Chlamydia, male infertility and azoospermia.

The preceding section detailed the association of C. trachomatis with chronic epididymitis and epididymal granuloma formation. Under these circumstances it is reasonable to suppose that chlamydial infection will lead to blockage of the epididymis and thus to infertility due to azoospermia [lay reader: lack of adequate sperm numbers]. A critical review of the literature found it biologically plausible that gonorrhoea and/or chlamydia could cause male infertility. There is clinical and pathologic evidence linking these pathogens to urethritis, linking urethritis to epididymo-orchitis, and linking epididymo-orchitis to infertility. Retrospective epidemiological studies also support an association between the presence of antibodies to chlamydiae in semen or serum and male infertility. However many of these studies are small, lack proper control groups, and have inadequate statistical power even where significance is achieved [Ness et al., 1997]. Chlamydial infection of the upper genital tract of men leads to the presence both white blood cells and of antichlamydial antibodies in semen. It has been suggested in a number of studies that the presence of antibody to C. trachomatis is correlated with the presence of white blood cells in semen [leukocytospermia; Ochsendorf et al., 1999] and with the development of an autoimmune response to spermatozoa [see for example ; Witkin et al., 1995].

It has been demonstrated for Ureaplasma urealyticum that infection, by inducing leukocytospermia, can lead to elevated levels of leukocyte-derived reactive oxygen species which damage sperm by causing peroxidation of lipid [Potts et al., 2000]. Damaging proteases are also present. Leukocytospermia is commoner in infertile men than fertile men, is associated with decreased sperm numbers and impaired sperm motility and it can be shown that products of white blood cells in sperm damage sperm function as measured by hamster ovum penetration in the laboratory [Wollf, 1995]. Normally, white blood cells in semen are thought to originate from the epididymis as only very low numbers are present in vasectomized men. Asymptomatic prostatitis may also be a source. In both cases persisting C. trachomatis infection would provide an appropriate inflammatory stimulus. However other studies have concluded that leucocytospermia per se did not significantly affect sperm functions or autoimmune responses to sperm [Haberman & Krause, 1999; Ochsendorf et al., 1999]. Ness et al., 1997 in their critical review of the literature found that there was no consistent epidemiological evidence that either chlamydial or gonococcal infection altered sperm characteristics. Various methodological improvements were suggested for future studies.

The following figures are part of a presentation on male infertility authored by MEW and given at the meeting of the European Academy of Dermato-Venereology in Prague, October 2002.


Fig 2. Title slide. All figures © M. E. Ward 2002 except where otherwise stated.	Fig 3. Pathogens suspected to be associated with male infertility. Very little is known about infection and male infertility compared to female infertility. Yet it is likely to be significant.	Fig 4. Methodological problems with existing studies of male infertility.	Fig 5. Possible pathogenic mechanisms for infection-induced male infertility.

Fig 6. Infection, epididymitis and the vas.	Fig 7. What chlamydia can do to tubal epithelium, in this case the murine oviduct. Scanning electron micrograph showing normal tubal epithelium 7 days after inoculation of saline.	Fig 8. What chlamydia can do to tubal epithelium. Scanning electron micrograph showing damaged tubal epithelium 7 days after inoculation of oviduct with saline containing 10⁵ IFU of C. trachomatis. The epithelium has largely been lost and the tube is blocked with mucus and cellular debris.	Fig 9. Experimental chlamydial epididymitis in rats, showing the potential of chlamydiae to cause damage to the epididymitis. Scarring occlusion of the epdidymis or vas analogous to that occurring in the oviduct would lead to infertility due to azoospermia.

Fig 10. Adeno-associated parvovirus is also linked to effects on spermatogenesis.	Fig 11. Direct effects of bacterial pathogens on sperm.	Fig 12. The speculated role of auto-immune antibody in the pathogenesis of male infertility.	Fig 13. Concluding quote.

Genital tract infection in men

Chlamydia and male infertility

References