Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Tennessee, 956 Court Avenue, Room D324, Memphis, Tennessee 381632116 USA
Extensive investigations have been conducted to evaluate the potential role of antisperm antibodies (ASA) in infertile men and women. It was originally demonstrated in 1932 that injection of spermatozoa into the peritoneal cavity of female guinea pigs could induce temporary sterilization (Baskin, 1932). In the male and female, ASA may be found systemically (in the blood and lymph) and in local secretions (in seminal or cervicovaginal fluids) (Kutteh et al., 1995
). Antibodies in the blood and lymph belong predominantly to the immunoglobulin G (IgG) isotype, while those found in external secretions are predominantly of the IgA isotype (Marshburn and Kutteh, 1994
; Mazumdar and Levine, 1998
). Many questions still remain on the role of ASA in reproduction (Table I
). Indeed a recent survey of the diagnosis and management of ASA in the UK indicated little consensus in testing methods, significant levels, and management of ASA (Krapez et al., 1998
).
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Proposed therapies for sperm-bound ASA
ASA may result in a state of subfertility but would rarely prevent fertility completely in couples (Dondero et al. 1979; Marshburn and Kutteh, 1994
). Proposed treatments for subfertility secondary to sperm-bound ASA have evolved in several directions (Table II
). These treatments include: (i) methods to reduce the production of ASA (condom use); (ii) processing spermatozoa to decrease the effect of ASA (washing, enzymatic treatment); (iii) separation of ASA bound spermatozoa from non-bound spermatozoa (split ejaculate, depletion); (iv) suppression of antibody production (steroids); and (v) overcoming possible ASA interference (insemination, IVF). Each of these therapies has its advocates. However, in recent years, treatment has advanced to IVF and intracytoplasmic sperm injection (ICSI).
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There are many proposed mechanisms for ASA-mediated infertility, but most are thought to act via impairment of processes that lead to oocyte fertilization and embryo development (Haas, 1996). Original studies with sperm-bound with ASA demonstrated decreased penetration of the zona pellucida (Haas et al., 1980
). Experimental data indicate several possible sites where ASA may interfere with IVF (Table III
).
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In the absence of clear scientific data concerning sperm-bound ASA, most IVF centres have established policies based on their best interpretation of available data. The policy at our unit for the last 2 years has been to screen all male partners for direct ASA (using IBT) prior to IVF. If either IgG or IgA ASA are >50% we have counselled the couple and suggested that half of the oocytes should undergo ICSI. Of course, if other indications for ICSI are present, e.g. prior IVF cycle with <20% fertilization, or low sperm parameters, ICSI would be performed on all oocytes (Hamberger et al., 1998). Using this strategy, we identified 14 men with
50% IgG or IgA ASA out of 215 cases (6.5%), however, there were eight men who otherwise would not have shown indications for ICSI. From these eight couples, four benefited by enhanced fertilization with the ICSI procedure and the other four had no benefit when comparing ICSI with conventional fertilization. In the absence of clear scientific data, many practitioners have used cost effectiveness to determine the usefulness of certain medical strategies. Using the method reported previously (Culligan et al., 1998
), the cost-benefit ratio of our protocol was calculated. The cost of ASA testing was $21 500 ($100x215 patients) plus the additional charge of ICSI ($1000xeight cases) for a total cost of $29 500. When evaluated based on the four individuals who benefited by ICSI, the total cost per case was $7375 ($29 500 ÷ four couples). An alternative policy might be not to test anyone for sperm-bound ASA and to treat everyone with conventional IVF, unless there were other indications for ICSI. If failed fertilization cycles occurred, a subsequent cycle would be treated with ICSI (as is standard in many centres). If this alternative strategy was used in our centre, the total cost would have been $33 500 for four IVFICSI cycles ($8375xfour couples). For a programme of our size the choice of which strategy to use is not clear. Thus, based on the reports summarized above and our own personal experience, therapy for the majority of cases of sperm-bound ASA-associated infertility remains empiric and largely unproven.
Notes
This debate was previously published on Webtrack 82, August 20, 1999
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