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Biomedical subjects

E H Ng

Publications and source records attributed to E H Ng.

At least 19 recordsLinked to original sources
PubMed2001

Demonstration of mixed properties of RU486 in progesterone receptor (PR)-transfected MDA-MB-231 cells: a model for studying the functions of progesterone analogues.

Progesterone antagonist RU486 (mifepristone) has been implicated for many anti-neoplastic and obstetrical applications. But the compound has demonstrated undesired agonist-like effect depending on cell, tissue and species studied. Using PR-transfected breast cancer cells MDA-MB-231, this report describes the similarities and differences between progesterone- and RU486-mediated effects on cell growth, cell differentiation and, at the molecular level, on the activation of p44/p42 MAP kinases (MAPK). Like progesterone, RU486 inhibited cells growth by arresting the cells in G0/G1 phase of the cell cycle. In contrast to progesterone that induced cell spreading, RU486 induced a multipolar, stellate morphology. RU486-treated cells showed no increase of stress fibers, nor was there any increase of focal adhesions as progesterone-treated cells did. Furthermore, despite of the fact that both compounds inhibited cell growth, RU486 significantly stimulated the activation of p44/p42 MAP kinases whereas progesterone markedly inhibited the activation. Nonetheless, the effects of RU486 were PR-mediated and RU486 was able to antagonize the effect of progesterone on cell growth and focal adhesion. In conclusion, RU486 can act not only as a progesterone antagonist, a progesterone agonist but also induced morphological and molecular changes that were distinct from progesterone-mediated effects in PR-transfected MDA-MB-231 cells. The non-progesterone-like effect of RU486 may be mediated through a pathway that is different from the progesterone-mediated pathway, or it is the result of a blockade of certain critical step(s) in the progesterone-mediated pathway. In any case, undesired side effects of antiprogestin may create clinical complications. PR-transfected MDA-MB-231 breast cancer cells provide a model for studying the functions of progesterone analogues.

Breast Neoplasms↗
PubMed2001

Seasonal variation in breast cancer diagnosis in Singapore.

This study investigates seasonality in the diagnosis of 3219 female breast carcinoma cases reported between 1995-8 in Singapore. There is little evidence of marked seasonal variation. Angular regression suggested that observed differences in peak diagnosis with respect to menopausal status, tumour size, ER and PR status may be chance.

Adult↗
PubMed2001

Paracervical block with and without conscious sedation: a comparison of the pain levels during egg collection and the postoperative side effects.

OBJECTIVE: To compare the pain levels during egg collection and the subsequent postoperative side effects in patients receiving a paracervical block (PCB) with and without conscious sedation. DESIGN: A prospective, randomized, double-blind, and placebo-controlled study. SETTING: A tertiary assisted reproduction unit. PATIENT(S): 150 patients undergoing egg collection. INTERVENTION(S): Randomized to receive PCB only (control group) and PCB in conjunction with conscious sedation (sedation group). MAIN OUTCOME MEASURE(S): Vaginal and abdominal pain levels; severity of postoperative side effects. RESULT(S): The median pain levels during vaginal punctures were 12.0 (2.5th--97.5th centiles: 0--84.3) and 30.0 (2.5th--97.5th centiles: 0--100) in the sedation and placebo groups, respectively. The corresponding median abdominal pain levels were 16.5 (2.5th--97.5th centiles: 0--100) and 43.0 (2.5th--97.5th centiles: 0--100). The pain levels were significantly higher in the placebo group than the sedation group. There were no significant differences between the two groups in the severity of nausea, vomiting, dizziness, and drowsiness. CONCLUSION(S): Patients who received only a PCB during the egg collection experienced 2.5 times higher levels of vaginal and abdominal pain as compared to those who received both PCB and conscious sedation. The use of PCB along is not recommended for all patients but it may be considered with selected patients after they have been given extensive counseling.

Abdominal Pain↗
PubMed2001

Colour Doppler analysis of peri-implantation utero-ovarian haemodynamics in women with excessively high oestradiol concentrations after ovarian stimulation.

BACKGROUND: Gonadotrophins are used in many assisted reproduction units to achieve a better success rate by increasing the number of replaced embryos. However, high oestradiol concentrations are associated with altered physiological functions and its complications. We investigated whether high oestradiol concentrations (> or =20 000 pmol/l) after ovarian stimulation in infertile women would affect the uterine haemodynamics at the time of embryo transfer. METHODS: Colour Doppler indices of utero-ovarian arteries and endometrial colour signals were measured. Fifty-eight women undergoing ovarian stimulation for IVF were classified according to serum oestradiol concentrations on the day of human chorionic gonadotrophin injection into moderate responders (oestradiol <20 000 pmol/l; n = 39) and high responders (oestradiol > or =20 000 pmol/l; n = 19). RESULTS: Haemodynamic parameters were significantly lower in high responders; the uterine arterial pulsatility index (PI) and resistance index (RI) were (median; range) 1.87 (0.84-2.82) and 0.79 (0.57-0.90) respectively; ovarian artery PI was 0.57 (0.40-1.12) and RI was 0.43 (0.33-0.64). In moderate responders the uterine PI and RI were 2.63 (1.46-5.92) and 0.88 (0.77-1.10) respectively. Ovarian PI was 0.81 (0.32-3.72) and RI was 0.55 (0.23-0.97). The number of women showing endometrial colour signals was significantly lower in high responders (63%) than in moderate responders (92%) (P < 0.05). A further increase in oestradiol (> or =25 000 pmol/l; n = 8) showed significantly (P = 0.03) fewer endometrial colour signals [1.5 (0-8)] compared with moderate responders [4 (0-14)]. CONCLUSION: Despite low uterine PI and RI, the endometrial blood flow in high responders appears to be impaired. This may contribute to the decline in implantation efficiency noted in high responders.

Adult↗
PubMed2001

Ultrasound-guided embryo transfer: a prospective randomized controlled trial.

BACKGROUND: Recent reports suggested that ultrasound guidance during embryo transfer might improve the pregnancy rate. METHODS: A prospective randomized controlled trial was performed to compare embryo transfer under ultrasound guidance versus the clinical touch method. A total of 800 embryo transfers was studied; 400 were randomized to ultrasound-guided transfers and 400 were randomized to the clinical touch group. Of these, 441 were fresh cycles and 359 were frozen-thawed cycles. RESULTS: The clinical pregnancy rate was 26.0% in the ultrasound-guided group and 22.5% in the clinical touch group; the difference was not statistically significant. The ongoing pregnancy rate was 23.5% in the ultrasound-guided group compared with 19.0% in the clinical touch group and the difference was again not statistically significant. The implantation rate was slightly higher in the ultrasound-guided group (15.3%) than the clinical touch group (12.0%) (P = 0.048). There were no differences in the incidences of ectopic pregnancy, miscarriage and multiple pregnancy between the two groups. CONCLUSIONS: A significant improvement in implantation rate was observed following the use of ultrasound guidance during embryo transfer. The extent of improvement in the pregnancy rate may depend on the specific techniques and methods of embryo transfer used in individual centres.

Abortion, Spontaneous↗
PubMed2001

HMG is as good as recombinant human FSH in terms of oocyte and embryo quality: a prospective randomized trial.

Previous studies have demonstrated that the use of recombinant human follicle stimulating hormone (rhFSH) for ovarian stimulation may be associated with a better outcome than human menopausal gonadotrophin (HMG), probably due to the absence of LH, higher FSH bioactivity and better quality of oocytes and embryos when rhFSH is used. Very few studies have examined the effects of different gonadotrophins on oocyte and embryo quality. In this prospective study, 40 women undergoing ovarian stimulation for intracytoplasmic sperm injection were randomized to receive a standard protocol of either HMG or rhFSH in down-regulated cycles. Prior to microinjection, each denuded oocyte was videotaped to assess nuclear maturity, morphology of zona pellucida, oocyte and polar body and the zona thickness, and diameters of oocyte and ooplasma. Fertilization and subsequent embryo development of each oocyte were followed. The embryologists were blind to the type of gonadotrophin each patient had received for stimulation. No significant differences were found between the two groups with regard to the demographic data, the ovarian responses and pregnancy/implantation rates. The percentage of metaphase II oocytes in the HMG and rhFSH groups were similar (86.9 versus 87.4% respectively). All other parameters assessing oocyte and embryo quality were also comparable between the two groups.

Adult↗
PubMed2001

Morphometric analysis of peri-implantation endometrium in patients having excessively high oestradiol concentrations after ovarian stimulation.

The present study investigated whether high oestradiol concentrations after ovarian stimulation in infertile women affect endometrial development around the time of implantation. The glandular and stromal components of the endometrium were assessed by morphometric criteria. Endometrial biopsies were taken on day 7 (+/-1) after the ovulating dose of human chorionic gonadotrophin in stimulation cycles and on day 7 after the LH surge in natural cycles. Women (n = 38) undergoing assisted reproduction treatment were evaluated: 12 women in natural cycles, 11 women in stimulation cycles with oestradiol <20,000 pmol/l and failed fertilization after oocyte collection (moderate responders) and 15 women with an oestradiol concentration of > or =20,000 pmol/l in stimulation cycles (high responders). High responders showed delayed glandular maturation and advanced stromal morphology, whereas moderate responders demonstrated synchronous development of glandular and stromal features. In natural cycles, the glands were in phase. The effect of excessively high oestradiol concentrations could be explained by quantitative evaluation of the endometrial biopsies as gland--stromal dyssynchrony, which indicates a deficient secretory transformation of the endometrium that represents a suboptimal endometrial environment for implantation. This substantiates our previous clinical observation of significantly lower pregnancy rates in IVF cycles of women with high oestradiol concentrations (> or =20,000 pmol/l).

Adult↗
PubMed2001

Measurement of serum CA-125 concentrations does not improve the value of Chlamydia trachomatis antibody in predicting tubal pathology at laparoscopy.

Chlamydia antibody testing (CAT) has been used to predict tubal pathology associated with Chlamydia infection, the leading cause of pelvic inflammatory disease (PID). Tubal pathology not related to C. trachomatis is unlikely to be identified by CAT alone. A correlation between serum CA-125 concentrations and the severity of adnexal inflammation during acute PID was demonstrated. The objectives of this study were to determine the prevalence of C. trachomatis infection in an Asian infertile population and to assess the role of a combination of serum CA-125 and CAT in the prediction of tubal pathology as shown by laparoscopy. A total of 110 consecutive women attending an infertility clinic for work-up were recruited. Blood was taken for CAT and CA-125 on the day of hospital admission and an endocervical swab was taken for culture of C. trachomatis prior to laparoscopy. Two (1.8%) women had C. trachomatis found in the endocervix and 28 (25.5%) women had CAT of > or = 1:32. Serum CA-125 concentrations were > 35 IU/ml in 11 (10%) women. The discriminative capacity of CAT in the diagnosis of tubal pathology including both proximal and distal obstruction was not improved by measuring serum CA-125, regardless of the threshold values of serum CA-125 concentration.

Adult↗
PubMed2001

Effects of metformin on ovulation rate, hormonal and metabolic profiles in women with clomiphene-resistant polycystic ovaries: a randomized, double-blinded placebo-controlled trial.

BACKGROUND: Metformin, an insulin-sensitizing agent, has been used successfully as the first-line drug to induce ovulation in women with polycystic ovary syndrome. There are, however, very few studies evaluating metformin treatment in women with clomiphene citrate (CC)-resistant polycystic ovaries (PCO). METHODS: Twenty infertile Chinese women aged <40 years, who had ultrasound features of PCO and remained anovulatory on CC, were randomized by computer using the sealed envelope method to receive placebo or metformin 500 mg three times a day for 3 months. Hormonal and metabolic profiles were determined before the therapy and were repeated after 3 months for women who failed to become pregnant within this period. Clomiphene was then added for one cycle to those women who did not ovulate after taking placebo or metformin alone. RESULTS: The median ovulation rate in the placebo group was 0% (range: 0--50%) after placebo only and 6.9% (range: 0--50%) after placebo and CC, whereas the corresponding rates in the metformin group were 0% (range: 0--22%) and 0% (range: 0--22%) respectively. There was no improvement in the ovulation rate despite a significant reduction of body mass index, serum testosterone and fasting leptin concentrations in the metformin group. CONCLUSIONS: Metformin treatment may result in successful ovulation only in certain subgroups of these women.

Adult↗
PubMed2001

Use of gonadotrophin releasing hormone (GnRH) antagonist (cetrotide) during ovarian stimulation for in-vitro fertilization treatment: multiple doses and single dose.

OBJECTIVES: To report preliminary experience in using the GnRH antagonist (Cetrotide) and to compare the multiple dose and single dose protocols. METHODS: Fifteen patients received multiple doses and another 10 patients received the single dose protocol of GnRH antagonist during ovarian stimulation for IVF treatment. Outcome measures included the duration/dosage of gonadotrophin and number of oocytes aspirated. RESULTS: All patients had successful oocyte retrieval after the hCG injection. The single dose group had a significantly shorter duration of gonadotrophin but fewer frozen embryos than the multiple dose group. CONCLUSIONS: Both protocols were effective in preventing premature LH surges. The stimulation regimen was simplified by reducing the total treatment period, the dosage and duration of gonadotrophin. There may be differences in ovarian responses between the two protocols.

Adult↗
PubMed2001

Transfer of two embryos instead of three will not compromise pregnancy rate but will reduce multiple pregnancy rate in an assisted reproduction unit.

OBJECTIVE: To compare the pregnancy rates and multiple pregnancy rates of cycles initiated in 1998 and in 1999, during which 3 and 2 embryos were advised to be replaced, respectively. STUDY DESIGN: A retrospective study RESULTS: There were no differences between 1998 and 1999 in the pregnancy rate per cycle started or per transfer, implantation rate and the multiple pregnancy rates, despite a significantly lower number of embryos replaced in 1999. A significantly higher implantation rate was found in cycles with frozen embryos than those without. Using logistic regression analysis, the chance of pregnancy was significantly improved only by the presence of frozen embryos in the fresh cycles with an odds ratio of 2.0 (95% confidence interval: 1.3-3.0) whereas the chance of multiple pregnancy was significantly increased by replacing 3 embryos instead of 2 (odds ratio: 2.1, 95% confidence interval: 1.1-4.2). CONCLUSION: Patients should be advised to have 2 embryos replaced without jeopardizing the pregnancy rates in the fresh cycles. The risk of multiple pregnancy is significantly increased when 3 embryos are transferred instead of 2.

Adult↗
PubMed2001

Defective glucose-dependent insulinotropic polypeptide receptor expression in diabetic fatty Zucker rats.

Glucose-dependent insulinotropic polypeptide (GIP) is a peptide hormone that is released postprandially from the small intestine and acts in concert with glucagon-like peptide (GLP)-1 to potentiate glucose-induced insulin secretion from the pancreatic beta-cell. In type 2 diabetes, there is a decreased responsiveness of the pancreas to GIP; however, the insulin response to GLP-1 remains intact. The literature suggests that the ineffectiveness of GIP in type 2 diabetes may be a result of chronic homologous desensitization of the GIP receptor. Yet, there has been no conclusive evidence suggesting that GIP levels are elevated in diabetes. The hypothesis of the present study is that one cause of decreased responsiveness to GIP in type 2 diabetes is an inappropriate expression of the GIP receptor in the pancreatic islet. This hypothesis was tested using a strain of diabetic fatty Zucker rats. The obese rats displayed basal GIP levels similar to the control animals; however, they were unresponsive to a GIP infusion (4 pmol.min(-1). kg(-1)), whereas the lean animals displayed a significant reduction in blood glucose (GIP levels, 50% control after 60 min, P < 0.05) as well as a significant increase in circulating insulin. GIP also potently stimulated first-phase insulin secretion from isolated perifused islets (10.3 +/- 3.0 x basal), and GIP and GLP-1 potentiated insulin secretion from the perfused pancreas (6 x control area under the curve [AUC]) from lean animals. GIP yielded no significant effect in the Vancouver diabetic fatty Zucker (VDF) rat pancreases, whereas GLP-1 elicited an eightfold increase of insulin secretion from the perfused VDF pancreas. Islets from lean animals subjected to static incubations with GIP showed a 2.2-fold increase in cAMP, whereas GIP failed to increase islet cAMP in the VDF islets. Finally, the expression of both GIP receptor mRNA and protein was decreased in islets from VDF rats. These data suggest that the decreased effectiveness of GIP in the VDF rat and in type 2 diabetes may be a result of a decreased receptor expression in the islet.

Animals↗
PubMed2001

In vitro fertilization and embryo transfer during natural cycles.

OBJECTIVE: To report the results of in vitro fertilization and embryo transfer (IVF/ET) performed during natural cycles. STUDY DESIGN: A prospective clinical study. RESULTS: Thirty-two cycles were started in 19 patients who had regular ovulatory cycles and tubal factors or unexplained infertility only as the cause of infertility. Egg collection was performed in 12 cycles, and four pregnancies resulted from ET in eight cycles. The pregnancy rates were 12.5% per cycle initiated, 33.3% per retrieval cycle and 50% per transfer. CONCLUSION: Natural cycle IVF/ET offers a low-cost alternative to patients with infertility.

Adult↗
PubMed2001

A comparative study of raw and prepared semen samples from two consecutive days.

OBJECTIVE: To study and compare raw and prepared semen samples from two consecutive days by conventional sperm parameters, various motility characteristics of spermatozoa determined by computer-aided sperm analysis and calcium ionophore-induced acrosome reaction. STUDY DESIGN: Semen samples of male partners in couples undergoing 81 cycles of double intrauterine insemination were studied. The first sample was produced after abstinence of 2-7 days and the second, 24 hours after the first. Both samples were processed by isolate sperm separation medium. RESULTS: Semen volume, sperm concentration and total motile spermatozoa were significantly reduced in day 2 raw and prepared samples, whereas normal morphology, motility characteristics and percentage of acrosome-reacted spermatozoa increased significantly in day 2 inseminated samples as compared to day 1. Oligospermic, asthenospermic and teratozoospermic samples showed a significant improvement in concentration, various motility characteristics and normal morphology of spermatozoa in day 2 samples as compared to day 1. CONCLUSION: Men with normal samples showed improvements in normal morphology and acrosome-reacted spermatozoa, whereas those with subnormal semen samples from day 1 showed a significant improvement in concentration, various spermatozoal velocities and normal morphology on day 2.

Acrosome Reaction↗
PubMed2001

Effect of progesterone on the invasive properties and tumor growth of progesterone receptor-transfected breast cancer cells MDA-MB-231.

One of the potential therapeutic interventions to hormone-independent breast cancer would be to reactivate the expression of estrogen receptor or progesterone receptor (PR) in the tumor cells so as to render the tumor responsive to the hormones. We have reported previously that progesterone markedly inhibited cell growth and induced remarkable focal adhesions in PR-transfected MDA-MB-231 cells. The aim of this study was to determine the effects of progesterone on the invasive properties and in vivo tumor growth of PR-transfected MDA-MB-231 cells. It was found that progesterone has increased cell resistance to trypsin digestion and increased cell attachment to extracellular matrix proteins, especially laminin and fibronectin. In vitro invasion assays using modified Boyden chambers showed that progesterone increased cell migration through matrix protein-coated membranes. However, Northern blotting analysis demonstrated that progesterone strongly down-regulated (up to 60-fold) the gene expression of urokinase plasminogen activator and increased (up to 5-fold) the expression of tissue-type plasminogen activator in these cells. This pattern of gene regulation suggested an inhibition of cell invasiveness because numerous clinical studies have indicated that low levels of urokinase plasminogen activator and high levels of tissue-type plasminogen activator in breast cancer are associated with favorable prognosis. Furthermore, animal studies showed that progesterone strongly inhibited the tumor formation and growth in Scid mice. After 12 weeks of inoculation, the median weight of tumors in the progesterone-treated group was 25 mg compared with 203 mg in the placebo group (P < 0.001). These results suggest that progesterone may provide effective treatment for estrogen receptor- and PR-negative breast cancer if the PR expression were reactivated. Alternatively, activation of progesterone-mediated molecular pathways in hormone-independent breast cancer may achieve similar therapeutic effects.

Animals↗