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Conception rates in couples where autoimmunity to sperm is detected
FERTIIJTY AND STERILITY Copyright c 1985 The American Fertility Society
Vol. 43, No.5, May 1985 Printed in U.SA.
Conception rates in couples where autoimmunity to sperm is detected
Bessie Ayvaliotis, M.D. Richard Bronson, M.D. * David Rosenfeld, M.D . . George Cooper, Ph.D. Department of Obstetrics and Gynecology, Division of Human Reproduction, North Shore University Hospital, Cornell University Medical College, Manhasset, New York
In men with autoimmunity to sperm, a varying proportion of spermatozoa in the ejaculate are found to have surface-bound immunoglobulins. We asked whether the extent of autoimmunity, as judged by this criterion, would have predictive value in determining the chance of conception. Infertile couples where husbands were found to have antisperm antibodies were treated for other factors leading to impaired reproduction, but no specific treatment was offered for reduction of these antibodies. The chance of pregnancy for those couples where autoimmunity to sperm was the sole definable factor leading to infertility was 15.3% when most spermatozoa were antibody-bound. A significantly greater number of wives whose husbands had < 50% of their sperm bound by immunoglobulins conceived (66.7%; P < 0.005). Fertil Steril43:739, 1985
Immunities to sperm were described, as early as 1959, as a possible cause of infertility.l A recent prospective study has shown that the likelihood of conception increases and the time to conception decreases as larger numbers of motile sperm are observed within cervical mucus. 2 Sperm-reactive antibodies are known to affect sperm penetration into, and motility within, cervical mucus. 3 - 5 The purpose of this study was to determine pregnancy rates in infertile couples where surface-bound immunoglobulins had been demonstrated on the husband's spermatozoa and to correlate the chance of conception with the extent of autoimmunity to sperm, as reflected by immunobead binding.
Received October 2, 1984; revised and accepted January 10, 1985. *Reprint requests: Richard Bronson, M.D., Division of Human Reproduction, North Shore University Hospital, 300 Community Drive, Manhasset, New York 11030. Vol. 43, No.5, May 1985
MATERIALS AND METHODS
The records of all infertile couples followed at the Division of Human Reproduction, North Shore University Hospital, between January 1980 and June 1983 were analyzed. Indications for immunologic studies included postcoital tests where abnormal swimming behavior was observed within well-estrogenized cervical mucus (complete immobilization, shaking motion of sperm without progression, or restricted tail beating), impaired mucus penetration by spermatozoa (where fewer than five motile sperm per highpower field were observed despite a normal semen analysis), and unexplained infertility. The evaluation also consisted of semen analysis and seminal fluid Ureaplasma culture, basal body temperature charting, endometrial biopsy, hysterogram, and laparoscopy where indicated. The length of follow-up ranged from 6 to 46 months. During this time, other factors leading to infertility were addressed, but no specific treatment was offered Ayvaliotis et aI. Autoimmunity to sperm
739
for autoimmunity to spermatozoa other than donor insemination, which was rejected by most c.ouples. Immunoglobulins were detected on the surface of motile spermatozoa by immunobead binding. 6 The extent of autoimmunity was judged by the proportion of spermatozoa antibody-bound as well as the regional binding of antibodies to the sperm surface, i.e., whether on the sperm head or tail. Couples were categorized into those where 50% or more of spermatozoa in the ejaculate were antibody-bound (high level) and those where < 50% were antibody-bound (low level). Because the etiology of infertility was often multifactorial, the study population was further divided into four groups: (1) no other cause of infertility was found in either partner; (2) the woman was apparently normal, but in the face of a significant male factor (semen volume, < 2 ml; sperm concentration, < 20 millionlml; motility, < 45%; oval heads, < 45%); (3) a female factor leading to infertility was present (inadequate luteal phase, as documented by two endometrial biopsies; oligoovulation, i.e., cycle length more than 45 days; endometriosis, peri adnexal adhesions, and immunities to sperm); and (4) both the man and woman were abnormal. RESULTS
Autoimmunity to spermatozoa was demonstrated in 131 men from 1025 couples screened for antisperm antibodies. Five habitual aborters, two women with absent fallopian tubes, and three women who had undergone artificial insemination with donor semen were eliminated from the study. Thirteen couples were lost to follow-up. Sixty-eight of the remaining 108 couples had primary infertility and 40 had secondary infertility. There were 35 couples where no other cause of infertility was found, 10 couples with additional semen abnormalities only, 47 couples in which a female factor was also present, and 16 where both male and female abnormalities were detected during the evaluation. Whereas nearly equal proportions of couples where husbands manifested high levels (61.5%) versus low levels (46.4%) of antisperm antibodies had been followed for at least 18 months following the diagnosis of autoimmunity to spermatozoa, there were many more couples with low-level antibodies who had been followed for less than 1 year (42.4% versus 17.4%). Despite the longer du740
Ayvaliotls et a1. Autoimmunity to sperm
Table 1. Pregnancy Outcome in 108 Couples Where Husbands Manifested Autoimmunity to Spermatozoa Clinical category
Normal men and women Normal men and abnormal women Abnormal men and normal women Abnormal men and women All groups
Proportion of couples pregnant Level of antibodyantibody- significance b a bound bound
> 50% sperm"" 50% sperm
4/26
6/9
P < 0.005
6/16
13/31
NS
0/6
3/4
P < 0.01
217
1/9
NS
12/55
23/53
P < 0.05
aAs determined by immunobead binding of sperm washed free of seminal fluid. bChi-square analysis. NS, not significant.
ration offollow-up, the pregnancy rate for couples where at least 50% of spermatozoa were antibodybound (high leveD-for the total study population and irrespective of the location of regional antibody binding to the sperm surface-was 21.8%, compared with 43.4% for couples with low-level binding (P < 0.05, chi-square analysis). These differences were of even greater significance for the 35 couples where no other cause of infertility was found (15.3% versus 66.7%; P < 0.005; Table 1). In those cases where high levels of autoimmunity to sperm were detected, the location of antibody binding on the sperm surface (head versus tail) did not influence the chance of conception (Table 2). DISCUSSION
A wide variation has been found in the proportion of spermatozoa that are antibody-bound in the ejaculates of men with autoimmunity to sperm. 5 This study has documented that the Table 2. Pregnancy Outcome in 108 Couples Where Husbands Manifested Autoimmunity to Spermatozoa Location and extent of antibody binding to sperm surfacea High head High tail High head Low tail Low head High tail Low head Low tail
No. of couples
No. pregnant
17
5 (19.2%)
8
1 (12.5%)
30
6 (20.0%)
53
23 (43.3%)
aHigh head and/or tail binding indicates at least 50% of sperm antibody-bound in ejaculate, as determined by immunobead binding.
Fertility and Sterility
chance of conception varies with the extent of autoimmunity, as reflected in the proportion of sperm exhibiting such antibodies. These results are not unexpected, in that a correlation has previously been found between the level of autoimmunity to sperm and the number of motile spermatozoa observed at postcoital testing. 5 Evidence has also been provided by several laboratories of an impaired ability of antibody-bound spermatozoa to penetrate both zona-free hamster eggs 7-9 and the human zona pellucida. 10 The chance of conception was greatest in those couples where antibody binding was < 50%; i.e., most sperm were free of detectable surface-bound immunoglobulins. The pregnancy rate of 67% in this group reinforces the premise that those sperm in autoimmune men that fail to bind immunobeads are indeed free of antisperm antibodies. These pregnancy rates approach those expected for couples with idiopathic infertility in the absence of antisperm antibodies. n , 12 Conversely, the low pregnancy rates for couples with high levels of autoimmunity to sperm (the majority antibody-bound) are consistent with the hypothesis that these spermatozoa should be considered impaired in their ability to fertilize eggs. In a recent study, Mathur et al. 13 found a correlation between the titers of antisperm antibodies in serum and the chance of conception. Compari'Sons of antisperm antibodies present in serum and semen have demonstrated that approximately 20% of men will have circulating humoral sperm-reactive antibodies in the absence of any detectable immunoglobulins on the sperm surface. 14 Hence, any study utilizing serologic tests solely for the detection of antisperm antibodies would then be expected to include a group of men whose autoimmunity to sperm played no role in their impaired reproduction. The ability to detect immunoglobulins bound to the living sperm surface has allowed us to confirm that all men included in this study possessed antisperm antibodies within their reproductive tract secretions. Despite this finding, spontaneous pregnancy rates ranged from 15% to 67% in the absence of treatment directed against their autoimmunity to sperm. Spontaneous remission of immunity to sperm in women is not uncommon. Three separate studies have now documented pregnancy rates of 40% in couples where the wives have been found to have antisperm antibodies present in their sera. 15- 17 In one study, 15 isoantibodies to spermaVol. 43, No.5, May 1985
tozoa were no longer detectable in nearly one third of these women at 1 year follow-up. Routine testing of the husbands, at the time of conception, was not performed systematically in the present study, and so spontaneous remission of autoimmunity cannot be excluded. As other autoimmune phenomena wax and wane, the production of antisperm antibodies may also vary through time. Ejaculatory frequency has also been shown to influence the extent of antibody binding to spermatozoa. 18 The daily production rate of sperm may exceed the rate of secretion and/or transudation of antisperm antibodies within the reproductive tract. A first ejaculate might "clear" the reproductive tract secretions of significant quantities of antibodies, allowing a second population of sperm to be exposed, at subsequent ejaculation, to lower concentrations of these antibodies. These results support the premise that treatment, whether with high-dose, short-term corticosteroids or intrauterine insemination following in vitro techniques directed toward diminishing the extent of sperm-bound immunoglobulins, may result in an improved chance of conception. In addition, they provide background rates of conception against which such treatments must be judged and emphasize the need to perform controlled studies in evaluating methods of treatment of immunities to spermatozoa.
REFERENCES 1. Riimke P, Hellinger G: Auto-antibodies against spermatozoa in sterile men. Am J Clin Pathol 32:357, 1959 2. Hull MGR, Savage PE, Bromham DR: Prognostic value of the postcoital test: prospective study based on time-specific conception rates. Br J Obstet Gynaecol 89:299, 1982 3. Fjallbrant BO: Cervical mucus penetration by human sperm treated with anti spermatozoal antibodies from rabbit and man. Acta Obstet Gynecol Scand 48:71, 1969 4. Jager S, Kremer J, Kuiken J, Van Slochteren-Draaisma T: Immunoglobulin class of antispermatozoal antibodies from infertile men and inhibition of in vitro sperm penetration in cervical mucus. Int J Androl 3:1, 1980 5. Bronson RA, Cooper GW, Rosenfeld DL: Autoimmunity to spermatozoa: effect on sperm penetration of cervical mucus as reflected by postcoital testing. Fertil Steril 41:609, 1984 6. Bronson R, Cooper G, Rosenfeld D: Ability of antibodybound human sperm to penetrate zona-free hamster ova in vitro. Fertil Steril 36:778, 1981 7. Haas GG Jr, Sokoloski JE, WolfDP: The interfering effect of human IgG antisperm antibodies on human sperm penetration of zona-free hamster eggs. AmJ Reprod Immunol 1:40, 1980
Ayvaliotis et al. Autoimmunity to sperm
741
8. Bronson RA, Cooper GW, Rosenfeld DL: Complement-mediated effects of sperm head-directed human antibodies on the ability of human spermatozoa to penetrate zonafree hamster eggs. Fertil Steril 40:91, 1983 9. Alexander NJ: Antibodies to human spermatozoa impede sperm penetration of cervical mucus or hamster eggs. Fertil Steril 41:433, 1984 10. Bronson RA, Cooper GW, Rosenfeld DL: Sperm-specific isoantibodies and autoantibodies inhibit the binding of human sperm to the human zona pellucida. Fertil Steril 38:724, 1982 11. Collins JA, Wrixon R, Janes LB, Wilson E: Treatment-independent pregnancy assay in infertile couples. N Engl J Med 309:1201, 1983 12. Rousseau S, Lord J, Lepage Y, Van Campenhout J: The expectancy of pregnancy for "normal" infertile couples. Fertil Steril 40:768, 1983 13. Mathur S, Williamson HO, Baker ME, Rust PF, Holtz GL, Fudenberg HH: Sperm motility on postcoital testing correlates with male autoimmunity to sperm. Fertil Steril 41:81,1984
742
Ayvaliotis et aI. Autoimmunity to sperm
14. Bronson R, Cooper G, Rosenfeld D: Membrane-bound sperm-specific antibodies: their role in infertility. In Bioregulators in Reproduction, Edited by H Vogel, G Jagiello. New York, Academic Press, 1981, p 521 15. Jones WR: Immunological factors in male and female infertility. In Immunological Aspects of Reproduction and Fertility Control, Edited by JP Hearn. Baltimore, University Park Press, 1980, p 128 16. Nicrota M, Dondero F, Coghi 1M: Followup studies in infertile women with antisperm antibodies. In Immunological Factors in Human Reproduction, Serono Symposium, Vol 45, Edited by S Shulman, F Dondero, M Nicrota. New York, Academic Press, 1982, p 37 17. Bronson RA, Cooper GW, Rosenfeld DL: Sperm-reactive antibodies: their role in reproductive failure in women. Presented at the Thirty-First Annual Meeting of the Society for Gynecologic Investigation, March 21 to 24, 1984, San Francisco, California 18. Bronson RA, Cooper GW, Rosenfeld DL: Use of freezethawed sonicated human sperm as an in vitro immunoabsorbent. Am J Reprod Immunol 2:162, 1982
Fertility and Sterility
Vol. 43, No.5, May 1985 Printed in U.SA.
Conception rates in couples where autoimmunity to sperm is detected
Bessie Ayvaliotis, M.D. Richard Bronson, M.D. * David Rosenfeld, M.D . . George Cooper, Ph.D. Department of Obstetrics and Gynecology, Division of Human Reproduction, North Shore University Hospital, Cornell University Medical College, Manhasset, New York
In men with autoimmunity to sperm, a varying proportion of spermatozoa in the ejaculate are found to have surface-bound immunoglobulins. We asked whether the extent of autoimmunity, as judged by this criterion, would have predictive value in determining the chance of conception. Infertile couples where husbands were found to have antisperm antibodies were treated for other factors leading to impaired reproduction, but no specific treatment was offered for reduction of these antibodies. The chance of pregnancy for those couples where autoimmunity to sperm was the sole definable factor leading to infertility was 15.3% when most spermatozoa were antibody-bound. A significantly greater number of wives whose husbands had < 50% of their sperm bound by immunoglobulins conceived (66.7%; P < 0.005). Fertil Steril43:739, 1985
Immunities to sperm were described, as early as 1959, as a possible cause of infertility.l A recent prospective study has shown that the likelihood of conception increases and the time to conception decreases as larger numbers of motile sperm are observed within cervical mucus. 2 Sperm-reactive antibodies are known to affect sperm penetration into, and motility within, cervical mucus. 3 - 5 The purpose of this study was to determine pregnancy rates in infertile couples where surface-bound immunoglobulins had been demonstrated on the husband's spermatozoa and to correlate the chance of conception with the extent of autoimmunity to sperm, as reflected by immunobead binding.
Received October 2, 1984; revised and accepted January 10, 1985. *Reprint requests: Richard Bronson, M.D., Division of Human Reproduction, North Shore University Hospital, 300 Community Drive, Manhasset, New York 11030. Vol. 43, No.5, May 1985
MATERIALS AND METHODS
The records of all infertile couples followed at the Division of Human Reproduction, North Shore University Hospital, between January 1980 and June 1983 were analyzed. Indications for immunologic studies included postcoital tests where abnormal swimming behavior was observed within well-estrogenized cervical mucus (complete immobilization, shaking motion of sperm without progression, or restricted tail beating), impaired mucus penetration by spermatozoa (where fewer than five motile sperm per highpower field were observed despite a normal semen analysis), and unexplained infertility. The evaluation also consisted of semen analysis and seminal fluid Ureaplasma culture, basal body temperature charting, endometrial biopsy, hysterogram, and laparoscopy where indicated. The length of follow-up ranged from 6 to 46 months. During this time, other factors leading to infertility were addressed, but no specific treatment was offered Ayvaliotis et aI. Autoimmunity to sperm
739
for autoimmunity to spermatozoa other than donor insemination, which was rejected by most c.ouples. Immunoglobulins were detected on the surface of motile spermatozoa by immunobead binding. 6 The extent of autoimmunity was judged by the proportion of spermatozoa antibody-bound as well as the regional binding of antibodies to the sperm surface, i.e., whether on the sperm head or tail. Couples were categorized into those where 50% or more of spermatozoa in the ejaculate were antibody-bound (high level) and those where < 50% were antibody-bound (low level). Because the etiology of infertility was often multifactorial, the study population was further divided into four groups: (1) no other cause of infertility was found in either partner; (2) the woman was apparently normal, but in the face of a significant male factor (semen volume, < 2 ml; sperm concentration, < 20 millionlml; motility, < 45%; oval heads, < 45%); (3) a female factor leading to infertility was present (inadequate luteal phase, as documented by two endometrial biopsies; oligoovulation, i.e., cycle length more than 45 days; endometriosis, peri adnexal adhesions, and immunities to sperm); and (4) both the man and woman were abnormal. RESULTS
Autoimmunity to spermatozoa was demonstrated in 131 men from 1025 couples screened for antisperm antibodies. Five habitual aborters, two women with absent fallopian tubes, and three women who had undergone artificial insemination with donor semen were eliminated from the study. Thirteen couples were lost to follow-up. Sixty-eight of the remaining 108 couples had primary infertility and 40 had secondary infertility. There were 35 couples where no other cause of infertility was found, 10 couples with additional semen abnormalities only, 47 couples in which a female factor was also present, and 16 where both male and female abnormalities were detected during the evaluation. Whereas nearly equal proportions of couples where husbands manifested high levels (61.5%) versus low levels (46.4%) of antisperm antibodies had been followed for at least 18 months following the diagnosis of autoimmunity to spermatozoa, there were many more couples with low-level antibodies who had been followed for less than 1 year (42.4% versus 17.4%). Despite the longer du740
Ayvaliotls et a1. Autoimmunity to sperm
Table 1. Pregnancy Outcome in 108 Couples Where Husbands Manifested Autoimmunity to Spermatozoa Clinical category
Normal men and women Normal men and abnormal women Abnormal men and normal women Abnormal men and women All groups
Proportion of couples pregnant Level of antibodyantibody- significance b a bound bound
> 50% sperm"" 50% sperm
4/26
6/9
P < 0.005
6/16
13/31
NS
0/6
3/4
P < 0.01
217
1/9
NS
12/55
23/53
P < 0.05
aAs determined by immunobead binding of sperm washed free of seminal fluid. bChi-square analysis. NS, not significant.
ration offollow-up, the pregnancy rate for couples where at least 50% of spermatozoa were antibodybound (high leveD-for the total study population and irrespective of the location of regional antibody binding to the sperm surface-was 21.8%, compared with 43.4% for couples with low-level binding (P < 0.05, chi-square analysis). These differences were of even greater significance for the 35 couples where no other cause of infertility was found (15.3% versus 66.7%; P < 0.005; Table 1). In those cases where high levels of autoimmunity to sperm were detected, the location of antibody binding on the sperm surface (head versus tail) did not influence the chance of conception (Table 2). DISCUSSION
A wide variation has been found in the proportion of spermatozoa that are antibody-bound in the ejaculates of men with autoimmunity to sperm. 5 This study has documented that the Table 2. Pregnancy Outcome in 108 Couples Where Husbands Manifested Autoimmunity to Spermatozoa Location and extent of antibody binding to sperm surfacea High head High tail High head Low tail Low head High tail Low head Low tail
No. of couples
No. pregnant
17
5 (19.2%)
8
1 (12.5%)
30
6 (20.0%)
53
23 (43.3%)
aHigh head and/or tail binding indicates at least 50% of sperm antibody-bound in ejaculate, as determined by immunobead binding.
Fertility and Sterility
chance of conception varies with the extent of autoimmunity, as reflected in the proportion of sperm exhibiting such antibodies. These results are not unexpected, in that a correlation has previously been found between the level of autoimmunity to sperm and the number of motile spermatozoa observed at postcoital testing. 5 Evidence has also been provided by several laboratories of an impaired ability of antibody-bound spermatozoa to penetrate both zona-free hamster eggs 7-9 and the human zona pellucida. 10 The chance of conception was greatest in those couples where antibody binding was < 50%; i.e., most sperm were free of detectable surface-bound immunoglobulins. The pregnancy rate of 67% in this group reinforces the premise that those sperm in autoimmune men that fail to bind immunobeads are indeed free of antisperm antibodies. These pregnancy rates approach those expected for couples with idiopathic infertility in the absence of antisperm antibodies. n , 12 Conversely, the low pregnancy rates for couples with high levels of autoimmunity to sperm (the majority antibody-bound) are consistent with the hypothesis that these spermatozoa should be considered impaired in their ability to fertilize eggs. In a recent study, Mathur et al. 13 found a correlation between the titers of antisperm antibodies in serum and the chance of conception. Compari'Sons of antisperm antibodies present in serum and semen have demonstrated that approximately 20% of men will have circulating humoral sperm-reactive antibodies in the absence of any detectable immunoglobulins on the sperm surface. 14 Hence, any study utilizing serologic tests solely for the detection of antisperm antibodies would then be expected to include a group of men whose autoimmunity to sperm played no role in their impaired reproduction. The ability to detect immunoglobulins bound to the living sperm surface has allowed us to confirm that all men included in this study possessed antisperm antibodies within their reproductive tract secretions. Despite this finding, spontaneous pregnancy rates ranged from 15% to 67% in the absence of treatment directed against their autoimmunity to sperm. Spontaneous remission of immunity to sperm in women is not uncommon. Three separate studies have now documented pregnancy rates of 40% in couples where the wives have been found to have antisperm antibodies present in their sera. 15- 17 In one study, 15 isoantibodies to spermaVol. 43, No.5, May 1985
tozoa were no longer detectable in nearly one third of these women at 1 year follow-up. Routine testing of the husbands, at the time of conception, was not performed systematically in the present study, and so spontaneous remission of autoimmunity cannot be excluded. As other autoimmune phenomena wax and wane, the production of antisperm antibodies may also vary through time. Ejaculatory frequency has also been shown to influence the extent of antibody binding to spermatozoa. 18 The daily production rate of sperm may exceed the rate of secretion and/or transudation of antisperm antibodies within the reproductive tract. A first ejaculate might "clear" the reproductive tract secretions of significant quantities of antibodies, allowing a second population of sperm to be exposed, at subsequent ejaculation, to lower concentrations of these antibodies. These results support the premise that treatment, whether with high-dose, short-term corticosteroids or intrauterine insemination following in vitro techniques directed toward diminishing the extent of sperm-bound immunoglobulins, may result in an improved chance of conception. In addition, they provide background rates of conception against which such treatments must be judged and emphasize the need to perform controlled studies in evaluating methods of treatment of immunities to spermatozoa.
REFERENCES 1. Riimke P, Hellinger G: Auto-antibodies against spermatozoa in sterile men. Am J Clin Pathol 32:357, 1959 2. Hull MGR, Savage PE, Bromham DR: Prognostic value of the postcoital test: prospective study based on time-specific conception rates. Br J Obstet Gynaecol 89:299, 1982 3. Fjallbrant BO: Cervical mucus penetration by human sperm treated with anti spermatozoal antibodies from rabbit and man. Acta Obstet Gynecol Scand 48:71, 1969 4. Jager S, Kremer J, Kuiken J, Van Slochteren-Draaisma T: Immunoglobulin class of antispermatozoal antibodies from infertile men and inhibition of in vitro sperm penetration in cervical mucus. Int J Androl 3:1, 1980 5. Bronson RA, Cooper GW, Rosenfeld DL: Autoimmunity to spermatozoa: effect on sperm penetration of cervical mucus as reflected by postcoital testing. Fertil Steril 41:609, 1984 6. Bronson R, Cooper G, Rosenfeld D: Ability of antibodybound human sperm to penetrate zona-free hamster ova in vitro. Fertil Steril 36:778, 1981 7. Haas GG Jr, Sokoloski JE, WolfDP: The interfering effect of human IgG antisperm antibodies on human sperm penetration of zona-free hamster eggs. AmJ Reprod Immunol 1:40, 1980
Ayvaliotis et al. Autoimmunity to sperm
741
8. Bronson RA, Cooper GW, Rosenfeld DL: Complement-mediated effects of sperm head-directed human antibodies on the ability of human spermatozoa to penetrate zonafree hamster eggs. Fertil Steril 40:91, 1983 9. Alexander NJ: Antibodies to human spermatozoa impede sperm penetration of cervical mucus or hamster eggs. Fertil Steril 41:433, 1984 10. Bronson RA, Cooper GW, Rosenfeld DL: Sperm-specific isoantibodies and autoantibodies inhibit the binding of human sperm to the human zona pellucida. Fertil Steril 38:724, 1982 11. Collins JA, Wrixon R, Janes LB, Wilson E: Treatment-independent pregnancy assay in infertile couples. N Engl J Med 309:1201, 1983 12. Rousseau S, Lord J, Lepage Y, Van Campenhout J: The expectancy of pregnancy for "normal" infertile couples. Fertil Steril 40:768, 1983 13. Mathur S, Williamson HO, Baker ME, Rust PF, Holtz GL, Fudenberg HH: Sperm motility on postcoital testing correlates with male autoimmunity to sperm. Fertil Steril 41:81,1984
742
Ayvaliotis et aI. Autoimmunity to sperm
14. Bronson R, Cooper G, Rosenfeld D: Membrane-bound sperm-specific antibodies: their role in infertility. In Bioregulators in Reproduction, Edited by H Vogel, G Jagiello. New York, Academic Press, 1981, p 521 15. Jones WR: Immunological factors in male and female infertility. In Immunological Aspects of Reproduction and Fertility Control, Edited by JP Hearn. Baltimore, University Park Press, 1980, p 128 16. Nicrota M, Dondero F, Coghi 1M: Followup studies in infertile women with antisperm antibodies. In Immunological Factors in Human Reproduction, Serono Symposium, Vol 45, Edited by S Shulman, F Dondero, M Nicrota. New York, Academic Press, 1982, p 37 17. Bronson RA, Cooper GW, Rosenfeld DL: Sperm-reactive antibodies: their role in reproductive failure in women. Presented at the Thirty-First Annual Meeting of the Society for Gynecologic Investigation, March 21 to 24, 1984, San Francisco, California 18. Bronson RA, Cooper GW, Rosenfeld DL: Use of freezethawed sonicated human sperm as an in vitro immunoabsorbent. Am J Reprod Immunol 2:162, 1982
Fertility and Sterility