Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We present methods for implementing arbitrary permutations of qubits under interaction constraints. Our protocols make use of previous methods for rapidly reversing the order of qubits along a path. Given nearest-neighbor interactions on a path of length n , we show that there exists a constant ϵ ≈ 0.034 such that the quantum routing time is at most ( 1 - ϵ ) n , whereas any SWAP-based protocol needs at least time n - 1 . This represents the first known quantum advantage over swAP-based routing methods and also gives improved quantum routing times for realistic architectures such as grids. Furthermore, we show that our algorithm approaches a quantum routing time of 2 n / 3 in expectation for uniformly random permutations, whereas SWAP-based protocols require time n asymptotically. Additionally, we consider sparse permutations that route k ≤ n qubits and give algorithms with quantum routing time at most n / 3 + O k 2 on paths and at most 2 r / 3 + O k 2 on general graphs with radius r .

Randomized controlled trials in sub-Saharan Africa have shown that permethrin-treated bed nets and curtains reduce all-cause child mortality by 15-33% in areas with low or high but seasonal malaria transmission. This report describes the study site for a community-based, group-randomized, controlled trial in an area of high and year-round malaria transmission in western Kenya. We outline the development of the human and physical infrastructure required to conduct this trial and discuss some of the difficulties encountered and lessons learned in conducting it.

A group-randomized controlled trial of insecticide (permethrin)-treated bed nets (ITNs) was conducted in an area of high perennial malaria transmission in western Kenya to test the effect of ITNs on all-cause mortality in children 1-59 months of age. Child deaths were monitored over a two-year period by biannual household census in Asembo (1997-1998) and in Gem (1998-1999). Overall, 1,722 deaths occurred in children 1-59 months followed for 35,932 child-years. Crude mortality rates/1,000 child-years were 51.9 versus 43.9 in control and ITN villages in children 1-59 months old. The protective efficacy (PE) (95% confidence interval) adjusted for age, study year, study site, and season was 16% (6-25%). Corresponding figures in 1-11- and 12-59-month-old children in control and ITN villages were 133.3 versus 102.3, PE = 23% (11-34%) and 31.1 versus 28.7, PE = 7% (-6-19%). The numbers of lives saved/1,000 child-years were 8, 31, and 2 for the groups 1-59, 1-11, and 12-59 months old, respectively. Stratified analysis by time to insecticide re-treatment showed that the PE of ITNs re-treated per study protocol (every six months) was 20% (10-29%), overall and 26% (12-37%) and 14% (-1-26%) in 1-11- and 12-59-month-old children, respectively. ITNs prevent approximately one in four infant deaths in areas of intense perennial malaria transmission, but their efficacy is compromised if re-treatment is delayed beyond six months.

The effect of insecticide (permethrin)-treated bed nets (ITNs) on the spatial distribution of malaria vectors in neighboring villages lacking ITNs was studied during a randomized controlled trial of ITNs in western Kenya. There was a trend of decreased abundance of Anopheles gambiae with decreasing distance from intervention villages both before (P = 0.027) and after (P = 0.002) introduction of ITNs, but this trend was significantly stronger after ITNs were introduced (P = 0.05). For An. funestus, no pre-intervention trend was observed (P = 0.373), but after the intervention, a trend of decreased abundance with closer proximity to intervention compounds developed (P = 0.027). Reduction in mosquito populations in villages lacking ITNs was most apparent in compounds located within 600 meters of intervention villages. Sporozoite infection rates decreased in control areas following the introduction of ITNs (P < 0.001 for both species), but no spatial association was detected between sporozoite rates and distance to nearest intervention village. We conclude that high coverage of ITNs is associated with a community-wide suppression of mosquito populations that is detectable in neighboring villages lacking ITNs, thereby affording individuals residing in these villages some protection against malaria.

According to the endocrine model of hereditary dizygotic twinning, high FSH is responsible for multiple ovulation and pregnancy. Our study explored the underlying neuroendocrine causes. In a prospective clinical study, we compared the third day of menses parameters of episodic secretion of LH and FSH, the pituitary response to LHRH, plasma estradiol, and dimeric inhibin A and B in 16 regularly menstruating and 9 postmenopausal mothers of dizygotic twins with a family history of twinning and 14 premenopausal and 9 postmenopausal controls. Seven of 16 premenopausal mothers of twins had abnormally high FSH levels of more than 10 IU/L compared with 1/14 in controls (P = 0.024). In the premenopausal mothers of twins, mean FSH concentrations (P = 0.025) and FSH pulse frequency (P = 0.003) were significantly elevated, whereas FSH pulse amplitude and FSH response to LHRH were unaltered. For LH, neither the secretory parameters nor the response to LHRH was different. There were no differences between estradiol and inhibin A and B levels. Postmenopausal mothers of twin and controls did not differ with respect to the secretory pattern of LH and FSH. We conclude that under equal ovarian feedback conditions, premenopausal mothers of a dizygotic twin have hyper stimulation by endogenous FSH caused by neuroendocrine, hypothalamic, or pituitary mechanisms. This is the result of altered responsiveness to ovarian feedback and/or pituitary or suprapituitary, non-LHRH-like mechanisms that stimulate pulsatile FSH.

Objective: Gonadotropin secretion was evaluated to predict hypogonadotropic hypogonadism (HH) in 36 children suspected of having HH., Methods: LH was measured for 24 h at 10-min intervals, and FSH and estradiol or testosterone at 1-hour intervals. Twenty boys (age 15.7, range 13.2-19.3 years) and 16 girls (age 16.1, range 13.0-20.6 years) were studied., Results: LH pulses were detected in 9 boys and 5 girls. HH was confirmed in all 11 LH apulsatile boys and in 8 of 11 LH apulsatile girls. Random FSH values of < or =1.11 and < or =2.86 IU/l in boys and girls, respectively, discriminated patients with LH pulses from patients without (sensitivity for lack of LH pulses 97 and 100%, respectively). In boys testicular volume was not discriminatory. In 1 girl LH pulses were observed without estradiol production, suggesting LH neurosecretory dysfunction., Conclusions: Low FSH levels in adolescence are strongly related to a lack of LH pulses. Lack of LH pulses is highly suspect for HH. FSH may be a tool in the differentiation between HH and delayed puberty.

Sex steroids are important contributors to the pubertal growth spurt. Both androgens and estrogens have been related to this moment of rapid growth, but the role of estrogens is thought to be the most important one. Since exogenous estrogens are not capable to induce an appropriate growth spurt in girls, there might be an additional contributing factor involved. In a recent pilot study of 32 healthy pubertal girls, we found that the peak height velocity (HV) is preceded by relatively high levels of dehydroepiandrosterone sulfate and androstenedione (delta4A) as compared with the end-pubertal level. In the present study we evaluated HV in relation to dehydroepiandrosterone sulfate and delta4A levels in 149 healthy girls of various Tanner stages. HV was correlated with delta4A and estradiol levels in Tanner stages I-III. These results suggest that, like estrogens, delta4A might be an important stimulator of the female growth spurt.

Objective: To evaluate the role of endogenous feedback in monofollicular growth during low-dose gonadotrophin therapy in polycystic ovary syndrome (PCOS) by measuring FSH levels in a group of patients cotreated with a GnRH agonist (GnRH-a) (group B) compared with patients not cotreated with an agonist (group A)., Design: Prospective randomized study., Setting: University tertiary care Reproductive Endocrinology Unit., Patients: Women with clomiphene citrate-resistant PCOS., Main Outcome Measures: Follicle-stimulating hormone, E2, and inhibin levels, follicular growth., Results: In group A, FSH levels decreased significantly from 7.3 mIU/mL (conversion factor to SI unit, 1.00) at day -5 to 5.9 mIU/mL at day 0 (day that hCG was administered) despite a constant dose, whereas they remained at a level of 7.4 mIU/mL in group B. The rate of monofollicular growth was significantly higher in group A (80%) than in group B (22%). No significant differences in E2 levels or inhibin levels were found between the groups., Conclusions: The absence of a decrease of FSH during GnRH-a treatment in association with a lower rate of monofollicular growth suggests that endogenous feedback during low-dose step-up ovulation induction in PCOS plays an important role. The absence of this feedback mechanism in the presence of normal inhibin levels suggests that negative feedback control by inhibin during follicular stimulation is minimal.

Objective: The use of GnRH agonists for desensitization of the pituitary is widespread in gynaecological practice. For indications such as contraception and treatment of uterine leiomyomata partial desensitization may suffice. With respect to partial desensitization of the pituitary we have addressed three basic questions: (1) Is the degree of pituitary desensitization dependent on the dose of agonist used? (2) What is the optimal way to measure the degree of pituitary desensitization? (3) Is it possible to create a standard to express the degree of pituitary desensitization?, Design and Patients: Twenty-four women were randomized into 4 groups of 6 women. To achieve pituitary desensitization, the groups received 0.1, 0.25, 0.5 and 1.0 microgram/min GnRH respectively, for 6 weeks., Measurements: Pituitary desensitization was measured by gonadotrophin levels and responses to a 100-micrograms bolus of GnRH and an oestradiol benzoate challenge-test., Results: The level of LH and the responses of LH and FSH to the GnRH challenge showed significant dose-dependent suppression. Multiple regression indicated the LH response to the GnRH challenge was the best way to measure pituitary desensitization. From the LH responses to the GnRH-challenge a 'standard curve' was established for the assessment of the degree of pituitary desensitization., Conclusion: The LH response to the GnRH challenge test is the best available measure of pituitary desensitization during GnRH agonist treatment.

Objective: Guided by the favorable results of pulsatile gonadotrophin-releasing hormone (GnRH) in the recovery phase after GnRH agonist (GnRH-a) in PCOS, two hypotheses concerning the recovery phase were tested: (1) The resistance to clomiphene citrate will be broken in the recovery phase. (2) Stimulation with (i) a fixed dose of follicle stimulating hormone (FSH) or (ii) with the GnRH-a itself is equally effective in inducing ovulation as pulsatile GnRH., Design: After discontinuation of a 17-21 days GnRH-a treatment, ovulation induction was attempted with clomiphene citrate (CC) or with a fixed dose of FSH or with GnRH-a itself in three separate pilot trials. A previously reported group of 12 patients, treated with pulsatile GnRH in the recovery phase served as control., Patients: Three groups of six patients having PCOS. The group treated with CC was a selected CC-resistant group., Results: No CC-treated patient ovulated. After FSH stimulation two patients ovulated, and one patient ovulated on stimulation with a low dose of the GnRH-a. Endocrine observations in the recovery phase showed an early rise of FSH as compared to the rise of LH and androgens., Conclusion: This study could not demonstrate any effect of the recovery phase with respect to facilitation of follicular growth in PCOS. Both tested hypotheses were rejected: (1) The resistance to CC appeared not to be broken by the GnRH-a treatment and (2) subsequent stimulation with FSH or with the GnRH-a itself were not as effective as stimulation with pulsatile GnRH. An extensive further study of the mentioned modalities did not seem feasible.

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.

The possibilities and limitations of basal body temperature (BBT) records as an adjunct in the management of infertility were re-evaluated. To assess its accuracy as an index of ovulation, 172 charts were analyzed by three different physicians. While the average true positive rate was 90%, the false negative rate was only 2%. The remaining graphs (8%) were classified as non-interpretable, probably reflecting measurement problems. Retrospective assessment of 210 biphasic records showed the thermal nadir to occur within 1 day of the urinary luteinizing hormone (LH) surge in 75% of the cases, and in 90% when 2 days where considered. This confirms BBT as a relatively accurate guide for retrospective identification of the periovulatory period. Moreover, results of a study conducted to investigate how patients experienced daily recording of BBT graphs suggest that the method is well accepted by a high proportion of women. From all these it appears that there are many indications where BBT graphs can still be applied. Development of new electronic devices may further improve the reliability, acceptability and applications of the BBT records in the fertility investigation.

The effects of Bordetella pertussis (B. pertussis) on autonomic receptor function were investigated in vivo in the cardiovascular and in particular in the coronary vascular system of the pig. For this purpose the pigs were injected i.p. with B. pertussis vaccine 4 days prior to the experiment. Blood pressure, heart rate, cardiac output, coronary flow, left ventricular pressure and its dP/dt were measured. B. pertussis induced an increase in the baseline values for heart rate, cardiac output, coronary flow and maximal rate of rise of left ventricular pressure (maxLVdP/dt). Left ventricular end diastolic pressure and coronary vascular resistance were decreased. Dose-response curves were made for the beta 2-sympathicomimetic salbutamol. Pretreatment with B. pertussis reduced the effect of salbutamol on LVEDP and maxLVdP/dt. Furthermore, the effects of salbutamol on coronary flow and coronary vascular resistance were nearly completely inhibited. In conclusion, the present in vivo study in pigs evidenced hyporesponsiveness of the coronary and cardiac beta 2-adrenoceptors.