Auto Antibodies to Spermatozoa in Subfertile Human Males

Hendry, William Forbes (1992) Auto Antibodies to Spermatozoa in Subfertile Human Males. MD thesis, University of Glasgow.

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The diagnosis and treatment of immunological infertility in human males has been the subject of much controversy. Antisperm antibodies (ASA) have therefore been measured in all subfertile males seen by the author since 1975. A number of separate studies were completed, and these have been amalgamated and critically reviewed to form this thesis. The first problem was to find out which tests gave results which were clinically significant. Sera from over 500 subfertile men were tested for circulating unbound antibody by gelatin agglutination test (GAT), sperm immobilisation test (SIT) and an indirect immunofluorescence test (IFT) using standardised internationally accepted laboratory methods. The results were compared with each other, and correlated with the results of sperm-cervical mucus contact (SCMC) tests, since failure of penetration was known to be associated with impaired fertility. Significant titres of GAT, which correlated with SIT and with failure of cervical mucus penetration were found in 8.5% of patients. IFT gave disparate results and was discontinued. Over the ensuing years GAT, a macroscopic spermagglutination test, was gradually superceded by the microscopic tray agglutination test (TAT) which was slightly more sensitive and allowed more tests to be done on serum and seminal plasma. A screening test for ASA bound to patients' spermatozoa was also needed. The direct mixed erythrocyte-spermatozoa antiglobulin reaction (MAR) was carefully assessed in 2 separate studies and found to be quick and technically simple, it gave reproducible results, and it was applicable to most semen samples. Furthermore, the results correlated well with estimations of serum unbound antibody measured by GAT or TAT. This technique was also used to define the class of antibody bound to the patients' spermatozoa. Failure of penetration of cervical mucus was found to be associated with IgA antibodies, which correlated with estimations of ASA in seminal plasma. A direct immunobead test (IBT) was compared with MAR and found to give similar results, but was more labour intensive and time consuming since the spermatozoa had to be washed free of unbound immunoglobulin in the seminal plasma. Medical treatment was developed for men with ASA. Criteria for entry to treatment studies were as follows: GAT or TAT positive in serum at titre 32 or more, and/or in seminal plasma at any titre, plus a poor post coital test (PCT) in the female partner with demonstrably impaired sperm penetration of cervical mucus on crossed hostility testing. After preliminary medical checks, and after ensuring that the female partner was ovulating and had patent fallopian tubes, various corticosteroid regimes were used. Initially, long term low dose prednisolone (15mg daily for 6 months), was compared with cyclical high dose methylprednisolone (96mg daily from day 21-28 of female partner's cycle). Although the success rate was higher with the latter regime, serious side effects occurred and it was abandoned. An alternative cyclical regime was introduced (prednisolone 40/80mg daily from day 1-10 of female partner's cycle) which was as effective as the higher dose regime, and free of serious side effects. It was then subjected to prospective multicentre double blind controlled trial and shown to be significantly more effective than placebo. The relationship between ASA and testicular obstruction was studied in infertile men with unilateral or bilateral blocks, and in men undergoing vasectomy reversal. ASA were found, often in high titres, in three quarters of 80 men with unilateral blocks, half of whom had moderate or severe oligozoospermia despite having normal testicular biopsies. Following surgical and/or medical treatment one-third of those with adequate follow-up produced pregnancies; paradoxically, the best results occurred in those starting with the lowest sperm counts. Removal of irreparably blocked testes lead to profound falls in ASA titres in 10 men. Histological examination of the removed testes showed mononuclear cell infiltration in epididymes, rete testes and in some cases, seminiferous tubules. Amongst 370 infertile men with bilateral blocks, serum ASA were found in over half of those with acquired obstruction following infection, but in few (16%) of those with congenital absence of vasa. Follow up studies on 60 men after surgical correction of obstructive azoospermia showed that pregnancies were produced by a significantly higher proportion (60%) of those negative for ASA compared to those positive for ASA in any titre, only one-third of whom were successful. Unfortunately, the best surgical groups were those with post infective blocks, who also had the highest incidence of ASA. Men undergoing vasectomy reversal were different. Although ASA were found in sera of almost 80% of men before reversal, seminal plasma ASA were present in only 10% before reversal rising to almost 30% afterwards, which was significantly less than the 65% observed in an unselected series of spontaneously infertile men, and in the men with unilateral testicular obstruction.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Additional Information: Adviser: Jack Cohen
Keywords: Medicine
Date of Award: 1992
Depositing User: Enlighten Team
Unique ID: glathesis:1992-75836
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 19 Dec 2019 09:15
Last Modified: 19 Dec 2019 09:15

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