Antispermatozoal antibodies in men with urethritis.

Antispermatozoal antibodies have been measured by the tray agglutination test (TAT) in three groups of patients with urethritis attending a clinic for sexually transmitted diseases and in one control group of men without urethritis. In 3 of 17 (17.6%) patients with acute nongonococcal urethritis (NGU) the serum TAT was positive at titers of 1:16 or more; and in 1 of these patients in whom Chlamydia was grown, the TAT titer rose from 1:4 before treatment, to 1:8 at 2 weeks, and 1:16 at 4 weeks, indicating probable immunization against sperm antigens at the time of infection. A rise in titer from 0 to 1:8 occurred in a second patient with NGU. Six (15.6%) of 39 patients with recurrent NGU and 2 (16.6%) of 12 patients with gonorrhea followed by postgonococcal urethritis also had positive antisperm antibody titers of 1:16 or more. None of 27 control subjects had positive antisperm antibody titers. These observations indicate that development of antisperm antibodies can be stimulated in some individuals by NGU.

Cyclic prednisolone therapy for male infertility associated with autoantibodies to spermatozoa.

Seventy-six subfertile men with significant titers of antisperm antibodies were treated with a new corticosteroid regimen, consisting of prednisolone, 40 mg daily, rising to 80 mg daily if antibody titers did not fall, given from days 1 to 10 of the partner's menstrual cycle, for up to nine cycles. Twenty-five (33%) of the partners became pregnant during a treatment cycle, more than twice the expected incidence without treatment. No serious complications occurred, although one half of the patients had transient minor side effects. This regimen appears to be encouraging and suitable for further assessment in a prospective controlled trial.

Cryopreservation of semen in men with testicular tumour or Hodgkin's disease: results of artificial insemination of their partners.

After cryopreservation of semen from men with testicular tumours or Hodgkin's disease the success rate of artificial insemination of their partners was analysed. The cumulative probability of pregnancy at 6 months was 45%. The chance of pregnancy was greater when timing of ovulation was predicted with measurements of urinary luteinising hormone. Sperm density and sperm motility were also important in predicting the likelihood of pregnancy.

Semen analysis in testicular cancer and Hodgkin's disease: pre- and post-treatment findings and implications for cryopreservation.

Over a 7-year period, seminal analysis has been performed on 208 patients with testicular tumours, after orchiectomy, but before any other treatment. Only 22% of 54 patients with seminomas, and 29% of 154 patients with teratomas or mixed tumours, had sperm counts exceeding 10 million per ml. Very low sperm counts were observed in some patients who had previously fathered children. Post-treatment sperm counts were done in 117 patients, 80 of whom had received multiple drug chemotherapy: 42 of these men had pre- and post-treatment sperm counts. Overall, 24% of men receiving chemotherapy recovered sperm counts greater than 10 million per ml up to 3 years after therapy. Surprisingly, such recovery was seen in 35% of 23 men with initially poor sperm counts, but in only 26% of 19 with good initial counts. Only 27% of 49 patients with Hodgkin's disease had initial sperm counts of more than 10 million per ml; after chemotherapy only 1 of 29 patients recovered to this level. Only one quarter of these young men had semen which was adequate for cryopreservation. Artificial insemination with semen preserved in liquid nitrogen has been performed in 15 couples: 2 normal babies have been produced and a third pregnancy is progressing normally.

Exploratory scrototomy in 168 azoospermic males.

In 168 azoospermic males with normal or only slightly raised serum FSH levels, serum antisperm antibodies were measured, and the site of obstruction or the nature of the failure of spermatogenesis was defined by exploratory scrototomy with inspection of epididymes, vasography and testicular biopsy. When possible, surgical reconstruction was done by side-to-side epididymovasostomy, with vasovasostomy when necessary using 6/0 Prolene and no splints. Acquired blocks of cauda epididymis (34 cases) and vas (23 cases) were significantly more commonly associated with serum antisperm antibodies than congenital bilateral absence of vasa (29 cases) or blocks at the caput epididymis (48 cases), most of which were associated with sinusitis, bronchitis or bronchiectasis (Young's syndrome). Many of the former patients came from abroad, whereas most of the latter came from the British Isles. Sperm counts of 10 million per ml or more were produced by 23 (45%) of 51 adequately followed up patients with acquired blocks following surgical reconstruction, and 11 pregnancies (21.5%) were produced. Amongst those with spermatozoa in the ejaculate after surgery, serum antisperm antibodies were found significantly less often in those whose wives became pregnant compared with those who failed to produce pregnancies. It is concluded that failure of surgical treatment in some of these cases may have an immunological basis. No success was achieved with other groups.

A comparative study of zinc, copper, cadmium, and lead levels in fertile and infertile men.

Eighty infertile men and 38 men of known fertility were studied for investigation of both the importance of zinc, copper, cadmium, and lead to fertility and the possible interrelationships between these trace elements. The infertile men had higher mean concentrations of plasma copper than those of proven fertility. The difference was statistically significant (P less than 0.01) but was of small magnitude (approximately 1.5 mumol mean difference). The concentrations of plasma zinc, erythrocyte zinc, whole blood lead and cadmium, and seminal plasma zinc and copper did not differ significantly between infertile and fertile men. There was a significant positive relationship between sperm density and seminal plasma zinc concentration in the fertile, but not in the infertile, men. The infertile men with antisperm antibodies or counts greater than 20 million/ml had significantly higher mean levels of seminal plasma zinc than infertile men with oligospermia. The higher semen zinc in these two groups may reflect an abnormal fragility of the spermatozoa, resulting in the release of zinc, but the absence of significant overall differences between fertile and infertile men suggests that measurement of the concentration of zinc in plasma or zinc and copper in seminal plasma has little value in the routine investigation of infertility.

The value of the mixed antiglobulin reaction (MAR test) as an addition to routine seminal analysis in the evaluation of the subfertile couple.

A mixed erythrocyte-spermatozoa antiglobulin reaction (MAR test) for IgG antibodies has been done on semen specimens supplied by the male partners in 720 subfertile couples during a two-year period. The test was possible in all except 69 patients (9.5%). Antisperm antibodies were detected in 48 (10%) of 484 men with normal sperm counts, 18 (23%) of 78 with low sperm motility, and 19 (15%) of 128 with low counts. In 204 patients, antisperm antibodies were also measured by serum sperm-agglutination tests: The results showed a highly significant correlation with the results of MAR testing. It is concluded that the MAR test should be a routine part of seminal analysis, since the presence of IgG antisperm antibodies can be established in about 10% of men who might otherwise be passed as normal, and such antibodies can be positively excluded in a further 78% of the male partners of infertile marriages.

The diagnosis of unilateral testicular obstruction in subfertile males.

Thirty-two subfertile males with sperms in the ejaculate and unilateral testicular obstruction are reported: the diagnosis was established by exploration of scrotum in 26, clinically in 2, 3 had had previous partially successful epididymovasostomies, and 1 had had an epispadias repair. The past medical history gave relevant information in 27 (84%), and useful findings were made on clinical examination in a further 3 cases. Fifteen patients had sperm counts over 20 million per ml, and 15 were less than 10 million per ml. Twenty-six (81%) had serum antisperm antibodies detected by tray agglutination test (TAT), 21 (81%) of whom had evidence of head-to-head (HH) agglutinins in pure or mixed form. Comparison with 162 vasectomised males and 160 naturally infertile males with antisperm antibodies showed that 55% of the former and 24% of the latter had HH agglutinins on TAT, differences that were highly significant on statistical analysis. Evidence of obstruction was found in 14 (37%) of 38 naturally infertile males with antisperm antibodies and HH or mixed agglutination, but only in 12 (10%) of 122 with TT agglutinins: this difference was also highly significant. Clinical history, physical examination and serum antisperm antibodies, especially if HH agglutinins are present, can suggest the possibility of unilateral testicular obstruction, but confirmation of the diagnosis requires exploration of scrotum.

Mixed erythrocyte-spermatozoa antiglobulin reaction (MAR test) for IgA antisperm antibodies in subfertile males.

A mixed antiglobulin reaction (MAR test), using antibody-coated red cells and spermatozoa, has been used to detect the presence of either IgA or IgG on he surface of the spermatozoa. Group O Rh-positive red cells were sensitized with serum containing anti-D, which was partly IgA, though mainly IgG. Spermatozoa were added to the sensitized red cells and tested either with anti-IgA or anti-IgG. MAR (IgA) test results were negative or doubtful in 42 (44%) of 94 samples with positive or strongly positive MAR (IgG) tests. Positive MAR (IgA) tests showed a highly significant correlation with the presence of antisperm antibodies in seminal plasma. Significantly impaired sperm penetration of cervical mucus was demonstrated for 15 patients, 12 of whom had positive MAR (IgA) tests, whereas good sperm penetration was observed for 5 patients with negative or dubious MAR (IgA) tests; all 20 patients had strongly positive MAR (IgG) tests and positive serum antisperm antibody tests.

The results of intermittent high dose steroid therapy for male infertility due to antisperm antibodies.

Forty-five males who had been infertile for 2 to 10 (average 5.3) years, with significantly positive antisperm antibody tests (serum spermagglutination titers more than 32) and demonstrably improved sperm penetration of cervical mucus, were treated with repeated 7-day courses of methylprednisolone (MP) 32 mg three times a day from days 21 to 28 (in a few cases days 1 to 7) of their wives' menstrual cycles. Antisperm antibody tests were repeated after treatment and related to the occurrence of pregnancy in the wife. Fourteen wives (31%) became pregnant in a cycle following treatment of the husband. The production of pregnancy was always associated with a marked drop in sperm immobilizing titer and usually with disappearance of antibodies from seminal plasma; both of these effects were sometimes observed without a significant change in serum spermagglutination titers. Three patients (6%) had transient severe side effects, and 14 (26%) have had mild side effects, out of 54 patients treated so far.

Enhanced seminal plasma ribonuclease activities in azoospermia, severe oligiozoospermia, and asthenozoospermia.

Acid and alkaline ribonuclease (RNAase) activities were measured in human seminal plasma. The samples were obtained from patients attending an Infertility Clinic and were separated into groups according to the concentration and motility of spermatozoa. Levels of acid and alkaline RNAase activities in seminal plasma were, respectively, 22 and 13 times the values found in blood plasma. The severe oligozoospermic and azoospermic groups showed significantly higher alkaline RNAase activities in the seminal plasma than the normozoospermic group. The group with sperm motility < 50% showed significantly higher acid and alkaline RNAase activities than the group with motility greater than or equal to 50%. Enhanced RNAase activities may be involved in the process of bringing about a reduced formation and maturation and a reduced motility of spermatozoa.

Steroid treatment of male subfertility caused by antisperm antibodies.

47 subfertile men with significant titres of antisperm antibodies were treated with one of two steroid regimens. The results were assessed by changes in sperm-counts and in serum antibody titres and by subsequent pregnancies. 15 oligozoospermic men were treated with prednisone 5 mg three times a day for 3--12 months. Sperm-counts became normal in 10 men and 4 of their wives became pregnant. 14 men with normal sperm-counts received the same treatment: antibody titres fell slightly and 3 of their wives became pregnant. 18 other men with normal sperm-counts were given one or more courses of methylprednisolone 96 mg/day for 7 days. There was a more pronounced fall in antibody titres in these men, and 7 of their wives became pregnant. Testicular biopsies in 3 men with high titres of antibodies and very low sperm-counts which became normal with prednisone showed adequate spermatogenesis; however, focal round-cell infiltration of seminiferous tubules was observed in 1 case. It is suggested that a steroid-responsive immune orchitis can occur spontaneously in man, and may contribute to the infertility of men with antisperm antibodies.

Fructose and hormone levels in semen: their correlations with sperm counts and motility.

Levels of fructose, growth hormone (GH), prolactin (HPr), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and 5alpha-dihydrotestosterone (DHT) were determined in semen. The samples were obtained from patients attending an infertility clinic and separated into four groups according to the number of spermatozoa. Levels of HPr, LH, and FSH showed significant positive correlations with sperm counts. Significant differences in fructose and hormone levels were found between various groups. Expressed as concentrations of hormones or fructose per milliliter of semen, none of the hormones showed a significant negative correlation with sperm motility whereas fructose showed a significant negative correlation. Expressed as amounts per ejaculate of semen, only prolactin showed a significant positive correlation with sperm motility. The significance of these findings is discussed.

Sperm/cervical-mucus crossed hostility testing and antisperm antibodies in the husband.

The behaviour of sperms has been investigated in preovulatory cervical mucus in 44 infertile couples. In 22 couples, immobilising and agglutinating autoantibodies were detected in the husband's sera in high titres. In 10 couples, antisperm antibodies were detected in the husbands by indirect immunofluorescent testing. In 12 couples, no evidence of antisperm antibodies was found in either husbands or wives. The results obtained with husband and wife were compared with the behaviour of the husband's sperms in cervical mucus from fertile donors, and with the behaviour of sperms from fertile donors in the wives' mucus. This crossed hostility test indicated that high tires of immobilising and agglutinating antisperm antibodies in the husband effectively prevented the sperms from penetrating the cervical mucus, even though the sperms appeared normal on seminal analysis. Antibodies detected by indirect immunofluorescence did not have this effect. Poor penetration was also observed with low sperm motility or poor cervical mucus. It is concluded that this test, taken with the postcoital test, could provide a useful screen for immunological causes of infertility and an accurate test for the clinical relevance of antisperm antibody tests.

The clinical significance of antisperm antibodies in male subfertility.

Sera from 591 men attending Fertility Clinics have been tested for agglutinating, immobilising and immunofluorescent antisperm antibodies. There was good correlation between the presence of high titres (more than 1/32) of agglutinating and immobilising antibodies which were found in 50 patients (8.5%). 27 of these men had normal sperm counts, but crossed hostility testing showed that in 21 of 22 couples the sperms were unable to penetrate the cervical mucus, apparently because of the antibodies. 17 patients were treated with prednisone for an average of 6 months and 1 pregnancy was produced. 17 patients were treated with methylprednisolone for 7 days and 1 pregnancy resulted. No correlation was found between the present of immunofluorescent antibodies and the other antibodies of impaired sperm penetration of cervical mucus.

PIP: Between September 1975-March 1977, sera from 591 men attending the Fertility Clinic at Chelsea Hospital in London were tested for agglutinating, immobilizing, and immunofluorescent antisperm antibodies. The 3 techniques used to test are described. Results of the testing were correlated with the patients' clinical state and findings on seminal analysis. When antisperm antibodies were found, the behavior of the husband's sperm was studied in the cervical mucus of his wife. This result was compared with behavior of donor sperm with no antisperm antibodies and with donor cervical mucus. Test data indicate that high titers of immobilizing and agglutinating antibodies did prevent the sperm from effectively penetrating cervical mucus. This was not true with antibodies detected by immunofluorescent techniques. The crossed hostility testing is necessary in cases of marital infertility to identify which partner in the marriage has the antibodies. Treatment for infertility resulting from antisperm antibodies is steroid therapy combined with sperm washing and insemination.