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Clinical Relevance of Recent World Health Organization Workshops* on Human Sperm and Trophoblast Antigens
Vol. 46, No.5, November 1986 Copyright
©
1986 The American Fertility Society
Clinical Relevance of Recent World Health Organization Workshops* on Human Sperm and Trophoblast Antigens Rapid developments in the use of monoclonal antibodies to identify and study human reproductive tract antigens prompted two recent international workshops sponsored by the World Health Organization (WHO) on the state ofthe art of the application of monoclonal antibodies to molecular events underlying human reproduction. The workshops entailed worldwide distribution and testing of a coded panel of 67 mouse monoclonal antibodies reactive with human sperm and 45 monoclonal antibodies reactive with human trophoblast membrane antigens. The antibodies were produced in 29 laboratories and evaluated in 42 laboratories with expertise in biochemical, immunohistologic, and other immunologic tests and tests of reproductive cell function. The overall objective was to assess the applicability of monoclonal antibodies for an understanding of reproductive processes and for identifying reproductive tissue-specific antigens that may be candidates for antifertility vaccines. The workshops brought forth several clinically important caveats. Many of the monoclonal antibodies tested in the workshops have been previously reported in the clinical literature to be tissue-specific. However, when the monoclonal antibodies were subjected to rigorous specificity testing in independent laboratories, in most cases reproductive tissue-specific antigenicity was elusive. All but three antisperm and two antitrophoblast antibodies cross-reacted with cellular elements in nonreproductive tissues. The two tissuespecific anti trophoblast antibodies showed highly restricted cross-species reactivity; on the other hand, the three tissue-specific antisperm antibodies cross-reacted widely with sperm from other mammalian species, including mice. This will
*WHO sponsored workshops on Monoclonal Antibodies to Human Sperm and Trophoblast Antigens, Toronto, Canada, June 30, 1986. The Sperm Antigen Workshop was also supported by funds from Family Health International and the Agency For International Development. A detailed report is to be published in the Journal of Reproductive Immunology.
978
Letters-to-the-editor
Printed in U.8A.
enable studies of mechanisms of antisperm immunologic infertility and development of antisperm vaccine protocols in animal models. Over half of the antisperm antibodies affected sperm function in at least one of a variety of conventional sperm function assays: sperm motility, sperm agglutination, cervical mucus penetration, hamster egg penetration, and mouse in vitro fertilization. There was, however, marked discordance in results between participating laboratories, indicating the need for standardization of sperm function and antisperm antibody tests. It also highlighted a clinical and research need for additional reproductive tissue-specific reagents. The inefficiency in the mouse hybridoma approach in producing truly reproductive specific antibodies suggests that new approaches such as human monoclonal antibodies or cDNA difference libraries should be explored. A comprehensive panel of monoclonal antibodies to spermatozoa could be clinically useful, not only as standardization aids for sperm antibody assays but also for dissecting components of sperm cell function that contribute to male infertility. A panel of monoclonal antibodies that identify sperm surface markers associated with sperm functional capabilities (e.g., capacitation markers, motility markers, egg receptor and penetration markers) could provide the basis of a new clinical infertility test. In addition, germ cell and trophoblast monoclonal antibodies assessed in these workshops may provide additional reagents for the identification, classification, and immunotherapy of germ cell and gestational trophoblast malignancies. Monoclonal antibodies to trophoblast antigens could also prove clinically useful in studies of immunologic mechanisms underlying recurrent spontaneous abortion and the isolation of trophoblast antigen(s) as possible immunogenes) for treatment of recurrent abortion. Antitrophoblast antibodies may also be applied to the development of antifertility vaccines and may also provide an approach to the separation of trophoblast cells from maternal blood as an alternative to amniocentesis and chorionic villous sampling for prenatal genetic studies. Monoclonal antibodies to sperm and trophoblast antigens are crucial tools for understanding reproductive processes. These workshops, which Fertility and Sterility
were the first of their kind in this field, provided an important forum for scientific exchange and established a system of collaborating laboratories and comprehensive biochemical, immunohistologic, and functional assays which could be used as a framework for the objective assessment and distribution of new reproductive tissue antibodies and probes as they become available in the field.
Joseph A. Hill, M.D. Deborah J. Anderson, Ph.D. Department of Obstetrics and Gynecology Harvard Medical School Boston, Massachusetts Peter M. Johnson, Ph.D. Department of Immunology University of Liverpool Liverpool, United Kingdom August 25,1986
Comment Drs. Hill and Johnson have written an informative resume of two recent workshops which will ultimately have an impact on the practice of infertility and reproductive endocrinology. The hybridoma technology ushered in by Kohler and Milstein's discovery in 19751 has not yet fulfilled all of its bright clinical expectations at the clinical level. However, this resume outlines some of the future uses of these techniques and should be of interest to our readers. Paul G. McDonough, M.D., Letters Editor REFERENCE 1. Kohler G, Milstein C: Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495, 1975
Open-Ended Vasectomy To the Editor: Congratulations on the publication of the long awaited report from Errey and Edward on openended vasectomy. 1 I would question, however, the exclusive focus in the introductory and discussion sections, on epididymal compliance to the poorly resorbable spermatozoa. 2 The testis has been Vol. 46, No.5, November 1986
#
shown in laboratory species3 and in man 4 to have histologic features of hydrotestis after successful vas occlusion, similar to those of hydronephrosis after ureteral occlusion. Surely, some of the symptoms seen after successful vas occlusion fail to occur after the open-ended technique because the caput epididymidis remains free to reabsorb most of testicular fluid production, its normal function. Similarly, improved pregnancy rates should be expected after open-ended vasectomy because there is less destruction of the seminiferous tubules.
Anthony H. Horan, M.D. 707 East Cedar South Bend, Indiana 46617 July 11,1986 REFERENCES 1. Errey BB, Edwards IS: Open-ended vasectomy: an assessment. Fertil Steril 45:843, 1986 2. Ball RY, Setchel BP: The passage of spermatozoa to regional lymph nodes in testicular lymph following vasectomy in rams and boars. J Reprod Fertil 68:145, 1983 3. Horan AH: When and why does occlusion of the vas deferens affect the testis? Fertil Steril26:317, 1975 4. Jarow JP, Budin RE, Dym M, Zirkin BR, Noren S, Marshall FF: Quantitative changes in the human testis after vasectomy: a controlled study. N Engl J Med 313:1252, 1985
Reply of the Author: We share Dr. Horan's expectation that vasovasostomy following open-ended vasectomy should result in improved pregnancy rates, compared with those of reanastomosis following standard vasectomy techniques. Time will tell whether we are right. We also agree that standard vasectomy techniques are followed by changes in the testes, but there appears to be no evidence that these changes are harmful, except that they make it less likely that fertility can be restored, and in a few men may contribute to some discomforts, which are rarely severe. One of the main reasons for considering a change in vasectomy technique to the open-ended modification is the possibility that the success rate of vasovasostomy operations will thereby be improved. We think we have shown that there is nothing to be lost by this change in technique, in that careful fascial separation of the ends of the Letters-to-the-editor
979
©
1986 The American Fertility Society
Clinical Relevance of Recent World Health Organization Workshops* on Human Sperm and Trophoblast Antigens Rapid developments in the use of monoclonal antibodies to identify and study human reproductive tract antigens prompted two recent international workshops sponsored by the World Health Organization (WHO) on the state ofthe art of the application of monoclonal antibodies to molecular events underlying human reproduction. The workshops entailed worldwide distribution and testing of a coded panel of 67 mouse monoclonal antibodies reactive with human sperm and 45 monoclonal antibodies reactive with human trophoblast membrane antigens. The antibodies were produced in 29 laboratories and evaluated in 42 laboratories with expertise in biochemical, immunohistologic, and other immunologic tests and tests of reproductive cell function. The overall objective was to assess the applicability of monoclonal antibodies for an understanding of reproductive processes and for identifying reproductive tissue-specific antigens that may be candidates for antifertility vaccines. The workshops brought forth several clinically important caveats. Many of the monoclonal antibodies tested in the workshops have been previously reported in the clinical literature to be tissue-specific. However, when the monoclonal antibodies were subjected to rigorous specificity testing in independent laboratories, in most cases reproductive tissue-specific antigenicity was elusive. All but three antisperm and two antitrophoblast antibodies cross-reacted with cellular elements in nonreproductive tissues. The two tissuespecific anti trophoblast antibodies showed highly restricted cross-species reactivity; on the other hand, the three tissue-specific antisperm antibodies cross-reacted widely with sperm from other mammalian species, including mice. This will
*WHO sponsored workshops on Monoclonal Antibodies to Human Sperm and Trophoblast Antigens, Toronto, Canada, June 30, 1986. The Sperm Antigen Workshop was also supported by funds from Family Health International and the Agency For International Development. A detailed report is to be published in the Journal of Reproductive Immunology.
978
Letters-to-the-editor
Printed in U.8A.
enable studies of mechanisms of antisperm immunologic infertility and development of antisperm vaccine protocols in animal models. Over half of the antisperm antibodies affected sperm function in at least one of a variety of conventional sperm function assays: sperm motility, sperm agglutination, cervical mucus penetration, hamster egg penetration, and mouse in vitro fertilization. There was, however, marked discordance in results between participating laboratories, indicating the need for standardization of sperm function and antisperm antibody tests. It also highlighted a clinical and research need for additional reproductive tissue-specific reagents. The inefficiency in the mouse hybridoma approach in producing truly reproductive specific antibodies suggests that new approaches such as human monoclonal antibodies or cDNA difference libraries should be explored. A comprehensive panel of monoclonal antibodies to spermatozoa could be clinically useful, not only as standardization aids for sperm antibody assays but also for dissecting components of sperm cell function that contribute to male infertility. A panel of monoclonal antibodies that identify sperm surface markers associated with sperm functional capabilities (e.g., capacitation markers, motility markers, egg receptor and penetration markers) could provide the basis of a new clinical infertility test. In addition, germ cell and trophoblast monoclonal antibodies assessed in these workshops may provide additional reagents for the identification, classification, and immunotherapy of germ cell and gestational trophoblast malignancies. Monoclonal antibodies to trophoblast antigens could also prove clinically useful in studies of immunologic mechanisms underlying recurrent spontaneous abortion and the isolation of trophoblast antigen(s) as possible immunogenes) for treatment of recurrent abortion. Antitrophoblast antibodies may also be applied to the development of antifertility vaccines and may also provide an approach to the separation of trophoblast cells from maternal blood as an alternative to amniocentesis and chorionic villous sampling for prenatal genetic studies. Monoclonal antibodies to sperm and trophoblast antigens are crucial tools for understanding reproductive processes. These workshops, which Fertility and Sterility
were the first of their kind in this field, provided an important forum for scientific exchange and established a system of collaborating laboratories and comprehensive biochemical, immunohistologic, and functional assays which could be used as a framework for the objective assessment and distribution of new reproductive tissue antibodies and probes as they become available in the field.
Joseph A. Hill, M.D. Deborah J. Anderson, Ph.D. Department of Obstetrics and Gynecology Harvard Medical School Boston, Massachusetts Peter M. Johnson, Ph.D. Department of Immunology University of Liverpool Liverpool, United Kingdom August 25,1986
Comment Drs. Hill and Johnson have written an informative resume of two recent workshops which will ultimately have an impact on the practice of infertility and reproductive endocrinology. The hybridoma technology ushered in by Kohler and Milstein's discovery in 19751 has not yet fulfilled all of its bright clinical expectations at the clinical level. However, this resume outlines some of the future uses of these techniques and should be of interest to our readers. Paul G. McDonough, M.D., Letters Editor REFERENCE 1. Kohler G, Milstein C: Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495, 1975
Open-Ended Vasectomy To the Editor: Congratulations on the publication of the long awaited report from Errey and Edward on openended vasectomy. 1 I would question, however, the exclusive focus in the introductory and discussion sections, on epididymal compliance to the poorly resorbable spermatozoa. 2 The testis has been Vol. 46, No.5, November 1986
#
shown in laboratory species3 and in man 4 to have histologic features of hydrotestis after successful vas occlusion, similar to those of hydronephrosis after ureteral occlusion. Surely, some of the symptoms seen after successful vas occlusion fail to occur after the open-ended technique because the caput epididymidis remains free to reabsorb most of testicular fluid production, its normal function. Similarly, improved pregnancy rates should be expected after open-ended vasectomy because there is less destruction of the seminiferous tubules.
Anthony H. Horan, M.D. 707 East Cedar South Bend, Indiana 46617 July 11,1986 REFERENCES 1. Errey BB, Edwards IS: Open-ended vasectomy: an assessment. Fertil Steril 45:843, 1986 2. Ball RY, Setchel BP: The passage of spermatozoa to regional lymph nodes in testicular lymph following vasectomy in rams and boars. J Reprod Fertil 68:145, 1983 3. Horan AH: When and why does occlusion of the vas deferens affect the testis? Fertil Steril26:317, 1975 4. Jarow JP, Budin RE, Dym M, Zirkin BR, Noren S, Marshall FF: Quantitative changes in the human testis after vasectomy: a controlled study. N Engl J Med 313:1252, 1985
Reply of the Author: We share Dr. Horan's expectation that vasovasostomy following open-ended vasectomy should result in improved pregnancy rates, compared with those of reanastomosis following standard vasectomy techniques. Time will tell whether we are right. We also agree that standard vasectomy techniques are followed by changes in the testes, but there appears to be no evidence that these changes are harmful, except that they make it less likely that fertility can be restored, and in a few men may contribute to some discomforts, which are rarely severe. One of the main reasons for considering a change in vasectomy technique to the open-ended modification is the possibility that the success rate of vasovasostomy operations will thereby be improved. We think we have shown that there is nothing to be lost by this change in technique, in that careful fascial separation of the ends of the Letters-to-the-editor
979