Sperm antibodies after vasectomy with fulguration.

Whether antisperm antibodies develop after vasectomy probably depends on several variables, 1 of which may be the surgical technique. The levels of serum antisperm antibodies were compared in men vasectomized by 1 techniques: vasoligation and fulguration. No difference in the incidence of spermagglutinating antibody was found in the 2 groups. However, immobilizing antibodies were observed in 43 per cent of the men undergoing vasoligation but in only 29 per cent of the men vasectomized by fulguration.     

Vasovasostomy--a 15-year experience.

OBJECTIVE: This study aimed to evaluate the results of vasovasostomies performed in the authors' clinic over 15 years. MATERIAL AND METHODS: Between 1983 and 1998 39 vasovasostomies were performed using a macroscopic technique. The medical charts were reviewed and a postal survey was sent to 36 of these patients. The patients were invited to visit the outpatient department and to give semen for analysis and a blood sample for determination of serum antisperm antibodies and serum follicle-stimulating hormone. Twenty-five patients filled in the questionnaire and 10 patients were obtained for further semen and serum analyses. RESULTS: The overall pregnancy rate was 56% (14/25 respondents). Three of these 14 men used an assisted reproduction method with their own ejaculated sperm. The postoperative patency was recorded in the medical charts only sporadically. The age and the interval between the vasectomy and vasectomy reversal averaged 42 years and 8.6 years, respectively. Those men who could father a child had a somewhat shorter mean obstructive interval than those who failed (8.0 vs 9.3 years), although the difference was not statistically significant in this small patient sample. The serum follicle-stimulating hormone concentrations were normal, with no association with the pregnancy rate. CONCLUSION: Macroscopic vasovasostomy is an effective means of re-establishing fertility in vasectomized men.     

Immunological effects of vasectomy

It is only recently that the adverse effects of vasectomy have become the subject of numerous scientific and at times speculative articles in medical and in lay periodicals. In this review of the literature on the immunological effects of vasectomy, attention is directed to the following: immunological response; cellular immunity; effects on testes and epididymis, and systemic effects of sperm autoantibodies. In 1970, 50% of vasectomized men were found to have circulating spermatozoal antibodies. A more recent survey provides confirmation for this finding and presents an incidence of only 2% of agglutinating antibodies and 0% of immobilizing antibodies in a fertile control population. Some recent and convincing studies have shown sperm agglutinating and immobilizing antibodies to remain either at the same titer level or actually to increase 5-12 years postoperatively. Titers range from 2 to 2048 among different patients. The highest incidence of titers is 1 year after vasectomy, but titers can be found as early as 6 months or as late as 20 years postoperatively. The wide range in titers can be explained in terms of technical problems in immune assays, since only immunoglobulins and not those antibodies part of immune complex systems can be measured. Since sperm antigens are in abundant supply in vasectomized men because of the continuous resorption of spermatozoa after vasectomy, possibly undetectable antibody titers actually reflect high levels of antisperm antibodies circulating in the form of immune complexes. Also it may be possible that the variety in measured titers of autoantibodies, as well as the nonuniversal (70%) antibody response in a vasectomized population, is a variable dependent on genetic content and, therefore, an individual characteristic. The fact that hormonal reponse takes place rather readily after vasectomy makes at least some degree of cellular response a necessary occurrence. Studies by Alexander and Anderson, which show delayed hypersensitivity skin responses to sperm antigens, indicate at least some degree of cell mediated response. A recent study draws a strong correlation between the presence of sperm agglutinins in the seminal fluid of vasovasostomized men and persistent infertility. It is likely that autoantibodies to sperm as a result of vasectomy have a significant role in persistent infertility in vasovasostomized individuals. The greatest controversy at present concerns the immunologic effect of vasectomy on various organ systems. The incidence and degree of atherosclerotic changes in lower primates are increased after vasectomy, but whether vasectomy has the same effect in men has not as yet been determined.     

Analysis of spermatozoa from the proximal vas deferens of vasectomized men

This study assessed the condition of spermatozoa from the proximal vas deferens of men after vasectomy. The fluids of both proximal vas deferens were collected from 67 vasectomized men by cannulating the vas deferens at the time of vasectomy reversal. Selected sperm parameters were analysed after incubation of the spermatozoa for 30 min at 37°C. Spera concentration in the proximal vas from vasectomized men (16 312 ± 21 496 million per ml, geometric mean: 7948 ± 398 million per ml) was significantly higher than that of fertile men and was maintained at a constant level independent of the duration of vas obstruction. The means of sperm motility (36.2 ± 26.2%), spermatozoa with normal morphology (50.7 ± 21.7%), sperm viability (53.0 ± 25.3%) and hypo-osmotic swelling test (HOS-test, 53.9 ± 21.7%) were statistically lower than the respective values for normal fertile men. There was no significant correlation between the duration of vas obstruction and the above semen parameters. In 46.4% of vas fluids all spermatozoa were immotile and this condition was more common after 3 years of vasectomy. Immotile spermatozoa in the proximal vas fluids at the time of vasectomy reversal may be an important factor for predicting semen quality and fertilizing ability after vasovasostomy. There were no significant differences in the results of sperm-cervical mucus penetration test (CMPT) between spermatozoa fiom vasectomized and fertile men. Antisperm antibodies on the surface of spermatozoa from the vas of vasectomized men were determined by the immunobead test (IBT; 78.6% for IgG, 32.1% for IgA) and sperm cervical mucus contact test (SCMC, 36.4%). The presence of antisperm antibodies on the spermatozoa from the vas of vasectomized men may explain, in part, the lower pregnancy rate after vasovasostomy. These parameters of spermatozoa from the proximal vas of vasectomized men may closely reflect those in the cauda epididymis after vasectomy.     

A prospective study of antisperm antibody development in acute epididymitis

The association between acute epididymitis and development of antisperm antibodies was investigated by the gelatin agglutination technique in prospectively collected serum samples from 27 patients. Agglutinating antisperm antibodies, mainly of the IgG class, were detected in seven men (27 per cent), a significantly increased frequency compared to prevalences previously found among blood donors and men from infertile couples. The antibodies developed de novo in four patients (15 per cent). The increased incidence of positive sera and the kinetics of the antibody responses strongly indicate a causal link between acute epididymitis and autoimmunization against spermatozoa. In the majority of the patients the antibody titers were low, being of only theoretical importance in respect to later fertility.     

Immunological status of patients before and after vasovasostomy as determined by the immunobead antisperm antibody test

With the immunobead antisperm antibody test a prospective study was conducted to evaluate the immune status of 55 men before and after vasectomy reversal. A third of the vasectomy patients (19 of 55) had significant serum-sperm antibodies (20 per cent binding or more) detected by the indirect immunobead antisperm antibody test. Of 31 vasovasostomy patients 12 (38 per cent) had significant sperm-surface antibodies (20 per cent binding or more) by the direct immunobead antisperm antibody test. Preoperative serum assays correctly classified the antibody status of 69 per cent of the vasectomy patients. The immunological impact of spermatic granuloma formation, duration of vasal obstruction, patient age and presence of sperm in the vasal fluid at operation also were assessed. An inverse relationship between the proportion of antibody-bound sperm and the percentage of motile sperm in the ejaculate of vas reversal patients was found with videomicrographic semen analysis. The percentage motility was significantly lower among patients with greater quantities of sperm-surface antibodies. No other parameter of semen analysis showed this difference when compared for positive or negative immunobead antisperm antibody test results.     

Changes in testis of guinea pig after vasectomy.

Thirty adult guinea pigs were bilaterally vasectomized and subsequently sacrificed at one, three, and six months after operation. Cell counts were performed on five seminiferous tubules from each animal to identify and quantitate changes in spermatogenesis. Forty-three per cent of the animals had alterations in spermatogenesis that were characterized by generalized hypospermatogenesis and presence of multinucleated spermatids. There was a high incidence (93 per cent) of sperm-agglutinating antibodies in the vasectomized group. Sperm antibodies were not detected in the normal and sham-operated animals. Mean testicular weights and seminiferous tubule diameters were significantly reduced in the hypospermatogenic animals. The intersitial tissue of the vasectomized and sham-operated animals was morphologically indistinguishable from that of unoperated animals.     

Hypergonadotropic hypogonadism and sperm abnormalities in men born with benign sacrococcygeal teratoma

To elucidate the hypothetical role of a primary germ cell defect in the development of a germ cell tumor, with subsequent testicular dysfunction, the authors studied a series of men who had surgery performed for a benign sacrococcygeal teratoma when newborns. The mean levels of serum testosterone and gonadotropins did not differ from the control patients. However, gonadotropin-releasing hormone stimulation caused exaggerated responses of serum luteinizing hormone and follicle-stimulating hormone. Testicular size was small in three of eight patients. Semen analysis showed abnormal semen quality in five of eight patients. Only one patient had no evidence of testicular dysfunction. The results indicate that men born with benign sacrococcygeal teratoma may have Leydig cell dysfunction, abnormal spermatogenesis, or both. It was speculated that the associated abnormalities may have a common etiology: for instance, they might be due to a congenital germ cell defect.     

Quantitative testicular biopsy in congenital and acquired genital obstruction

To determine if congenital obstruction of the genital tract is associated with significant testicular histopathological conditions compared to acquired forms of obstruction we performed testicular biopsy in 8 vasectomized men and 5 men with vasal agenesis. Quantitative analysis of the seminiferous tubular and epithelial parameters demonstrated a statistically significant increase in tubular wall thickness in the vasectomized group. There was no significant difference among the groups with reference to the mean number of late spermatids per seminiferous tubules, mean number of Sertoli cells per seminiferous tubules, mean number of seminiferous tubules per field (100 times) or mean seminiferous tubular diameter. We conclude that despite a lifelong duration of obstruction, men with vasal agenesis demonstrate a more favorable testicular histological status compared to men after vasectomy. This finding may have therapeutic implications when considering assisted pregnancy techniques as a method of treatment of male genital tract atresia.     

Semen quality and endocrine parameters after acute testicular torsion.

Of 16 postpubertal patients evaluated following testicular torsion 9 were treated with detorsion and bilateral orchiopexy (detorsion group), and 7 were treated with ipsilateral orchiectomy and contralateral orchiopexy (orchiectomy group). Each patient was evaluated with regard to semen quality, endocrine parameters (follicle-stimulating hormone, luteinizing hormone and testosterone) and the presence or absence of semen antisperm antibodies. These data were compared to similar data from a group of proved fertile semen donors. The semen quality in the detorsion group did not differ significantly from that of controls (p = 0.25) but follicle-stimulating hormone was significantly elevated compared with that of controls before and after stimulation with gonadotropin-releasing hormone. The orchiectomy group, which had been subjected to prolonged torsion (mean 69 hours), demonstrated a significant decrease in semen quality compared with semen quality in controls (p = 0.001), with average sperm density of only 29.0 million per ml. Baseline and post-stimulation levels of follicle-stimulating hormone in the orchiectomy group were also significantly abnormal when compared with those in controls and in the detorsion group. Our study demonstrates that testicular damage (changes in semen quality and/or endocrine parameters) occurs in the ipsilateral and contralateral testis following torsion, regardless of treatment modality. However, with early intervention by detorsion and testicular salvage, subsequent semen quality is likely to remain within normal limits. Late surgical intervention, even with removal of the nonviable testes, may result in significant impairment of semen quality.     

A 15-year followup of a nonmicrosurgical technique for vasovasostomy

A 15-year followup was summarized for patients who had nonmicrosurgical vasectomy reversal. Over-all pregnancy rates were 45 per cent (43 per cent for the first 8 years and 49 per cent for the next 7 years) and 73 per cent of the pregnancies occurred within 1 year after vasectomy reversal. Patients who achieved pregnancy compared to those who did not had significantly better sperm motility and a lower incidence of antisperm antibodies. The data indicate that nonmicrosurgical techniques can be used successfully to reverse vasectomy more economically and more rapidly than the microsurgical approach, while contributing to a reasonable pregnancy rate.     

Surgically reversible hypothalamic hypopituitarism due to aqueductal stenosis. Case report

A 13-year-old girl was referred for evaluation of the deceleration in her rate of linear growth, an arrest in the progression of her pubertal maturation, and bifrontal headaches. Detailed endocrinological and radiological studies revealed the following abnormalities: partial growth hormone deficiency, prepubertal luteinizing hormone and follicle-stimulating hormone responses to exogenous gonadotropin-releasing hormone, aqueductal stenosis with obstructive hydrocephalus, and marked focal dilation of her third ventricle. Ventriculoperitoneal shunting resulted in increased linear growth, resumption of pubertal development, and correction of her documented neuroendocrine abnormalities.     

Simplified gonadotropin-releasing hormone (GnRH) stimulation test

Provocative gonadotropin-releasing hormone (GnRH) stimulation testing indirectly assesses testicular function with more sensitivity than determination of basal gonadotropin levels alone. Unfortunately, the drawbacks of multiple blood sampling and high cost have limited the clinical usefulness of this test. We herein present a simplified, two-point, thirty-minute GnRH stimulation test. Statistical analysis of data from 55 men with normal baseline gonadotropin levels, reveal that this simplified test is just as accurate as the traditional test (p less than 0.0001) without the latter's attendant difficulties. In addition, we found that normal basal gonadotropin levels had little correlation to the actual responses obtained from GnRH stimulation testing (r = 0.20 and r = 0.39 for luteinizing hormone and follicle-stimulating hormone, respectively).     

Differences in the antigen pattern recognized by antisperm antibodies in patients with infertility and vasectomy

PURPOSE: Antisperm antibodies may impair sperm fertilizing capacity. They are found in infertile patients and in men after vasectomy. Little is known to date of the biochemical nature of the antigens that induce the production of antisperm antibodies. MATERIALS AND METHODS: Sperm membrane proteins were prepared from donor spermatozoa, separated by 1-dimensional polyacrylamide gel electrophoresis and exposed to seminal plasma samples of 36 infertile men and 34 after vasectomy containing antisperm antibodies. RESULTS: Ten antigenic protein bands with different molecular weight were recognized by antisperm antibodies. Antisperm antibodies binding to the antigen band at 55 kDa. were significantly more common in infertile men, while those binding to the 72 kDa. band were more common after vasectomy. Significant differences also occurred in the incidence of detecting the 55 kDa. antigen band by the antisperm antibodies of patients with and without varicocele. Comparing antisperm antibodies from patients with or without a history of genital diseases or trauma did not reveal significant differences in the antigens detected. CONCLUSIONS: It seems likely that the development of antisperm antibody binding to different antigens is related to the mode of antibody induction. Since the antigenic properties of spermatozoa change during passage through the epididymis, the antigens detected by antisperm antibodies from men with vasectomy are mostly related to epididymal passage. The identification of human sperm antigens is essential for understanding the mechanism by which antisperm antibodies influence the fertilization capacity of spermatozoa. It is also necessary for the potential development of reliable diagnostic methods for antisperm antibodies that are relevant to infertility.     

Prevention of autoimmunization to spermatozoa by passive antibody

The objective of this investigation was to determine if sperm antibody formation after vasectomy in guinea pigs can be inhibited by passive administration of antiserum to spermatozoa. Sperm antibody was obtained by bleeding vasectomized guinea pigs which had spermagglutinating antibody titers of 1:16 or higher. Gamma globulin was obtained by ammonium sulfate precipitation. Vasectomized guinea pigs were injected with immune gamma globulin and normal gamma globulin for a period of two weeks after vasectomy. In the group receiving normal gamma globulin the serum titer of sperm-agglutinating antibody reached 1:32 and remained at that level for the duration of the study. In guinea pigs receiving immune gamma globulin detectable serum titers of sperm-agglutinating antibody did not develop. The investigation suggests that sperm antibody formation can be prevented by treating vasectomized animals with passive sperm antibody to spermatozoa.     

Vasectomy: Study of Circulating Immune-Complexes and its Correlation with Antisperm Immunity in Man, with a Twelve-Month Follow-up Study

Circulating immune-complexes (CIC) have been detected in sera of vasectomized subjects using the Clq Binding Assay. Results seem to indicate that CIC are a feature of the early post-operative period and a consequence of acute immunization against sperm antigens. The progressive disappearance of CIC from the third month after vasectomy with the simultaneous increase in antisperm antibody percentage and titre suggests that CIC could be a temporary feature in vasectomized men and do not lead to a chronic disease, related to a Type III immune reaction.     

Studies on pituitary-gonadal endocrine function in XYY men.

Serum luteinizing and follicle-stimulating hormones and testosterone levels were studied in 11 patients with 47-XYY chromosomes and a comparison was made to normal men and patients with other testicular diseases, including Klinefelter's syndrome. Serum follicle-stimulating hormone levels in patients with XYY chromosomes were elevated significantly in comparison to those in normal men but lower than those in men with Sertoli cell only syndrome and Klinefelter's syndromes. Serum luteinizing hormone levels were somewhat elevated and serum testosterone levels were somewhat low in comparison to normal men, although the difference was not significant. Results of the short-term human chorionic gonadotropin stimulation test suggested almost normal Leydig cell reserve capacity in patients with XYY chromosomes.     

Gonadal dysfunction after testicular torsion: luteinizing hormone and follicle-stimulating hormone response to gonadotropin releasing hormone

We studied 14 postpubertal patients at an average of 33 months after treatment for testicular torsion. Of these patients 11 had been treated by detorsion and 3 by orchiectomy. Five normal male volunteers of the approximate age of the study group served as controls. The patients treated by detorsion were subdivided into 3 groups based on the degree of atrophy of the detorsed testicle: group 1--no testicular atrophy (5), group 2--25 per cent testicular atrophy (2) and group 3--greater than 90 per cent testicular atrophy (4). Mean duration of torsion was greatest in the orchiectomy group (161 hours) compared to 6, 16 and 29 hours for groups 1, 2 and 3, respectively. The serum luteinizing hormone and follicle-stimulating hormone response to an intravenous bolus of 100 mcg. synthetic gonadotropin releasing hormone was measured in all patients. All groups had a greater mean follicle-stimulating hormone response to gonadotropin releasing hormone stimulation than controls (p less than 0.05). Patients who underwent orchiectomy had the greatest follicle-stimulating hormone response to gonadotropin releasing hormone stimulation. Mean luteinizing hormone response to gonadotropin releasing hormone stimulation was normal in patients without atrophy (group 1) but it was greater than controls in patients who had atrophy (groups 2 and 3) or who underwent orchiectomy (p less than 0.05). Several conclusions could be made from our study. All patient groups treated for torsion had evidence of testicular dysfunction. Patients who underwent orchiectomy displayed more testicular dysfunction than patients who had atrophy after detorsion. Testicular dysfunction after torsion is more likely to involve spermatogenic before Leydig cell function.     

Formation of antisperm autoantibodies in rats vasectomized at prefertile age

Bilateral vasectomy was performed in 40 inbred Lewis rats. Twenty prefertile rats were operated upon at the age of 2-3 weeks and 20 adult rats at the age of 10-11 weeks. Sera were sampled 16 and 8 weeks later respectively. Circulating antisperm antibodies were demonstrated in 90% of the vasectomized rats by means of the indirect immunofluorescence technique. No significant difference between the two groups could be found. Sham-vasectomy was performed in 20 rats age 2-3 weeks and in 20 rats aged 10-11 weeks. No antisperm antibodies could be detected in sera from either of these groups 16 and 8 weeks respectively postoperatively. Also, no antisperm antibodies could be demonstrated in sera sampled from 5 control rats at the age of 2-3 weeks or in sera sampled preoperatively from the 40 rats aged 10-11 weeks. Sperm granulomas were observed in 95% of the rats vasectomized at the age of 2-3 weeks, almost, all granulomas being located in the epididymis. 95% of the rats vasectomized at the age of 10-11 weeks also developed sperm granulomas. These were located in the proximal end of the vas deferens. The difference in distribution was significant (p less than 0.001).     

Predictive parameters of successful varicocele repair

A total of 130 men presenting with oligospermia and clinically identifiable scrotal varicoceles was evaluated, treated surgically and followed for 1 year for pregnancy rate. The treatment outcome was compared to an age-matched cohort of 83 oligospermic men who had received empirical medical therapy with clomiphene citrate (25 mg. per day) for the same 1-year interval. This study was done to contrast treatment modalities in infertility and not as a strict control. Only eugonadotropic patients in both groups were used for comparison. In the varicocele group the over-all pregnancy rate was 38.5 per cent. Four variables (a lack of testicular atrophy, sperm density greater than 50 million per ejaculate, sperm motility 60 per cent or more and serum follicle-stimulating hormone values less than 300 ng. per ml.) proved to be accurate preoperative predictors of postoperative pregnancy success. Four other variables (varicocele size and laterality, sperm forward progression greater than 2 and normal sperm morphology 60 per cent or more) did not yield statistically significant rates of improvement in pregnancy postoperatively. The pregnancy rate of the eugonadotropic patients undergoing varicocele repair was 45.8 per cent. Despite statistical similarity in patient age, sperm density and mean gonadotropin levels the medically treated patients had a pregnancy rate of only 25.5 per cent, significantly lower than the surgically treated patients. In summary, patients with an identifiable varicocele had a greater chance of achieving a pregnancy following surgical correction than did those treated with empirical drug therapy. In addition, certain preoperative variables in the physical and laboratory analyses appeared to portend a greater surgical response.