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Biomedical subjects

J Schoemaker

Publications and source records attributed to J Schoemaker.

At least 73 records · Page 4Linked to original sources
PubMed1995

Ovulation induction in premature ovarian failure: a placebo-controlled randomized trial combining pituitary suppression with gonadotropin stimulation.

OBJECTIVES: To determine the effect of pituitary suppression with a GnRH agonist (GnRH-a) on the success of ovulation induction with exogenous gonadotropins in patients with premature ovarian failure (POF). DESIGN: Placebo-controlled, randomized, double-blind study. The data were analyzed with a Fisher exact test. SETTING: A tertiary care academic center for Reproductive Endocrinology and Fertility. PATIENTS: Thirty patients with POF, 15 in each group. INTERVENTIONS: The study consisted of four phases: phase 1, no interventions; phase 2, a 4-week period in which the patients received either 1,000 micrograms intranasal buserelin acetate daily or placebo; phase 3, a 3-week period during which the patients additionally received hMG in weekly augmented doses, two, four, and six ampules daily in the first, second, and third weeks, respectively. Ovulation was induced whenever the follicular diameter reached 18 mm and/or total 24-hour estrogen excretion > 140 micrograms (500 nmol). Luteal support was 5,000 IU hCG every 72 hours; phase 4, no interventions. RESULTS: Follicular growth was seen in five patients of the agonist group and in four patients of the placebo group. Three of 15 patients in the agonist group ovulated versus none in the placebo group. The difference was not statistically significant. CONCLUSIONS: The fact that 3 of 15 cycles cotreated with a GnRH-a were ovulatory versus none in the placebo-treated group appeared not to be enough evidence to demonstrate that pituitary suppression with a GnRH-a improves the success of ovulation induction with exogenous gonadotropins in patients with POF.

Adult↗
PubMed1995

Analysis of peripheral blood lymphocyte subsets, NK cells, and delayed type hypersensitivity skin test in patients with premature ovarian failure.

PROBLEM: Premature ovarian failure (POF) probably belongs to the group of autoimmune endocrinopathies. Cell-mediated immune parameters were investigated. Sex steroids have a profound effect on the immune system. POF patients and postmenopausal control women (PM) were tested with or without estrogen substitution. METHOD: A novel FACS analysis system (using double labeling techniques) was used in 30 patients with POF to enumerate the subjects of peripheral blood lymphocytes and NK cells. Eighteen PM women and 30 healthy men and women served as controls. We also tested the delayed type hypersensitivity skin test (DTH) toward Candida in the POF patient group to be informed on their cell-mediated immune function. RESULTS: The numbers of blood lymphocytes, CD3+, CD4+ and CD8+T cells, were not abnormal in POF patients. However, HLA-DR+T cells were increased in POF patients and in PM women (P < 0.05). These elevated numbers were partially reversible by estrogen substitution. The number of CD19+ cells (B cells) was elevated, whereas CD3-/CD16+/CD56+ cells (NK cells) were decreased in POF patients (P < 0.05), irrespective of estrogen substitution. DTH skin tests toward 0.1% Candidin (0.1 ml intradermal injection) were negative in 11 out of 20 tested POF patients, compared to only 2 out of 10 tested controls (P < 0.05). CONCLUSION: POF patients show numerous immune cell abnormalities. These abnormalities were only partially due to estrogen deficiency. We hypothesize that these abnormalities either lead to ovarian autoimmunity or may have direct effects on the ovarian function.

Adult↗
PubMed1995

Chronic naltrexone treatment induces desensitization of the luteinizing hormone pulse generator for opioid blockade in hyperprolactinemic patients.

The aim of this study was to assess the possibility that ovulation might be induced in seven amenorrheic hyperprolactinemic women by treatment with naltrexone (50 mg/day) for 4-5 weeks. None of the patients ovulated. Increases in LH levels, LH area under the curve, FSH levels, and the number of LH pulses per 6 h were observed in all patients, 2-8 h after the beginning of naltrexone administration. However, all of these parameters had returned to the pretreatment range on day 7. The LH area under the curve, LH levels, FSH levels, and the number of LH pulses per 6 h on day 1 were significantly higher compared to the values on either day 0 (basal levels) or day 7. These data show that long term opioid receptor blockade induces desensitization of the hypothalamic-pituitary unit for the effects of opioid receptor blockade. Due to the induced desensitization, naltrexone is not an effective drug for ovulation induction in hyperprolactinemic patients.

Adult↗
PubMed1994

The response of the pituitary-ovarian axis to pulsatile administration of gonadotropin-releasing hormone in long-term oral contraceptive users.

OBJECTIVE: Our purpose was to differentiate between pituitary and hypothalamic feedback effects of oral contraceptives. STUDY DESIGN: Twenty micrograms of gonadotropin-releasing hormone was administered intravenously at 90-minute intervals for 4 days to 14 long-term users of a combined oral contraceptive (30 micrograms of ethinyl estradiol and 150 micrograms of levonorgestrel), starting at different moments in the pill cycle. On the fourth day of administration the pulsatile release of luteinizing hormone was determined by blood sampling every 10 minutes for 6 hours. The sensitivity of the pituitary was determined before, during, and after treatment with gonadotropin-releasing hormone by a 100 micrograms gonadotropin-releasing hormone challenge test. On each sampling day serum estradiol, progesterone, and prolactin levels were measured, and ovarian ultrasonography was performed. RESULTS: After 4 days of pulsatile gonadotropin-releasing hormone administration every exogenous gonadotropin-releasing hormone bolus was followed by an endogenous luteinizing hormone pulse of high amplitude (median 3.30 U/L). Both serum luteinizing hormone and follicle-stimulating hormone levels increased significantly (p < 0.001). The increase in follicle-stimulating hormone levels was accompanied by an increase in serum estradiol (p < 0.01). The luteinizing hormone response to a 100 micrograms bolus of gonadotropin-releasing hormone decreased during gonadotropin-releasing hormone treatment (p < 0.01), whereas the follicle-stimulating hormone response did not change. CONCLUSION: Pituitary sensitivity is not impaired during oral contraceptive use, suggesting that oral contraceptives exert their negative feedback effects predominantly at the hypothalamic level.

Adult↗
PubMed1994

CA-125 levels in cervical mucus during the menstrual cycle.

OBJECTIVE: To determine CA-125 levels in cervical mucus (CM) during the menstrual cycle and their relationship to gonadal steroids and ovulation. DESIGN: Prospective study. SETTING: Two academic tertiary referral centers. PARTICIPANTS: Thirteen women with a normal fertility work-up. INTERVENTIONS: CA-125 and protein concentrations were measured in CM aspirated from the endocervical canal on alternate days in the early follicular and luteal phases and on a daily basis during the periovulatory period. Results were correlated with hormonal determinations, serum CA-125 levels, and ultrasound examination. RESULTS: Twenty ovulatory nonconceptional cycles were analyzed. Although the mean (+/- SD) concentration of CA-125 in CM (173,900 +/- 128,900 arbitrary U/mL) appeared relatively constant along the cycle, a large variation among the different samples was observed, ranging from 9,000 to 830,000 arbitrary U/mL. No clear trend could be detected as related to hormonal changes and ovulation. However, when the mucus CA-125 concentration was multiplied by the total volume of the correspondent sample, a clear periovulatory increase of total CA-125 levels was found. This was further supported by a similar trend showed by the calculated CA-125:protein concentration ratio. CONCLUSIONS: CA-125 is present in CM in high concentrations that vary widely along the cycle. Although no cyclical variation in CA-125 concentration could be determined, there was an apparent increase of total CA-125 levels parallel to the augmented mucus production during the periovulatory period. This further suggests a possible involvement of this glycoprotein in the secretory process of endocervical glands.

Adult↗
PubMed1994

Follicle stimulating hormone (FSH) dynamics of low dose step-up ovulation induction with FSH in patients with polycystic ovary syndrome.

Pharmacodynamics of follicle stimulating hormone (FSH) were studied during low dose step-up gonadotrophin therapy in patients with polycystic ovary syndrome (PCOS). To obtain stable levels of FSH, Metrodin was administered i.v. By making daily determinations, the FSH concentration was slowly increased in steps of approximately 1 IU/l. A total of 16 patients were treated for a maximum of three treatment cycles. Out of 38 treatment cycles, in 26 (68%) a single dominant follicle developed. The overall ovulation rate was 78%. FSH concentrations were evaluated with regard to intra- and interindividual variability of the FSH threshold and with regard to the relationship between FSH concentrations, FSH dose and treatment outcome. The high variability of the FSH threshold, ranging from 5.7 to 12 IU/l, appeared to be mainly a function of inter-individual variability. Higher FSH concentrations were associated with multifollicular growth as opposed to monofollicular growth, whereas the increases in concentration from a substimulating to a stimulating level were not. Multifollicular growth might thus be associated with a higher elevation of FSH concentration above the threshold. Different patterns of FSH concentration in the course of the growth phase of the dominant follicle in mono- compared to multifollicular cycles suggested a difference in the effect of endogenous FSH on the plasma concentration. Endogenous feedback on FSH release may therefore still play a role during treatment with exogenous FSH.

Adult↗
PubMed1994

Time schedules of intrauterine insemination after urinary luteinizing hormone surge detection and pregnancy results.

A urinary luteinizing hormone (LH) test (LH Color, Organon, Oss, The Netherlands), was used to time intrauterine insemination in 177 cycles. Morning and evening urine samples were tested. In 58 women (33%) the test was positive in the morning urine sample. Fifteen of these patients were inseminated 8-10 h thereafter and one patient (6.7%) conceived. The remaining 43 women were inseminated the following day, 25-31 h after LH detection, and seven pregnancies (16.3%) ensued. In 119 cycles showing a positive urinary test in the evening sample, insemination was performed the next day, between 17 and 23 h after the LH surge, and 18 patients (15.1%) became pregnant. Statistical analysis showed no significant differences in pregnancy rates between the three different schedules, or in the time of insemination between conceptional and non-conceptional cycles within each group. Most ovulations occurred between 16 and 28 h after the positive test was observed. These findings suggest that while the lifespan of the gametes allows a relatively long period for fertilization, from 8 to 31 h after urinary LH surge detection, better results may be expected when inseminating about 24 (+/- 6) h after the positive test.

Adult↗
PubMed1993

The relationship between follicle-stimulating hormone dose and level and its relevance for ovulation induction with adjuvant gonadotropin-releasing hormone-agonist treatment.

OBJECTIVE: To investigate the effect of a GnRH agonist (GnRH-a) on the FSH threshold level and the relationship between the FSH dose and the FSH level of patients suffering from polycystic ovarian syndrome (PCOS). DESIGN: The stimulation with low-dose FSH in PCOS (group 1) was compared with the subsequently performed stimulation with low-dose FSH combined with GnRH-a in another group of patients suffering from the same syndrome (group 2). SETTING: Specialist Reproductive Endocrine Unit. PATIENTS: Suffering from clomiphene citrate-resistant PCOS. MAIN OUTCOME MEASURES: The FSH threshold level for ongoing follicular growth and the relationship between dose and level of FSH. RESULTS: In 15 patients in group 1 and in 13 patients in group 2, respectively, 39 and 32 stimulation cycles were performed. Below and above threshold values of FSH of group 1 and 2 did not differ significantly. For the equation stable level of FSH (Y mIU/mL) = A X infusion rate of FSH (X IU/24 h) + basal level of FSH (B mIU/mL), the median A of group 1 was 0.027 and A of group 2 was 0.055 (significant difference). CONCLUSIONS: In PCOS, a change of the FSH threshold level for ongoing follicular growth induced by the GnRH-a could neither be proven nor ruled out. The use of a GnRH-a resulted in larger FSH level increases per IU/24 h of FSH administered and might therefore interfere with the effect of low-dose FSH treatment.

Adjuvants, Pharmaceutic↗
PubMed1993

Pulsatile gonadotrophin releasing hormone stimulation after medium-term pituitary suppression in polycystic ovary syndrome.

Ovulation induction in the polycystic ovary syndrome with pulsatile gonadotrophin releasing hormone (GnRH) in the recovery phase after treatment with a GnRH agonist (GnRHa) during 6-8 weeks has been reported to improve ovulation and pregnancy rates and to normalize follicular phase luteinizing hormone (LH) levels. We studied the results of stimulation with pulsatile GnRH after a shorter 'medium-term' period of 3 weeks of treatment with a GnRHa by comparing a cycle without GnRHa pre-treatment with a cycle with GnRHa (post-GnRHa) pre-treatment in 12 patients. We could prove no significant clinical improvement in post-GnRHa cycles. Ovulation rates were similar. However, in the post-GnRHa cycles, two ongoing pregnancies were observed versus one spontaneous abortion in the cycles without GnRHa pre-treatment. This observation might be explained by the fact that follicular phase LH levels in post-GnRHa cycles were significantly decreased.

Adult↗
PubMed1993

The effects of a gonadotrophin-releasing hormone agonist on treatment with low dose follicle stimulating hormone in polycystic ovary syndrome.

The objective of this study was to investigate whether the incidence of monofollicular growth during stimulation with low dose follicle stimulating hormone (FSH) changes when adjuvant gonadotrophin-releasing hormone agonist (GnRHa) pre-treatment is administered in polycystic ovary syndrome (PCOS). One group of patients (group 1) suffering from clomiphene resistant PCOS was stimulated with low dose FSH. The results were compared with those from another group of similar patients (group 2) subsequently stimulated with low dose FSH combined with GnRHa. In group 1 15 patients had 39 stimulation cycles performed; in group 2 13 patients had 33 stimulation cycles performed. In group 1 44% of cycles were monofollicular, whilst the corresponding figure in group 2 was 14% (P = 0.04). Evidence was found for postponed atresia in group 2. In both groups 1 and 2 inter-individual and intra-individual variability of the FSH dose inducing follicular growth were observed. We concluded that during the use of GnRHa, stimulation with low dose FSH less frequently resulted in monofollicular growth, possibly due to postponed atresia. Furthermore, the use of GnRHa does not abolish the inter- and intra-individual variability of the FSH dose inducing ongoing follicular growth.

Adult↗
PubMed1993

Pharmaco-dynamics of human menopausal gonadotrophin (HMG) and follicle-stimulating hormone (FSH). The importance of the FSH concentration in initiating follicular growth in polycystic ovary-like disease.

Using a randomized double-blind cross-over design, the pharmaco-dynamic and pharmaco-kinetic properties of 'pure' follicle-stimulating hormone (FSH) (Metrodin) and human menopausal gonadotrophin (HMG) (Pergonal) were studied in 24 women with polycystic ovary-like disease (PCOD) during induction of ovulation. Fifty-six cycles were stimulated with FSH and 60 cycles with HMG, according to a standard protocol. Gonadotrophins were administered i.v. in a pulsatile fashion using pulse frequencies of either 30 or 120 min. The cycles stimulated with either 30 or 120 min pulse intervals showed no differences among themselves. During the stimulation phase, the FSH and HMG stimulated cycles showed equal and dose dependent FSH concentrations (mean +/- SD). The luteinizing hormone (LH) concentrations (mean +/- SD) were also equal but unchanged compared to the mean basal concentration. The LH, FSH, total urinary oestrogen excretion, and testosterone profiles (mean +/- SD) obtained from cycle days -10 to 0 as well as the pregnanediol profiles obtained from cycle days 0 to +14 showed no differences either. The occurrence of an endogenous preovulatory LH surge was significantly more frequent in the cycles stimulated with a pulse interval of 30 min compared to the cycles stimulated with a pulse interval of 120 min. The addition of LH as provided in HMG did not influence the FSH threshold concentration above which initiation of follicular growth occurred, since no differences were found in the FSH 'stable' concentrations between FSH and HMG stimulated cycles. However, intra- and inter-individual variation in the FSH 'stable' concentration at which follicular growth was initiated became obvious.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Pituitary responsiveness after administration of a GnRH agonist depot formulation: Decapeptyl CR.

OBJECTIVE: This study was focused on the pattern of LH release from the pituitary during the initial response to high dose GnRH agonist administration. Secondly, the pattern of LH release and the pituitary responsiveness to physiological and pharmacological stimulation during long-term pituitary suppression by a high dose GnRH agonist was studied. In addition, the relation between serum agonist levels and pituitary function and responsiveness was investigated. DESIGN: DTrp6GnRH in microcapsules (Decapeptyl CR) was administered i.m. to 12 women on the third day of the cycle. High-rate blood sampling was carried out during the first 48 hours after the injection. Secondly, high-rate blood sampling for 6 hours and a GnRH challenge were performed before and weekly after administration, from week 4 till week 9. All samples were assayed for LH and FSH. LH patterns were analysed by applying a computerized pulse detection program. In the second or third week an oestradiol benzoate test was performed. Finally, triptorelin levels were measured before and weekly after administration. PATIENTS: Twelve patients, suffering from tubal infertility and recruited from the waiting list for in-vitro fertilization/embryo transfer (IVF/ET) participated in the study. RESULTS: During the first 48-hour period, LH and FSH levels demonstrated a rapid rise to peak values after 4 hours, subsequently declining to nearly normal levels. E2 rose to peak values at 12 hours and returned to the follicular range thereafter. LH pulse patterns showed a rapid increase in pulse intervals leading to a near absence of LH pulses at the end of the 48-hour period. From the fourth till the seventh week after agonist administration, LH pulse patterns showed a markedly increased pulse interval, decreased pulse amplitude, and a severely decreased mean LH level. In the same period, LH responses to GnRH were severely blunted or absent. Restoration of the pre-injection LH pulse pattern and the LH response to GnRH was observed during the eighth and ninth week. Oestradiol benzoate challenges showed an E2 rise to preovulatory levels in response to the injections. However, no changes were observed in LH and FSH concentrations. Triptorelin levels showed a peak within 48 hours and gradual decline towards pretreatment values in week eight. CONCLUSIONS: It is concluded from the study, that after administration of triptorelin depot in the early follicular phase, desensitization of the pituitary starts to develop within 24 hours. Pituitary responsiveness is completely absent in the second week and continues to exist until the eighth week after injection, when the agonist has disappeared from the circulation. These findings suggest profound alterations in GnRH receptor availability and post-receptor pathways, that prevent the pituitary from responding to physiological stimuli.

Adult↗