Human Reproduction, Vol. 19, No. 5, 1235,
May 2004
© 2004 European Society of Human Reproduction and Embryology
Sperm autoimmunity
Andrology Laboratory, Division of Laboratory Services,The Royal Women’s Hospital, Carlton 3053, Australia.
1 To whom correspondence should be addressed. e-mail: gary.clarke{at}wch.org.au
Dear Sir,
I have read with interest the Debate article by Bohring and Krause (2003
) on immune infertility and the subsequent Letter to the Editor of Check (2003) and the reply of Krause (2003). I would like to reply to the question posed by Dr Check about the possible existence of complement in female reproductive tract fluids other than cervical mucus, and to make some comments regarding the treatment of men with sperm autoimmunity.
First, there is an extensive early literature on the subject of humoral immune factors in the female reproductive tract, which was reviewed in detail by Schumacher (1980). In brief, it was concluded that some complement components had been detected in endometrial fluid, but in quite low amounts when compared with levels in serum. Subsequently, in early work from this laboratory (Clarke et al., 1984), we found that human follicular fluid contained representative complement components (C3 and C4) and immunoglobulins (IgG and IgA) at levels only marginally below their concentrations in blood plasma. Thus, the complement components were at 77–96% of blood plasma levels. However, IgM was present in follicular fluid at only 9.5% of the blood plasma level. Similar results were reported by Kay et al. (1985). Considering the significant levels of complement in follicular fluid, it is feasible that antibody-coated sperm would be immobilized in the vicinity of the oocyte were they to get that far naturally, or with the assistance of intrauterine insemination (IUI). If not immobilized, then it is also possible that the antibodies on the sperm surface could block fertilization (Clarke et al., 1985).
With respect to treatment protocols for sperm autoimmunity, we previously have found corticosteroid treatment to be a highly effective means of reducing sperm antibody levels and concomitantly improving semen quality so that better quality samples could be cryopreserved for later use in assisted reproductive technique (ART) procedures (Baker et al., 1983). More recently, we have reported on our experience with the successful use of ICSI to circumvent the sperm autoimmune condition (Clarke et al., 1997). This is now our method of choice for assisting men with sperm autoimmunity.
My personal view is that the main effector molecule in sperm autoimmunity is secretory IgA, that it acts predominantly to block cervical mucus penetration, and that its efficacy at the cervical level is determined more by the density of secretory IgA antibodies on the sperm surface than by the exact antigen specificity of the antibody. However, I strongly support research efforts to identify and characterize sperm antigens because I believe that this is crucial to the understanding of the aetiology of sperm autoimmunity and to the development of an effective sperm-directed immunocontraceptive vaccine.
References
Baker HWG, Clarke GN, Hudson B, McBain JC, McGowan MP and Pepperell RJ (1983) Treatment of sperm autoimmunity in men. Clin Reprod Fertil 2,55–71.[Medline]
Bohring C and Krause W (2003) Immune infertility: towards a better understanding of sperm (auto)-immunity. The value of proteomic analysis. Hum Reprod 18,915–924.
Check JH (2003) Present options for treating sperm autoimmunity before proteomic analysis is available. Hum Reprod 18,2489–2490.
Clarke GN, Hsieh C, Koh SH and Cauchi MN (1984) Sperm antibodies, immunoglobulins, and complement in human follicular fluid. Am J Reprod Immunol 5,179–181.[Medline]
Clarke GN, Lopata A, McBain JC, Baker HWG and Johnston WIH (1985) Effect of sperm antibodies in males on human in-vitro fertilization (IVF). Am J Reprod Immunol Microbiol 8,62–66.[Web of Science][Medline]
Clarke GN, Bourne H and Baker HWG (1997) Intracytoplasmic sperm injection for treating infertility associated with sperm autoimmunity. Fertil Steril 68,112–117.[CrossRef][Web of Science][Medline]
Kay DJ, Boettcher B, Yovich JL and Stanger JD (1985) Antispermatozoal antibodies in human follicular fluid. Am J Reprod Immunol 7,113–117.
Krause W (2003) Present options for treating sperm autoimmunity before proteomic analysis is available: reply. Hum Reprod 18,2490–2491.
Schumacher GFB (1980) Humoral immune factors in the female reproductive tract and their changes during the cycle. In: Dhindsa DS and Schumacher GFB (eds), Immunological Aspects of Infertility and Fertility Regulation. Elsevier North Holland, Amsterdam.
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