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Biomedical subjects

Y S Moon

Publications and source records attributed to Y S Moon.

At least 55 records · Page 3Linked to original sources

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↗

A simple handling technique for mammalian oocytes and embryos during preparation for transmission electron microscopy.

Due to their small size, mammalian oocytes and embryos pose unique problems during preparation for transmission electron microscopy. This paper outlines a method which combines protein embedding with centrifugation to locate the specimens on the face of a Beem capsule mould. This method facilitates both the processing of oocytes with minimal loss and rapid location of the specimens within the block for simultaneous sectioning, staining and examination.

Animals↗

Effects of hydroxyflutamide on rats treated with a superovulatory dose of pregnant mare serum gonadotropin.

Immature female rats treated with superovulatory doses of pregnant mare serum gonadotropin (PMSG) were used to study the effects of the antiandrogen hydroxyflutamide on steroid production, particularly the biologically active androgens, in two experiments. In the first experiment, animals were given either 5 mg hydroxyflutamide or vehicle alone at 30 and 36 h following 40 IU PMSG. Compared with the vehicle group, hydroxyflutamide treatment significantly reduced the percentage of degenerate oocytes recovered from oviducts (p less than 0.05). Serum levels of testosterone and androstenedione, and their aromatized product 17 beta-estradiol, significantly decreased (p less than 0.05) in the hydroxyflutamide-treated group; however, nonaromatizable androgen, 5 alpha-dihydrotestosterone, was not affected. In the second experiment, ovaries obtained 48 h after stimulation with 4 or 40 IU PMSG were incubated with and without hydroxyflutamide (10(-5) M) and (or) testosterone (10(-7) M) to study [4-14C]pregnenolone metabolism to major steroids. In 40 IU stimulated ovaries, hydroxyflutamide significantly decreased the metabolism of pregnenolone to progesterone (p less than 0.01) and androstenedione (p less than 0.01), while the production of 17 beta-estradiol increased significantly (p less than 0.05); however, pregnenolone conversions to testosterone and 5 alpha-dihydrotestosterone were not affected. Testosterone completely reversed the hydroxyflutamide-induced alteration of pregnenolone metabolism. In contrast, there was no difference in the pregnenolone conversion patterns between untreated and hydroxyflutamide or hydroxyflutamide plus testosterone groups in 4 IU stimulated ovaries. Present results confirm our previous finding that hydroxyflutamide decreases the percentage of abnormal oocytes recovered from superovulating rats and indicates that this hydroxyflutamide effect may be partly mediated by altered ovarian steroidogenesis following inhibition of androgen binding in the ovary.

Androgens↗

The chromosomal complements of cleaved human embryos resulting from in vitro fertilization.

Chromosome preparations were made from 25 cleaved abnormal human embryos at the two- to eight-cell stage after in vitro fertilization. Morphologically, these embryos showed either variable degrees of degeneration or an abnormal number of pronuclei before first cleavage. Among 14 successfully karyotyped embryos, only 3 had a normal chromosomal complement. Eleven showed chromosomal abnormalities, including triploidy, haploidy, and mosaicism. This finding documents a high incidence of chromosomal errors in morphologically abnormal early preimplantation embryos.

Chromosome Aberrations↗

A comparison of fructosamine and glycosylated haemoglobin measurements at a diabetic clinic.

Fructosamine or glycosylated haemoglobin (HbA1) measurements are most useful in the diabetic clinic if results are available when the patient is seen, with minimum waiting time. Fructosamine measurements have the advantage of being cheaper and faster to perform on large numbers of patients than HbA1 measurements. In order to assess the acceptability of fructosamine as a complete alternative to HbA1, fructosamine, HbA1 and random plasma glucose measurements were made on all patients attending the diabetic clinic for a 6-week period. Either the fructosamine or the HbA1 result was made available when the patient was seen and the other result was given at the end of the clinic for comment as to whether or not it would have altered management. The clinicians indicated that in 7% of cases, the HbA1 result would have altered management if available when the patient was seen, whereas in 2.5% of cases, the fructosamine result would have altered management. The commonest discrepancy was disproportionate elevation of HbA1 with a normal or near normal fructosamine. For the whole group, 32% had a normal fructosamine but only 16% a normal HbA1. The best overall correlation was between HbA1 and glucose (r = 0.67). Fructosamine correlated less well with both HbA1 (r = 0.55) and glucose (r = 0.51). Thus fructosamine was an acceptable alternative to HbA1 in most cases but caution is required, particularly in patients with persistently normal fructosamine results for whom additional HbA1 checks are advised.

Biomarkers↗

Serum levels of soluble interleukin-2 receptor in pulmonary tuberculosis.

It is well known that the activation of cell mediated immunity has an important role in the pathogenesis of pulmonary tuberculosis and the production of the protective immunity against Mycobacterium tuberculosis. During the activation of T-cell by Interleukin-1 released from the macrophage, not only Interleukin-2 but also the soluble Interleukin-2 receptor (sIL-2R) molecule is released into the extracellular fluid. In vitro study reveals that the level of this sIL-2R is well correlated with the degree of activation of the T-cell. We therefore carried out this study to evaluate the significance of the serum IL-2R level in determining the disease activity of pulmonary tuberculosis. The level of sIL-2R was measured by sandwich ELISA method. The level of sIL-2R in 42 patients with bacteriologically -proven active pulmonary tuberculosis (29 far and moderately advanced pulmonary tuberculosis, age: 30.3 +/- 10.3 yrs; 13 minimal pulmonary tuberculosis, age: 34.4 +/- 15.3 yrs) was 1111 +/- 424 mu/ml, which was significantly higher than the normal control group (age: 31.0 +/- 9.9 yrs) (365 +/- 143 mu/ml) and inactive pulmonary tuberculosis group (age: 37.3 +/- 16.9 yrs) (465 +/- 131 mu/ml). But there was no significant difference between 29 patients with advanced pulmonary tuberculosis (1138 +/- 405 mu/ml) and 13 patients with minimal pulmonary tuberculosis (1051 +/- 474 mu/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of a superovulatory dose of pregnant mare serum gonadotropin on follicular steroid contents and oocyte maturation in rats.

Our previous study has shown that superovulatory treatment with pregnant mare serum gonadotropin (PMSG) in rats caused marked alterations in ovarian and serum steroid responses and coincidental increase in degenerate oocytes (Yun et al., 1987). This study examined the effects of superovulatory treatment (20 IU PMSG) on follicular steroid contents and oocyte maturation. Immature female rats aged 28-30 days were injected with 4 or 20 IU PMSG and sacrificed at 24, 48, 60, and 72 hr. Compared to control regimen, follicular content of progesterone (P) in superovulated rats significantly (P less than .05) increased at 48 hr. Androgen (A) content significantly (P less than .01) decreased below control level at 24 hr but significantly (P less than .05) increased above control level at 48 hr and 60 hr. There was no significant change in 17 beta-estradiol (E) content between the two groups. In control regimen, the ratio of A/E sharply decreased and the ratios of P/E and P/A increased steadily from 24 hr. However, superovulatory regimen showed a consistently steady state in the overall ratios of follicular steroids after 24 hr. Nuclear maturation of the majority of control oocytes recovered from oviducts at 72 hr was synchronized at metaphase II, whereas superovulated oocytes displayed different stages varying from prophase I to metaphase II at 24, 48, and 72 hr. The results provide direct evidence of atypical ovulations in superovulated oocytes with premature or asynchronous nuclear maturation and demonstrate a close relationship between meiotically aberrant oocytes and abnormal follicular steroidogenesis following superovulation with PMSG in rats.

Animals↗

Effects of clomiphene citrate on ovarian function in hypophysectomized rats.

On Days 28-30 of age, hypophysectomized rats were treated with oestradiol-17 beta (0.1 mg/day) and/or clomiphene citrate (0.1 mg/day). Subsequent treatment with PMSG (10 i.u., on Day 31) and hCG (10 i.u., on Day 33) was identical for all animals. Rats were killed on Day 34. Treatment with oestradiol-17 beta alone resulted in ovulations of 45.1 +/- 5.5 oocytes/rat (mean +/- s.e.m.). There were no ovulations among animals treated with clomiphene citrate alone but treatment with oestradiol-17 beta and clomiphene citrate resulted in a significant (P less than 0.05) reduction (23.1 +/- 7.6 oocytes/rat) in ovulatory response. Similarly, ovarian weights and serum progesterone concentrations were highest in the oestradiol-17 beta-treated rats, intermediate in those given oestradiol plus clomiphene citrate and the lowest in rats receiving clomiphene citrate alone. We suggest that clomiphene citrate exerts direct ovarian antiovulatory and oestrogen-antagonist actions.

Animals↗

Clinical and endocrine response to pulsatile intravenous gonadotropins in refractory anovulation.

We investigated the endocrine response to an experimental protocol in which human menopausal gonadotropin was delivered in pulses every 90-120 minutes by an automated pump. Thirty clomiphene citrate- and gonadotropin-releasing hormone-unresponsive anovulatory women were studied over 107 treatment cycles. In response to episodic intravenous (IV) delivery, pulses of FSH and LH were demonstrable in the circulation. In four World Health Organization (WHO) group I anovulatory women, ovulation occurred in all cycles (N = 8); the pregnancy rate per cycle was 63% and the cumulative pregnancy rate 100%. In 26 WHO group II patients, 42.4% of treatment cycles were in 12 women previously refractory to the intramuscular route of administration; the rate for ovulation was 86% (total of 99 cycles), the pregnancy rate per ovulatory cycle was 14%, and the cumulative pregnancy rate 56%. A mild phlebitis occurred at the site of the IV catheter in 24% of treatment cycles. Intravenous delivery of gonadotropins in small pulses had a dose-sparing effect and was an effective method of treating anovulatory infertile patients refractory to other conventional methods of ovulation induction.

Adult↗

Chromosome analysis of human oocytes failing to fertilize in vitro.

To assess the contribution of chromosome anomalies to the high failure of in vitro fertilization (IVF), 94 unfertilized eggs from 43 women participating in the IVF program were cytogenetically investigated. The mean age of the oocyte donors was 33.6 years. Chromosome karyotypes were obtained in 65 of 94 oocytes: 34 oocytes (52.3%) had a normal haploid chromosome complement; 10 (15.4%) were hypohaploid; 7 (10.8%) were hyperhaploid; 8 were diploid; and 6 were hypodiploid or hyperdiploid (from 36 to 53). Eleven eggs showed prematurely condensed chromosomes of the G1-phase from sperm, as well as a set of maternal metaphase II chromosomes. These results are compared to similar reports in the literature.

Adult↗

Direct effects of clomiphene citrate on the steroidogenic capability of human granulosa cells.

The effects of clomiphene citrate (CC), 17 beta-estradiol (E2), and human chorionic gonadotropin (hCG) on the accumulation of progesterone (P) and 20 alpha-hydroxy-4-pregnen-3-one (20 alpha-OHP) in cultured human granulosa cells (GC) were examined. In addition, the metabolism of [4-14C]pregnenolone and accumulation of [4-14C]P in response to CC and E2 were determined. The authors conclude the following: (1) the dose-dependent inhibition of P and 20 alpha-OHP production by CC in GC was not reproduced by E2, (2) hCG abolished these effects of CC, (3) these inhibitory actions of CC were not associated with altered 3 beta-hydroxysteroid dehydrogenase activity nor P catabolism indicating that, (4) these actions by CC on the GC occur at some step(s) during steroidogenesis preceding the formation of pregnenolone. These findings may explain, at least in part, the luteal deficiency experienced by women treated with CC, and they also provide a rationale for the use of hCG supplementation during ovulation induction with CC.

20-alpha-Dihydroprogesterone↗

Effects of an antiandrogen, flutamide, on oocyte quality and embryo development in rats superovulated with pregnant mare's serum gonadotropin.

Increased oocyte degeneration in rats is associated with enhanced ovarian androgen secretion following superovulation with pregnant mare's serum gonadotropin (PMSG). To determine whether androgens may be causally related to oocyte degeneration, we examined the effects of an antiandrogen, flutamide, on oocyte quality and embryo development after induction of superovulation with PMSG. Immature female Sprague-Dawley rats were used for two experiments. In the first experiment, the females received either 5 mg flutamide or vehicle alone 30 and 36 h after 40 IU PMSG and were killed at 48, 60, and 72 h. Although total number of oocytes was not significantly different between the two groups, flutamide significantly reduced the percentage of degenerate oocytes ovulated at all the time intervals examined (p less than 0.01). In the second experiment, the females were given 4 IU PMSG (control) or 40 IU PMSG with either 5 mg flutamide or vehicle. The rats were mated and then killed on Days 2, 3, 4, and 5 of pregnancy. Compared to control, flutamide did not effectively prevent the early loss of preimplantation embryos nor the developmental retardation which took place in the vehicle-treated rats after Day 2. However, flutamide treatment was associated with a significant decrease in embryo degeneration and a significant increase in the percentage of cleaved embryos on Day 2 (p less than 0.01). Compared to levels associated with the vehicle regimen, ovarian and/or serum androgen levels in the flutamide-treated rats significantly decreased at 60 h (p less than 0.01) and on Day 2 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

Time-dependent effects of follicle-stimulating hormone on progesterone metabolism by cultured rat granulosa cells.

The effects of FSH on the accumulation of endogenous progesterone and 20 alpha-hydroxy-4-pregnen-3-one as well as on the metabolism of [4-14C]progesterone were studied in 24, 48 and 72 h cultures of rat granulosa cells. FSH stimulated the accumulation of both progesterone and 20 alpha-hydroxy-4-pregnen-3-one by 6-18 fold and 2.5-44 fold, respectively. Short term exposure (24 h) to FSH resulted in the ratio of progesterone to 20 alpha-hydroxy-4-pregnen-3-one accumulations significantly increased (by 2.6 fold), while the reverse was observed for the longer (48 and 72 h) cultures whereby control levels of the ratio of progesterone to 20-alpha-hydroxy-4-pregnen-3-one were significantly greater (by 50% and 270%, respectively) than those of FSH-treated cultures. Effects of FSH on [4-14C]progesterone were also time-dependent. Twenty-four hour cultures were associated with FSH induced inhibition of 20 alpha-reduced metabolites of progesterone (by 55%) while the 48 and 72 h exposures to FSH resulted in a significant increase of the 20 alpha-reduced metabolites above control levels (by 73% and 230%, respectively). Consequently, it is postulated that FSH may exert biphasic time-dependent actions on 20 alpha-hydroxysteroid dehydrogenase activity with short term inhibitory and longer term stimulatory effects.

20-Hydroxysteroid Dehydrogenases↗

Effects of superovulatory doses of pregnant mare serum gonadotropin on oocyte quality and ovulatory and steroid hormone responses in rats.

Immature rats (aged 28 days) were injected with 4, 20, or 40 IU pregnant mare serum gonadotropin (PMSG) and sacrificed every 6 or 12 hr. Control rats (4 IU) ovulated between 60 and 72 hr, whereas rats given superovulatory doses of PMSG (20 and 40 IU) ovulated between 24 and 72 hr. The oocyte count from the superovulated rats increased slightly between 24 and 36 hr and markedly between 48 and 72 hr. Degenerated oocytes were recovered 48 and 36 hr after administration of 20 and 40 IU PMSG, respectively. Thereafter, the proportion of degenerated oocytes was dose dependent and reached a maximum at 72 (30.9%, 20 IU) and 60 hr (61.0%, 40 IU). 17 beta-estradiol content of the superovulated ovaries increased significantly (P less than 0.01) from 36 hr and was maximal at 60 (20 IU) or 54 hr (40 IU), when compared to the control regimen. Administration of 40 IU PMSG resulted in a biphasic increase of progesterone content with the peaks at 36 and 60 hr. Androgen content of the superovulated ovaries was lower than control levels during the first 36 hr but was significantly (P less than 0.01) higher thereafter. The results suggest that these alterations in the steroid response (particularly androgens) from 36 hr onward following superovulation may be responsible for the coincidental occurrence of abnormal oocytes, possibly by disturbing the specific intrafollicular steroid environment essential for complete maturation. In addition, oocyte aging that is due to earlier activation by the exogenous luteinizing hormone activity may be a contributing factor.

Androgens↗

Actions of LH/hCG on accumulation and catabolism of progestins in cultured rat granulosa cells.

Immature hypophysectomized rats were treated with estradiol-17 beta and follicle-stimulating hormone. Granulosa cells were isolated and incubated for 24 h with or without varying doses of ovine luteinizing hormone (NIMADD-oLH-24) or human chorionic gonadotropin (NIADDK CR 125) and accumulations of progesterone and 20 alpha-hydroxy-4-pregnen-3-one were determined. The cells were reincubated for 3 h with [4-14C]progesterone (0.5 nmol/mL) and the radiolabelled metabolites were separated and quantified. Both LH (0.04-1.0 ug/mL) and hCG (0.04-1.0 ug/mL) enhanced the accumulation of endogenous progesterone (by up to 300 and 150%, respectively) and 20 alpha-hydroxy-4-pregnen-3-one (by up to 90 and 85%, respectively) producing dose-dependent increases of the ratio of progesterone to 20 alpha-hydroxy-4-pregnen-3-one (by up to 125 and 70%, respectively). Studies of the metabolism of [1-14C] progesterone have demonstrated that both LH and hCG led to a dose-dependent decrease of the utilization of radiolabelled progesterone (down to 64 and 70%, respectively, of the control value). This effect was associated with an LH- and hCG-dependent inhibition of 20 alpha-hydroxysteroid dehydrogenase activity (down to 60 and 70%, respectively, of the control value) but had no significant effect on 5 alpha-reductase. The present results indicate that LH and hCG stimulate accumulation of progesterone at least in part by decreasing the 20 alpha-hydroxysteroid dehydrogenase activity.

20-Hydroxysteroid Dehydrogenases↗

Effects of prostaglandins E2 and F2 alpha on progesterone metabolism by rat granulosa cells.

Rat granulosa cells were cultured with or without PGE2 and/or PGF2 alpha. Accumulation of endogenous progesterone and 20 alpha-hydroxy-4-pregnen-3-one was determined. Additionally, [4-14C]progesterone metabolism was assessed. PGE2 increased progesterone accumulation, in part, by decreasing progesterone catabolism to 20 alpha-reduced progestins. In contrast, PGF2 alpha stimulated 20 alpha-hydroxysteroid dehydrogenase activity, thus increasing progesterone catabolism. Combined treatment with PGE2 and PGF2 alpha augmented progesterone accumulation to levels above controls but below those attained with PGE2 alone. These data indicate that PGE2 and PGF2 alpha exert opposite effects on progesterone production and catabolism and that the ratio of PGE2 to PGF2 alpha in the local granulosa cell milieu may be of importance in determining overall progesterone output.

Animals↗

Inhibition of human chorionic gonadotropin production by prolactin from term human trophoblast.

In vivo suppression of prolactin concentrations by bromocriptine near term, in a pregnant woman with a prolactinoma, was followed by augmentation of human chorionic gonadotropin levels. Suspension of drug therapy at 38 weeks of gestation was followed by a reversal of this sequence of events. In vitro, both ovine prolactin and human prolactin added to explants of term placental trophoblast significantly inhibited human chorionic gonadotropin production from this tissue. Although, with ovine prolactin, this inhibitory effect was demonstrable up to 5 micrograms/ml of ovine prolactin in the culture medium, only doses of 0.1 to 0.2 micrograms/ml of human prolactin significantly suppressed human chorionic gonadotropin production. Overall, 0.1 and 0.2 micrograms/ml of ovine prolactin and human prolactin most consistently suppressed human chorionic gonadotropin production to a statistically significant extent. In general, the concentrations in the culture medium of both ovine prolactin and human prolactin that inhibited human chorionic gonadotropin production in vitro were comparable to the concentrations of prolactin present in the mother and fetus. These in vivo and in vitro observations suggest that prolactin inhibits human chorionic gonadotropin production from term human trophoblast.

Adult↗

Relationship of gonadotropin-releasing hormone, danazol, and prostaglandin blockade to ovarian enlargement and ascites formation of the ovarian hyperstimulation syndrome in the rabbit.

The effects of pharmacologic doses of gonadotropin-releasing hormone, danazol, and indomethacin on the clinical and endocrinologic features of the ovarian hyperstimulation syndrome were studied in the rabbit. The ovarian hyperstimulation syndrome was induced with Pergonal (75 IU of follicle-stimulating hormone and 75 IU of luteinizing hormone) and a follicle-stimulating hormone-dominant gonadotropin preparation (85 IU of follicle-stimulating hormone and 53 IU of luteinizing hormone). None of the three agents tested were effective in suppressing the ovarian enlargement and ascites formation in these animals. Ascites developed despite quite significant variations in plasma and intraovarian sex steroid hormone and intraovarian prostaglandin F levels induced by danazol and indomethacin. Ascites develops in hyperstimulated women in association with both follicular and luteal hyperstimulation. In contrast, the ascites response in the hyperstimulated rabbit develops in the presence of follicular hyperstimulation alone without a significant degree of luteal hyperstimulation.

Animals↗