EFFECTS OF KALLIKREIN ON SPERM MOTILITY, CAPILLARY TUBE TEST, AND PREGNANCY RATE IN AN AIH PROGRAM
Syst Biol Reprod Med Downloaded from informahealthcare.com by RMIT University on 03/13/15 For personal use only.
I. GERHARD, B. ROTH, W.EGGERT-KRUSE, and B. RUNNEBAUM From 1984 to 1986, 172 couples were enrolled in an artificial insemination homologous (AM)program, because of negative postcoital test, fair F’T,positive FT with unexplained infertility, and impotentia coeundi. Patients were randomly assigned to the following procedures: AIH with native semen (N, n 68), washed sperm (V, n 50), semen mixed with kallikrein (K, 5 IE/ml semen, n 45), and timed intercourse. The overall pregnancy rate (PR) was 22% per couple (13% inseminations, 9% spontaneous). PR from insemination (spontaneous) was 13% (8), 13% (13), 23% (0) in F’T negative, fair, and positive patients, respectively, and 18% (9), 13% (7), and 11% (9) in AIH groups N, V, and K. Among in vitro studies with K added semen, an improvement of sperm motility was demonstrated in half of the specimens. In the capillary tube test (CTT), with wives’ cervical mucus, a deterioration was more frequently seen than an improvement after 2 h, independent of the early effect of K in semen, K induced changes of C’IT were less pronounced when donors’ cervical mucus was used. The results of the in vitro studies offer an explanation for the low PR in the AIH program with K.
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Key Words: Kallikrein; Sperm; Motility; Pregnancy; Semen; AIH; Insemination; Postcoital test; Capillary test tube.
INTRODUCTION Kallikrein (K) is a proteinase that is supposed to improve sperm motility when administered orally or intramuscularily to men with asthenozoospermia. After addition of K to semen samples invitro, an increase of progressive sperm motility was observed by several authors [11, 2 1, 26, 331. In addition, K improved sperm motility in frozen semen samples [14, 301. Therefore, this supposed positive effect of K was used in artificial insemination homologous (AIH). AIH is usually applied in couples with impaired quality of cervical mucus, oligoasthenozoospermia, or immunological infertility [ l , 8, 17, 19, 20, 351. Dependent on the group of patients chosen, pregnancy rate (PR) varied significantly. It was usually below 20% in couples
Received August 16, 1989; accepted September 1989. From the Department of Gynecological Endocrinology, Women’s Hospital, University of Heidelberg, Voa-Str. 9, FRG . Presented in part at the ESCO VIII Joint Congress, Budapest 1987. Address reprint requests to: Prof. Dr. I. Gerhard, Department of Gynecological Endocrinology, Women’s Hospital, University of Heidelberg, Voa-Str. 9, FRG, Heidelberg, West Germany. ARCHIVES OF ANDROLOGY 24:129-145 (1990) Copyright 0 1990 by Hemisphere Publishing Corporation
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who were inseminated because of a male factor [ l , 16, 17, 351. Therefore, it was the aim of this study to improve pregnancy rates with AIH by the addition of K to semen specimens and to examine the influence of K on sperm motility and functional sperm capacity in capillary tube tests (CTT).
Syst Biol Reprod Med Downloaded from informahealthcare.com by RMIT University on 03/13/15 For personal use only.
MATERIALS AND METHODS From 1984 to 1986, 172 couples were enrolled in an insemination program at the Infertility Unit of the Department of Gynecology and Obstetrics at the University of Heidelberg. Mean duration of infertility was 6 years (range: 1 to 15 years). Mean age of the women was 29 years; of the men, 32 years. In 817 treatment cycles, 997 inseminations were performed (mean number of cycles: 5.8; range: 1 to 13). Extensive hormonal analyses had been carried out on all women, and treatment performed whenever necessary, so that all women exhibited ovulatory cycles documented by basal body temperature (BBT) dating and endometrial biopsy. (For further details concerning the hormonal checks and adequate therapy see reference 10.) Tuba1 patency was proven in all women by hysterosalpingography and/or laparoscopy. In the men, at least two semen analyses had been performed. In cases of reduced sperm parameters, the men were systemically treated with K, androgens, tamoxifen, gonadotropins, and whatever necessary. If microbial screening revealed potentially pathogenic bacteria in semen or cervical mucus, specific therapy was applied based on antimicrobial susceptibility testing, as described previously [6, 71. Sperm analysis was performed according to World Health Organization (WHO) criteria. In brief, in our patients, median of semen volume was 2.5 ml (range: 0.3 to 8.5); median sperm count 38 millionlml (range: 1 to 235); percentage progressive motility-median 30% (range: 5 to 80); immobile sperm-median 50 (10 to 95). Postcoital testing (PT) was performed in all but five couples who were inseminated because of an impotentia coeundi. It was evaluated on the day of presumed ovulation (by BBT chart, cervical mucus, and ultrasound) 8 to 12 h after intercourse, following a 5-day period of abstinence. Cervical mucus was gently aspirated and progressively motile spermatozoa were counted microscopically in a minimum of 10 fields; the mean was taken. PT was defined as normal-27 progressive motile spermatozoa/high power field (HPF); fair (2 to 6 progressive motile spermatozoa/HPF), and negative (
Syst Biol Reprod Med Downloaded from informahealthcare.com by RMIT University on 03/13/15 For personal use only.
I. GERHARD, B. ROTH, W.EGGERT-KRUSE, and B. RUNNEBAUM From 1984 to 1986, 172 couples were enrolled in an artificial insemination homologous (AM)program, because of negative postcoital test, fair F’T,positive FT with unexplained infertility, and impotentia coeundi. Patients were randomly assigned to the following procedures: AIH with native semen (N, n 68), washed sperm (V, n 50), semen mixed with kallikrein (K, 5 IE/ml semen, n 45), and timed intercourse. The overall pregnancy rate (PR) was 22% per couple (13% inseminations, 9% spontaneous). PR from insemination (spontaneous) was 13% (8), 13% (13), 23% (0) in F’T negative, fair, and positive patients, respectively, and 18% (9), 13% (7), and 11% (9) in AIH groups N, V, and K. Among in vitro studies with K added semen, an improvement of sperm motility was demonstrated in half of the specimens. In the capillary tube test (CTT), with wives’ cervical mucus, a deterioration was more frequently seen than an improvement after 2 h, independent of the early effect of K in semen, K induced changes of C’IT were less pronounced when donors’ cervical mucus was used. The results of the in vitro studies offer an explanation for the low PR in the AIH program with K.
-
-
-
Key Words: Kallikrein; Sperm; Motility; Pregnancy; Semen; AIH; Insemination; Postcoital test; Capillary test tube.
INTRODUCTION Kallikrein (K) is a proteinase that is supposed to improve sperm motility when administered orally or intramuscularily to men with asthenozoospermia. After addition of K to semen samples invitro, an increase of progressive sperm motility was observed by several authors [11, 2 1, 26, 331. In addition, K improved sperm motility in frozen semen samples [14, 301. Therefore, this supposed positive effect of K was used in artificial insemination homologous (AIH). AIH is usually applied in couples with impaired quality of cervical mucus, oligoasthenozoospermia, or immunological infertility [ l , 8, 17, 19, 20, 351. Dependent on the group of patients chosen, pregnancy rate (PR) varied significantly. It was usually below 20% in couples
Received August 16, 1989; accepted September 1989. From the Department of Gynecological Endocrinology, Women’s Hospital, University of Heidelberg, Voa-Str. 9, FRG . Presented in part at the ESCO VIII Joint Congress, Budapest 1987. Address reprint requests to: Prof. Dr. I. Gerhard, Department of Gynecological Endocrinology, Women’s Hospital, University of Heidelberg, Voa-Str. 9, FRG, Heidelberg, West Germany. ARCHIVES OF ANDROLOGY 24:129-145 (1990) Copyright 0 1990 by Hemisphere Publishing Corporation
129
130
1. Gerhard et al.
who were inseminated because of a male factor [ l , 16, 17, 351. Therefore, it was the aim of this study to improve pregnancy rates with AIH by the addition of K to semen specimens and to examine the influence of K on sperm motility and functional sperm capacity in capillary tube tests (CTT).
Syst Biol Reprod Med Downloaded from informahealthcare.com by RMIT University on 03/13/15 For personal use only.
MATERIALS AND METHODS From 1984 to 1986, 172 couples were enrolled in an insemination program at the Infertility Unit of the Department of Gynecology and Obstetrics at the University of Heidelberg. Mean duration of infertility was 6 years (range: 1 to 15 years). Mean age of the women was 29 years; of the men, 32 years. In 817 treatment cycles, 997 inseminations were performed (mean number of cycles: 5.8; range: 1 to 13). Extensive hormonal analyses had been carried out on all women, and treatment performed whenever necessary, so that all women exhibited ovulatory cycles documented by basal body temperature (BBT) dating and endometrial biopsy. (For further details concerning the hormonal checks and adequate therapy see reference 10.) Tuba1 patency was proven in all women by hysterosalpingography and/or laparoscopy. In the men, at least two semen analyses had been performed. In cases of reduced sperm parameters, the men were systemically treated with K, androgens, tamoxifen, gonadotropins, and whatever necessary. If microbial screening revealed potentially pathogenic bacteria in semen or cervical mucus, specific therapy was applied based on antimicrobial susceptibility testing, as described previously [6, 71. Sperm analysis was performed according to World Health Organization (WHO) criteria. In brief, in our patients, median of semen volume was 2.5 ml (range: 0.3 to 8.5); median sperm count 38 millionlml (range: 1 to 235); percentage progressive motility-median 30% (range: 5 to 80); immobile sperm-median 50 (10 to 95). Postcoital testing (PT) was performed in all but five couples who were inseminated because of an impotentia coeundi. It was evaluated on the day of presumed ovulation (by BBT chart, cervical mucus, and ultrasound) 8 to 12 h after intercourse, following a 5-day period of abstinence. Cervical mucus was gently aspirated and progressively motile spermatozoa were counted microscopically in a minimum of 10 fields; the mean was taken. PT was defined as normal-27 progressive motile spermatozoa/high power field (HPF); fair (2 to 6 progressive motile spermatozoa/HPF), and negative (
