PubMed Health⌕ Search

Biomedical subjects

B C Fauser

Publications and source records attributed to B C Fauser.

At least 91 records · Page 5Linked to original sources
PubMed1993

Development of a human granulosa cell culture model with follicle stimulating hormone responsiveness.

In order to study the effects of follicle-stimulating hormone (FSH) on differentiation of granulosa cells, a well-defined and validated in-vitro culture system is indispensable. In this study, pooled follicular aspirates were stimulated in vitro with FSH and luteinizing hormone (LH) for 2, 4 and 6 days, either immediately after plating or after 7 days of preincubation. Cultures were assayed for progesterone and oestradiol production. Fresh cells displayed very high basal progesterone production which could be stimulated with LH but not FSH. After preincubation, addition of LH and FSH resulted in dose-dependent increases of progesterone and oestradiol. When cultured on human fibronectin-coated wells, similar basal but higher progesterone concentrations after stimulation were observed. In comparison with serum-free media, addition of Serum-Plus resulted in higher basal and stimulated progesterone concentration, possibly due to the presence of serum factors. This study demonstrates firstly that after 7 days preincubation, cultures gained responsiveness to FSH but remained responsive to LH during 4 days of stimulation. This suggests a persisting differentiated cell population in vitro. Secondly, the use of human fibronectin extracellular matrix and serum promotes steroid production, either due to factors promoting cell growth and function or to availability of steroid precursors. Therefore one has to be cautious with interpretation of data obtained from this widely used culture system, employing highly differentiated cells obtained after ovarian stimulation for in-vitro fertilization for study of local regulation of granulosa cell function.

Basal Metabolism↗
PubMed1993

The relation between clinical manifestations of polycystic ovary syndrome and beta-cell function.

OBJECTIVE: Hyperandrogenism in patients with polycystic ovary syndrome has been shown to correlate with hyperinsulinaemia of insulin resistance. We have investigated if basal levels of insulin and the response to the intravenous administration of glucagon can reveal insulin resistance in patients with polycystic ovary syndrome. PATIENTS: Nine obese (BMI > 25 kg/m2) and nine non-obese (BMI 19-25 kg/m2) women with PCOS, chosen from a population of 91 women attending the infertility clinic, and 19 normally cycling women (seven obese, 12 non-obese) were studied. Oligo or amenorrhoea, hirsutism, and 12 or more follicles in a given ovary were selection criteria. MEASUREMENTS: Glucagon, 1 mg, was given intravenously to 18 of the 91 women and to the control subjects. Blood was taken at -5, 0, 5, 10 and 15 minutes for measurements of integrated areas under the response curve for insulin, C-peptide and glucose, respectively. Basal blood samples were drawn for fasting insulin, C-peptide, glucose, testosterone, sex hormone-binding globulin (SHBG), free fatty acids and IGF-I measurements. The free androgen index was calculated according to the formula FAI = testosterone x 100/SHBG. RESULTS: There were no significant differences in maximal increment and area under the response curve for glucose, C-peptide and insulin. FAI was significantly higher in all patients with features of polycystic ovary syndrome. However, fasting insulin levels were significantly higher only in obese patients when compared with obese control subjects and lean patients. CONCLUSIONS: The administration of 1 mg glucagon i.v. did not distinguish patients with polycystic ovary syndrome from control subjects. The mild insulin resistance of polycystic ovary syndrome is related only to obesity and is therefore unlikely to play an important role in the hyperandrogenism associated with the syndrome.

Adult↗
PubMed1993

Growth of the dominant follicle is similar to normal in patients with gonadotrophin-stimulated polycystic ovary syndrome exhibiting monofollicular development during a decremental dose regimen.

The aim of this study was to investigate the late follicular phase of seven gonadotrophin-treated patients with polycystic ovary syndrome (PCOS) exhibiting monofollicular growth and to compare developmental characteristics with the dominant follicle in seven regularly cycling control women. Daily serum follicle-stimulating hormone (FSH) levels in patients with PCOS decreased more rapidly compared to controls (-0.3 +/- 0.2 IU/day in controls versus -0.7 +/- 0.4 IU/day in PCOS; p < 0.02). No statistically significant differences were seen in daily increase (30% in controls and PCOS) and mean peak levels (825 +/- 94 pmol/l in controls versus 937 +/- 231 pmol/l in PCOS) of oestradiol (E2) serum levels when comparing both groups. Mean daily growth of the dominant follicle (1.7 +/- 0.4 mm in controls versus 1.9 +/- 0.6 mm in PCOS) was not significantly different. It is concluded from the present study that in patients with PCOS treated with gonadotrophin plus adjuvant gonadotrophin-releasing hormone agonist, development of a single follicle can occur using a decreasing dose regimen resulting in decreasing serum FSH levels. In addition, growth and oestrogen production by the dominant follicle in PCOS is not significantly different from follicle growth under normal conditions.

Adult↗
PubMed1992

Effects of gonadotropin releasing hormone agonist addition to gonadotropin induction of ovulation in polycystic ovary syndrome patients.

Meta-analysis of all randomised trials published so far, was performed to compare the effect of additional gonadotropin releasing hormone (GnRH)-agonist treatment to exogenous gonadotropins for ovulation induction in clomiphene-resistant polycystic ovary syndrome (PCOS) patients. Five clinical studies were included, of which only one showed significant differences in pregnancy rate. In addition, pretreatment with GnRH-agonist was once reported to lead more often to cancellation of medication. Combining the results of all five trials, a significant difference in favour of additional GnRH-agonist administration could only be observed for pregnancy rate. No significant differences in ovulation rate could be found. Due to the relative small number of patients in each separate group, no conclusions could be drawn concerning the influence of GnRH-agonist treatment on gonadotropin doses necessary to induce ovulation, and the incidence of multiple pregnancy, abortion and ovarian hyperstimulation.

Female↗
PubMed1992

Growth patterns of ovarian follicles during induction of ovulation with decreasing doses of human menopausal gonadotropin following presumed selection in polycystic ovary syndrome.

Data presented in this study indicate that ovulation can be induced in patients with PCOS using a GnRH analogue combined with hMG in a decreasing dose regimen. Based on the observed decline in functional, medium sized follicles in the late follicular phase, it may be speculated that the risk of ovarian hyperstimulation during gonadotropin induction of ovulation in patients with PCOS can be reduced.

Adult↗
PubMed1992

17 beta-Oestradiol, androstenedione and inhibin levels in fluid from individual follicles of normal and polycystic ovaries, and in ovaries from androgen treated female to male transsexuals.

OBJECTIVE: The aim was to monitor carefully follicular growth arrest in polycystic ovaries by assay of hormones in individual follicles. DESIGN AND PATIENTS: Fluid from follicles less than or equal to 10 mm was obtained from ovaries of 16 regularly cycling women between days 1 and 12 of the follicular phase (controls, n = 120 follicles), polycystic ovaries of five women with polycystic ovary syndrome (n = 43), and polycystic ovaries from 14 long-term testosterone treated female to male transsexuals (n = 120). MEASUREMENTS: Fluid was assayed for oestradiol, androstenedione, and immunoactive inhibin. Luteinizing hormone, follicle-stimulating hormone, and testosterone levels were estimated in serum. RESULTS: Median serum LH was lower in transsexuals than in controls (P less than 0.05), and in polycystic ovary syndrome (P less than 0.01). Median serum testosterone was not significantly different between polycystic ovary syndrome and transsexuals, and was elevated in both groups as compared to controls (P less than 0.01). Oestradiol was present in all follicles obtained from polycystic ovaries of polycystic and transsexual patients, in which no follicle greater than 10 mm could be detected. In the three groups, between-patient differences in mean oestradiol, androstenedione, inhibin, and androstenedione/oestradiol ratio were significantly larger than expected in view of the variation between follicles within individuals. Taking into account this between-patient difference, no significant differences could be established between the three groups for all endocrine parameters. The percentage of presumed healthy follicles (androstenedione/oestradiol ratio less than or equal to 4) was 12% in controls, 17% in polycystics, and 14% in transsexuals, and was not significantly different between groups. CONCLUSIONS: The results may indicate that (1) abnormally high circulating androgen concentrations with or without elevated LH levels disturb the process of selection, and could therefore play a role in the pathogenesis of polycystic ovaries; (2) in polycystic ovaries from polycystic ovary syndrome and transsexual patients, aromatase activity is present in vivo in small antral follicles, and the proportion of presumed healthy follicles is not different from that encountered in normal ovaries; (3) oestradiol levels are not different between non-dominant follicles of normal and polycystic ovaries, suggesting that only enhancement of aromatase activity by FSH may be disrupted in polycystic ovaries, (4) because androstenedione levels are not different comparing follicles of normal and polycystic ovaries, hyperandrogenaemia in the syndrome seems to originate from the abnormally high number of cystic atretic follicles generally observed in polycystic ovaries; (5) marked variation in the endocrine follicular microenvironment within and between-women precludes pooling fluid from several follicles.

Adult↗
PubMed1992

The significance of a single serum LH measurement in women with cycle disturbances: discrepancies between immunoreactive and bioactive hormone estimates.

OBJECTIVE: We evaluated the significance of single serum LH estimates (as assessed by radiometric assay (IRMA) and Leydig cell in-vitro bioassay (BIO)) for the diagnosis of polycystic ovary syndrome (PCOS) in women with infertility and cycle abnormalities. DESIGN: Hormonal and clinical comparisons between subgroups were made based on classification according to (a) rigid clinical and endocrine (excluding LH) characteristics of PCOS, (b) elevated IRMA-LH concentrations, (c) BIO-LH levels. In addition, androgen modulation of LH biopotency was studied in these patients. PATIENTS: Ninety-nine women presenting at our infertility Unit with oligo/amenorrhoea. MEASUREMENTS AND RESULTS: Of the total study group, 35 women were diagnosed positive as PCOS and 42 showed elevated IRMA-LH levels. Only 51% (n = 18) of PCOS patients showed elevated IRMA-LH levels, and in PCOS significantly higher levels of BIO-LH, androstenedione, oestrone, and BIO/IRMA-LH ratios were found as compared to non-PCOS patients. In the group with elevated IRMA-LH only 43% (n = 18) of subjects were diagnosed as PCOS, and no difference in BIO/IRMA-LH ratios was found. With increasing BIO-LH levels the probability of PCOS rises sharply (P < 0.001), whereas this probability is of only marginal significance (P < 0.06) for IRMA-LH. In the total study group a correlation is observed between serum testosterone (T) levels and IRMA-LH (r = 0.47), and BIO-LH (r = 0.51) concentrations. This correlation is absent comparing serum T and BIO/IRMA-LH ratios (r = 0.15). CONCLUSIONS: Results presented in this study indicate that (1) women with infertility and oligo/amenorrhoea classified based on signs of PCOS or IRMA-LH levels, exhibit different clinical and endocrine characteristics, (2) only 51% of PCOS women exhibit elevated IRMA-LH concentrations, and only 43% of women with elevated IRMA-LH were diagnosed as PCOS, (3) IRMA-LH levels are a poor predictor of PCOS, whereas the predictive value of BIO-LH is better, (4) elevated BIO/IRMA-LH ratios in PCOS are dependent on alterations in BIO-LH, rather than IRMA-LH concentrations, and (5) no correlation was observed between serum T levels and BIO/IRMA-LH ratios.

Adult↗
PubMed1992

How to discriminate between normal and polycystic ovaries: transvaginal US study.

Transvaginal sonography was used in 29 women with regular menstrual cycles and 52 patients with the polycystic ovary syndrome to determine cutoff levels in the size and number of ovarian follicles and ovarian echogenicity and volume for diagnosis of polycystic ovaries. Median values of the mean size and number of follicles and ovarian volume were, respectively, 5.1 mm, 5.0, and 5.9 mL in control subjects and 3.8 mm, 9.8, and 9.8 mL in patients. Ovarian stroma echogenicity was normal in 26 control subjects (90%) and moderately increased in three control subjects (10%), whereas it was markedly increased in 28 patients (54%), moderately increased in 21 patients (40%), and normal in 13 patients (6%). The sensitivity and specificity of moderately or markedly increased echogenicity of ovarian stroma in the diagnosis of polycystic ovaries was 94% and 90%, respectively. The greatest power of discrimination between normal and polycystic ovaries was obtained with combined measurement of follicular size and ovarian volume (sensitivity, 92% [48 of 52 patients]; specificity, 97% [28 of 29 control subjects]).

Adult↗
PubMed1992

Melatonin and melatonin-progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation.

Although melatonin (MEL) controls seasonal reproductive cyclicity in some mammalian species, its role in women is controversial. In this study data are presented related to the influence of MEL or MEL-progestin combinations on the pituitary-ovarian axis and ovulation in 32 women. MEL was administered in a dosage of 300 mg to 12 women for 4 months [to 8 women daily (days 1-30) and to 4 women on days 5-17 of the cycle]. MEL was also combined with the synthetic progestin norethisterone (NET) in an attempt to evaluate MEL's effect on a partially suppressed pituitary-ovarian axis. In 16 women, 4 combinations were tested on 4 women each on days 1-21: dosages of 300 mg MEL/0.75 mg NET, 75 mg MEL/0.75 mg NET, 7.5 mg MEL/0.75 mg NET, and 75 mg MEL/0.30 mg NET. In addition, 2 women were medicated with 300 mg MEL alone, and 2 were medicated with 300 mg MEL/0.15 mg NET on days 1-21 for 2 months. During the study, LH, FSH, estradiol (E2), and progesterone (P4) blood levels were determined at regular intervals. After a period of 4 months, daily administration of 300 mg MEL (days 1-30) caused significantly decreased mean LH levels compared to those in 8 nonmedicated controls (P less than 0.001). Also compared to nonmedicated control data, a significant inhibition of P4 in the first and fourth medication months (P less than 0.001) was observed. LH and E2 inhibition reached significance in the fourth medication month (P less than 0.005). Also, the treatments of 300 mg MEL (days 5-17) and 75 mg MEL combined with 0.3 mg NET caused a significant decrease in LH, E2, and P4 levels compared to those in the nonmedicated control group in the first and fourth medication months (P less than 0.05). The data further suggest an additive or synergistic effect between MEL and NET. The medications did not alter sleep-wake rhythms and were not complicated by any side-effects. The presented data suggest that MEL and MEL/NET combinations inhibit ovarian function in women, and that MEL/NET combinations can emerge as effective oral contraceptives.

Adult↗
PubMed1992

Human recombinant follicle-stimulating hormone induces growth of preovulatory follicles without concomitant increase in androgen and estrogen biosynthesis in a woman with isolated gonadotropin deficiency.

To evaluate the importance of luteinizing hormone (LH) for normal estrogen production and subsequent development of ovarian follicles, a woman with isolated gonadotropin deficiency (LH; 0.37 IU/L, FSH 1.2 IU/L) was monitored during recombinant human follicle-stimulating hormone (hFSHrec) administration with respect to ovarian follicular growth and steroid production. During the first week (75 IU/day hFSHrec im) a significant rise in serum FSH (4.9 IU/L) was observed in the absence of changes in serum estradiol (E2) concentrations (36-76 pmol/L). During the following five days 150 IU/day hFSHrec was administered resulting in a further increase of serum FSH levels (maximum 8.5 IU/L). Development of multiple follicles--maximum diameter 22 mm as observed by transvaginal sonography--emerged together with a minor rise in E2 levels (from 76 to 236 pmol/L) and with a minimal increase in endometrial thickness (below 6 mm). Six days following the last injection of hFSHrec, aspiration of 3 follicles (13, 15 and 18 mm) was performed and low intrafollicular androstenedione (AD) (less than 675 nmol/L) and E2 (less than 9400 pmol/L) concentrations as compared to normal follicles were found. These first data on hFSHrec administration in the human suggest that; a) FSH alone can induce growth of preovulatory follicles, b) follicle growth does occur in the presence of subnormal E2 levels, c) LH is needed for adequate AD biosynthesis as substrate for aromatase activity. This indicates that growth and steroidogenic granulosa cell activity may be differentially regulated.

Adult↗
PubMed1991

Transvaginal sonography and abnormal ovarian appearance in menstrual cycle disturbances.

Transvaginal ultrasound examinations were performed in 37 oligo- or a-menorrheic women to describe ovarian changes and potential correlations with clinical and some biochemical features of polycystic ovarian syndrome (PCOS). Findings were compared between the right and left ovary and between each of three subsequent examinations of the same ovary. In any one ovary, no significant difference was found between mean ovarian volume, stroma echogenicity, mean follicle number and size. Correlation between ovarian volume and follicle number was strong in all examinations. Follicle number in both ovaries correlated significantly with ovarian stroma echogenicity and some biochemical markers of PCOS. These observations validate the usefulness of transvaginal sonography in demonstrating numerous correlations in menstrual cycle disturbances. The strong necessity to reevaluate sonographic criteria of PCOS is highlighted.

Adult↗
PubMed1991

Ovarian morphology in long-term androgen-treated female to male transsexuals. A human model for the study of polycystic ovarian syndrome?

Descriptions of the effect of androgens on ovarian human tissues are exceptional. This opportunity was provided for us by 17 women with transsexualism--female to male transsexuals (TSX)--who had been given androgens for a mean period of 21 months before hystero-salpingo-oophorectomy took place. Twenty-nine ovaries from TSX and 14 control ovaries from 13 regularly cycling women were examined. As compared with controls, TSX ovaries were enlarged and displayed a two-fold increase in cystic follicles and a 3.5-fold increase in atretic follicles; the ovarian cortex was collagenized and three-times thicker. Theca interna hyperplasia and luteinization were uniformly observed in TSX cystic follicles. Stromal hyperplasia was a constant finding in TSX ovaries, accompanied by clusters of luteinized stromal cells in 12 cases. Eventually, these findings met the histological criteria for the diagnosis of polycystic ovaries. These observations demonstrate that androgens alone may induce polycystic changes. The assumption that the role of androgens is pivotal at the follicular level--inducing follicle growth arrest and accelerating cystic changes--in the genesis of polycystic ovaries is reinforced.

Adolescent↗
PubMed1991

Serum bioactive and immunoreactive luteinizing hormone and follicle-stimulating hormone levels in women with cycle abnormalities, with or without polycystic ovarian disease.

Serum steroid, gonadotropin, and alpha-subunit levels were assessed in 35 women with cycle abnormalities [11 with and 24 without polycystic ovarian disease (PCOD) according to strict clinical and biochemical criteria] and 8 regularly cycling women in the early (cycle day 3 or 4) and mid (cycle day 7 or 8) follicular phase. LH and FSH levels were estimated using two immunological techniques [RIA and immunoradiometric assay (IRMA)] and in vitro bioassays (BIO), using mouse Leydig cells and rat granulosa cells, respectively. In PCOD patients mean alpha-subunit, free androgen index [FAI; testosterone x 100/sex hormone-binding globulin (SHBG)], androstenedione, estrone, and estradiol (E2) were significantly elevated compared to levels in the early follicular phase of control cycles and non-PCOD patients. In addition, in PCOD patients mean IRMA-LH and RIA-LH levels were distinctly increased (2.8- to 3.6 fold, respectively; both comparisons, P less than 0.001) compared to control values, but in the same order of magnitude (1.3- to 1.4-fold increments) as that in non-PCOD patients. However, the median BIO-LH level in PCOD patients was 5.9-fold higher than that in non-PCOD patients and 4.0-fold higher than the BIO-LH in the early follicular phase of control women. Consequently, the median BIO/IRMA-LH ratio was 4.8-fold higher in PCOD patients compared to non-PCOD patients. In women with cycle abnormalities, individual BIO/IRMA-LH ratios correlated with BIO-LH (rs = 0.48), FAI (rs = 0.39), free estrogens (E2/SHBG ratios; rs = 0 0.47), and dehydroepiandrosterone sulfate (rs = 0.60) concentrations. Mean IRMA-, RIA-, and BIO-FSH levels and BIO/IRMA-FSH ratios were not significantly different when various groups were compared. Although RIA- and IRMA-LH levels showed good correlation (rs = 0.88), RIA-LH levels were consistently higher, resulting in distinctly higher RIA-LH/FSH ratios (mean, 4.5) compared to IRMA-LH/FSH ratios (median, 1.8) in PCOD patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗