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Effects of a pure antiandrogen on gonadotropin secretion in normal women and in polycystic ovarian disease
200
Citations from the Literature
Gestational diabetes mellitus: pregnancy? Philipson EH; Super DM
Does it recur in subsequent
Department of Obstetrics and Gynecology, Cleveland Metropolitan General Hospital, Cleveland, OH 44109; USA American Journal of Obstetrics and Gynecology/l60/6 (1324 -1331)/1989/ The recurrence of glucose intolerance was examined in 36 women with an index pregnancy complicated by gestational diabetes who received antepartum care at the same institution because of a subsequent pregnancy. Standard oral or intravenous glucose tolerance tests were used to document glucose intolerance or gestational diabetes. Twenty patients had gestational diabetes in the subsequent pregnancy, whereas one third of the patients tested did not demonstrate an abnormality of carbohydrate metabolism. The patients with consecutive pregnancies by gestational diabetes were heavier and were delivered of heavier neonates than the patients who did not develop gestational diabetes again. Unlike the nondiabetic group, the patients who remained gestationally diabetic weighed significantly more in the subsequent pregnancy than in the index pregnancy. These results indicate that patients with gestational diabetes should be tested in subsequent pregnancies because of the impact of gestational diabetes on birth weight. However, these results also suggest that the glucose tolerance test may not be a reliable test for the detection of abnormal carbohydrate metabolism.
FERTILITY AND STERILITY The effect of gonadotropin
suppression on the induction ovulation in premature ovarian failure patients
of
Surrey ES; Cedars MI Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of California Los Angeles School of Medicine, Los Angeles, CA; USA Fertility and Sterility/SZ/l (36-41)/1989/ Ovulation induction in patients with hypergonadotropic premature ovarian failure is rarely successful. The authors have attempted to reproduce the results of recent case reports that suggest that ovulation and pregnancy can be successfully achieved when estrogen therapy precedes or coincides with ovarian stimulation with human menopausal gonadotropins (hMG). Fourteen patients with idiopathic premature ovarian failure underwent gonadotropin suppression and attempted ovulation induction with at least one of three regimens, which were as follows: (1) Group A: estrogen-induced suppression followed by hMG stimulation (n = 4). (2) Group B: estrogeninduced suppression followed by hMG stimulation with concomitant estrogen therapy (n = 10). (3) Group C: gonadotropin-releasing hormone agonist-induced gonadotropin suppression followed by concomitant hMG stimulation (n = 6). Despite complete gonadotropin suppression and highdose hMG therapy in all three groups, ovulation occurred in only a single patient in group C. Pregnancy did not ensue. These data fail to corroborate previous case reports.
Factors influencing neonatal morbidity in gestational diabetic pregnancy
Nordlander E; Hanson U; Persson B Department of Obstetrics and Gynecology, Karolinska Hospital, S-104 01 Stockholm; Sweden British Journal of Obstetrics and Gynaecology/96/6 (671678)/1989/ The influence of obstetric factors and indices of maternal blood glucose control on neonatal morbidity was examined in 261 women with gestational diabetes. A reference group of 218 women, matched for age and day of delivery, within 1 week, was used for comparison. Perinatal morbidity was significantly more frequent in the gestational diabetic pregnancies (23%) than in the reference group (13%), whereas the occurrence of large-for-gestational-age infants was not different between the groups. Infants born to women with gestational diabetes were categorized to a no-morbidity group (n = 200) and a morbidity group (n = 61). The group with morbidity had significantly shorter gestational age at delivery, higher frequency of caesarean section, higher maternal pre-pregnancy weight and higher area under the glucose tolerance curve. There was no significant difference in third-trimester blood glucose between the groups. Discriminant analysis revealed that the most significant influence on neonatal morbidity was gestational age at delivery. After correction for this factor the only factor with added significance for neonatal morbidity was maternal prepregnancy weight. The present study clearly illustrates that other factors beside blood glucose control are of importance for neonatal outcome in gestational diabetic pregnancy. Int J Gynecol Obstet 31
Effects of a pure antiandrogen on gonadotropin normal women and in polycystic ovarian disease
secretion in
Couzinet B; Thomas G; Thalabard JC; Brailly S; Schaison G Service d’Endocrinologie et des Maladies de la Reproduction, Hopital Bieetre, 94270 Kremlin-Bicetre; France Fertility and Sterility/SZ/l (42--50)/1989/ To assess the role of androgens in gonadotropin regulation in women, we studied the effects of a pure nonsteroidal antiandrogen, Anandron (Cassenne, Paris, France). Nine normally cycling women (group 1) with acne and/or seborrhoea and nine patients with polycystic ovarian disease (PCOD) (group 2) received Anandron (100 mg twice a day) and a placebo. Both treatments were administered orally, in a cross-over randomized design, for two consecutive cycles (group 1) or months (group 2) separated by one cycle or 1 month. Luteinizing hormone (LH) pulse frequency and amplitude (cluster analysis), basal and gonadotropin-releasing hormone (GnRH)-stimulated plasma LH/follicle-stimulating hormone (FSH) levels were determined on day 5 of each treatment or placebo cycle. On days 5, 10, 20 and 24 each cycle or month, plasma estradiol (EC*,), estrone (EC,,), testosterone (T), dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone sulfate (DHAS), sex hormone-binding globulin (SHBG) levels, and urinary androstanediol glucuronide (3 alpha-diol G) were measured. Plasma progesterone (P) levels were determined on days 20 and 24 of each cycle (group 1) and on days 5, 10, 20 and 24 (group 2). In both groups, seborrhoea and acne
Citations from the Literature decreased markedly within the first month and practically disappeared after 2 months of Anandron treatment. No adverse side effects were reported. None of the normal patients had any disturbance of menstrual cycles as assessed by basal body temperature shift, ultrasonography and plasma P levels. In PCOD patients, cycles remained anovulatory. Anandron, which interacts only with the androgen receptor, induced no significant change in the mean levels, frequency, or amplitude of LH pulses or in LH and FSH responsiveness to GnRH in either group. Plasma concentrations of Eu,, E,,,, T, DHT, A, DHAS, and urinary 3 alpha-diol G were not modified by Anandron when compared with placebo cycles. Plasma SHBG did not change in normal women, but increased significantly in PCOD. In summary, this study adds further support to the hypothesis that androgens (apart from their aromatization to estrogens) do not directly play a role in gonadotropin regulation in normal women and in the distortion of gonadotropin secretion in PCOD.
Genetic analysis of DNA from single human oocytes: A model for preimplantation diagnosis of cystic fibrosis
Coutelle C; Williams C; Handyside A; Hardy K; Winston R; Williamson R Department of Human Molecular Genetics, Central Institute of Molecular Biology, Academy of Sciences of the German Democratic Republic, 1115 Berlin-Buch; German Democratic Republic BR. MED. J/298/6690(22-24)/1989/ Gene sequences in human oocytes were studied to investigate the possibility of diagnosing inherited or sporadic genetic disease before implantation after in vitro fertilisation. By specific amplification the possibility of analysing the DNA from single human oocytes for a specific gene was shown, and genotypes for markers closely linked to cystic fibrosis and Duchenne muscular dystrophy were determined. Single oocytes were used to approximate the total amount of DNA present in a single cell taken for biopsy from a 4-16 cell blastocyst. With a new technique for specific DNA amplification, the polymerase chain reaction, these data can be obtained within several hours of cell isolation. Extreme care must be taken to avoid any contamination of the sample with DNA from other sources. With this technique genotyping for single gene disorders is feasible with an accuracy and on a time scale that would allow implantation of the zygote after in vitro fertilisation without freezing.
Reproductive failure because of autoantibodies: infertility and pregnancy wastage
Unexplained
Gleicher N; El-Roeiy A; Confino E; Friberg J Department of Obstetrics and Gynecology, Mount Sinai Hospital Medical Center, Chicago, IL 60608; USA American Journal of Obstetrics and Gynecology/l60/6 (1376 -1385)/1989/ Abnormal polyclonal B cell activation has been demonstrated in patients with endometriosis. To determine whether the noted B cell abnormalities were primarily a feature of the
201
disease endometriosis or its manifestations of infertility and pregnancy wastage, we investigated antibody profiles in 26 female patients with unexplained infertility (group A) and 24 patients with unexplained pregnancy wastage (group B) but without documented endometriosis. Group A and B patients exhibited an unusual incidence of gammopathies (10 of 26 patients in group A and 11 of 24 in group B), with a majority representing immunoglobulin M gammopathies. Mean immunoglobulin M values were significantly elevated in both groups (P < 0.03 and P < 0.05, respectively Student t-test), whereas immunoglobulin G was significantly increased only among group B patients (P < 0.05, Student t-test). Lupud anticoagulant by tissue thromboblastin inhibition test was abnormally elevated in 2 of 26 group A and 2 of 24 group B patients. Activated partial thromboplastin time values were abnormal in only 3 of 26 group A and 2 of 24 group B women. Immunoglobulin G, immunoglobulin M, and immunoglobulin A autoantibodies to two phospholipid antigens, five histones, and four polynucleotide autoantibodies were detected in 23 of 26 (88%) group A patients and 17 of 24 (70.8%) group B patients. We conclude that some patients with unexplained infertility and pregnancy wastage suffer from polyclonal B cell activation. It is therefore tempting to speculate that autoantibody abnormalities may be causally related to infertility and pregnancy loss.
Effect of peritoneal fluid on sperm motility distribution using objective measurements
and velocity
Soldati G; Piffaretti-Yanez A; Campana A; Marchini M; Luerti M; Balerna M Andrology Laboratory, Gynaecological Endocrinology Unit, La Carita Hospital, 6600 Locarno; Switzerland Fertility and Sterility/52/i (113- 119)/1989/ The aim of this study was to analyze in vitro the effect(s) of peritoneal fluid (PF) on sperm motility. Seventy PFs obtained during laparoscopy were tested on motile-rich sperm suspensions. Proportion of motile sperm and velocity distribution were evaluated by multiple-exposure photography technique. At time (t) = 0, PFs increased both sperm parameters as compared with control (P < 0.01). Maximum effect was observed at t = 5 hours: 32 (45%) PFs increased and 5 (7%) decreased the proportion of motile sperm, while 8 (11 Vo) PFs increased and 4 (6Vo)decreased sperm velocity. No correlation was found between a particular infertile group and a definite negative effect. However, 70% of PFs from fertile women maintained or increased the proportion of motile sperm at t = 5 hours, compared with 36% in the total infertile group. Comparison of the sperm motility effect(s) of a given PF on different ejaculates revealed that the effects observed also were influenced by the sperm sample tested. In conclusion, PFs can maintain or increase the motility of spermatozoa as function of time. However, some PFs can inhibit sperm motility and these effect(s) can be influenced by the sperm sample.
Int
J
Gynecol
Obstet
31
Citations from the Literature
Gestational diabetes mellitus: pregnancy? Philipson EH; Super DM
Does it recur in subsequent
Department of Obstetrics and Gynecology, Cleveland Metropolitan General Hospital, Cleveland, OH 44109; USA American Journal of Obstetrics and Gynecology/l60/6 (1324 -1331)/1989/ The recurrence of glucose intolerance was examined in 36 women with an index pregnancy complicated by gestational diabetes who received antepartum care at the same institution because of a subsequent pregnancy. Standard oral or intravenous glucose tolerance tests were used to document glucose intolerance or gestational diabetes. Twenty patients had gestational diabetes in the subsequent pregnancy, whereas one third of the patients tested did not demonstrate an abnormality of carbohydrate metabolism. The patients with consecutive pregnancies by gestational diabetes were heavier and were delivered of heavier neonates than the patients who did not develop gestational diabetes again. Unlike the nondiabetic group, the patients who remained gestationally diabetic weighed significantly more in the subsequent pregnancy than in the index pregnancy. These results indicate that patients with gestational diabetes should be tested in subsequent pregnancies because of the impact of gestational diabetes on birth weight. However, these results also suggest that the glucose tolerance test may not be a reliable test for the detection of abnormal carbohydrate metabolism.
FERTILITY AND STERILITY The effect of gonadotropin
suppression on the induction ovulation in premature ovarian failure patients
of
Surrey ES; Cedars MI Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of California Los Angeles School of Medicine, Los Angeles, CA; USA Fertility and Sterility/SZ/l (36-41)/1989/ Ovulation induction in patients with hypergonadotropic premature ovarian failure is rarely successful. The authors have attempted to reproduce the results of recent case reports that suggest that ovulation and pregnancy can be successfully achieved when estrogen therapy precedes or coincides with ovarian stimulation with human menopausal gonadotropins (hMG). Fourteen patients with idiopathic premature ovarian failure underwent gonadotropin suppression and attempted ovulation induction with at least one of three regimens, which were as follows: (1) Group A: estrogen-induced suppression followed by hMG stimulation (n = 4). (2) Group B: estrogeninduced suppression followed by hMG stimulation with concomitant estrogen therapy (n = 10). (3) Group C: gonadotropin-releasing hormone agonist-induced gonadotropin suppression followed by concomitant hMG stimulation (n = 6). Despite complete gonadotropin suppression and highdose hMG therapy in all three groups, ovulation occurred in only a single patient in group C. Pregnancy did not ensue. These data fail to corroborate previous case reports.
Factors influencing neonatal morbidity in gestational diabetic pregnancy
Nordlander E; Hanson U; Persson B Department of Obstetrics and Gynecology, Karolinska Hospital, S-104 01 Stockholm; Sweden British Journal of Obstetrics and Gynaecology/96/6 (671678)/1989/ The influence of obstetric factors and indices of maternal blood glucose control on neonatal morbidity was examined in 261 women with gestational diabetes. A reference group of 218 women, matched for age and day of delivery, within 1 week, was used for comparison. Perinatal morbidity was significantly more frequent in the gestational diabetic pregnancies (23%) than in the reference group (13%), whereas the occurrence of large-for-gestational-age infants was not different between the groups. Infants born to women with gestational diabetes were categorized to a no-morbidity group (n = 200) and a morbidity group (n = 61). The group with morbidity had significantly shorter gestational age at delivery, higher frequency of caesarean section, higher maternal pre-pregnancy weight and higher area under the glucose tolerance curve. There was no significant difference in third-trimester blood glucose between the groups. Discriminant analysis revealed that the most significant influence on neonatal morbidity was gestational age at delivery. After correction for this factor the only factor with added significance for neonatal morbidity was maternal prepregnancy weight. The present study clearly illustrates that other factors beside blood glucose control are of importance for neonatal outcome in gestational diabetic pregnancy. Int J Gynecol Obstet 31
Effects of a pure antiandrogen on gonadotropin normal women and in polycystic ovarian disease
secretion in
Couzinet B; Thomas G; Thalabard JC; Brailly S; Schaison G Service d’Endocrinologie et des Maladies de la Reproduction, Hopital Bieetre, 94270 Kremlin-Bicetre; France Fertility and Sterility/SZ/l (42--50)/1989/ To assess the role of androgens in gonadotropin regulation in women, we studied the effects of a pure nonsteroidal antiandrogen, Anandron (Cassenne, Paris, France). Nine normally cycling women (group 1) with acne and/or seborrhoea and nine patients with polycystic ovarian disease (PCOD) (group 2) received Anandron (100 mg twice a day) and a placebo. Both treatments were administered orally, in a cross-over randomized design, for two consecutive cycles (group 1) or months (group 2) separated by one cycle or 1 month. Luteinizing hormone (LH) pulse frequency and amplitude (cluster analysis), basal and gonadotropin-releasing hormone (GnRH)-stimulated plasma LH/follicle-stimulating hormone (FSH) levels were determined on day 5 of each treatment or placebo cycle. On days 5, 10, 20 and 24 each cycle or month, plasma estradiol (EC*,), estrone (EC,,), testosterone (T), dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone sulfate (DHAS), sex hormone-binding globulin (SHBG) levels, and urinary androstanediol glucuronide (3 alpha-diol G) were measured. Plasma progesterone (P) levels were determined on days 20 and 24 of each cycle (group 1) and on days 5, 10, 20 and 24 (group 2). In both groups, seborrhoea and acne
Citations from the Literature decreased markedly within the first month and practically disappeared after 2 months of Anandron treatment. No adverse side effects were reported. None of the normal patients had any disturbance of menstrual cycles as assessed by basal body temperature shift, ultrasonography and plasma P levels. In PCOD patients, cycles remained anovulatory. Anandron, which interacts only with the androgen receptor, induced no significant change in the mean levels, frequency, or amplitude of LH pulses or in LH and FSH responsiveness to GnRH in either group. Plasma concentrations of Eu,, E,,,, T, DHT, A, DHAS, and urinary 3 alpha-diol G were not modified by Anandron when compared with placebo cycles. Plasma SHBG did not change in normal women, but increased significantly in PCOD. In summary, this study adds further support to the hypothesis that androgens (apart from their aromatization to estrogens) do not directly play a role in gonadotropin regulation in normal women and in the distortion of gonadotropin secretion in PCOD.
Genetic analysis of DNA from single human oocytes: A model for preimplantation diagnosis of cystic fibrosis
Coutelle C; Williams C; Handyside A; Hardy K; Winston R; Williamson R Department of Human Molecular Genetics, Central Institute of Molecular Biology, Academy of Sciences of the German Democratic Republic, 1115 Berlin-Buch; German Democratic Republic BR. MED. J/298/6690(22-24)/1989/ Gene sequences in human oocytes were studied to investigate the possibility of diagnosing inherited or sporadic genetic disease before implantation after in vitro fertilisation. By specific amplification the possibility of analysing the DNA from single human oocytes for a specific gene was shown, and genotypes for markers closely linked to cystic fibrosis and Duchenne muscular dystrophy were determined. Single oocytes were used to approximate the total amount of DNA present in a single cell taken for biopsy from a 4-16 cell blastocyst. With a new technique for specific DNA amplification, the polymerase chain reaction, these data can be obtained within several hours of cell isolation. Extreme care must be taken to avoid any contamination of the sample with DNA from other sources. With this technique genotyping for single gene disorders is feasible with an accuracy and on a time scale that would allow implantation of the zygote after in vitro fertilisation without freezing.
Reproductive failure because of autoantibodies: infertility and pregnancy wastage
Unexplained
Gleicher N; El-Roeiy A; Confino E; Friberg J Department of Obstetrics and Gynecology, Mount Sinai Hospital Medical Center, Chicago, IL 60608; USA American Journal of Obstetrics and Gynecology/l60/6 (1376 -1385)/1989/ Abnormal polyclonal B cell activation has been demonstrated in patients with endometriosis. To determine whether the noted B cell abnormalities were primarily a feature of the
201
disease endometriosis or its manifestations of infertility and pregnancy wastage, we investigated antibody profiles in 26 female patients with unexplained infertility (group A) and 24 patients with unexplained pregnancy wastage (group B) but without documented endometriosis. Group A and B patients exhibited an unusual incidence of gammopathies (10 of 26 patients in group A and 11 of 24 in group B), with a majority representing immunoglobulin M gammopathies. Mean immunoglobulin M values were significantly elevated in both groups (P < 0.03 and P < 0.05, respectively Student t-test), whereas immunoglobulin G was significantly increased only among group B patients (P < 0.05, Student t-test). Lupud anticoagulant by tissue thromboblastin inhibition test was abnormally elevated in 2 of 26 group A and 2 of 24 group B patients. Activated partial thromboplastin time values were abnormal in only 3 of 26 group A and 2 of 24 group B women. Immunoglobulin G, immunoglobulin M, and immunoglobulin A autoantibodies to two phospholipid antigens, five histones, and four polynucleotide autoantibodies were detected in 23 of 26 (88%) group A patients and 17 of 24 (70.8%) group B patients. We conclude that some patients with unexplained infertility and pregnancy wastage suffer from polyclonal B cell activation. It is therefore tempting to speculate that autoantibody abnormalities may be causally related to infertility and pregnancy loss.
Effect of peritoneal fluid on sperm motility distribution using objective measurements
and velocity
Soldati G; Piffaretti-Yanez A; Campana A; Marchini M; Luerti M; Balerna M Andrology Laboratory, Gynaecological Endocrinology Unit, La Carita Hospital, 6600 Locarno; Switzerland Fertility and Sterility/52/i (113- 119)/1989/ The aim of this study was to analyze in vitro the effect(s) of peritoneal fluid (PF) on sperm motility. Seventy PFs obtained during laparoscopy were tested on motile-rich sperm suspensions. Proportion of motile sperm and velocity distribution were evaluated by multiple-exposure photography technique. At time (t) = 0, PFs increased both sperm parameters as compared with control (P < 0.01). Maximum effect was observed at t = 5 hours: 32 (45%) PFs increased and 5 (7%) decreased the proportion of motile sperm, while 8 (11 Vo) PFs increased and 4 (6Vo)decreased sperm velocity. No correlation was found between a particular infertile group and a definite negative effect. However, 70% of PFs from fertile women maintained or increased the proportion of motile sperm at t = 5 hours, compared with 36% in the total infertile group. Comparison of the sperm motility effect(s) of a given PF on different ejaculates revealed that the effects observed also were influenced by the sperm sample tested. In conclusion, PFs can maintain or increase the motility of spermatozoa as function of time. However, some PFs can inhibit sperm motility and these effect(s) can be influenced by the sperm sample.
Int
J
Gynecol
Obstet
31