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Biomedical subjects

D C Schoot

Publications and source records attributed to D C Schoot.

11 recordsLinked to original sources
PubMed2000

A randomized controlled study comparing the endocrine effects of pulsatile intravenous gonadotropin-releasing hormone after gonadotropin-releasing hormone agonist pretreatment versus clomiphene citrate in patients with polycystic ovary syndrome.

OBJECTIVE: To compare the endocrine changes in the follicular phase in infertile patients with polycystic ovary syndrome (PCOS) treated with either pulsatile IV GnRH after GnRH-agonist (GnRH-a) down-regulation or clomiphene citrate (CC). DESIGN: Subgroup analysis within a randomized, controlled, multicenter study. SETTING: Women referred to the Infertility Clinic, Catharina Hospital Eindhoven, The Netherlands. PATIENT(S): Twenty-eight infertile patients with PCOS. INTERVENTIONs): Patients were randomly assigned to pulsatile IV GnRH (10-20 microgram/90 min) after GnRH-a down-regulation or CC (50-150 mg; cycle days 3-7). Patients were monitored on alternate days with ovarian sonography and serum concentrations of E(2), LH, and FSH. Serum P and sonography confirmed ovulation. MAIN OUTCOME MEASURE(S): Serum concentrations of E(2), LH, and FSH were assessed before treatment was started and after each ovarian sonography. RESULT(S): In ovulatory cycles, no statistically significant differences were observed during the follicular phase comparing serum concentrations of E(2), LH, and FSH between the treatments. However, a significant increase in LH occurred in the GnRH group. CONCLUSION(S): No significant endocrine differences were observed between GnRH and CC treatment. However, there was a significant increase in the serum LH concentration during the follicular phase in the GnRH group. Increments of LH in the GnRH group may be due to recovery of endogenous LH secretion.

Adult↗
PubMed1995

Initial estradiol response predicts outcome of exogenous gonadotropins using a step-down dose regimen for induction of ovulation in polycystic ovary syndrome.

OBJECTIVE: To study ovarian stimulation and response patterns during a gonadotropin step-down dose regimen for induction of ovulation by applying a decremental dose regimen in polycystic ovary syndrome (PCOS) patients. DESIGN: The present prospective study involves 28 infertile clomiphene citrate-resistant PCOS patients during gonadotropin-induced cycles using a modified step-down dose regimen (and adjuvant GnRH agonist medication). Applied gonadotropin doses included initial daily doses of 150 IU IM followed by two reducing steps (37.5 IU each) based on sonographic criteria to a final daily dose of 75 IU IM. SETTING: Anovulatory infertile women in an academic referral center. INTERVENTION: Daily blood withdrawal and transvaginal pelvic ultrasound. MAIN OUTCOME MEASURES: Serum FSH and E2 concentration and follicle growth were investigated daily during gonadotropin administration. RESULTS: An initial 2.1-fold increase in serum FSH levels was observed followed by a subsequent decrease of 10% (median) per day for 4 days. Growth of ovarian follicles was sustained and ovulation achieved (midluteal P, 11.7 +/- 1.3 ng/mL; conversion factor to SI unit, 3.180; mean +/- SD) in 22 patients. Major variability in day 3 E2 increase (range, 67 to 866 pg/mL; conversion factor to SI unit, 3.671)--not related to differences in FSH serum concentrations and without changes in follicle number and size--suggests differences in ovarian sensitivity for FSH stimulation. A strong correlation (r = 0.82) was found between day 3 E2 increase and the chance of ovulation. Moreover, E2 levels on the day of gonadotropin dose reduction predict (r = 0.68) chances of late follicular phase E2 levels exceeding 871 pg/mL (conversion factor to SI value, 3.671). CONCLUSIONS: These findings provide the endocrine basis for the concept of gonadotropin induction of ovulation using a step-down dose regimen. Initial E2 increase (before initiation of follicle growth) represent differences in ovarian sensitivity to gonadotropins and predict treatment outcome.

Buserelin↗
PubMed1994

Recombinant human follicle-stimulating hormone and ovarian response in gonadotrophin-deficient women.

Seven women suffering from hypogonadism due to previous hypophysectomy, isolated gonadotrophin deficiency, or Kallman's syndrome [median age 39 years (range 24-45)] volunteered to participate in a study to assess ovarian response following multiple-dose administration of recombinant human follicle-stimulating hormone (rhFSH; Org 32489). Baseline serum FSH and luteinizing hormone (LH) concentrations were 0.25 (< 0.05-1.15) IU/l and 0.06 (< 0.05-0.37) IU/l, respectively. Subjects received daily i.m. injections of rhFSH for 3 weeks (week 1: 75 IU/day, week 2: 150 IU/day, week 3: 225 IU/day). Blood sampling and sonographic investigations were performed on alternate days. Steady-state FSH concentrations were reached approximately 3-5 days after alterations of the doses administered. Maximum FSH concentrations were between 7.1 and 11.8 IU/l, whereas serum LH concentrations remained unchanged. Due to absent follicle development and lack of a rise in immunoreactive inhibin (INH) (response failure possibly due to early ovarian failure or resistant ovary syndrome) in two subjects, analysis of ovarian response was restricted to five volunteers. Serum androstenedione levels showed no significant changes during rhFSH administration. Although serum immunoreactive INH concentrations reached normal late follicular values [659 (388-993) IU/l], serum oestradiol revealed only a minor increase [77 (18-210) pmol/l]. Moreover, growth of (multiple) ovarian follicles was observed up to pre-ovulatory sizes (> 15 mm) in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The step-down principle in gonadotrophin treatment and the role of GnRH analogues.

This chapter has focused on the step-down principle for gonadotrophin induction of ovulation in women suffering from clomiphene-resistant anovulation. The physiological rationale of this approach has been highlighted. Under normal conditions, FHS levels surpassing the FSH threshold initiate gonadotrophin-dependent growth of a cohort of follicles (this process is referred to as 'recruitment'). Due to negative feedback actions, the FSH levels decrease and FSH is above the threshold for only a limited number of days (the 'FSH window'). Around the mid-follicular phase, selection of a dominant follicle takes place; in addition to relatively low serum FSH concentrations, intraovarian regulation appears to be important for this process. In the conventional step-up or low dose step-up protocols for gonadotrophin induction of ovulation, administered doses are kept constant once an 'adequate' ovarian response is observed, resulting in high FSH serum levels in the late follicular phase and a broad FSH window. This contradicts normal circumstances and may give rise to unintended interference with the selection process by continuously stimulating follicles to enter the growing pool. This may result in multiple follicle development which, in turn, may be related to higher rates of multiple pregnancies and ovarian hyperstimulation. Potential mechanisms underlying arrested follicle maturation in PCOS are also discussed since they appear to be of relevance for the induction of ovulation. Disturbed selection can be overcome in the majority of cases by elevating the serum FSH concentrations through the administration of exogenous gonadotrophins to surpass the elevated FSH threshold in these patients. Data obtained by our group so far suggest that in PCOS patients treated with gonadotrophins in a step-down fashion, follicles continue to mature and can be stimulated to ovulation. Moreover, the number of functionally active medium-sized follicles seems to be reduced. If monofollicular development is observed in these patients, growth rates and oestrogen serum levels are indistinguishable from unstimulated normal development of the dominant follicle. In our initial series of over 200 cycles of gonadotrophin treatment according to the step-down principle in clomiphene-resistant anovulatory patients, 84% of cycles were ovulatory and pregnancy was achieved in 18% of the cycles (giving a cumulative pregnancy rate of 51%). Moreover, the overall complication rate appears to be low. The potential advantages and critical points of adjuvant treatment with GnRH analogues is also discussed. It has been clearly demonstrated that premature luteinization can be prevented effectively. Various other potential advantages of cotreatment seems to justify adjuvant medication with GnRH agonists.(ABSTRACT TRUNCATED AT 400 WORDS)

Anovulation↗
PubMed1993

Luteal function following ovulation induction in polycystic ovary syndrome patients using exogenous gonadotrophins in combination with a gonadotrophin-releasing hormone agonist.

The luteal phase was studied in 12 polycystic ovary syndrome (PCOS) patients following ovulation induction using exogenous gonadotrophins combined with a gonadotrophin-releasing hormone agonist (GnRH-a). Human menopausal gonadotrophin (HMG) was preceded by 3 weeks of treatment with GnRH-a (buserelin; 1200 micrograms/day intra-nasally) and administered in a step-down dose regimen starting with 225 IU/day i.m. GnRH-a was withheld the day before administration of human chorionic gonadotrophin (HCG; 10,000 IU i.m.). Blood sampling and ultrasound monitoring was performed every 2-3 days until menses. The luteal phase was significantly shorter in PCOS patients as compared to eight regularly cycling controls: 8.8 (3.3-11.4) days [median(range)] versus 12.8 (8.9-15.9) days (P = 0.01). Median peak values for progesterone did not show significant differences comparing both groups: 52.3 (17.1-510.3) nmol/l versus 43.0 (31.2-71.1) nmol/l, respectively (P = 0.8). The interval between the day of the progesterone peak and return to baseline was significantly shorter in the PCOS patients than in controls: 2.5 (0.3-4.9) days versus 4.2 (3.9-10.5) days (P < 0.005). Luteinizing hormone (LH) concentrations during the luteal phase as reflected by area under the curve were significantly lower in PCOS as compared to controls: 4.4 (1.6-21.0) IU/l x days and 49.0 (27.8-79.6) IU/l x days, respectively (P < 0.001). In conclusion, patients with PCOS may suffer from insufficient luteal phases after ovulation induction using HMG/HCG in combination with a GnRH-a. The corpus luteum apparently lacks the support of endogenous LH and may be stimulated only by the pre-ovulatory injection of HCG.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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↗