Selection of the dominant ovarian follicle and hormonal enhancement of the natural cycle.
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Female↗
Biomedical subjects
R S Schenken
Publications and source records attributed to R S Schenken.
Periovulatory hormonal dynamics: relationship of immunoassayable gonadotropins and ovarian steroids to the bioassayable luteinizing hormone surge in rhesus monkeys.
The relationship between ovarian steroids and LH during the midcycle gonadotropin surge is controversial. Recent demonstration of temporal and quantitative differences in immunoassayable LH (I-LH) and bioassayable LH (B-LH) at midcycle have further clouded this issue. To evaluate the relationship of I-LH, FSH, and ovarian steroids to the onset of the midcycle B-LH surge, blood samples were obtained from five chronically catheterized rhesus monkeys at 2-h intervals for 5-6 days. The plasma was assayed for FSH, LH, 17 beta-estradiol (E2), progesterone (P4), and 17 alpha-hydroxyprogesterone (17-OHP) by RIA and for LH by a rat interstitial cell testosterone in vitro bioassay. The initiation of the B-LH surge served as time zero (to) for the temporal analysis of changes in plasma hormone levels. The I-LH and FSH surges were initiated 6.4 +/- 2.2 h (mean +/- SEM) and 5.2 +/- 1.9 h, respectively, after the onset of the B-LH surge. Although the duration of the ascending limb of the surge was similar for B-LH, I-LH, and FSH, the mean +/- SEM total duration of the B-LH surge (34.5 +/- 3.5 h) was significantly longer (P less than 0.025) than those of I-LH (24.4 +/- 5.0 h) and FSH (27.6 +/- 2.3 h). Before the onset of the B-LH surge (to - 4 h), the ratio of B-H to I-LH was unity; however, during the acme of gonadotropin secretion (to + 12-16 h), the B-LH to I-LH ratio approached 6:1. Doubling times for B-LH, I-LH, and FSH were similar during the ascending phase of the surge. Plasma E2 concentrations increased continuously from to - 40 h to to, with a mean +/- SEM doubling time of 32.6 +/- 4.7 h. Peak E2 concentrations occurred within 6 h after the onset of the B-LH surge. Plasma P4 concentrations began to increase at to - 6 h in four monkeys and at to in one monkey. Plasma P4 concentration plateaued from to to to + 24 h, then increased rapidly, with a mean +/- SEM doubling time of 20.5 +/- 2.9 h. Although there were significant individual variations in plasma 17-OHP concentrations, a definite increase in 17-OHP occurred by to - 10 h, and peak concentrations occurred at to + 1 h.(ABSTRACT TRUNCATED AT 400 WORDS)
17-alpha-Hydroxyprogesterone↗
Progesterone and 17 alpha-hydroxyprogesterone advance the estrogen-induced bioassayable luteinizing hormone surge in castrate monkeys.
Recent studies have demonstrated marked disparities between bioassayable (BIO) versus radioimmunoassayable concentrations of luteinizing hormone (LH) at midcycle. Other studies in intact women and monkeys have indicated that progesterone (P) may facilitate estrogen induction of the preovulatory gonadotropin surges. We have combined the study of these observations as follows: long-term castrate female monkeys were given estradiol benzoate with and without subsequent P or 17 alpha-hydroxyprogesterone (17-OHP) injections. Plasma was collected during a selected 24-hour interval via a chronic indwelling femoral vein cannula. Initially, estrogen-negative feedback decreased the pulsatility and circulating levels of gonadotropins. P and 17-OHP treatment (after estradiol) hastened initiation of the BIO-LH surge by up to 8 hours. Although estrogen-positive feedback alone enhanced the biologic activity of LH, P and 17-OHP expedited the midcycle-like BIO-LH surges.
17-alpha-Hydroxyprogesterone↗
Etiology of infertility in monkeys with endometriosis: measurement of peritoneal fluid prostaglandins.
To study the relationship between peritoneal fluid prostaglandins and infertility associated with endometriosis, we autografted endometrial or adipose tissue to the pelvic peritoneum in 21 monkeys. Peritoneal washings were collected prior to tissue transplantation and during a subsequent laparotomy performed for biopsy of the implants. Monkeys were mated and peritoneal washings were collected during three subsequent cycles. The content of prostaglandin F2 alpha (PGF2 alpha) in adipose tissue autografts was significantly less (p less than 0.05) than in endometrial tissue autografts. The PGF2 alpha concentration in peritoneal fluid increased significantly (p less than 0.05) only in monkeys that developed moderate or severe endometriosis. Prostaglandin E levels in tissue autografts or peritoneal fluid were similar in all animals. Infertility in monkeys with endometriosis was associated with luteinized unruptured follicles, luteal phase defects, and pelvic adhesions. Although PGF2 alpha concentrations in peritoneal washings obtained during these cycles were increased in comparison with those of ovulatory cycles, the difference was not significant. A relationship between spontaneous abortion and prostaglandin concentrations in peritoneal fluid was not established.
Animals↗
Pulsatile progesterone secretion: its relevance to clinical evaluation of corpus luteum function.
Pulsatile progesterone (P) secretory patterns were characterized in rhesus macaques (n = 13) during the midluteal phase (cycle days 18 to 20) of the normal ovarian/menstrual cycle. Sixty high-amplitude (greater than 1 ng/ml) P pulses were observed during a total of 169 hours of sampling. Typically, P pulses had an ultradian periodicity of 2 hours and were independent of detectable luteinizing hormone (LH) and prolactin (PRL) pulses in 70% of instances. LH pulses were associated with a concomitant P and PRL pulse in 100% to 80% of occasions, respectively. Pulsatile P release was augmented by exogenous cynomolgus monkey LH and suppressed by administration of a gonadotropin-releasing hormone antagonist. Two individuals with apparently normal ovulation and once daily plasma P concentrations within the normal range demonstrated a nonpulsatile P profile. These findings encourage clinical investigations to characterize pulsatile P secretion in normal women and patients in whom corpus luteum dysfunction is suspected.
Animals↗
Etiology of infertility in monkeys with endometriosis: luteinized unruptured follicles, luteal phase defects, pelvic adhesions, and spontaneous abortions.
To elucidate the etiology of infertility due to endometriosis, we autografted endometrial or adipose tissue to the pelvic peritoneum of 21 cynomolgus monkeys. These primates were divided into five groups: control animals with adipose tissue autografts (n = 5), animals with microscopic endometriosis (n = 5), animals with mild endometriosis (n = 5), animals with moderate endometriosis (n = 4), and animals with severe endometriosis (n = 2). During three subsequent menstrual cycles, each animal underwent (1) serial assay of peripheral serum gonadotropins and steroids; (2) mating timed according to daily serum 17 beta-estradiol; and (3) laparotomy to document an ovulatory stigma. The chemical and term pregnancy rates were lower among monkeys with moderate or severe endometriosis, as compared with control animals. The impaired fertility in monkeys with endometriosis appeared to be mediated primarily by failure of follicular rupture and/or pelvic adhesions.
Abortion, Spontaneous↗
Ovulation induction using "pure" follicle-stimulating hormone in monkeys.
Recently we have demonstrated that administration of a "pure" follicle-stimulating hormone (FSH) preparation (Urofollitropin, Serono Laboratories, Inc., Randolph, MA) to normally cycling monkeys induces multiple follicular development. In these earlier studies, a spontaneous luteinizing hormone (LH) surge was uncommon; no attempt was made to induce ovulation with exogenous human chorionic gonadotropin (hCG). In this study, multiple follicular development and ovulation were induced in normally cycling monkeys by daily follicular phase administration of "pure" FSH followed by hCG. Short-term administration of "pure" FSH during the early or late follicular phase also induced multiple follicular development; however, multiple ovulations subsequent to a spontaneous LH surge never occurred. One monkey treated in the late follicular phase did demonstrate a spontaneous LH surge and single ovulation following late follicular phase FSH treatment. These findings suggest that administration of "pure" FSH alone, to enhance the natural ovarian cycle, may be useful for inducing multiple follicular development, but that ovulatory competence is usually dependent on exogenous LH/hCG.
Animals↗
Follicle-stimulating hormone increases ovarian vein nonsteroidal factors with gonadotropin-inhibiting activity.
Normally cycling monkeys were treated with 50 IU/day of "pure" follicle-stimulating hormone (FSH) on days 1 through 11 of the menstrual cycle. Ovarian venous serum (OVS) was collected on day 10; then all right ovarian follicles were aspirated. On day 11, OVS was collected again. Gonadotropin-inhibiting activity was determined in each sample by measuring the suppression of gonadotropin secretion by rat anterior pituitary cells in culture. OVS obtained on day 10 suppressed basal FSH secretion by approximately 45% and luteinizing hormone-releasing hormone stimulated luteinizing hormone secretion by approximately 50% (P less than 0.05, versus castrate serum). On day 11, OVS from the left ovary continued to suppress gonadotropin secretion, whereas OVS from the right ovary demonstrated significantly less gonadotropin-inhibiting activity. These findings demonstrate that exogenous FSH increases OVS concentrations of a nonsteroidal ovarian factor(s) with gonadotropin-inhibiting activity.
Animals↗
Effect of porcine follicular fluid on the postcastration secretion of gonadotropins in rhesus monkeys.
Porcine follicular fluid (pFF) contains a nonsteroidal factor(s) that modifies pituitary secretion of both FSH and LH under certain physiological and experimental conditions. The aim of this study was to further define the activity of pFF on basal and pulsatile gonadotropin secretion after bilateral oophorectomy in monkeys. Sexually mature female rhesus monkeys underwent bilateral oophorectomy during the early follicular phase of the menstrual cycle. For 10 consecutive days, beginning on the day of surgery, monkeys were given twice daily sc injections of 2.5 ml normal saline (group I, control; n = 3), 2.5 ml steroid-free pFF (group II; n = 3), or 5.0 ml steroid-free pFF (group III; n = 3). Blood was drawn daily for 32 days, beginning the day before castration. One day before and on days 6 and 20 after castration, monkeys were placed in a restraining chair, and blood samples were drawn every 15 min for 6 h via an indwelling venous catheter. All samples were radioimmunoassayed for FSH and LH. In group I, a significant increase in serum FSH and LH occurred on days 3 and 6 postcastration, respectively. A significant increase in serum FSH did not occur until day 13 postcastration in groups II and III. Serum LH was significantly increased on days 10 and 9 postcastration in groups II and III, respectively. The LH pulse frequency ranged from 60-105 min and did not change after castration in control or pFF-treated animals. The LH pulse increment was significantly increased on day 6 postcastration in group I, but not until day 20 postcastration in groups II and III. Only minor oscillations in FSH were found until day 20 postcastration, at which time there was no significant difference in FSH pulse frequency or increment among groups. These findings demonstrate that a nonsteroidal factor(s) in pFF suppresses basal FSH and LH concentrations and LH pulse increment in monkeys after surgical castration. Further, because LH, but not FSH, concentrations began to increase during pFF treatments, these data suggest a temporal disparity in the effects of pFF on FSH and LH secretory profiles.
Animals↗
Follicle-stimulating hormone induced ovarian hyperstimulation in monkeys: blockade of the luteinizing hormone surge.
The availability of a pure human FSH preparation for studies of the primate ovarian/menstrual cycle permitted novel experiments on gonadotropic stimulation of follicular growth in monkeys. Administration of pure FSH on days 1 through 12 of the menstrual cycle resulted in significant ovarian hyperstimulation, as manifested by the development of multiple (bilateral) ovarian follicles and sustained high serum estradiol levels (approximately 400 pg/ml). In spite of overt follicular development and concurrent increases in serum estradiol, timely LH surges were not elicited. Similarly, during FSH-induced ovarian hyperstimulation, GnRH effects on LH secretion were blunted. Equivalent FSH treatments of long term ovariectomized monkeys had no discernible effects on estrogen-induced LH surges or GnRH responses. Our interpretation is that when supraphysiological FSH levels persist into the late follicular phase, thereby overriding selection of the single dominant follicle of the natural cycle, secretion of an ovarian factor(s) blocks estrogen-induced LH surges.
Animals↗
Conservative surgery versus expectant management for the infertile patient with mild endometriosis.
During an 8-year period, the records of 90 patients with mild pelvic endometriosis diagnosed by endoscopy were reviewed to determine whether conservative surgical treatment resulted in higher pregnancy rates than expectant management. Forty-five patients were found to have mild endometriosis as the only abnormality in a complete fertility workup. Sixteen patients were managed expectantly, and 75% became pregnant in 1 year. Twenty-nine patients had conservative surgery, and 72.4% conceived in 1 year. This surgery-to-pregnancy interval was similar in both groups. Sixty patients had mild endometriosis only or mild endometriosis and anovulation corrected by clomiphene citrate. The pregnancy rate in 1 year was 72.2% in 18 patients managed expectantly and 76.2% in 42 patients treated with conservative surgery. The surgery-to-pregnancy interval was 5 and 6 months, respectively. These results suggest that expectant management should be considered prior to medical or surgical treatment of infertile patients with mild endometriosis.
Adult↗
Treatment of premature labor with beta sympathomimetics: results with isoxsuprine.
This prospective study presents a protocol for the treatment of premature labor with beta sympathomimetics and the results when isoxsuprine was used. Seventy-two patients from 25 to 36 weeks' gestation were treated. All patients were placed at bed rest, hydrated, and given parenteral sedation prior to the intravenous use of isoxsuprine. Treatment was continued via the intramuscular and oral routes until the thirty-seventh week of gestation. Three patients (4.2%) were delivered of infants during the initial infusion, and 15 (20.2%) were delivered of infants within 2 weeks after the onset of therapy. Forty-nine (68%) were delivered of infants after 37 weeks' gestation, and their infants weighed more than 2,500 grams. Maternal side effects were common, but none necessitated termination of therapy. There were six neonatal deaths, the causes of which were respiratory distress syndrome in two infants, necrotizing enterocolitis in one, group B streptococcal sepsis in one, congenital anomalies with sepsis in one, and multiple congenital anomalies in one.
Adrenergic beta-Agonists↗
Surgical induction of endometriosis in the rabbit: effects on fertility and concentrations of peritoneal fluid prostaglandins.
The association of endometriosis and infertility is well know. However, the exact mechanisms involved remain unclear. To study the effect of endometriosis on fertility, an experimental model was developed using New Zealand White rabbits. Endometrium obtained from one uterine horn was surgically implanted into the peritoneum, and the viability of the implants was demonstrated histologically. Adipose tissue was implanted in another group of animals which served as a control. The induction of endometriosis significantly impaired fertility rates (25%) as compared with the control group (75%). The decrease in fertility was independent of adhesion formation and primarily due to a defect in ovulation; however, a postovulatory effect cannot be excluded. Peritoneal fluid prostaglandin (PG) F concentrations increased significantly after the induction of endometriosis, whereas PGE concentrations and the PGF:PGE ratio showed no change. There was no change in PGF or PGE levels in the control group. The increased PGF in peritoneal fluid may alter follicular rupture, ovum transport, corpus luteum function, or implantation, thus representing a mechanism by which endometriosis may cause infertility.
Adipose Tissue↗
Reoperation after initial treatment of endometriosis with conservative surgery.
One hundred and fifty-three patients with pelvic endometriosis met the study criteria of inferility, tissue diagnosis, treatment with conservative surgery, and adequate follow-up. The extent of disease was classified according to Acosta and and associates. Pregnancy rates were 10 to 100% in various subclassifications of patients; these pregnancy rates were related to the extent of disease and the existence of concurrent inferitility factors. One hundred and seventeen patients were followed up for three years. Reoperation in this group was carried out in 28 patients for recurrent pain and/or persistent infertility. Each patient had diagnostic laparoscopy preceding relaparotomy. The reoperation rate was 40.6% in those patients who remained infertile, whereas this rate was only 3.7% in those patients who conceived following initial operation. The incidence of conception after a second conservative procedure was 12%. However, an equal number of patients in this group required total abdominal hysterectomy as a third procedure for control of recurrent pain. Thus, repeat conservative surgery should play a secondary role in the treatment of patients with infertility and recurrent endometriosis.
Anovulation↗
Composition of the extracellular matrix of the peritoneum.
OBJECTIVE: To localize the extracellular matrix proteins collagen I, collagen IV, fibronectin, and laminin in the peritoneal membrane. STUDY DESIGN: Peritoneal biopsies (n = 13) from the anterior abdominal wall and the uterine serosa (n = 3) were incubated with antibodies to collagen IV, laminin, collagen I, and fibronectin. Specimens were examined using light and confocal laser scanning microscopy. RESULTS: All of the extracellular matrix (ECM) proteins were present immediately under the mesothelium. Collagen (Col) IV and laminin (LM) were seen in the smooth muscle of microvascular structures, in the subendothelial basement membrane, and were present in a fascicular pattern in the peritoneal stroma. Collagen I was distributed diffusely in the peritoneal stroma. Fibronectin was also present in the subendothelial basement membrane. CONCLUSIONS: The resolution of the confocal microscope allowed for localization of extracellular matrix proteins in relation to the mesothelium. The presence of collagen IV, laminin, collagen I, and fibronectin under the mesothelium suggests that cells invading the peritoneum must have the ability to degrade and remodel this matrix.
Adult↗
Mesothelium expression of integrins in vivo and in vitro.
OBJECTIVE: To characterize the expression of alpha subunits of integrin adhesion molecules in peritoneal tissue in vivo and in vitro. METHOD: Peritoneum from the anterior abdominal wall (n = 22) and the serosa of the posterior uterus (n = 11) was obtained from women of reproductive age without endometriosis who were undergoing surgery for benign conditions. Immunohistochemical studies were performed on serial sections of peritoneum from the anterior abdominal wall, the uterine serosa, mesothelial monolayer cultures, and peritoneum explants from the abdominal wall using monoclonal antibodies to alpha subunits of integrin adhesion molecules. Electron microscopy was performed to localize these adhesion molecules in the mesothelium. RESULTS: The mesothelial expression of alpha integrin subunits was identical in the anterior peritoneum and uterine serosa. In vivo the mesothelium strongly expressed alpha 2 and alpha 3 and variably expressed alpha 6. In the monolayer cultures there was moderate/strong staining for alpha 2, alpha 3, and alpha 5; there was minimal expression of alpha v. In the explants there was moderate/strong expression of alpha 2, alpha 3, alpha 5, and alpha v; alpha 6 was variably expressed. The ultrastructure of the mesothelium was unique in the anterior peritoneum, uterine serosa, and the monolayer cultures. The integrin subunits were distributed throughout the cytoplasm, were expressed in the plasma membrane, and were present on the surface (i.e., towards the peritoneal cavity) of the mesothelium. CONCLUSION: Integrins are expressed by the mesothelium of the peritoneum. The mesothelium expression of integrins in vivo differs from that of the mesothelium integrin expression in monolayer culture and explant culture.
Antigens, CD↗
Cocaine impairs follicular phase pulsatile gonadotropin secretion in rhesus monkeys.
OBJECTIVE: To assess cocaine's effect on follicular phase pulsatile gonadotropin secretion in normally cycling rhesus monkeys. METHODS: Sixteen monkeys were paired by body weight and randomized to receive intravenous saline (n = 8) or cocaine (4 mg/kg, n = 8) daily on cycle days 2 to 14. Monkeys were chronically cannulated to allow frequent blood collections without anesthesia. Blood samples were obtained every 15 minutes for 8 hours in early (EFP; cycle days 1 to 5), mid-(MFP; cycle days 6 to 10), and late (LFP; cycle days 11 to 15) follicular phase. Plasma concentrations of LH, FSH, and estradiol-17 beta (E2) were determined by radioimmunoassay. Pulses were identified by cluster analysis. Statistical differences were determined by analysis of variance (ANOVA) and Sidak's multiple comparison test. RESULTS: Seven out of eight monkeys in the control group demonstrated timely ovulation. Only one monkey in the cocaine-treated group ovulated. Similar gonadotropin pulse intervals (70 to 90 minutes) were observed throughout the follicular phase in both the controls and cocaine-treated monkeys. LH and FSH pulse amplitudes increased significantly from the EFP/MFP to the LFP in controls. In cocaine-treated monkeys, gonadotropin pulse amplitudes remained at EFP/MFP levels throughout the study period. The mean gonadotropin pulse amplitude and the mean E2 levels in the LFP were significantly greater in controls as compared with cocaine-treated monkeys (P < .001). CONCLUSION: These findings demonstrate that cocaine suppresses the normal increase in LH and FSH pulse amplitude seen in the LFP. Further studies are in progress to determine the mechanism of cocaine's disruption of the hypothalamic-pituitary-ovarian axis.
Animals↗
Low-dose follicular-phase cocaine administration disrupts menstrual and ovarian cyclicity in rhesus monkeys.
OBJECTIVE: To evaluate the effects of daily low-dose follicular-phase cocaine administration on menstrual cyclicity, ovulation rates, corpus luteum function, and hormone levels in rhesus monkeys. METHOD: Normally cycling, drug-naive, adult rhesus monkeys were randomized to receive either 1 mg/kg of cocaine (n = 7), 2 mg/kg of cocaine (n = 7), or normal saline (n = 7) daily on cycle days 2 to 14. Daily blood samples were obtained through indwelling catheters for measurement of serum gonadotropins and ovarian steroids. Daily vaginal swabs were obtained to determine onset of menses. Laparoscopy was performed 2 days after the midcycle estrogen peak to document ovulation. Daily caloric intakes as well as pretreatment and posttreatment weights were recorded. RESULTS: Two of seven monkeys receiving 1 mg/kg per day and two of seven monkeys receiving 2 mg/kg per day of cocaine had timely ovulation and normal menstrual cycle lengths. One monkey receiving the 2-mg/kg dose ovulated on cycle day 24 and had a short luteal phase (7 days) with a mean progesterone level of 2.4 ng/mL. All seven saline-treated control monkeys ovulated normally; the mean cycle length was 29 days and all had adequate luteal phases. The difference in ovulation rates between cocaine-treated and control monkeys was statistically significant (P = .003). There were no differences in basal levels of LH or FSH between treatment groups. There were no significant differences in weight change or caloric intake among groups. One third of the subsequent menstrual cycles in cocaine-treated monkeys were of abnormal duration. CONCLUSION: Daily low-dose follicular-phase cocaine administration disrupts menstrual cyclicity and folliculogenesis. This effect is independent of weight loss, caloric intake, and basal gonadotropin levels. Cocaine exposure may have a persistent effect on menstrual and ovarian cyclicity in some monkeys.
Animals↗