     

Factors that influence fertility after vasovasostomy in rats

OBJECTIVE: To determine if fertility after vasovasostomy of immunologically responsive Lewis rats differs from that of the less responsive Sprague-Dawley strain and to relate fertility to antisperm antibodies, fluid flow in the vas deferens, and testicular structure. DESIGN: Male rats received: (1) bilateral vasectomies; (2) vasectomies followed 3 months later by vasovasostomy; or (3) sham operations. SETTING: Research laboratory. MAIN OUTCOME MEASURES: Fertility was assessed by caging males with three females for 2 weeks and subsequently counting implantation sites. Antisperm antibodies were measured with an enzyme-linked immunosorbent assay, fluid flow through vas deferens segments was tested in vitro, and testicular structure was studied microscopically. RESULTS: Nearly all vasovasostomized Lewis rats were infertile (33 of 34), whereas 62% (18 of 29) Sprague-Dawley rats were fertile after vasovasostomy (P less than 0.001). In fertile Sprague-Dawley males, significant correlations existed between: (1) implantation sites or females impregnated; and (2) antisperm antibodies early after vasectomy, vas flow, and testicular morphology. CONCLUSIONS: Genetic differences affect fertility after vasovasostomy. Fertility after vasovasostomy is also influenced in a multifactorial manner by the immune response, mechanical elements, and structural changes in the reproductive tract.     

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.     

Vasectomy: consequences of autoimmunity to sperm antigens.

Data from studies examining the effects of vasectomy in a large number of nonhuman primates vasectomized for periods ranging up to 14 years are summarized, and these findings and speculations are used as a framework with which to review the subject of autoimmunity and vasectomy. Attention is directed to autoimmunity to sperm antigens following vasectomy (factors affecting antisperm antibody levels, characteristics of circulating antisperm antibodies, antisperm antibodies in seminal plasma, and cellular immunity following vasectomy), and immunopathology of antisperm autoimmunity (local effects on the male reproductive tract and systemic effects on the male reproductive tract). The 6 hypotheses that have been advanced to explain individual variations in dynamics and types of antisperm antibodies produced following vasectomy are reviewed. 3 tests are commonly used to detect free antisperm antibodies after vasectomy: 1) the spermagglutination test; 2) the sperm immobilization test; and 3) the immunofluorescence test. Spermagglutinating (SA) antibodies, the most common type of antibody produced after vasectomy, occur in approximately 2/3 of vasectomized men and in a majority of vasectomized rhesus monkeys. Sperm-immobilizing (SI) antibodies are also produced in a large percentage (40%) of vasectomized men and rhesus monkeys. About 30% of vasectomized men also have antiprotamine antibodies.     

A fifteen-year study of alterations in semen quality occurring after vasectomy reversal

Semen quality was evaluated in 256 men at 2, 4, 6, and 12 months after vasectomy reversal. Total sperm counts were normal and averaged 91 X 10(6) sperm per ejaculate. The percentage of live sperm was decreased below normal to 36% and hypo-osmolarity values indicated only 41% of the sperm with normal membranes. Progressive motility and the total progressively motile sperm count were reduced and averaged 25% and 27 million, respectively. Approximately 50% of the patients had positive titers of sperm agglutinating and/or sperm immobilizing antibodies. Sperm morphology indicated tail and head shape defects with increases in both tapered and immature sperm. A fertility score combining several sperm parameters averaged only 37% of normal. All of these values remained constant with time after reversal except for progressive motility (increased), oval head shapes (increased), and tapered sperm (decreased). This study has demonstrated that characteristic defects occur in sperm (decreased). This study has demonstrated that characteristic defects occur in sperm motility, sperm membrane function and morphology, in addition to specimen fertility scores, after a vasectomy reversal and need to be taken into consideration when advising and treating these patients for subsequent fertility difficulties.     

Infertility in mice after unilateral vasectomy

The effects of unilateral vasectomy upon fertility and antisperm antibody production were studied using DBA/1J mice. Thirty-six males underwent either unilateral vasectomy, unilateral orchiectomy, or sham surgery. In vivo effects upon fertility were monitored by matings. Antisperm antibody titers were measured monthly. In vitro fertilization was performed in the presence of serum obtained 4 months postoperatively, and serum testosterone levels were also determined. After 3 months, only 1 male in the vasectomy group induced a pregnancy (1 of 12), while all but 1 of the males in the two control groups induced a pregnancy (20 of 21). The geometric mean antisperm antibody titer was 1:169 in the vasectomy group, while the orchiectomy and sham surgery groups had titers of 1:4 and 1:14, respectively (P less than 0.0001). The percentage of eggs fertilized in vitro in the presence of serum from experimental mice fell from 80% in the two control groups to 40% in the unilateral vasectomy group. Unilateral vasectomy induced infertility in DBA/1J mice and an antisperm antibody response. Sera containing these antibodies inhibited in vitro fertilization. This suggests that infertility after unilateral vasectomy may be immunologically mediated by antisperm antibodies.     

输精管吻合家兔不育原因的研究——Ⅰ.血清抗精子抗体分析

本实验证明,输精管吻合术后不育组(VIG)血清抗精子抗体阳性检出率和效价与输精管吻合育组(VFG)比较无差异(p>0.05);VIG的精子密度显著地低于VFG(p<0.01)和假手术组(SOG)p<0.001;精子膜ADA活力,VIG明显地低于SOG(p<0.01),VFG与SOG比较无差异(p>0,05);精子膜ADA活力与精子密度呈显著的负相关(r=-0.60,p<0.01);睾丸ACE活力与精子密度呈正相关(r=0.59,p<0.01),而与ADA活力呈有意义的负相关(r=-0.52,p<0.02)。因此,吻合术后不育与血清抗精子抗体效价无直接关系,而与精子密度降低、功能障碍有关。     

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.     

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。     

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)     

The infertile male--diagnosis

PURPOSE: To discuss a variety of tests used to diagnose the subfertile male and to impart based on clinical experience, reading, and personal research, this editor's view of the relative value of these tests. METHODS: The tests discussed include motile density, sperm morphology, the hypo-osmotic swelling test, antisperm antibodies, sperm chromatin structure assay, DNA integrity tests, reactive oxygen species, sperm penetration assay, sperm-zona pellucida binding tests, sperm creatine kinase activity, plasma membrane mannose-ligand receptor assay, and nuclear morphology. RESULTS: Except when extremely low (< 2.5 x 10(6)/ml) motile density does not identify the subfertile male very well. In contrast to other studies, my group's data suggest that neither low normal morphology by WHO standards or strict criteria identify the subfertile male. The best predictor of male subfertility is the hypo-osmotic swelling test when it is < 50%, which does not result in fertilization failure, but implantation failure. A high percentage of sperm coated by antisperm antibodies is very predictive of fertilization failure. CONCLUSIONS: The physician must be careful when concluding that the male is subfertile or fertile based on standard tests of concentration, motility, and especially morphology.     

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.     

Failure of intrauterine insemination in male immunological infertility in cases in which all spermatozoa are antibody-coated.

OBJECTIVE: To determine if the overcoming of the cervical mucus barrier removes the interference of sperm-bound antibodies with fertility. DESIGN: Prospective case series. SETTINGS: University-based intrauterine insemination (IUI) homologous program. PATIENTS: Nineteen patients with all spermatozoa in the ejaculate coated by antisperm antibodies. As control group, 86 consecutive patients without antisperm antibodies, treated for oligoasthenozoospermia or mucus hostility. INTERVENTIONS: Intrauterine inseminations (at least 3 attempts per couple). MAIN OUTCOME MEASURES: The outcome of IUIs, demographic, and seminal parameters were compared between the two groups. RESULTS: No pregnancy occurred in the couples with male immunological infertility, treated by 110 IUIs. Twenty-three pregnancies occurred in 22 (25.6%) of the control group couples who were treated by 411 IUIs. In the group of patients without antisperm antibodies, we demonstrated that the pregnancy rate (PR)/couple in oligoasthenozoospermia without teratozoospermia was similar to that achieved in normozoospermia (35% versus 38.9%), whereas it was significantly affected by teratozoospermia (3.6%). Only three patients with antisperm antibodies had teratozoospermia. Comparing the PR per couple and per cycle between the two groups of patients (with and without antisperm antibodies), excluding the patients with teratozoospermia, significant differences resulted (P less than 0.005 and P less than 0.005, respectively). The motile sperm count was not significantly different between the two groups, which also resulted to be homogeneous for demographic data. Moreover, the motile sperm count was not different between the patients with and without antisperm antibodies, who had successful IUI. CONCLUSIONS: The analysis of this trial suggests that the failure of IUI in the treatment of male immunological infertility is imputable to antisperm antibodies when they involve all spermatozoa, regardless of semen quality.     

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.     

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.     

影响人显微外科输精管吻合术后复育的多因素研究

为探究影响人显微外科输精管吻合术后复育的因素，我们以22项指标对56伊］显微外科输精管吻合术后的男子进行了连续3年的随访观察。其结果全部精液中均复现了精子，而复育率为66．1％。经Logistic回归分析等统计方法处理，表明丈夫年龄、妻子年龄、妻子曾孕否、吻合次数、吻合本前血清FSH、LH、T、输精管结节精子肉芽肿等8个因素对妻子受孕无明显影响，而绝育年限、精子密度、精子前向运动、活动、存活、正常形态、穿卵率和吻合前后血清TAT、SIT、术后精液MAR、IBT结合IgG和IgA等14个因素都有明显影响。     

Antisperm antibodies to sperm surface antigens in women with genital tract infection

Antisperm antibodies to sperm surface antigens in nulligravid women with primary upper genital tract infections were measured by the sperm mixed agglutination reaction assay. As many as 56% of women with a primary episode of pelvic inflammatory disease had antisperm antibodies. In addition, 69% of those women with no history of genital tract infection but with laparoscopic evidence of past pelvic infection had significant levels of circulating antisperm antibodies. Electroimmunoblots of sperm preparations probed with the sera of women who had either known or presumed upper genital tract infection revealed a uniformly recognized 69 kd antigen. In contrast, women with circulating antisperm antibodies before primary upper genital tract infection recognized up to five distinct sperm antigen determinants of 27, 54, 131, 146, and 174 kd. It is a distinct possibility that genital tract infections may lead to immunopotentiation of antisperm antibodies that could affect fertility.     

Leukocytospermia is associated with poor semen quality

Semen samples from 179 infertility patients were analyzed for type and number of white blood cells (WBC) by a combination of immunologic techniques. Forty-one (23%) had more than 10(6) WBC/mL semen (leukocytospermia). Semen parameters in patients with less than 10(6) WBC/mL were similar to those of 15 fertile donors. In contrast, the leukocytospermic group had significant reductions in total sperm number, percent sperm motility, sperm velocity, motility index, and total number of motile sperm. Patients with high concentrations of monocytes/macrophages (greater than 5 X 10(5)/mL; n = 27) had significantly reduced ejaculate volume; patients with high numbers of T lymphocytes (greater than 10(5)/mL; n = 19) had a significant reduction in sperm velocity; and patients with high levels of granulocyte elastase in semen (greater than 1,000 ng/mL; n = 26) had significant reductions in ejaculate volume, total sperm number, and total motile sperm number. There was no correlation between the presence of antisperm antibodies and leukocytospermia. Our data suggest that leukocytospermia may occur frequently in male infertility patients and show that elevated levels of WBC in semen are associated with poor semen quality. This provides further rationale for white blood cell testing in semen of male infertility patients, since antibiotic or anti-inflammatory therapy may be helpful in appropriately selected cases.     

Ultrastructural changes in the rabbit epididymis following vasectomy and clip occlusion

Adult male rabbits were subjected to vasectomy, tantalum clip occlusion and sham operations. Caput and cauda regions of epididymis were studied with electron microscope at intervals of 15 days and 15 months after operation. Vasectomized and clip occluded subjects revealed similar changes when compared with sham operated animals. The epithelium remained functionally active even after vasectomy and clip occlusion as indicated by the presence of all characteristic complements of cellular organelles. Increased number of vacuoles and electron dense bodies indicated enhanced absorptive and digestive mechanisms at 15 months of vasectomy and clip occlusion. Disposal of continuously producing spermatozoa following vas occlusion may take place by intraluminal disintegration of sperm and subsequent phagocytosis by epididymal epithelium as evidenced by presence of identifiable parts of spermatozoa and flocculent material in caput and cauda regions.     

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.