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Biomedical subjects

K J Thong

Publications and source records attributed to K J Thong.

At least 19 recordsLinked to original sources
PubMed2004

A comparison of psychological functioning in couples undergoing frozen-thawed embryo replacement in various stages of treatment using the Mean Affect Adjective Check List (MAACL).

PURPOSE: The objectives were to identify the stage(s) of frozen embryo replacement cycle where the couples are most vulnerable to psychological dysfunction. Assessment was performed by using the Mean Affect Adjective Check-List (MAACL). METHODS: Thirty couples completed the MAACL questionnaire at the following stages: (a) pretreatment (visit 1), (b) before embryo transfer (visit 2), and (c) before pregnancy test (visit 3). Each partner had to complete a separate questionnaire set. RESULTS: For both partners, the depression score for visit 3 was significantly higher and the sensation seeking and positive affect scores were significantly lower than the corresponding scores for earlier visits. Anxiety scores were similar for all visits. For men, the hostility scores were significantly higher between visits 1 and 2 while in women the same was reported between visits 3 and 2. CONCLUSIONS: Psychological counselling should be targeted at couples especially after embryo transfer. MAACL is a useful method for measuring psychological dysfunction in these couples.

Adult↗
PubMed2003

A prospective randomized clinical trial comparing 150 IU and 225 IU of recombinant follicle-stimulating hormone (Gonal-F*) in a fixed-dose regimen for controlled ovarian stimulation in in vitro fertilization treatment.

OBJECTIVE: To compare fixed daily doses of the recombinant FSH (rFSH) Gonal-F (150 IU vs. 225 IU) for ovarian stimulation in IVF-ET. DESIGN: Single-center prospective, randomized study. Assisted conception unit of a university hospital. One hundred twenty-four women aged 23-41 years participated in the study. Exclusion criteria were as follows: FSH of >10 IU/L, polycystic ovarian syndrome, one ovary or previous ovarian surgery, previous poor response to ovarian stimulation, or ovarian hyperstimulation syndrome (OHSS). INTERVENTION(S): Randomized to commence 150 IU or 225 IU of Gonal-F per day without dose alterations during treatment. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved and total rFSH dose. RESULT(S): More oocytes were retrieved in women aged or=33 years), the number of oocytes retrieved in the two groups were similar. No significant differences were found for fertilization rate, number of embryos formed and cryopreserved, and pregnancy rates between the two groups. The total rFSH dose used was higher in the 225-IU group (2,595.0 +/- 510.0 vs. 1,897.5 +/- 457.5 IU). The cancellation rate due to insufficient ovarian response was higher in the 150-IU group (15.0% vs. 3.3%). All cases of ovarian hyperstimulation syndrome (n = 4) occurred in the 225-IU group. CONCLUSION(S): Two hundred twenty-five IU is more effective than 150 IU in younger women but requires a higher total dose of Gonal-F. The use of 225 IU in older women did not result in a higher oocyte yield, suggesting that 225 IU of rFSH does not compensate for the age-related decline in the number of follicles available for stimulation.

Adult↗
PubMed2003

The administration of the GnRH antagonist, cetrorelix, to ooctye donors simplifies oocyte donation.

BACKGROUND: We report our experience on the efficacy of a new regimen of the GnRH antagonist, cetrorelix, and recombinant FSH, Gonal-F, for controlled ovarian stimulation in a donor oocyte programme. METHODS AND RESULTS: Six oocyte donors were commenced on Gonal-F (150 IU) and two on Gonal-F 225 IU daily on day 4 together with cetrorelix 0.25 mg daily on day 8 until the day of administration of hCG. Six premenopausal recipients were down-regulated with intranasal Nafarelin 400 micro g twice daily; two women with premature menopause did not require down-regulation for synchronization between donor and recipient cycles. The median (range) of oocytes retrieved and the median (range) fertilization rates were 7 (3-13) and 50% (0-71%) respectively. With the exception of a recipient who had failed fertilization, seven recipients had two embryos transferred. The median (range) number of days of ovarian stimulation, cetrorelix administration and number of Gonal-F ampoules administered for ovarian stimulation were 9 (7-12) days, 5 (3-8) and 18 (14-24) respectively. The clinical pregnancy rate per cycle was 50% (4/8) and one of the latter women miscarried at eight weeks gestation. Three women (37.3%) had full term deliveries. CONCLUSION: This preliminary study has shown that using a combination of cetrorelix and Gonal-F resulted in a high pregnancy rate, reduced the duration of treatment for the donor and simplified oocyte donation.

Adult↗
PubMed2002

Regulation of 11beta-hydroxysteroid dehydrogenase type 1 gene expression in human ovarian surface epithelial cells by interleukin-1.

BACKGROUND: Local modulation of 11beta-hydroxysteroid dehydrogenase (11betaHSD) activity, to promote increased availability of anti-inflammatory glucocorticoids, is proposed as a compensatory response to inflammatory stimuli. Human 11betaHSD type 1 (11betaHSD1) is principally an 11-oxoreductase that reversibly reduces cortisone to cortisol. METHODS: Since ovulation is an acute inflammatory process, we examined the influence of pro-inflammatory cytokines on expression of 11betaHSD1 mRNA and metabolism of cortisone to cortisol by human ovarian surface epithelium (HOSE) in vitro. RESULTS: Northern analysis showed an approximately 1.5 kb-sized 11betaHSD1 mRNA transcript in total RNA that was up-regulated approximately 3-fold by interleukin (IL)-1alpha (0.5 ng/ml) at 24 h. By real-time RT-PCR, induction of 11betaHSD1 mRNA by IL-1alpha was measurable at 6 h and maximal at 12 h. Primary HOSE cell cultures also showed low-level 11-oxoreductase activity that was stimulated time- and dose-dependently by IL-1alpha and IL-1beta. The 11betaHSD1 mRNA and 11-oxoreductase responses to 0.5 ng/ILalpha were both suppressed by IL-1 receptor antagonist (25 ng/ml). CONCLUSIONS: Cultured HOSE cells express IL-1-responsive 11betaHSD1 and 11-oxoreductase activity mRNA in vitro. An 11betaHSD1-catalysed increase in anti-inflammatory glucocorticoid activity caused by pro-inflammatory cytokines could contribute to the local resolution of inflammation during ovulation.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2001

Second trimester medical abortion with mifepristone and gemeprost: a review of 956 cases.

The treatment outcomes of 956 women undergoing second trimester termination of pregnancy with mifepristone and gemeprost were studied. The median gestational age was 16 weeks (range: 12-24 weeks). All women were treated with 200 mg mifepristone orally, followed 36 h later with 1 mg vaginal gemeprost administered every 6 h to a maximum of 4 doses in the first 24 h. A second course of 1 mg vaginal gemeprost was given 3-hourly in the next 12 h, if abortion had not occurred. Overall, 96.4% and 98.8% of the women aborted within 24 and 36 h, respectively. The median induction-to-abortion interval was 7.8 h (range: 0.5-109.9 h). The induction-abortion interval was longer in nulliparous women and women with a gestation age 17 weeks or above. Surgical evacuation of the uterus was performed in 11.5% of women for incomplete abortion or retained placenta. More multiparous women (16.7%) required surgical evacuation of uterus than did nulliparous women (7.3%; p <0.001). Ten (0.1%) women failed to abort with gemeprost and required other methods for abortion. In conclusion, a combination of mifepristone and gemeprost is a safe, effective, and noninvasive method of medical abortion for second trimester pregnancy.

Abortifacient Agents, Nonsteroidal↗
PubMed2000

Development-related increase in cortisol biosynthesis by human granulosa cells.

Antiinflammatory mechanisms are important in ovulation and may be regulated by cortisol (F). We previously showed that after administration of human (h)CG for ovulation induction, luteinized granulosa cells (LGC) abundantly express 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) messenger RNA but not 11betaHSD type 2 (11betaHSD2) messenger RNA. 11ssHSD1 is responsible for the reversible formation of antiinflammatory F from its inactive precursor cortisone (E), whereas 11betaHSD2 unidirectionally converts F to E through 11-oxidation. This pattern of gene expression predicts that LGC from periovulatory follicles would show increased activation of E to F, compared with granulosa cells from immature follicles (IGC), and that follicular fluid concentrations of E and F would alter accordingly. To test this hypothesis, we isolated IGC, thecal cells (TC), and follicular fluid, from ovaries of cyclic women, removed during surgery for benign gynecological disease. LGC and follicular fluid were aspirated from periovulatory follicles, 35 h after hCG injection, in patients undergoing in vitro fertilization treatment. In an 11betaHSD assay based on interconversion of tritiated E and F by cell suspensions in vitro, IGC (% conversion, 0.6 +/- 0.4, mean +/- SEM) and collagenase-dispersed TC (0.2 +/- 0.1%) were unable to convert E to F, whereas LGC (36.3 +/- 3.7%) were highly efficient at this reaction. Immature granulosa cells, LGC, and (to a lesser extent) TC were all able to convert F to E. Correspondingly, follicular fluid concentrations of total F and F:E ratios were significantly higher in periovulatory follicles, compared with immature follicles. Culturing IGC for 48 h in the presence of hFSH resulted in increased 11betaHSD1 reductase activity, paralleling stimulation of estrogen (aromatase activity) and progesterone biosynthesis. Similar treatment with hLH did not influence 11betaHSD1 reductase activity, except in a patient with more mature IGC, which also showed a significant increase in E-to-F conversion, as well as progesterone synthesis in response to hLH. These data confirm that 11betaHSD activity in the human ovary is developmentally regulated and gonadotropin responsive, favoring metabolism of F to E in immature follicles and E to F in periovulatory follicles. Increased formation of F by LGC in periovulatory follicles is consistent with an antiinflammatory function for this glucocorticoid at ovulation.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Routine antenatal screening for syphilis in Lothian: a study of the results 1988 to 1994.

A retrospective study was carried out of the cases of positive syphilis serology detected by routine antenatal screening within Edinburgh (and surrounding district) over the six years 1988 to 1994. The study demonstrated a low incidence of syphilis with only 15 pregnancies in 58,445 screened. In eight cases serology and history were suggestive of late latent syphilis and in the remainder of previous infection which had been treated. All women were delivered of liveborn infants at term without stigmata of congenital syphilis. Lack of identifiable risk factors in women with positive serology suggests that routine rather than selective screening should continue.

Adult↗
PubMed1996

A randomised study of two doses of gemeprost in combination with mifepristone for induction of abortion in the second trimester of pregnancy.

Two regimens of the prostaglandin E1 analogue, gemeprost, in combination with mifepristone were compared in a randomised trial for termination of pregnancy between 12-19 weeks. Thirty-six hours after treatment with 200 mg mifepristone, women were allocated at random to receive either 4 x 1 mg (Group I) or 4 x 0.5 mg (Group II) gemeprost by vaginal pessary every 6 hours (n = 50 in each group). If abortion had not occurred after 24 h, 5 x 1 mg of gemeprost was administered every 3 h to both groups of women. Although the median abortion interval was slightly shorter in the 1 mg group (7.8 h vs. 8.4 h, p = 0.5), the cumulative abortion rates at 24 h were similar (98% vs. 96%). Women in Group I required significantly more gemeprost to induce abortion than Group II (p < 0.0001). Parous women in both groups required significantly less of the prostaglandin to induce abortion. In Group II, the median abortion interval was significantly longer in primigravidae than multigravidae (9.5 h vs. 6.1 h; p < 0.02). There were no significant differences between the groups in the incidence of vomiting, diarrhoea or the request for analgesia. The results suggest that in parous women, the dose of gemeprost can be reduced to 0.5 mg every 6 h within the first 24 h without loss of clinical efficacy.

Abortifacient Agents, Nonsteroidal↗
PubMed1996

Effects of daily low dose mifepristone on endometrial maturation and proliferation.

Following an ovulatory control cycle, six women took 2 mg of mifepristone daily for 30 days. Endometrial biopsies were collected in the control cycle between 7 and 11 days after the plasma luteinizing hormone (LH) surge and on the corresponding day of the treatment cycle (days 19-28). In order to investigate the effects of unopposed oestrogen on the endometrium, persistent proliferative endometrium was obtained from six women with anovulatory infertility due to polycystic ovarian syndrome (PCOS) on a similar cycle day (days 21-23) following a progestogen-induced withdrawal bleed. Endometrium was evaluated for histology and immunolocalization of oestrogen receptors (ER), progesterone receptors (PR) and the cell proliferation markers [proliferating cell nuclear antigen (PCNA) and Ki67]. Treatment with mifepristone inhibited ovulation in four of the six subjects. In the two subjects in whom ovulation did occur, secretory transformation was delayed, suggesting that successful implantation of a blastocyst would be unlikely. In subjects who remained anovulatory during treatment, the histology and pattern of steroid receptor expression was similar to proliferative phase endometrium. In women with PCOS, mitoses and intense immunostaining for ER, PR and cell proliferation markers were observed in both glands and stroma. Although PCNA and Ki67 immunostaining were also present in mifepristone-treated endometrium from subjects who did not ovulate, there were no mitoses and significantly less ER immunostaining in spite of exposure to unopposed oestrogen for a similar duration. Since PCNA and Ki67 detect cells throughout all stages of the cell cycle this would suggest that mifepristone might affect the entry of cells into the mitotic phase of the cell cycle and, therefore, might prevent endometrial hyperplasia. These findings add further evidence to support the contraceptive potential and antiproliferative activity of daily low dose mifepristone.

Adult↗
PubMed1995

Metabolic regulation of androgen production by human thecal cells in vitro.

The association between hyperinsulinaemia and hyperandrogenism in many women with polycystic ovarian syndrome (PCOS) implies roles for insulin and insulin-like growth factors (IGFs) in the regulation of ovarian androgen production. The aim of the present study was to compare the abilities of insulin, IGF-I and IGF-II to stimulate androgen production by human thecal cells in vitro. Serum-free monolayer cell cultures were established from the ovaries of euandrogenic women undergoing hysterectomy with oophorectomy for non-ovarian indications. Androgen (androstenedione) production was determined after 4 days of culture in the presence of insulin or either of the IGFs (10-100 ng/ml), with and without a maximal stimulatory dose of luteinizing hormone (LH; 10 ng/ml). Interactions with inhibin (30 ng/ml), a putative paracrine regulator of ovarian androgen synthesis, were also tested. The three metabolic hormones exerted similar dose-related effects on androgen production (ED50 < or = 10 ng/ml), which were augmented 2- to 3-fold in the presence of LH and further increased several-fold by the additional presence of inhibin. No treatment with insulin or either IGF stimulated thecal cell growth, but all treatments caused striking morphological changes consistent with enhanced steroidogenesis. These results reveal potent regulatory effects of metabolic hormones on human thecal androgen synthesis, which imply (i) 'progonadotrophic' roles for insulin and IGF-I in regulating normal ovarian androgen production, (ii) a role for insulin in the aetiology of hyperandrogenism (both with and without hyperinsulinism) in PCOS and (iii) paracrine roles for granulosa-derived IGF-II and inhibin in regulating ovarian androgen production.

Adult↗
PubMed1995

Randomized trial of misoprostol and cervagem in combination with a reduced dose of mifepristone for induction of abortion.

Mifepristone (600 mg) in combination with a prostaglandin has been demonstrated to be a safe, acceptable alternative to vacuum aspiration for induction of abortion in the first 9 weeks of pregnancy. However, the efficacy and side-effects of different prostaglandins used in combination with mifepristone have not been assessed in a randomized trial. In this study, 800 women seeking an abortion at gestational age < or = 63 days amenorrhoea were randomized to receive either 0.5 mg gemeprost by vaginal pessary (group I) or 600 micrograms misoprostol (group II) by mouth approximately 48 h after taking 200 mg mifepristone by mouth. The side-effects and number of complete abortions were used as measures of efficacy. There was no significant difference in the rate of complete abortion between group I [96.7%; 95% confidence interval (CI) 94.9-98.5%, n = 391] and group II (94.6%; 95% CI 92.3-96.9, n = 386). It was not possible to assess the outcome with certainty in the remaining 23 women. However, there were significantly more ongoing pregnancies in the women who received misoprostol than in those who received gemeprost (nine versus one, P < 0.01) and in eight of these 10 women the gestation was > 49 days. Fewer women in group II required analgesia than in group I (48 versus 60%, P < 0.001) although the number requesting opiate was similar in each group (6.9 versus 5.2%, P > 0.4). The incidence of nausea and vomiting after misoprostol (47.8 and 21.9% respectively) was higher (P < 0.001) than after gemeprost (33.9 and 12% respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Abortifacient Agents, Nonsteroidal↗
PubMed1995

Failure of oestrogen induced luteinizing hormone surge in women treated with mifepristone (RU 486) every day for 30 days.

It has been demonstrated previously that administration of the antiprogestin mifepristone (RU 486; 1-5 mg daily) inhibits or delays both the pre-ovulatory luteinizing hormone (LH) surge and ovulation. To investigate this mechanism, dynamic tests of pituitary ovarian function were performed in six healthy women before and during the administration of mifepristone (2 mg daily for 30 days). On day 9 of the control and treatment cycles, samples of blood were collected every 15 min over 12 h for measurement of LH concentration. After 10 h, the responsiveness of the pituitary was tested by the i.v. injection of 10 micrograms of gonadotrophin-releasing hormone (GnRH). On day 10 of the control and treatment cycles, two patches releasing 200 micrograms/day of oestradiol were applied to skin on the abdomen for 3 days. Blood was collected at 24, 48, 59, 72, 81 and 96 h after application of the oestrogen patches for the measurement of gonadotrophin and ovarian hormone concentrations. Follicular development continued in all women during their treatment with mifepristone, and ovulation was suppressed (four women) or delayed (two women). There was no significant difference in the basal concentration of LH between the control and treatment cycles (mean +/- SE; 5.5 +/- 0.4 versus 7.7 +/- 0.4 IU/l respectively), or in the frequency (interpulse interval, 101 +/- 12 versus 105 +/- 13 min respectively) and the amplitude (2.1 +/- 0.4 versus 2.6 +/- 0.4 IU/l respectively) of LH pulses. The response to GnRH was similar. On day 10, the basal concentrations of LH, follicle-stimulating hormone (FSH), prolactin, oestradiol and progesterone and the diameter of the dominant follicle (15.7 +/- 1.8 versus 13.3 +/- 1.9 mm) were similar during control and treatment cycles. In control cycles, there were significant increases in the concentrations of LH and FSH within 72 h of application of the oestrogen patches. During treatment cycles, concentrations of FSH and LH remained low, and were significantly lower than the values observed during control cycles (P < 0.006). We conclude that the antiprogestin mifepristone disrupts ovulation by inhibiting the positive feedback effect of oestrogens and, hence, prevents or delays the generation of a pre-ovulatory LH surge.

Administration, Cutaneous↗
PubMed1995

Effect of daily low dose mifepristone on the ovarian cycle and on dynamics of follicle growth.

BACKGROUND AND OBJECTIVE: The antiprogestin mifepristone has been shown to disrupt folliculogenesis and endometrial maturation and, therefore, has the potential to be used as a novel form of contraception. The purpose of this study was to investigate further the effects of daily administration of a low dose of mifepristone (2mg) on the ovarian cycle and on the dynamics of follicle growth. SUBJECTS: Six healthy female volunteers were given 2mg mifepristone daily for 30 days following an ovulatory control cycle. MEASUREMENTS: Follicle growth was monitored with transvaginal ultrasonography and hormonal measurements in blood and urine were used to monitor effects on the ovarian cycle. In addition, concentrations of cortisol and ACTH in serum were measured to assess the effects of mifepristone on the pituitary-adrenal axis. RESULTS: Treatment with mifepristone retarded the follicular growth rate in all women (P = 0.01). Ovulation was inhibited in 4 of 6 subjects and appeared to be mediated through an effect on the hypothalamo-pituitary axis, as no surge of FSH or LH occurred. In these subjects the dominant follicle continued to grow and developed into a persistent follicle. In two cases the persistent follicle remained functional and ovulation occurred soon after stopping treatment. In the remaining two subjects, the dominant follicle developed into a non-functioning cyst ( > 30 mm) which persisted for one month after the end of the post-treatment cycle. In the two subjects who ovulated, the LH surge was delayed by 6 and 7 days but was followed by a luteal phase of normal length. There was no significant change in the concentration of ACTH or cortisol suggesting that treatment with mifepristone in this dose has little if any effect on the pituitary-adrenal axis. CONCLUSION: These findings add further evidence to support the contraceptive potential of mifepristone through effects on follicular development and on the menstrual cycle.

Adrenocorticotropic Hormone↗
PubMed1994

Decrease in human plasma gravidin levels after medical abortion.

The aim of this study was to determine if loss of pregnancy is associated with a decrease in plasma levels of gravidin, a phospholipase inhibitor thought to maintain pregnancy. Blood was taken from 28 women in the first trimester of pregnancy who had requested an abortion. The progesterone receptor antagonist, RU-486 was given on Day 0 for termination of pregnancy. Plasma gravidin levels were measured on day 0 and on day 2 just before the patients were given misoprostol, a prostaglandin E1 analogue (600 micrograms). In a small group of patients, plasma measurements were continued up to 42 days. By day 2, plasma gravidin levels had fallen significantly (100% to 94%, p = 0.010 in a paired t-test). Following treatment with prostaglandins and pregnancy loss, plasma gravidin levels continued to fall until day 14 when the non pregnant level was reached at 80% of the pregnant level. We conclude that a decrease in plasma gravidin levels is associated with loss of pregnancy. This may occur because progesterone action is blocked.

Abortion, Induced↗
PubMed1994

Lymphocyte subpopulations in early human pregnancy.

OBJECTIVE: To examine changes in lymphocyte subpopulations in early pregnancy using a methodologically appropriate study design that addresses previous sources of bias. METHODS: Thirty-seven healthy women without risk factors for human immunodeficiency virus (HIV) were reviewed when less than 9 weeks pregnant (median 51 days, range 44-61) and again at least 4 weeks following termination of pregnancy. No woman took the oral contraceptive pill. Blood was taken on each occasion at the same time of day under the same conditions of rest and food intake, transported immediately to the laboratory, and directly prepared for analysis. Lymphocyte surface markers were determined by staining with dual-colored, isotype-matched monoclonal antibody fluorescent conjugates, followed by whole blood lysis and subsequent flow cytometric analysis. RESULTS: Pregnancy was associated with a significant reduction in total lymphocytes (P < .0001) and also in CD4+ cells, whether expressed as a percentage of lymphocytes (P = .004), an absolute count (P = .0006), or a ratio (P = .01). Change was independent of the basal level except for lymphocytes, and almost all indices had significant correlations between pregnant and nonpregnant values. CONCLUSIONS: In this study design, each woman served as her own control and all factors remained constant except the pregnancy state. Early pregnancy causes a reduction in total lymphocytes of about 6% expressed as a percentage of total white cell count, and in CD4+ cells by 3% as a percentage of lymphocytes, or 100/mm3. We believe this fall can be accepted as definitive.

Adolescent↗
PubMed1993

The effects of mifepristone (RU486) on prostaglandin dehydrogenase in decidual and chorionic tissue in early pregnancy.

Prostaglandin dehydrogenase is the main inactivating enzyme for prostaglandins and therefore controls local levels of prostaglandins. Since there is some evidence that the expression of this enzyme is under progesterone control it is reasonable that one of the effects of antiprogestin is to reduce the concentration of this enzyme and thus increase the effective concentration of prostaglandin within tissue. We have investigated the amount of enzyme activity within decidua and chorionic villi from women receiving the antigestagen mifepristone (RU486) 12, 24 and 36 h prior to surgical abortion, and examined the effect on tissue concentrations of prostaglandin dehydrogenase. Women receiving mifepristone in all groups had a significant reduction in concentration of prostaglandin dehydrogenase enzyme in decidual tissue. There was also a marked reduction in prostaglandin dehydrogenase in decidual cells following RU486, as demonstrated by immunochemical methods. At this stage of pregnancy, prostaglandin dehydrogenase was present in abundance in cytotrophoblast cells of chorionic villi but virtually absent from syncytiotrophoblast. In chorionic villi after RU486 administration in vivo, there were no obvious differences in prostaglandin dehydrogenase distribution or reactivity in the majority of cases.

Abortion, Induced↗