0022-534 7/78/1192-0231$02. 00/0
Vol. 119, February Printed in U.SA.
THE JOURNAL OF UROLOGY
Copyright © 1978 by The Williams & Wilkins Co.
SIGNIFICANT IMMUNOLOGIC FACTORS IN MALE INFERTILITY SIDNEY SHULMAN,* DAVID T. MININBERG
AND
JOSEPH E. DAVIS
From the Sperm Antibody Laboratory, Departments of Urology and Microbiology, New Yark Medical College, New York and Valhalla, New York
ABSTRACT
A number of patients who suffer from involuntary infertility showed a sperm antibody in the blood serum as detected by 2 different methods of sperm agglutination. These techniques are the Kibrick method (gelatin agglutination test) and the F-D method, (tube-slide agglutination test). With the former technique 9 per cent of men and 18 per cent of women from infertile couples had a positive result, while the l~tter technique revealed 5 per cent of men and 15 per cent of women with positive results. Such cases are termed immunological infertility. Several cases of necrospermia also showed sperm antibody activity. In vasectomized men it has been shown that 50 to 60 per cent have sperm antibody during the first year postoperatively. To develop new methods for treatment of infertility immunosuppression by means of corticosteroid medication was applied. A 7-day regimen of 96 mg. per day methylprednisolone was studied. A drastic decrease of antibody level could be seen in some cases and the wives became pregnant. There has been approximately a 30 per cent success rate in a group of 15 such couples. It is now well established that sperm antibody may be the causative factor in many people who suffer from infertility.1-5 It is important to consider the nature of this immunologic factor, the means for its reliable detection and quantitation, and the possibilities for its removal. This antibody activity can be detected by a number of methods, including agglutination, immobilization, cytotoxicity and immunofluorescence. It is also true that the apparent demonstration of such an antibody activity is not always a demonstration of an actual antibody and one must be on guard and aware of the falsely positive results that can sometimes occur. A number of reports have described the association of this kind of activity with the occurrence of infertility in either men or women and, although usually the unexplained infertility has been the point of emphasis, we should not limit our thinking to this 1 kind of infertility or wrong interpretations will develop. The number of patients who complain of infertility seems to be increasing and the traditional option of favoring a process of adoption for its remedy is much less feasible today than in the past. Therefore, one must expect to have an increasing number of cases of this kind in the future. For several years we have been interested in developing better methods for detection of sperm antibody in patients who suffer from infertility. We as well as others have shown the significance of the several different antibody activities, generally by means of comparisons of the frequency s>f occurrence in large infertile and fertile populations. 6-B Finally, we have tried recently to develop methods of removal of these antibody activities so that the patient will receive successful treatment for the infertility problem. Herein we describe some results for each of these efforts. METHODS
Our laboratory studies included semen analysis for each
male patient and analysis of blood serum for each of the 2 partners in each couple for determination of sperm antibody. This antibody detection was done by either of 2 techniques of Accepted for publication April 29, 1977. Supported in part by the Sperm Antibody Laboratory Fund. Read at annual meeting of American Urological Association, Chicago, Illinois, April 24-28, 1977. * Requests for reprints: Sperm Antibody Laboratory, New York Medical College, 106th St. and 5th Ave., New York, New York 10029. 231
sperm agglutination, based on the Kibrick technique9 and the Franklin-Dukes technique, 10 as we have modified them. The Kibrick method (gelatin agglutination method) of sperm antibody detection. A fresh ejaculate of semen is diluted to 40 million sperm cells per ml. and then mixed with an equal volume of a 10 per cent gelatin solution. This preparation is then mixed with an equal volume of a 1:4 dilution of the (inactivated) serum to be tested. All dilutions are made with Baker's buffer. 1 After shaking, the mixtures are put into Kibrick tubes (3 mm. in diameter and 3 cm. in length) and incubated at 37C for 1 and 2 hours. The tubes are examined at each interval for visible clumps. Those sera that are positive are then tested again on another day in a dilution series. In this way a titer is obtained as a quantitative expression of activity. Results can be expressed as follows: 4 means a titer of 1:4,
Vol. 119, February Printed in U.SA.
THE JOURNAL OF UROLOGY
Copyright © 1978 by The Williams & Wilkins Co.
SIGNIFICANT IMMUNOLOGIC FACTORS IN MALE INFERTILITY SIDNEY SHULMAN,* DAVID T. MININBERG
AND
JOSEPH E. DAVIS
From the Sperm Antibody Laboratory, Departments of Urology and Microbiology, New Yark Medical College, New York and Valhalla, New York
ABSTRACT
A number of patients who suffer from involuntary infertility showed a sperm antibody in the blood serum as detected by 2 different methods of sperm agglutination. These techniques are the Kibrick method (gelatin agglutination test) and the F-D method, (tube-slide agglutination test). With the former technique 9 per cent of men and 18 per cent of women from infertile couples had a positive result, while the l~tter technique revealed 5 per cent of men and 15 per cent of women with positive results. Such cases are termed immunological infertility. Several cases of necrospermia also showed sperm antibody activity. In vasectomized men it has been shown that 50 to 60 per cent have sperm antibody during the first year postoperatively. To develop new methods for treatment of infertility immunosuppression by means of corticosteroid medication was applied. A 7-day regimen of 96 mg. per day methylprednisolone was studied. A drastic decrease of antibody level could be seen in some cases and the wives became pregnant. There has been approximately a 30 per cent success rate in a group of 15 such couples. It is now well established that sperm antibody may be the causative factor in many people who suffer from infertility.1-5 It is important to consider the nature of this immunologic factor, the means for its reliable detection and quantitation, and the possibilities for its removal. This antibody activity can be detected by a number of methods, including agglutination, immobilization, cytotoxicity and immunofluorescence. It is also true that the apparent demonstration of such an antibody activity is not always a demonstration of an actual antibody and one must be on guard and aware of the falsely positive results that can sometimes occur. A number of reports have described the association of this kind of activity with the occurrence of infertility in either men or women and, although usually the unexplained infertility has been the point of emphasis, we should not limit our thinking to this 1 kind of infertility or wrong interpretations will develop. The number of patients who complain of infertility seems to be increasing and the traditional option of favoring a process of adoption for its remedy is much less feasible today than in the past. Therefore, one must expect to have an increasing number of cases of this kind in the future. For several years we have been interested in developing better methods for detection of sperm antibody in patients who suffer from infertility. We as well as others have shown the significance of the several different antibody activities, generally by means of comparisons of the frequency s>f occurrence in large infertile and fertile populations. 6-B Finally, we have tried recently to develop methods of removal of these antibody activities so that the patient will receive successful treatment for the infertility problem. Herein we describe some results for each of these efforts. METHODS
Our laboratory studies included semen analysis for each
male patient and analysis of blood serum for each of the 2 partners in each couple for determination of sperm antibody. This antibody detection was done by either of 2 techniques of Accepted for publication April 29, 1977. Supported in part by the Sperm Antibody Laboratory Fund. Read at annual meeting of American Urological Association, Chicago, Illinois, April 24-28, 1977. * Requests for reprints: Sperm Antibody Laboratory, New York Medical College, 106th St. and 5th Ave., New York, New York 10029. 231
sperm agglutination, based on the Kibrick technique9 and the Franklin-Dukes technique, 10 as we have modified them. The Kibrick method (gelatin agglutination method) of sperm antibody detection. A fresh ejaculate of semen is diluted to 40 million sperm cells per ml. and then mixed with an equal volume of a 10 per cent gelatin solution. This preparation is then mixed with an equal volume of a 1:4 dilution of the (inactivated) serum to be tested. All dilutions are made with Baker's buffer. 1 After shaking, the mixtures are put into Kibrick tubes (3 mm. in diameter and 3 cm. in length) and incubated at 37C for 1 and 2 hours. The tubes are examined at each interval for visible clumps. Those sera that are positive are then tested again on another day in a dilution series. In this way a titer is obtained as a quantitative expression of activity. Results can be expressed as follows: 4 means a titer of 1:4,
