Lars Linnet

Antisperm antibodies and fertility after vasovasostomy: a follow-up study of 216 men.

A group of 216 vasovasostomized men were tested with the mixed antiglobulin reaction for immunoglobulin (Ig)G, IgA, and secretory IgA antisperm antibodies bound to the sperm membrane. Free antisperm antibodies in serum and seminal plasma were detected with the gelatin agglutination test and the tray agglutination test. The results were related to the conception rates. In a subgroup with a pure IgG response, the conception rate reached 85.7%, whereas only 42.9% of the men who also had IgA on the sperm induced pregnancy. When 100% of the spermatozoa were covered with IgA, the conception rate was reduced to 21.7%. The combination of IgA on all sperm and a strong immune response (titer in serum greater than or equal to 256) was associated with a conception rate of zero.

ASSOCIATION BETWEEN FAILURE TO IMPREGNATE AFTER VASOVASOSTOMY AND SPERM AGGLUTININS IN SEMEN

Sperm agglutinins emerging from the reopened part of the vas deferens were found in the seminal fluid of 10 out of 29 men after vasovasostomy. There was a strong association between the presence of these antibodies and the failure to impregnate over a period of 14 to 33 months. Of 20 couples, 11 pregnancies resulted among the 13 women whose men had no sperm agglutinins in the seminal fluid, but only 1 among the 7 whose men had such antibodies, 2p = 0.0044. The presence of sperm agglutinins in the seminal fluid was always associated with their presence in the serum, usually in a higher titre. Preoperative serum levels thus are highly predictive of ability to impregnate after reversal of vasectomy.

Clinical immunology of vasectomy and vasovasostomy

The increased popularity of vasectomy since the late 1960s has brought the world total to above 50 million with about 8 million performed in the US with an annual rate of about 500000. Although no increased morbidity from vasectomy has been shown in epidemiologic studies it has been shown that vasectomized men may encounter increased rates of atherosclerosis glomerulonephritis cancer and opportunistic infections. The hypothesis is that antigen components of sperm entering the circulation combine with the antibodies to form circulating immune complexes (CIC). Also half of the vasovasostomized men are reported to be fertile but about 1/3 of the operations are not followed by a pregnancy possibly because of antisperm antibodies. Regarding autoimmunization with spermatozoa the changes that take place in the blocked compartment of the genital tract are an increase in hydrostatic pressure distention of the epididymal tubules and the vas intraluminal phagocytosis nonphagocytic disintegration increased resporption epithelial phagocytosis of sperm and direct extravasation of sperm. The immune system probably reacts to sperm components as to foreign substances. A study of postvasectomy development of antisperm antibodies by the tray agglutination test showed that at 1 month 25% have reacted and after 1 year it is up to 60-70%. Sperm agglutinins have been detected up to 20 years after the operation. Several studies have shown that: 1) serum antibodies to the nuclear protamines develop in about 30% of vasectomized men; 2) an early response with spermagglutinating antibodies is associated with high sperm counts; 3) vasectomy increases diet-induced atherosclerosis; 4) 30% of 47 men studied 3 months postvasectomy were found to have CIC whereas 35 nonvasectomized men and 8 vasectomized 1 year earlier had negative samples; 5) in a study of 156 men examined 2 years postvasectomy 4% had CIC by 1 assay a finding not different than one found in a general population; in general it is not believed that increased levels of CIC are found in vasectomy patients; and 6) no significant increase in neoplasms has been found in vasectomied patients but a minor increase in geitourinary syndromes is found. A group of vasovasostomy patients with an immunologic subfertility factor can be identified on the basis of high serum titers. It is suggested that after 1 year men who have not been found to cause a pregnancy in spite of the presence of sperm should have seminal plasma and serum tested for spermagglutinating antibodies and treatment can include low-dose longterm steroids intermittent high dose steroids levamizole treatment semen dilution and sperm wash intrauterine insemination and in vitro fertilization and embryo transfer.

No increase in arteriolosclerotic retinopathy or activity in tests for circulating immune complexes 5 years after vasectomy.

On the basis of studies in monkeys, the hypothesis has been proposed that vasectomy induces the formation of circulating immune complexes (CICs), which--via activation of the complement system--may result in immune injury of the endothelium and thereby exacerbate atherosclerosis; the same mechanism has been suggested to cause retinal arteriolar changes in vasectomized men. We compared 46 men, 5 years after vasectomy, with 46 age-matched control subjects and found no difference in the distribution of arteriolosclerotic retinopathy gradings evaluated by ophthalmoscopy and fundus photography. Blood samples from the two groups were collected and handled identically, and no significant difference in activity was found in four different tests for CICs and two tests for split products of complement factor C3. Thus, the results do not support the hypothesis that changes mediated by CICs occur in vessels after human vasectomy.

Antisperm antibodies on epididymal spermatozoa

ABSTRACT: Still under debate is the location in the genital tract where antisperm antibodies transuded from serum and locally produced antibodies, respectively, become attached to the surface of the spermatozoa. The mixed antiglobulin reaction (MAR) for immunoglobulin (Ig) G, IgA, and locally produced secretory IgA (sIgA) could be carried out on motile spermatozoa from epididymis from 13 of 34 men undergoing vasovasostomy. Four months and one year after the operation the MAR was repeated on a fresh semen sample from all patients. It was found that transuded as well as locally produced antisperm antibodies were bound to spermatozoa at the epididymal level of the genital tract. The follow‐up results on semen were almost identical to the results obtained with epididymal spermatozoa.

A comparison of eight techniques for the evaluation of the auto-immune response to spermatozoa after vasectomy

The tray agglutination tests (TAT), gelatin agglutination test (GAT), side agglutination test (SAT), tube-slide agglutination test (TSAT), sperm immobilization test (SIT), ATP-release cytotoxicity test (ARCT), indirect immunofluorescence technique (IFT) on methanol-fixed, intact spermatozoa, and a lymphocyte transformation test (LTT) were compared using a maximum of 329 blood samples taken from 47 men before and after vasectomy. The TAT, GAT, TSAT, SIT and ARCT discriminated between the pre- and post-vasectomy samples, and the sensitivity for sperm antibodies decreased in that order. The activity in the IFT and the LTT did not change significantly after vasectomy. In the TAT the mode of agglutination varied with serum dilution; the results for the 1:4 dilution showed the best agreement with the SAT results. Almost all TAT activity was detected by a combination of GAT and TSAT. Sperm agglutinins were present in all serum samples positive in the two complement-dependent tests, SIT and ARCT. If improved in sensitivity, the ARCT, which lacks the subjective elements of microscopy, might be suitable for the screening of male sera in clinical work. For the present, we recommend the TAT.

Immunoglobulin Classes, Secretory Component, and Sperm Agglutinins in Semen After Vasovasostomy*

ABSTRACT: The immunoglobulin classes of the sperm‐agglutinating antibodies in the seminal fluid and serum from four vasovasostomized men, as well as in operatively obtained testis‐epididymis fluid from two of them, were investigated by specific solid‐phase absorption of IgG, IgM, and IgA. In two patients the major part of the seminal agglutinins was IgA, and in one IgG, indicating that both local production and diffusion of sperm agglutinins from serum to the testis‐epididymis compartment may take place. The total levels of immunoglobulins in seminal fluid generally increased after the operation, and IgM was present in two postvasovasostomy samples. This suggests a pathotopic potentiation effect of the vasectomy on the epithelial lining of the testis‐epididymis compartment. Comparison of the results of solid‐phase absorption with anti‐IgA and antisecretory component (SO pointed to the presence of “free” SC in postvasovasostomy seminal fluid.