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Biomedical subjects

R S Schenken

Publications and source records attributed to R S Schenken.

At least 19 recordsLinked to original sources
PubMed1992

Chromosomal analysis of pregnancy losses in patients undergoing assisted reproduction.

Chromosomal analysis was performed on products of conception from 18 patients having early pregnancy loss after assisted reproduction. Sonographic findings prior to obtaining tissue varied from gestational sacs consistent with a blighted ovum to fetal poles with cardiac activity. The mean age of the patients was 36.3 years. There were nine (50%) normal karyotypes, five (28%) autosomal trisomies, two cases of tetraploidy, one case of monosomy, and a case with two pericentric inversions. The results of this study suggest that patients undergoing assisted reproduction are not at an increased risk for chromosomal abnormalities.

Abortion, Spontaneous↗
PubMed1992

Cocaine impairs gonadotropin secretion in oophorectomized monkeys.

OBJECTIVE: Our objective was to determine whether cocaine alters gonadotropin secretion in oophorectomized monkeys. STUDY DESIGN: Oophorectomized monkeys with elevated gonadotropin levels were chronically cannulated to allow blood sampling every 15 minutes. Monkeys received either saline solution or 2 or 4 mg/kg cocaine hydrochloride as an intravenous bolus. Other oophorectomized monkeys were pretreated with either saline solution or 4 mg/kg cocaine 2 hours before bolus gonadotropin-releasing hormone administration, and plasma luteinizing hormone and follicle-stimulating hormone levels were measured every 15 minutes for 3 hours. Monkeys were also given either saline solution or 4 mg/kg of cocaine with gonadotropin-releasing hormone simultaneously, and plasma gonadotropin levels were measured every 15 minutes for 3 hours. Serum luteinizing hormone and follicle-stimulating hormone levels were measured by radioimmunoassay. RESULTS: Both doses of cocaine resulted in a significant decrease in luteinizing hormone levels compared with controls. Follicle-stimulating hormone levels were significantly decreased only with the 4 mg/kg dose of cocaine. There was no difference in luteinizing hormone and follicle-stimulating hormone responses to gonadotropin-releasing hormone in the cocaine-treated monkeys compared with saline solution-treated monkeys by using repeated-measures analysis of variance. CONCLUSION: These findings demonstrate that acute cocaine administration to oophorectomized primates inhibits basal luteinizing hormone-follicle-stimulating hormone secretion but not gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone release. In the absence of an effect on gonadotropin-releasing hormone-stimulated gonadotropin release, we conclude that the impaired luteinizing hormone-follicle-stimulating hormone secretion after cocaine administration is due in part to a direct effect of cocaine on gonadotropin-releasing hormone neurons or on hypothalamic neurotransmitter modulation of gonadotropin-releasing hormone release.

Analysis of Variance↗
PubMed1992

A prospective, randomized trial comparing two different intrauterine insemination regimens in controlled ovarian hyperstimulation cycles.

OBJECTIVE: To compare a single periovulatory intrauterine insemination (IUI) with a regimen employing two IUIs, one before ovulation and one after ovulation, in patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins (hMG) combined with human chorionic gonadotropin (hCG). DESIGN: A randomized, prospective trial. PARTICIPANTS: Thirty-one consecutive patients undergoing 49 cycles of controlled ovarian hyperstimulation/IUI were studied in a tertiary care setting. MAIN OUTCOME MEASURES: Ovulation was determined sonographically. The establishment of a clinical pregnancy was defined by either ultrasonographic verification of cardiac activity within an intrauterine fetus, or histologic confirmation of trophoblast in a surgical specimen. RESULTS: Clinical pregnancies developed in 2 of 23 cycles in the single insemination group, compared with 12 of the 23 cycles in the double insemination group. Cycle fecundity was significantly higher for group II (0.522) than for group I (0.087) patients (P = 0.003). CONCLUSION: In hMG/hCG cycles, two IUIs timed as described above are superior to one periovulatory insemination.

Cryopreservation↗
PubMed1992

Consecutive versus alternating cycles of ovarian stimulation using human menopausal gonadotrophin.

Ovarian stimulation is an effective treatment for patients with ovulatory dysfunction and unexplained infertility. An initial report has suggested that consecutive cycles of ovarian stimulation can be employed without causing a diminished response in the second cycle. However, this observation has neither been confirmed nor has a regimen of consecutive stimulation cycles been compared to one of alternating stimulation cycles. Accordingly, 44 consecutive and 54 alternating cycles of stimulation were evaluated in patients (n = 42) who were treated with human menopausal gonadotrophin (HMG) alone. Human chorionic gonadotrophin (HCG) 10,000 IU was administered i.m. when at least one follicle exceeded 16 mm in mean diameter, and this was followed by either intercourse or intrauterine insemination. Using each patient as her own control, we were unable to demonstrate any differences in mean HMG dose requirements, endocrine parameters or follicular development on the day of HCG administration, or ovulation rates in the second consecutive cycle compared to the second alternating cycle. Clinical pregnancies resulted significantly more often in a consecutive cycle (8/22) than in an alternating cycle (2/27, P = 0.029). We conclude that consecutive cycles of ovarian stimulation with HMG are not detrimental and may, in fact, result in increased cycle fecundity compared to alternating stimulation cycles.

Adult↗
PubMed1992

Phorbol esters stimulate in vitro GnRH release from the hypothalamus of the estrogen-primed, ovariectomized rat: inhibitory effects of cocaine.

The purpose of this study was (1) to characterize more fully the effects of phorbol esters to stimulate GnRH release in vitro and (2) to determine whether cocaine (which disrupts estrous cyclicity in rats) affected phorbol ester stimulation of GnRH release in vitro. Hypothalami were collected from ovariectomized rats injected subcutaneously with 50 micrograms/kg of 17 beta-estradiol benzoate the two previous mornings. Sagittal sections of this block of CNS tissue comprising the preoptic area/anterior hypothalamus and mediobasal hypothalamus/median eminence were perfused at a rate of 6.2 ml/h with a modified Krebs-Ringer buffer (pH 7.4) using a programmable perfusion system. Perfusion results showed that 10-min pulses of phorbol 12-myristate 13-acetate or phorbol 12,13-dibutyrate (PDBu) increased GnRH release in dose-dependent fashion (10(-10) to 10(-6) M) but had no effect on aminergic transmitter release. The biologically inactive alpha-phorbol was without effect on GnRH release. PDBu-stimulated GnRH release was blocked by both tetrodotoxin and cocaine, known inhibitors of Na+ influx. These results suggest a role for protein kinase C in regulating the release of GnRH. Our results that cocaine and tetrodotoxin attenuated phorbol ester stimulation of GnRH, presumably through inhibition of Na+ influx, suggest a direct biochemical mechanism for cocaine disruption of hypothalamic GnRH secretion and, consequently, cyclic reproductive function.

Animals↗
PubMed1991

Effects of clomiphene citrate and leuprolide acetate on luteal-phase hyperprolactinemia during ovarian stimulation with menopausal gonadotropins.

Hyperprolactinemia, a known modulator of reproductive function, occurs commonly in women undergoing ovarian stimulation with human menopausal gonadotropins (hMG). Clomiphene citrate (CC) and gonadotropin releasing hormone analogues (GnRHa), when administered during the luteal phase, attenuate the hyperprolactinemic response to hMG. We asked whether follicular-phase administration of CC and GnRHa, as employed clinically in women undergoing ovarian stimulation for in vitro fertilization or gamete intrafallopian transfer, would alter the incidence and severity of hMG-induced luteal-phase hyperprolactinemia. Seventy-five percent of all patients had at least one luteal prolactin level greater than 25 ng/ml, and 40% had mean luteal-phase prolactin levels greater than 25 ng/ml. The incidence of hyperprolactinemia was similar in pregnant and nonpregnant cycles. The incidence of hyperprolactinemia was similar for both the GnRH agonist-treated group and those given clomiphene citrate. The increase in mean luteal prolactin levels over the follicular-phase baseline level was significantly greater in the CC-treated group (P = 0.03). This was due to the significant suppression of follicular-phase baseline prolactin levels in patients receiving CC. We conclude that neither CC nor GnRHa administration in the follicular phase prevents luteal-phase hyperprolactinemia in women undergoing ovarian stimulation with hMG.

Clomiphene↗
PubMed1991

c-myc protooncogene polypeptide expression in endometriosis.

The c-myc protooncogene and its polypeptide product are important regulators of cell proliferation and differentiation, and ovarian steroids are believed to stimulate growth of various uterine cell types through altered expression of the c-myc gene. To determine whether c-myc expression may also be involved in the growth and development of endometriosis, we assessed c-myc expression in eutopic and ectopic endometrial tissue obtained from women undergoing surgery for endometriosis. Immunocytochemistry using a monoclonal antibody to the c-myc protein demonstrated positive staining of glandular and stromal cell nuclei, and cytoplasmic staining of glandular but not stromal cells in both eutopic and ectopic endometrium. These findings suggest that c-myc expression may be an important regulator of cell proliferation in endometriotic tissue.

Adult↗
PubMed1991

Follicular size at the time of human chorionic gonadotropin administration predicts ovulation outcome in human menopausal gonadotropin-stimulated cycles.

OBJECTIVE: The objectives of this study were: (1) to correlate follicle size by transvaginal sonography with ovulation outcome in cycles of controlled ovarian hyperstimulation with human menopausal gonadotropins; (2) to determine if follicular size on the day of human chorionic gonadotropin (hCG) administration predicts the incidence of ovulation; and, if so, (3) to derive a mathematical model that predicts the number of expected ovulations in any given cycle of controlled ovarian hyperstimulation. DESIGN: A retrospective analysis. PARTICIPANTS: Forty-nine consecutive patients undergoing 122 cycles of controlled ovarian hyperstimulation were studied in a tertiary care setting. MAIN OUTCOME MEASURES: Follicular size and evidence of ovulation were determined sonographically. The main outcome measure was the rate of ovulation per follicle size. RESULTS: The percentages of follicles measuring less than or equal to 14 mm, 15 to 16 mm, 17 to 18 mm, 19 to 20 mm, and greater than 20 mm on the day of hCG administration that subsequently ovulated were 0.5%, 37.4%, 72.5%, 81.2%, and 95.5%, respectively. CONCLUSIONS: (1) Follicular size on the day of hCG administration correlates with the incidence of ovulation. (2) The expected number of ovulations in any given controlled ovarian hyperstimulation cycle can be predicted with 95% confidence using the accompanying equation.

Chorionic Gonadotropin↗
PubMed1991

Immediately preovulatory levels of messenger ribonucleic acid for inhibin alpha-subunit are diminished in granulosa cells from successful in-vitro fertilization-embryo transfer.

Inhibin, a gonadal glycoprotein which suppresses pituitary gonadotrophin secretion, preferentially follicle stimulating hormone, has been extensively characterized. It consists of two covalently bound subunits, the alpha- and beta-subunits, encoded by separate genes. In this study, the expression of messenger ribonucleic acid (mRNA) for the inhibin alpha-subunit was studied by Northern blot analysis in granulosa cells of women undergoing in-vitro fertilization/embryo transfer (IVF/ET). Three patient groups were studied: women who failed to become pregnant (n = 11), women who became pregnant but experienced early spontaneous abortion (n = 3) and women who conceived normal ongoing pregnancies (n = 4). Granulosa cells were obtained at the time of follicle aspiration. Levels of alpha-subunit mRNA were 40% lower in patients establishing normal pregnancies than in those who failed to become pregnant or who spontaneously aborted. Thus, a relative diminution of immediately preovulatory levels of mRNA for inhibin alpha-subunit is a marker of success in clinical IVF/ET cycles. This marker of IVF/ET success can be related to previously established markers of success (increased follicular fluid oestradiol and decreased follicular fluid cyclic adenosine monophosphate) by known physiological mechanisms.

Adult↗
PubMed1991

Serum progesterone levels predict success of in vitro fertilization/embryo transfer in patients stimulated with leuprolide acetate and human menopausal gonadotropins.

Serum progesterone (P4) levels greater than 2.86 nmol/L (0.9 ng/mL) on the day of hCG administration are reportedly associated with decreased pregnancy rates in in vitro fertilization/embryo transfer (IVF/ET) cycles. To further assess this phenomenon we measured serial serum P4, LH, and estradiol levels in 115 consecutive patients undergoing stimulation for IVF/ET with midluteal leuprolide acetate and human menopausal gonadotropins. IVF/ET cycle outcome was retrospectively correlated with P4 levels on the day of hCG administration. Two critical breakpoints were identified, 1.27 nmol/L (0.4 ng/mL) and 286 nmol/L (0.9 ng/mL). Clinical pregnancies occurred in 9 of 18 patients in group I (P4, less than 1.27 nmol/L) compared to 11 of 81 patients in group II (1.27 less than P4 less than 2.86 nmol/L; P = 0.001) and 0 of 14 patients in group III (P4, less than or equal to 2.86 nmol/L) (P = 0.001). Eleven patients in group III had cryopreservation of embryos during that cycle. Six subsequently underwent frozen embryo transfer, and clinical pregnancies occurred in 2, both of whom have delivered. These findings demonstrate that even modest increases in serum P4 levels (greater than 1.27 nmol/L) are associated with reduced pregnancy rates in IVF/ET cycles. In addition, it appears that the mechanism may not exclusively involve poor oocyte quality.

Antineoplastic Agents↗
PubMed1991

Paracrine interactions between platelet-activating factor and prostaglandins in hormonally-treated human luteal phase endometrium in vitro.

Stromal cells and epithelial glands were separated after enzymic digestion of specimens obtained from 27 women at hysterectomy or endometrial biopsy during the luteal phase, and then cultured to confluence in vitro. PGE release into the culture medium (mean +/- s.e.m.: ng/mg protein/24 h) from gland cell cultures was not changed by oestradiol (17.6 +/- 1.3 for control and 25.5 +/- 2.8 for oestradiol, respectively). However, in the presence of oestradiol, PAF (5 ng/ml) significantly elevated PGE release to 44.2 +/- 5.8. No stimulation was observed in the presence of progesterone. Stromal cell medium had no effect on PGE release in gland cell cultures. PGE release was always much lower in stromal cell cultures than in glands (control: 4.7 +/- 0.6). PAF stimulated PGE release in the presence of oestradiol in these cells also; gland cell medium was without effect. In co-cultures of glandular and stromal cells, PGE release was more similar to that seen in gland cell cultures, with PAF being stimulatory under the influence of oestradiol. PGF release into the medium from the same gland cell cultures was significantly elevated by hormonal treatment, being greatest (62.0 +/- 11.3) with oestradiol alone, and was strongly inhibited in all wells by addition of PAF and stromal cell medium. In stromal cell cultures without hormonal addition, PGF levels (15.0 +/- 2.4) were similar to those seen in glands (18.1 +/- 3.1), and no stimulation was achieved by oestradiol (29.6 +/- 5.9). PAF was inhibitory on PGF release, while gland cell medium was without effect. Co-cultures gave PGF values generally similar to those of stromal cells; oestradiol was again stimulatory (55.0 +/- 9.3). PAF was significantly inhibitory in the presence of oestradiol. PAF (mean +/- s.e.m.: pmol/mg protein/24 h using a platelet serotonin release assay) in stromal cells was significantly increased from control [M199 alone] (0.31 +/- 0.12) by progesterone (1.00 +/- 0.17). Addition of PGE-2 (7.5 ng/ml) to progesterone-treated wells further increased PAF concentration (5.34 +/- 0.09), but was without effect in wells receiving oestradiol alone. Wells exposed to both hormones exhibited an intermediate response. Similar results were obtained with addition of gland cell culture medium, presumably due to its endogenous PGE content. In co-cultures, PAF concentrations were significantly elevated by progesterone alone (4.78 +/- 0.78) or when combined with oestradiol (2.38 +/- 0.51), but not by oestradiol alone. Treatment with PGE-2 caused no additional stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Cells, Cultured↗
PubMed1991

Macrophage-conditioned media enhance endometrial stromal cell proliferation in vitro.

It has been hypothesized that the activated peritoneal macrophages of endometriosis, rather than being a response to ectopic endometrium, may contribute to its pathogenesis. This study attempts to define the effect of macrophage-derived growth factors on endometrial stromal cell growth in vitro, as well as the interaction between estrogen and these growth factors. Mouse endometrial stromal cells were prepared and cultured in either a serum-containing, insulin-free medium or a serum-free, insulin-containing medium, and the effects of adding 10% macrophage-conditioned medium on [3H]thymidine incorporation were assessed. Results indicate that macrophage-conditioned medium will increase incorporation in the presence of insulin but not in insulin-free media. Serum can substitute for macrophage-conditioned medium, but the two together show no additive or synergistic effect. The effect of estrogen on this system was determined, and results indicate that estrogen will perform the function of insulin, with an optimal concentration of 10(-10) to 10(-12) mol/L. Thus macrophage-conditioned medium appears to function as a competence growth factor, and estrogen (in appropriate concentrations) functions as a progression growth factor.

Animals↗
PubMed1991

Surgically induced endometriosis does not alter peritoneal factors in the rabbit model.

OBJECTIVE: It was the purpose of this study to examine the cause and effect relationship between alterations in peritoneal factors and the presence of ectopic endometrium in the rabbit model. DESIGN: Forty rabbits had autologous endometrial or omental (control) tissue surgically implanted. Peritoneal fluid (PF) volume, macrophage number, and macrophage activation, as well as the number of implants with adhesions, were compared with values obtained during the initial surgery. The effect of hormonal treatment on these factors was evaluated at a third laparotomy. RESULTS: There was a significant increase (P less than 0.05) of adhesions in animals with endometrial implants. Peritoneal fluid volume, macrophage number, or macrophage activation were not increased in rabbits with endometrial implants as compared with controls, nor was there a response to hormonal manipulation. CONCLUSIONS: These results demonstrate that PF volume, macrophage number, and macrophage activation are not altered by endometrial implants in the rabbit model. This suggests that the increase in these peritoneal factors in women with endometriosis may not be caused exclusively by the presence of ectopic endometrial tissue.

Analysis of Variance↗
PubMed1990

Ovarian cyst aspiration prior to initiating ovarian hyperstimulation for in vitro fertilization.

Twenty-three consecutive patients presenting for in vitro fertilization were evaluated with transvaginal sonography on cycle day 3, prior to initiating ovarian hyperstimulation. Three of these patients were noted to have large ovarian cysts. All three underwent transvaginal aspiration of the cysts, followed immediately by initiation of ovarian hyperstimulation. Following oocyte retrieval, in vitro fertilization, and embryo transfer, all three women achieved pregnancy. We conclude that cyst aspiration is not contraindicated when an ovarian cyst is encountered in the follicular phase of an in vitro fertilization cycle.

Adult↗
PubMed1990

Gonadotropin-releasing hormone analogs in the treatment of endometriomas.

A limited number of small studies have assessed the efficacy of gonadotropin-releasing hormone agonists in the treatment of ovarian endometriomas. Most of these trials have not used quantitative measurements to evaluate the effects of therapy on disease resolution. The results available thus far suggest that nafarelin, buserelin, and histrelin offer modest degrees of efficacy, similar to that of danazol, in the management of patients with ovarian endometriotic cysts. Gonadotropin-releasing hormone agonists appear to be most efficacious when endometriomas are less than 1 cm in size.

Buserelin↗
PubMed1990

Expression of the human inhibin alpha-subunit gene in preovulatory granulosa-theca cells.

Inhibin, a gonadal peptide that suppresses pituitary follicle-stimulating hormone, with lesser or no effect on luteinizing hormone, has recently been purified and the complementary deoxyribonucleic acid sequences cloned. Inhibin contains two subunits, labeled alpha-subunit and beta-subunit. Here we report for the first time the detection of human inhibin alpha-subunit gene expression in preovulatory granulosa-theca cells by Northern analysis. The transcript is the same size as previously reported for human placenta and corpus luteum, suggesting that the same gene is being expressed in all three tissues. These findings are consistent with previously reported Southern analysis of deoxyribonucleic acid, which showed only one copy of the alpha-inhibin gene in the human genome. Thus current data strongly suggest that there is only one copy of the inhibin alpha-subunit gene in the human genome, and this same gene is expressed in granulosa-theca cells, corpus luteum, and placenta.

Animals↗
PubMed1990

Effects of gonadotropin-releasing hormone agonist and clomiphene citrate on estrogen/progesterone-induced hyperprolactinemia in monkeys.

The effects of follicular phase clomiphene citrate (CC) and two regimens of leuprolide acetate on estrogen-progesterone-induced hyperprolactinemia in nonhuman primates were studied. All groups received estradiol (E2) benzoate (12.5 micrograms intramuscularly on cycle days 2 to 33) and progesterone (P) (silastic implant for cycle days 14 to 33). A gonadotropin-releasing hormone agonist (GnRH-a) (Lupron 0.5 mg daily, TAP Pharmaceuticals, Chicago, IL) was administered from cycle day 2 to 14 in group II and from day 20 of the previous cycle until cycle day 14 in group III. Oral CC was given on cycle days 3 through 7 in group IV. No significant differences of mean E2 and P concentrations were noted between groups. Neither GnRH-a nor CC had an overall effect on E2/P-induced hyperprolactinemia. However, for the 5-day interval at the onset of the P treatment there was a significant increase in prolactin (PRL) secretion for group II (130.4 +/- 30.6) versus group I (53.9 +/- 3.3), group III (64.4 +/- 11.1), and group IV (68.8 +/- 14.3). This suggests that leuprolide may exert a delayed stimulatory effect on PRL secretion, or that complete suppression of the putative paracrine regulation of PRL stimulation may require more than 13 days of GnRH-a administration.

Animals↗