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Influence of sperm surface antibodies on spontaneous pregnancy rates
FERTILITY AND STERILITYt VOL. 70, NO. 2, AUGUST 1998 Copyright ©1998 American Society for Reproductive Medicine Published by Elsevier Science Inc. Printed on acid-free paper in U.S.A.
COMMUNICATIONS-IN-BRIEF
Influence of sperm surface antibodies on spontaneous pregnancy rates Katrin Abshagen, M.D., Hermann M. Behre, M.D., Trevor G. Cooper, Ph.D., and Eberhard Nieschlag, M.D. Institute of Reproductive Medicine, University of Mu¨nster, Mu¨nster, Germany
Objective: To determine the rates of spontaneous pregnancies among women whose infertile male partners had sperm surface antibodies. Design: Retrospective analysis. Setting: Infertility clinic of a university referral center. Patient(s): One hundred fifty-seven infertile couples; the male partner had IgA and/or IgG sperm surface antibody concentrations of .10%. Intervention: None. Main Outcome Measure(s): Spontaneous pregnancy rates (PRs) over 6 years. Result(s): Spontaneous PRs correlated negatively with antibody concentrations. Conclusion(s): Although the chance of spontaneous pregnancy among women whose partners had sperm antibody concentrations of ,50% was good, intracytoplasmic sperm injection should be recommended to patients with concentrations of .90%. (Fertil Sterilt 1998;70:355– 6. ©1998 by American Society for Reproductive Medicine.) Key Words: Sperm surface antibodies, pregnancy rates
Received October 8, 1997; revised and accepted March 23, 1998. Supported by the Interdisciplinary Clinical Research Center (IKF), Medical Faculty, University of Mu¨nster, Mu¨nster, Germany. Reprint requests: Eberhard Nieschlag, M.D., Institute of Reproductive Medicine, University of Mu¨nster, Domagkstraße 11, D-48129 Mu¨nster, Germany (FAX: 49-251-835-60-93; E-mail: [email protected]) 0015-0282/98/$19.00 PII S0015-0282(98)00154-X
The interference of sperm surface antibodies with sperm motility, sperm-mucus interaction, and fertilization/pregnancy rates (PRs) is well documented (1). Because immunosuppressive therapy for men with sperm antibodies fails to improve PRs (2), many patients are advised that assisted reproduction, in particular intracytoplasmic sperm injection (ICSI), represents their best chance of achieving a pregnancy. However, it is not clear how this advice should take antibody levels into consideration. To obtain a basis for therapeutic decisions, we studied patients with positive sperm surface antibodies and registered spontaneous pregnancies in those patients without any specific treatment.
MATERIALS AND METHODS Among the patients attending the Institute of Reproductive Medicine for infertility between 1987 and 1991, we identified 376 of 1,189 men tested with positive sperm surface antibodies as detected by the mixed antiglobulin reaction (MAR) test. Patients who underwent corticosteroid treatment or whose partners presented with tubal infertility or
anovulation were excluded from the evaluation. The patients’ mean (6SD) age at admission was 34.2 6 6 years and that of their partners was 31.8 6 6.2 years. The duration of infertility at the time of diagnosis ranged from 1.0 to 9.3 years (mean 6 SD, 2.9 6 1.8 years). Information about pregnancies among women whose partners had sperm surface antibodies was obtained directly from the files of 56 couples who attended our center, and questionnaires were sent to the remaining 320 patients. We received answers from 151 patients; thus, 207 couples could be evaluated. In 50 of these couples, assisted reproductive techniques were performed. Therefore, the natural course of the disease could be followed in 157 couples. Semen analysis and MAR tests for IgG and IgA antibodies were performed according to World Health Organization guidelines (3).
RESULTS In the 157 couples, 61 pregnancies occurred over the course of 6 years after diagnosis; i.e., pregnancies occurred without specific treat355
FIGURE 1 Cumulative pregnancy rates (number of couples achieving a spontaneous pregnancy/total number of couples in percent) over time for men with seminal antibodies on 10%–50% (F), 50%–90% (■), and .90% (Œ) of their sperm. (A), IgG antisperm antibodies; (B), IgA antisperm antibodies.
ment among couples in which 38.9% of the male partners were found to have sperm surface antibody concentrations of .10%. However, when antibody rates were correlated with PRs, a strong negative correlation was found. When categorizing the patients according to sperm-bound antibody levels, we found the following spontaneous PRs. IgG 10%– 49%: 50/115 or 43.5%, 50%–90%: 8/23 or 34.8%, and .90%:3/19 or 15.8%; IgA 10%– 49%: 16/29 or 55.2%, 50%– 89%: 6/17 or 35.3%, and .90%: 1/8 or 12.5%. Each category was significantly different from the others (P ,0.05 by x2 and Fisher’s exact tests).
concentrations. The higher the antibody concentrations, the lower the PRs and the longer it takes to achieve a pregnancy. Analysis of the data suggests that patients should be categorized and given therapeutic advice according to antibody percentages. Patients with IgG or IgA levels of ,50% should be informed about the relatively good chances of inducing a pregnancy spontaneously. Patients with rates of .50% should consider assisted reproduction techniques, whereas ICSI should be recommended for patients with rates of .90% (4)
The cumulative PRs over time are shown in Figure 1. When antibody rates were correlated with sperm parameters, only sperm motility was significantly lower in patients with IgG or IgA concentrations of .90%. None of the other parameters were correlated with antibody levels. All patients had IgG antibodies, but not all of them had IgA antibodies.
References
DISCUSSION The results confirm that sperm surface antibodies interfere with spontaneous pregnancy in relation to antibody
356
Abshagen et al.
Communications-in-brief
1. Collins JA, Burrows EA, Yeo J, Young Lai EV. Frequency and predictive value of antisperm antibodies among infertile couples. Hum Reprod 1993;8:592– 8. 2. Bals-Pratsch M, Do¨ren M, Karbowski B, Schneider HPG, Nieschlag E. Cyclic corticoid immunosuppression is unsuccessful in the treatment of sperm antibody related male infertility: a controlled study. Hum Reprod 1992;7:99 –104. 3. World Health Organization. Laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 3rd ed. New York. Cambridge University Press, 1992:3– 42. 4. Clarke GN, Bourne H, Baker HW. Intracytoplasmic sperm injection for treating infertility associated with sperm autoimmunity. Fertil Steril 1997;68:112–7.
Vol. 70, No. 2, August 1998
COMMUNICATIONS-IN-BRIEF
Influence of sperm surface antibodies on spontaneous pregnancy rates Katrin Abshagen, M.D., Hermann M. Behre, M.D., Trevor G. Cooper, Ph.D., and Eberhard Nieschlag, M.D. Institute of Reproductive Medicine, University of Mu¨nster, Mu¨nster, Germany
Objective: To determine the rates of spontaneous pregnancies among women whose infertile male partners had sperm surface antibodies. Design: Retrospective analysis. Setting: Infertility clinic of a university referral center. Patient(s): One hundred fifty-seven infertile couples; the male partner had IgA and/or IgG sperm surface antibody concentrations of .10%. Intervention: None. Main Outcome Measure(s): Spontaneous pregnancy rates (PRs) over 6 years. Result(s): Spontaneous PRs correlated negatively with antibody concentrations. Conclusion(s): Although the chance of spontaneous pregnancy among women whose partners had sperm antibody concentrations of ,50% was good, intracytoplasmic sperm injection should be recommended to patients with concentrations of .90%. (Fertil Sterilt 1998;70:355– 6. ©1998 by American Society for Reproductive Medicine.) Key Words: Sperm surface antibodies, pregnancy rates
Received October 8, 1997; revised and accepted March 23, 1998. Supported by the Interdisciplinary Clinical Research Center (IKF), Medical Faculty, University of Mu¨nster, Mu¨nster, Germany. Reprint requests: Eberhard Nieschlag, M.D., Institute of Reproductive Medicine, University of Mu¨nster, Domagkstraße 11, D-48129 Mu¨nster, Germany (FAX: 49-251-835-60-93; E-mail: [email protected]) 0015-0282/98/$19.00 PII S0015-0282(98)00154-X
The interference of sperm surface antibodies with sperm motility, sperm-mucus interaction, and fertilization/pregnancy rates (PRs) is well documented (1). Because immunosuppressive therapy for men with sperm antibodies fails to improve PRs (2), many patients are advised that assisted reproduction, in particular intracytoplasmic sperm injection (ICSI), represents their best chance of achieving a pregnancy. However, it is not clear how this advice should take antibody levels into consideration. To obtain a basis for therapeutic decisions, we studied patients with positive sperm surface antibodies and registered spontaneous pregnancies in those patients without any specific treatment.
MATERIALS AND METHODS Among the patients attending the Institute of Reproductive Medicine for infertility between 1987 and 1991, we identified 376 of 1,189 men tested with positive sperm surface antibodies as detected by the mixed antiglobulin reaction (MAR) test. Patients who underwent corticosteroid treatment or whose partners presented with tubal infertility or
anovulation were excluded from the evaluation. The patients’ mean (6SD) age at admission was 34.2 6 6 years and that of their partners was 31.8 6 6.2 years. The duration of infertility at the time of diagnosis ranged from 1.0 to 9.3 years (mean 6 SD, 2.9 6 1.8 years). Information about pregnancies among women whose partners had sperm surface antibodies was obtained directly from the files of 56 couples who attended our center, and questionnaires were sent to the remaining 320 patients. We received answers from 151 patients; thus, 207 couples could be evaluated. In 50 of these couples, assisted reproductive techniques were performed. Therefore, the natural course of the disease could be followed in 157 couples. Semen analysis and MAR tests for IgG and IgA antibodies were performed according to World Health Organization guidelines (3).
RESULTS In the 157 couples, 61 pregnancies occurred over the course of 6 years after diagnosis; i.e., pregnancies occurred without specific treat355
FIGURE 1 Cumulative pregnancy rates (number of couples achieving a spontaneous pregnancy/total number of couples in percent) over time for men with seminal antibodies on 10%–50% (F), 50%–90% (■), and .90% (Œ) of their sperm. (A), IgG antisperm antibodies; (B), IgA antisperm antibodies.
ment among couples in which 38.9% of the male partners were found to have sperm surface antibody concentrations of .10%. However, when antibody rates were correlated with PRs, a strong negative correlation was found. When categorizing the patients according to sperm-bound antibody levels, we found the following spontaneous PRs. IgG 10%– 49%: 50/115 or 43.5%, 50%–90%: 8/23 or 34.8%, and .90%:3/19 or 15.8%; IgA 10%– 49%: 16/29 or 55.2%, 50%– 89%: 6/17 or 35.3%, and .90%: 1/8 or 12.5%. Each category was significantly different from the others (P ,0.05 by x2 and Fisher’s exact tests).
concentrations. The higher the antibody concentrations, the lower the PRs and the longer it takes to achieve a pregnancy. Analysis of the data suggests that patients should be categorized and given therapeutic advice according to antibody percentages. Patients with IgG or IgA levels of ,50% should be informed about the relatively good chances of inducing a pregnancy spontaneously. Patients with rates of .50% should consider assisted reproduction techniques, whereas ICSI should be recommended for patients with rates of .90% (4)
The cumulative PRs over time are shown in Figure 1. When antibody rates were correlated with sperm parameters, only sperm motility was significantly lower in patients with IgG or IgA concentrations of .90%. None of the other parameters were correlated with antibody levels. All patients had IgG antibodies, but not all of them had IgA antibodies.
References
DISCUSSION The results confirm that sperm surface antibodies interfere with spontaneous pregnancy in relation to antibody
356
Abshagen et al.
Communications-in-brief
1. Collins JA, Burrows EA, Yeo J, Young Lai EV. Frequency and predictive value of antisperm antibodies among infertile couples. Hum Reprod 1993;8:592– 8. 2. Bals-Pratsch M, Do¨ren M, Karbowski B, Schneider HPG, Nieschlag E. Cyclic corticoid immunosuppression is unsuccessful in the treatment of sperm antibody related male infertility: a controlled study. Hum Reprod 1992;7:99 –104. 3. World Health Organization. Laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 3rd ed. New York. Cambridge University Press, 1992:3– 42. 4. Clarke GN, Bourne H, Baker HW. Intracytoplasmic sperm injection for treating infertility associated with sperm autoimmunity. Fertil Steril 1997;68:112–7.
Vol. 70, No. 2, August 1998