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Biomedical subjects

B H Yuen

Publications and source records attributed to B H Yuen.

At least 37 records · Page 2Linked to original sources
PubMed1994

Chromosome investigation in in vitro fertilization failure.

PURPOSE: A chromosomal complement of 227 human oocytes was studied to provide information on the frequency and type of chromosomal abnormalities in oocytes failing in vitro fertilization. RESULTS: Normal haploid chromosome complement was found in 54.6%; chromosomal abnormalities consisting of diploid sets were identified in 16.7% and aneuploidy was observed in 26%. Premature condensation of sperm chromosomes of the GI-phase was observed in 22.9% oocytes. Male infertility was correlated with an increase in the rate of aneuploidy when compared with tubal infertility. The rate of chromosome abnormalities for the oocytes recovered from women who had no fertilized oocytes was significantly higher compared to those with at least one oocyte fertilized. CONCLUSION: A high frequency of chromosome abnormalities in unfertilized oocytes suggests that natural selection against chromosome abnormalities may occur even prior to fertilization.

Adult↗
PubMed1994

Gonadotropin-releasing hormone (GnRH) and cyclic AMP positively regulate inhibin subunit messenger RNA levels in human placental cells.

Bioactive and immunodetectable levels of both inhibin and activin are present in the placenta, raising questions as to the regulatory control of their synthesis. This study was designed to determine the effect of cyclic AMP (cAMP) and gonadotropin-releasing hormone (GnRH) on inhibin subunit gene expression in short-term incubations of placental cells. A semi-quantitative polymerase chain reaction (PCR) technique was used after isolation of total RNA and first strand cDNA synthesis from mechanically dispersed trophoblast-enriched cells obtained from human placentae at term. The level of gene expression of inhibin subunits was higher for beta A and alpha-subunits mRNA compared to the beta B-subunit mRNA as determined by PCR in combination with Southern blotting or Northern hybridization. Steady-state levels of beta-actin mRNA did not change throughout the 6-h incubation period and was used as a control of PCR amplification of the respective inhibin subunit gene transcripts following treatments with 8-bromo cAMP or GnRH. 8-bromo cAMP dose-dependently increased all three inhibin subunit gene transcripts with maximal responses seen at 150 microM (alpha-subunit mRNA 2.3-fold, beta A-subunit mRNA 1.8-fold and beta B-subunit mRNA 2.8-fold over control). GnRH (100 nM) significantly increased inhibin alpha and beta B-subunit mRNA levels 2.9-fold and 2.0-fold, respectively (P < 0.01), but not beta A-subunit mRNA. Collectively, the present findings demonstrate that in human term placental cells, gene expression of all inhibin subunits is under the direct influence of cAMP and further support a modulatory role of local GnRH in placental trophoblasts during late pregnancy.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Exogenous gonadotropin therapy in World Health Organization groups I and II ovulatory disorders.

OBJECTIVE: To analyze cumulative conception rates and the prognostic factors influencing them during exogenous human menopausal gonadotropin (hMG) therapy for World Health Organization (WHO) group I or II ovulatory disorders. METHODS: A retrospective review was conducted of 468 treatment cycles in 146 women with ovulatory disorders refractory to conventional therapy. Cumulative conception rates were calculated, and the effects of diagnostic group, age, gravidity, and duration of infertility were examined using the Cox proportional hazards model. RESULTS: The cumulative proportion pregnant following six hMG cycles in WHO group I (0.89) was significantly greater than in the hyperandrogenic subgroup of WHO group II (0.30) (95% confidence interval [CI] 0.2-0.7, P = .006) or the luteal phase defect subgroup (0.35) (95% CI 0.07-0.6, P = .02). Conception rates in WHO group I did not differ significantly from those in the normoandrogenic oligo-ovulatory subgroup of WHO group II (0.63) (95% CI 0.3-1.3, P = .6). Conception rates were not influenced by duration of infertility or primary versus secondary infertility. Women 35 years or older had significantly lower conception rates than those aged 27 years or less (P = .04, hazard ratio 0.3, 95% CI 0.1-0.8). CONCLUSIONS: Cumulative conception rates following exogenous gonadotropin therapy for women with refractory ovulatory disorders were both diagnosis- and age-dependent. Treatment with hMG approximated or surpassed normal fertility rates in women with WHO group I and normoandrogenic WHO group II oligo-ovulation, but was significantly less successful at correcting the underlying defect in women with hyperandrogenic anovulation and luteal phase defects.

Adult↗
PubMed1993

The ascites in the ovarian hyperstimulation syndrome does not originate from the ovary.

OBJECTIVE: To evaluate the direct ovarian contribution to ascites formation in the ovarian hyperstimulation syndrome (OHSS) in a rabbit model. DESIGN: Prospective experimental study. SETTING: Research center of a university teaching hospital. PARTICIPANTS: New Zealand White rabbits. INTERVENTIONS: Both ovaries of the rabbits in the experimental group were enclosed within a pouch developed from the surrounding peritoneum and mesosalpinx by microsurgery. Animals in the control group did not undergo any surgical intervention. Ovarian hyperstimulation was induced by alternate day equine chorionic gonadotropin and intermittent human chorionic gonadotropin (hCG). MAIN OUTCOME MEASURES: Degree of ascites formation and the morphological and endocrinologic signs of ovarian hyperstimulation. RESULTS: The serial plasma estradiol and progesterone levels, ovarian weights, and ascites response were not statistically different between the two groups. CONCLUSIONS: Isolation of both ovaries from the peritoneal cavity does not prevent ascites formation in the OHSS. Increased transudation across extraovarian serosal surfaces contributes to ascites formation in OHSS.

Animals↗
PubMed1993

Sandostatin has no direct effect on ovarian steroidogenesis in vitro.

Rat granulosa and theca-interstitial cells from immature, oestradiol-treated rats were isolated and incubated for 144 h with follicle stimulating hormone (FSH), luteinizing hormone (LH), insulin alone or in combinations, and with two doses of sandostatin (10(-7) M and 10(-6) M per culture). Oestradiol and testosterone production by granulosa and theca-interstitial cells, respectively, was measured in culture media. The stimulatory effects of FSH alone and FSH with insulin but not insulin alone on oestradiol production by granulosa cells were observed. Similarly, increased testosterone concentrations after treatment with LH alone and LH with insulin but not insulin alone were found in media from theca-interstitial cells. The addition of high or low doses of sandostatin to the cultures did not affect the production of oestradiol or testosterone. It was concluded that sandostatin does not exert any direct effect on ovarian steroidogenesis in vitro.

Animals↗
PubMed1993

Insulin actions on ovarian steroidogenesis are not modulated by metformin.

Metformin, an agent used in treatment of non-insulin-dependent diabetes mellitus, is believed to act by potentiating the effects of insulin on glucose metabolism. This study was designed to determine whether metformin affects the actions of insulin on ovarian steroidogenic capability. Rat thecal-interstitial (T-I) and granulosa (G) cells were cultured in chemically defined media for 144 h with or without gonadotrophins [luteinizing hormone (LH) at 100 ng/ml or follicle stimulating hormone (FSH) at 100 ng/ml], insulin (1 microgram/ml) and/or metformin (1 and 5 micrograms/ml). Production of testosterone and progesterone by T-I cells, and 17 beta-oestradiol and progesterone by G cells were assessed. Insulin potentiated LH-dependent stimulation of testosterone production by T-I cells and FSH-dependent stimulation of 17 beta-oestradiol production by G cells, but did not significantly affect progesterone production by T-I cells or G cells in the presence or absence of gonadotrophins. Metformin did not affect any of the actions of insulin on steroidogenesis. These results suggest that insulin may modulate ovarian steroidogenesis via a pathway separate from that modulating glucose metabolism. Actions of insulin on steroidogenesis are selective with regard to stimulation of specific aspects of steroidogenesis and do not simply amplify gonadotrophin effects.

Animals↗
PubMed1993

Stimulation of progesterone secretion by recombinant follistatin-288 in human granulosa cells.

The effects of recombinant human follistatin (follistatin-288) on basal and hCG-stimulated progesterone secretion were examined in cultured human granulosa cells. Follistatin increased progesterone secretion in a dose-dependent manner. However, follistatin did not augment hCG- or cAMP-stimulated progesterone secretion. Time-course analysis revealed that follistatin increased progesterone secretion after 24 h of incubation. Follistatin also enhanced basal, but not hCG-stimulated, 20 alpha-hydroxyprogesterone accumulation, indicating that the increase in progesterone accumulation was not due to a blockade of the 20 alpha-hydroxylase metabolic pathway. In the presence of the phosphodiesterase inhibitor isobutylmethylxanthine, follistatin significantly increased intracellular cAMP accumulation to levels comparable to those induced by 1 IU/ml hCG. These results provide the first evidence of a stimulatory action of follistatin on progestin secretion in the human ovary, which is accompanied by an increased accumulation of intracellular cAMP levels. Follistatin may well be another potential regulator of steroid hormone production in human granulosa cells during the periovulatory period.

20-alpha-Dihydroprogesterone↗
PubMed1993

Acute stimulation of human chorionic gonadotropin secretion by recombinant human activin-A in first trimester human trophoblast.

Inhibin and activin are synthesized by the placenta, raising questions as to their functions in this tissue. The possibility of local regulation of other placental hormones critical during pregnancy was investigated by examining the effects of recombinant human inhibin-A and activin-A on hCG secretion. Potential interactions with GnRH-stimulated hCG secretion were also explored. First trimester human placental tissue was physically dissociated to isolate trophoblast cells. Cells were cultured on microcarrier beads for 7-10 days and loaded into 1.5-ml chambers in a perifusion system. After a 1-h control period, hormone treatments were administered in the perifusion medium for 5 min, and perifusate was collected for an additional 55 min. Perifusate fractions were analyzed for hCG concentration by RIA. Both activin and GnRH stimulated a rapid and transient hCG secretory response in the perifusion system. Unlike the effect of GnRH, the activin-stimulated hCG response was not blocked by concomitant treatment with a GnRH antagonist. The hCG RIA results were confirmed by preliminary experiments using a novel hCG bioassay. This suggested that activin did not facilitate hCG secretion by stimulation of endogenous GnRH release. Inhibin alone did not affect hCG secretion or GnRH-stimulated hCG secretion. However, treatment with inhibin and activin in combination resulted in a transient increase in hCG, followed by a decrease in hCG secretion to below pretreatment levels. The results suggested that in addition to GnRH, activin may play a role in the regulation of hCG secretion in first trimester placenta.

Activins↗
PubMed1993

Cytosolic free Ca2+ in human syncytiotrophoblast cells increased by gonadotropin-releasing hormone.

Effects of GnRH on free cytosolic Ca2+ concentrations ([Ca2+]i) were examined in individual first trimester human cytotrophoblast and syncytiotrophoblast cells by fura-2 microspectrofluorimetry. GnRH (10(-6) M) did not affect [Ca2+]i in cytotrophoblasts on days 2-9 of culture, with 50 cells tested each day. GnRH (10(-6) M) did not affect [Ca2+]i on days 2-3, but increased [Ca2+]i in 15% of culture-derived syncytiotrophoblasts on day 4 (8 of 52 cells) and in 48% on days 5-9 of culture (158 of 332 cells). Culture-derived syncytiotrophoblasts originated from four first trimester placentae. GnRH increased [Ca2+]i in a preliminary trial using syncytiotrophoblasts derived directly from a single first trimester placenta and cultured for 3 days (13 of 33 cells). Culture-derived first trimester syncytiotrophoblast cells that responded to 10(-6) M GnRH (28 of 63 cells) on day 6 also responded to GnRH at 10(-7) M (26 of 28 of the above cells), 10(-8) M (24 of 28 cells, 10(-9) M (22 of 28 cells), and 10(-10) M (3 of 28 cells). No cells responded to GnRH below a concentration of 10(-10) M. Desensitization of syncytiotrophoblasts by continuous GnRH perifusion (10(-6) M) and blockade of GnRH by competitive antagonism with Nal-Glu-GnRH (10(-6) M) suggested that effects of GnRH were receptor specific. The results provide direct evidence supporting the contention that the intracellular signaling resultant from GnRH receptor-ligand interactions in syncytiotrophoblasts may be at least partially mediated by transient increases in [Ca2+]i.

Calcimycin↗
PubMed1993

Ovarian response in World Health Organization group II anovulatory women during consecutive human menopausal gonadotropin cycles.

While ovulation induction with human menopausal gonadotropins (hMG) is commonly used to treat refractory ovulatory disorders, little is known about the characteristics of multiple consecutive treatment cycles. Since such cycles may be required to achieve pregnancy, it is important to ensure that the ovarian response is not compromised during consecutive cycles. We examined the ovarian response and cycle characteristics of 25 women with World Health Organization (WHO) group II ovulatory disorders who underwent three consecutive ovulatory hMG cycles. The total hMG dose and duration of treatment increased significantly between the first and third consecutive hMG cycles, although the final estradiol levels remained similar. While the mean numbers of follicles > or = 14 mm in diameter were comparable, the size of the largest follicle was significantly greater during the third cycle as compared to the first. These results suggest that while the ovary required more vigorous stimulation during subsequent cycles, the ultimate hormonal and follicular response did not appear to be compromised during this series of three consecutive cycles.

Adult↗
PubMed1992

The outcome of in vitro fertilization and embryo transfer in women with polycystic ovary syndrome failing to conceive after ovulation induction with exogenous gonadotropins.

OBJECTIVE: To assess the outcome of in vitro fertilization and embryo transfer (IVF-ET) in women with refractory polycystic ovarian syndrome (PCOS). DESIGN: Retrospective case series with an age-matched control group. SETTING: Ovulation induction and IVF programs in a tertiary referral center. PATIENTS AND INTERVENTIONS: Nine patients with PCOS who failed standard ovulation induction treatment (clomiphene citrate plus greater than or equal to 6 ovulatory human menopausal gonadotropin [hMG] cycles) underwent 19 cycles of IVF-ET. Forty age-matched tubal factor patients who completed 40 cycles of IVF-ET served as a control group. OUTCOME MEASURES: Demographic features and IVF-ET cycle characteristics were compared using Student's t-test and Fisher's exact test. RESULTS: Cycles of IVF-ET in patients with PCOS were associated with higher estradiol levels (5,222 versus 4,009 pmol/L), lower hMG requirements (15.8 versus 19.6 vials), greater numbers of oocytes (7.6 versus 5.6), and lower fertilization rates (56% versus 75%) compared with tubal factor cycles (P less than 0.05). However, the number of embryos transferred (3.9 versus 4.0) and the clinical pregnancy rate per embryo transfer (24% versus 25%) did not differ significantly between the two groups. CONCLUSION: These results suggest that conception failure after six or more ovulatory hMG cycles in patients with PCOS does not adversely affect subsequent IVF performance.

Adult↗
PubMed1992

Management of overstimulated gonadotrophin cycles with a controlled drift period.

In an attempt to avoid cancellation, 40 cycles which were biochemically overstimulated with exogenous gonadotrophins (oestradiol level inadvertently exceeding 5400 pmol/l) in 32 patients with polycystic ovarian syndrome, classified as Group II according to the World Health Organization, were managed by a controlled drift period. This involved a schedule where further human menopausal gonadotrophin (HMG) injections were withheld but monitoring continued with daily assays of serum oestradiol and frequent follicular ultrasound examinations. The mean oestradiol level at the start of the drift period was 9249 +/- 3465 (SD) pmol/l and dropped by 64.3 +/- 25.3% to 2945 +/- 1817 pmol/l at the end of 2.8 +/- 1.5 days of drift interval (range 1-8 days) at which time human chorionic gonadotrophin was administered. There was a significant increase in the size of the lead follicle and number of follicles greater than 14 mm in diameter during the drift period. The clinical pregnancy rate per cycle was 25% (10/40). The multiple pregnancy rate was 50% (5/10), and 2.5% (1/40) of the cycles were complicated by severe ovarian hyperstimulation syndrome (OHSS). These data indicate that cycles inadvertently overstimulated with gonadotrophin can be managed with a controlled drift period as an alternative to cancellation, yielding favourable pregnancy rates. The multiple pregnancy rate was 50%, twins in all instances and the rate of severe OHSS was 2.5%, which were within the range reported in the literature for HMG-stimulated cycles.

Chorionic Gonadotropin↗
PubMed1992

Cytosolic free calcium increased by prostaglandin F2 alpha (PGF2 alpha), gonadotropin-releasing hormone, and angiotensin II in rat granulosa cells and PGF2 alpha in human granulosa cells.

Cytosolic [Ca2+]i was measured using a microspectrofluorimetric technique. Prostaglandin F2 alpha (PGF2 alpha, 10(-6) M) transiently increased the concentration of free cytosolic Ca2+ ([Ca2+]i) in individual rat and human granulosa cells. In a study examining a total of 170 individual rat and human granulosa cells, approximately 100% of rat granulosa cells and 80% of human granulosa cells tested responded to PGF2 alpha (10(-6) M). In a dose-response trial, the magnitude of the [Ca2+]i response did not vary, although a decreasing number of cells responded to decreasing PGF2 alpha concentrations (10(-5) to 10(-9) M). PGE2 (10(-4) to 10(-6) M) did not affect [Ca2+]i in rat or human granulosa cells. GnRH (10(-6) M) increased [Ca2+]i in rat but not human granulosa cells. Over 90% of rat granulosa cells tested responded. Angiotensin II (ANG II, 10(-5) M) increased [Ca2+]i in approximately 25% of rat, but not human granulosa cells. Individual rat granulosa cells which responded to GnRH responded to PGF2 alpha and vice versa. Individual rat granulosa cells which responded to ANG II responded to PGF2 alpha and GnRH. Conversely, less than 30% of individual rat granulosa cells which responded to PGF2 alpha and GnRH responded to ANG II. Desensitization (pretreatment) of rat granulosa cells by continuous hormone perifusion suggested that effects of PGF2 alpha, GnRH, and ANG II on [Ca2+]i were receptor specific. However, the effects of combined hormone treatments on [Ca2+]i were not additive. The transient increase in [Ca2+]i in response to PGF2 alpha or GnRH, alone, may be maximal. Results of this study suggested that effects of PGF2 alpha, GnRH, and ANG II receptor-ligand interactions may be at least partially mediated by transient increases in [Ca2+]i in rat granulosa cells. Similarly, effects of PGF2 alpha, but not GnRH or ANG II, receptor-ligand interactions may be mediated by transient increases in [Ca2+]i in human granulosa cells.

Angiotensin II↗
PubMed1992

Luteinizing hormone-releasing hormone (LHRH)- and (hydroxyproline9)LHRH-stimulated human chorionic gonadotropin secretion from perifused first trimester placental cells.

(Hydroxyproline9)LHRH [(Hyp9)LHRH] has been isolated from human, sheep, rodent, and frog hypothalamus. (Hyp9)LHRH is the major LHRH moiety in fetal rat hypothalamus. This study compared 1) synthetic LHRH-stimulated hCG secretion from term trophoblast vs. first trimester placental cells and 2) the ability and specificity with which synthetic LHRH and (Hyp9)LHRH could stimulate hCG secretion from 8- to 12-week gestation placenta. Physically dissociated cells from multiple placentae were pooled, plated on microcarrier beads, and perifused in 1.5-ml chambers (1.5 x 10(6) cells/chamber). Effluent fractions were analyzed for hCG. Each chamber was its own control. Basal hCG secretion did not depend upon exogenous LHRH stimulation. The amplitude of LHRH-stimulated hCG pulses was greater from first trimester placental than term trophoblast cells (mean +/- SEM, 6.99 +/- 1.47 vs. 0.50 +/- 0.05 mIU/ml perifusate; peak minus basal; n = 4 chambers; P less than 0.01). LHRH and (Hyp9)LHRH (10(-9) M) increased hCG secretion from first trimester placental cells (5.02 +/- 1.29 vs. 8.64 +/- 1.61 and 4.36 +/- 0.58 vs. 7.44 +/- 1.01 mIU/ml; n = 15 and 9, respectively; P less than 0.01). At the concentrations used, LHRH and (Hyp9)LHRH seemed to stimulate hCG secretion equipotently (P greater than 0.05). Simultaneous perifusion with an LHRH antagonist, (Nal-Glu)LHRH blocked the hCG secretory response to LHRH or (Hyp9)LHRH (equimolar 10(-9) M concentrations; n = 5; P less than 0.05). (Nal-Glu)LHRH alone (10(-9) M) did not affect hCG secretion (n = 5; P greater than 0.05). The results suggested that first trimester placental cells are more responsive to LHRH than are term trophoblast cells. (Hyp9)LHRH is a potential physiological secretagogue of hCG.

Chorionic Gonadotropin↗
PubMed1992

Inhibition of progestin accumulation by activin-A in human granulosa cells.

The effects of activin and inhibin on steroidogenesis in the human ovary were investigated. Granulosa cells harvested from follicles of women undergoing oocyte recovery for in vitro fertilization were maintained in culture for 4 days before treatment in serum-free medium. Human recombinant inhibin-A and activin-A at concentrations of 100 ng/mL did not affect basal progesterone secretion (P greater than 0.05). Progesterone concentrations were increased 2- to 6-fold by hCG or FSH. Activin-A inhibited the progesterone response to hCG compared with that of cells treated with hCG alone (P less than 0.01). The effect of activin-A was dose dependent and significant at 16-18 h of treatment (P less than 0.01). Inhibin-A at the same concentrations as activin-A had no effect on the progesterone responses to hCG and FSH. The hCG-induced accumulation of 20 alpha-hydroxyprogesterone was also attenuated by simultaneous activin-A treatment compared to that in cells treated with hCG alone (P less than 0.01). To investigate the mechanism of action of activin-A, cells were treated with a cAMP analog (8-bromo-cAMP) or an activator of adenylate cyclase (forskolin), with or without activin-A. Activin-A had no effect on 8-bromo-cAMP-stimulated progesterone accumulation. Likewise, forskolin-stimulated progesterone accumulation was not affected by activin-A. The hCG-induced increase in intracellular cAMP was decreased by activin-A in the presence of a phosphodiesterase inhibitor, isobutylmethylxanthine (P less than 0.01). Thus, activin-A may inhibit progesterone production by suppression of gonadotropin-induced cAMP production. These results support an autocrine role of activin-A in the steroidogenic capacity of human ovarian cells.

Activins↗
PubMed1992

Rapid stimulation of human chorionic gonadotropin secretion by interleukin-1 beta from perifused first trimester trophoblast.

Placental trophoblast has been implicated as a major source of interleukin-1 beta (IL-1 beta), a cytokine that mediates immunological responses in the body. This study evaluated the effect of IL-1 beta on hCG secretion from 8- to 12-week-old placental trophoblast. Physically dissociated trophoblast cells collected from multiple placentae were cultured on carrier beads and loaded into chambers in a perifusion system. Medium was perifused through the chambers, and effluent was collected and assayed for hCG. Basal hCG secretion was not dependent on exogenous IL-1 beta or GnRH, but varied between mixed placental preparations and increased with duration of culture. Therefore, hCG secretion was expressed as a percentage of mean basal hCG secretion for any given chamber. IL-1 beta (10(-9) M) stimulated a rapid and transient hCG secretory response. hCG release increased by approximately 150% (P less than 0.05; n = 5) in response to the cytokine, but lower concentrations (10(-10) and 10(-11) M) were ineffective (P greater than 0.05; n = 3 each). GnRH stimulated hCG secretion by approximately 80% (P less than 0.05; n = 6). The hCG secretory profiles in response to IL-1 beta and GnRH were similar. Combined treatment with equimolar (10(-9) M) IL-1 beta and GnRH increased hCG secretion by approximately 150% (P less than 0.05; n = 5), stimulating hCG secretion as effectively as either hormone alone (P greater than 0.05). The stimulatory effect of GnRH on hCG secretion was blocked by the concomitant presence of a GnRH antagonist, Nal-Glu-GnRH (P less than 0.05; n = 5). However, simultaneous treatment with IL-1 beta and Nal-Glu-GnRH did not affect IL-1 beta-stimulated hCG secretion (100.5 +/- 3.6 vs. 162.9 +/- 10.2%; P less than 0.05; n = 7). The data suggest that IL-1 beta and GnRH stimulated a near-maximal physiological hCG secretory response, possibly through different receptor types. Alternatively, these two hormones may share a common signal transduction pathway, or IL-1 beta may influence a step distal to the coupling of GnRH to its receptor in the placental trophoblast.

Cells, Cultured↗