Luteal phase defects following agonist-triggered ovulation: a patient-dependent response.

The luteal phase (LP) of patients receiving triptorelin 0.1 mg to trigger ovulation was studied. Patients not pregnant in the first cycle with 0.1 mg were randomized into different groups for a second cycle: 0.1 mg again for patients who experienced a normal LP (group 1); patients affected with LP disorders were randomized into the following groups: 0.1 mg again (group 2); increasing dosage of triptorelin 0.5 mg once (group 3) or 0.1 mg three times (group 4); luteal support either with oral micronized progesterone (group 5) or human chorionic gonadotrophin (HCG) 1500 IU (group 6). Ovulation occurred in all cycles, but an inadequate LP was observed in 34.4% of the non-conceptional cycles. Patients demonstrating a normal LP as well as those affected with luteal disorders in their first cycle showed the same luteal pattern in their consecutive cycles triggered in the same way. In defective LP patients, increasing or repeating triptorelin doses did not restore the luteal phase or the pregnancy rate, both returning closer to normal after luteal support. Defective LP observed after agonist-triggered ovulation do not occur at random; therefore this patient-dependent response may be related to the personal characteristics of each patient's pre-ovulatory physiological surge profile.

[Comparison of different protocols of ovulation induction, by GnRH agonists and chorionic gonadotropin]. / Comparaison de différents protocoles de déclenchement de l'ovulation, par agonistes du GnRH et gonadotrophine chorionique.

OBJECTIVE: The aim of this study was to determine the best way of using a gonadotropin-releasing hormone agonist (GnRHa) for triggering ovulation and to analyse the reasons for short luteal phases. MATERIALS AND METHODS: Thirteen different regimens of GnRH-a administration were used to trigger ovulation using different dosages and either one, two or three administrations: triptorelin, buserelin spray, buserelin subcutaneously, leuprolide and nafarelin in 231 treatment cycles. Pregnancy rate and luteal phase duration were compared with those of a control group for whom ovulation was triggered with hCG. RESULTS: Ovulation with supraphysiologic elevation of both FSH and LH was achieved in the 13 GnRHa groups. For the five main groups analysed, GnRHa produced shorter and inadequate luteal phases than did hCG but no difference was found between agonists. Pregnancy rates were not statistically different between the agonist groups or in comparison with the hCG group. CONCLUSION: The use of GnRHa to trigger ovulation is efficient, despite short luteal phases, and has proven its utility in comparison with hCG. As the different modes of stimulation appear to yield comparable results, the cost of treatment should be a significant element to take into consideration.

Rapid leptin decrease in immediate post-exercise recovery.

OBJECTIVE: Leptin concentrations in humans are known to decrease in response to fasting. The aim of this work was to investigate whether leptin levels might also be modified by exercise-induced negative energy balance. SUBJECTS: Eight male runners reported in the morning from 0800 to 1200 h for (i) one resting session (sitting) and (ii) one exercise-and-rest session (2 h run and 2 h rest). MEASUREMENTS: Plasma leptin, free fatty acids (FFA), glycerol, cortisol and salivary cortisol were assayed in both sessions at 1200 h. RESULTS: After exercise-and-rest the leptin concentrations were lower than after rest (1.7 +/- 0.1 vs 2.5 +/- 0.2 micrograms/l, P < 0.05), i.e. a mean decrease of 30.3 +/- 4.5% (range 9.5-45.8). Plasma FFA, glycerol and cortisol concentrations increased: FFA 0.78 +/- 0.08 vs 0.18 +/- 0.04 mmol/l, glycerol 0.13 +/- 0.01 vs 0.04 +/- 0.01 mmol/l, and cortisol 428 +/- 36 vs 279 +/- 27 nmol/l. A negative correlation was found between plasma FFA and leptin levels (r = -0.5, P < 0.05) and between plasma glycerol and leptin levels (r = -0.05, P < 0.05). No correlation was found between leptin and cortisol levels. CONCLUSIONS: In normal subjects with low body fat, a strenuous exercise-and-rest lowers leptin levels by a mean of 30%. A role of lipolysis possibly via increased plasma free fatty acids and glycerol levels is suggested. Cortisol does not seem to be involved.

[Incidence of Creutzfeldt-Jakob disease in France, 1992-1995]. / Incidence de la maladie de Creutzfeldt-Jakob en France, 1992-1995.

BACKGROUND: Recent developments in animal and humans transmissible spongiform encephalopathies have motivated a study on incidence and risk factors of Creutzfeldt-Jakob disease (CJD) in France and 4 other European countries. METHODS: CJD cases were ascertained through a national network including 250 neurological departments or neuropathological laboratories. CJD cases were classified as definite, probable or possible. Overall incidence rate and age-standardized incidence rates by department were computed. Standardized incidence ratios and their 95% confidence intervals were computed for comparing observed and expected number of CJD cases in each department. RESULTS: Between 1992 and 1995, 216 CJD cases were registered (mean incidence rate: 0.87 per million inhabitants). The distribution of CJD cases was heterogeneous (p < 0.007). Nevertheless, the distribution of standardized incidence ratios fitted quite well a Poisson distribution. The observed number of CJD cases was significantly higher than expected in 4 departments and lower in 1 department. CONCLUSION: Incidence of CJD in France is similar to that observed in other European countries. Analysis of distribution of CJD cases by department showed a few significant differences which can be due to random fluctuations.

[Evaluation of 3 diagnostic methods in premature rupture of membranes: diamine-oxidase assay, alpha-fetoprotein assay, colorimetric method evaluating the pH]. / Evaluation de trois méthodes diagnostiques dans la rupture prématurée des membranes: dosage de la diamine-oxydase, dosage de l'alpha-foeto-protéine, méthode colorimétrique évaluant le pH.

The authors set out to assess the three diagnostic methods available which can detect early breaking of the membranes: radio-enzymatic assay of diamine-oxidase (DAO), radioenzymatic assay of alpha-fetoprotein (AFP), colorimetric method for determining pH (Amnicator). Between June 1991 and March 1992, 114 samples of vaginal secretions were taken from 104 pregnant patients being followed up at Maternity Unit A, Bordeaux (France). The results of the assays were expressed in quantitative terms (microU/ml for DAO and ng/ml for AFP); ROC (Receiver Operating Characteristic) curves were used to determine the positivity threshold in terms of the sensitivity and specificity (20 microU/ml for DAO and 15 ng/ml for AFP). The sensitivity of the pH test was 97.5%, which was significantly better than that of DAO (90.2%) and even that of AFP (82.9%). However, there was no difference between the specificities of the pH, DAO and AFP tests (93.3%, 96.6% and 93.5% respectively). The data were compared with those in the literature. The problems in collecting the vaginal secretions probably accounts for the better results of the colorimetric test. This is a reliable, fast and easily reproducible test; these qualities make it the preferred test in EBM, and it can be completed using a radioenzymatic method (DAO) or immunoradiometric test (AFP).

[Ovulation induction by endogenous LH released by the administration of an LHRH agonist after follicular stimulation for in vitro fertilization]. / Déclenchement de l'ovulation par la LH endogène libérée par l'administration d'un agoniste de la LHRH après stimulation folliculaire pour fécondation in vitro.

Sixty-seven patients whose ovulation was stimulated following a protocol of Clomiphene Citrate/HMG in order to carry out in vitro fertilisation were divided randomly in to two groups. In the first group ovulation was provoked by giving 10,000 IU HCG IM, but in the other group ovulation was provoked by releasing endogenous LH after the administration of Triptoreline in a dose of 0.1 mg in a dose subcutaneously three times in one day at 8 hour intervals. The number of oocytes recovered, cleavage and embryo transfer were compared between the two groups over 48 cycles. The number of conceptions was statistically significantly higher in the group that had triptoreline (28%) as compared with 17.4% pregnancies in the other group (p less than 0.01). These figures confirm that the endogenous LH surge provoked by giving an LHRH agonist can cause adequate final oocyte maturation. This property which is associated with a very low risk of hyperstimulation, should make it possible to stimulate ovulation when it is not used for IVF and so replace the usual injection of chorionic gonadotrophins.

Triggering ovulation with endogenous luteinizing hormone may prevent the ovarian hyperstimulation syndrome.

In a series of 126 therapeutic cycles in 48 patients with primary infertility and treated with HMG for anovulation or preparation to insemination, ovulation was triggered by endogenous LH instead of HCG when the patient was considered to be at high risk for ovarian hyperstimulation syndrome (OHS), (plasma oestradiol greater than 1200 pg/ml) and/or multiple pregnancy (greater than 3 follicles greater than 17 mm in diameter). The endogenous LH surge was provoked and maintained by intranasal buserelin 200 micrograms three times at 8-hourly intervals. In the 37 cycles with buserelin, no OHS occurred despite high preovulatory levels of oestradiol; a single twin pregnancy was recorded despite the presence of numerous mature preovulatory follicles. Conception results (21.6% pregnancy per therapeutic cycle) compared favourably with HCG administration (16.8%). It is concluded that, when ovulation must be triggered in a hazardous situation, the use of endogenous LH through the administration of a short-acting GnRH analogue prevents the complications of exaggerated follicular stimulation.

Nocturnal profile of growth hormone secretion during sleep induced by zolpidem: a double-blind study in young adults and children.

Overnight blood sampling for repeated growth hormone (GH) assays, regarded as the most physiological assessment of GH status, may induce some disturbances in patients' sleep and then in the evaluation of GH secretion. We studied the influence of a hypnotic drug, zolpidem (10 mg), on nocturnal GH profiles (GH peak, time to first and maximum GH peak, area under the curve, mean integrated concentration) over two nights at a 7-day interval, in a double-blind cross-over design in a group of 12 young adult volunteers (27.9 +/- 4.3 years), and in a group of 12 children (10.8 +/- 2.3 years) with short stature, in a parallel double-blind study. Mean GH profiles showed no difference between zolpidem-treated subjects and placebo-treated controls, either in adults or in children. Although in these experimental conditions, sleep onset latency was significantly reduced with zolpidem in the adult volunteers, the mean time to first GH peak remained unchanged. Furthermore, GH profile did not relate with sleep duration, sleep onset latency or number of awakenings. A hypnotic drug, such as zolpidem, given at bedtime, is therefore devoided of effect on nocturnal GH profile and may be used in young children for overnight blood sampling when needed.

A placebo-controlled trial of intranasal growth hormone-releasing hormone [GHRH(1-44)-NH2] administration in normal young adults.

Growth hormone-releasing hormone, GHRH(1-44), was administered intranasally to 16 healthy young adult male volunteers in a placebo-controlled study using a dose of 1,000 micrograms dissolved in two different solvent vehicles: water alone and water with the surface tension-lowering agent Tween 80 (0.12%). The growth hormone (GH)-releasing effects of intranasal GHRH as well as that of the vehicle were established and compared to the effects of 80 micrograms intravenous GHRH. Plasma GH response was assessed by frequent blood sampling over an 180-min period, using both peak response and area under the curve (AUC). The results show that the GH-release effects of intranasal GHRH are comparable whichever vehicle is used, and are similar, with the dose of 1,000 micrograms, to the response obtained following the administration of 80 micrograms intravenous GHRH. Peak GH responses to GHRH (means +/- SEM) were 25.6 +/- 4.2 ng/ml (1,000 micrograms GHRH with water), 32.9 +/- 9.1 ng/ml (1,000 micrograms with water plus Tween 80) and 36.3 +/- 7.8 ng/ml (80 micrograms i.v. administration) (not significant). There was no significant GH response to placebo. Mean peak GH responses occurred after approximately 30 min in all three active treatments (29.2 +/- 2.7, 33.9 +/- 3.2 and 30.9 +/- 3.9 min, respectively). The AUC values (ng.min.ml-1) were not statistically different: 1,914.4 +/- 386.7 (water), 2,176.2 +/- 599.9 (water plus Tween 80) and 2,419.2 +/- 506.9 (i.v.) (not significant). Intranasal GHRH administration was well tolerated in all subjects. Occasional local reactions consisted of a prickly sensation in the nostrils or sneezing irrespective of the vehicle used.(ABSTRACT TRUNCATED AT 250 WORDS)

[Normal values of osteocalcin in the blood over the course of life]. / Valeurs normales de l'ostéocalcine sérique au cours de la vie.

This study tends to settle the standard values of BGP circulating amount, which - attesting osteoblastic activity - varies according life periods. The lowest amounts are to be found in twenty five to forty five years adults; though varying all the day and night long, these amounts remain included between 3-7 ng/ml; particularly if the blood-test took place between 8 and 10 a.m.

[Rapid determination of plasma progesterone. Its value in ovarian stimulation for in vitro fertilization]. / Le dosage rapide de la progestérone plasmatique. Son intérêt dans la stimulation ovarienne pour fécondation in vitro.

Plasma Progesterone levels show definite variations during the periovulatory period of the superovulated cycle similar to those of the physiological cycle. The question arises whether the pattern of these variations is of significance with regard to the success rate of the IVF cycle. This prospective study was conducted with a rapid and highly sensitive radioimmunoassay of plasma progesterone labelled with Iodine 125. A total of 452 cycles were initiated in 328 patients (280 cycles using a clomiphene citrate-HMG regimen, 272 cycles using an association of LHRH analogues with HMG according to three different protocols). Ovarian response was monitored with sonography and rapid plasma radioimmunoassays of 17 beta-estradiol, progesterone and LH (in non-analogue cycles). Plasma progesterone in particular was assayed 17 hours before, at the time, and 7 hours after the administration of HCG. 10,000 UI IM for triggering ovulation. During the Clomiphene-HMG therapy when LH levels are instable, the plasma progesterone assay is highly discriminant between the beginning of a true LH peak (with concomitant rise of progesterone greater than 1 ng/ml, 15.7% of the cycles) and hectic variations of LH (no concomitant rise of progesterone, 4.3% of the cycles); the progesterone assay was also able to detect the occurrence of ovulation in 3 cycles without sensible variation of plasma LH (1.1% of the cycles). Pre- and post-ovulatory levels of plasma progesterone also demonstrate a prognosis significance with regard to the chances of success of the cycle, with all the different types of ovarian stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Osteocalcin in children of short stature and its nocturnal variations]. / L'ostéocalcine chez l'enfant de petite taille et ses variations nocturnes.

Serum osteocalcin (Gla-P) was measured in 65 children with normal stature for age and in 116 children with growth retardation, excluding endocrine disorders, in matched groups according to age: 1-6 years (n = 33); 7-10 years (n = 49); 11-14 years (n = 72); 15-18 years (n = 27). Thirty of these patients were retested at 2 weeks interval. In addition, Gla-P and growth hormone (hGH) were assayed in blood samples obtained every 20 minutes during sleep in 12 children with growth retardation. In younger children, Gla-P levels were significantly lower in patients with growth retardation, when compared with normal children. In contrast, this difference was no longer significant in children above 11, with either normal or delayed puberty. However, important intra-individual variations of Gla-P levels were observed on blood samples obtained at 2 weeks interval. A nocturnal periodicity in Gla-P was found; Gla-P rose slightly during sleep in the patients studied, maximum concentration being reached between 4 and 6 AM. No correlation between integrated concentrations of hGH and Gla-P was found. Gla-P determination may be of interest in the evaluation of young children with short stature. Standardized conditions of blood sampling for Gla-P use in children remain to be determined.

[Contribution of human menopausal gonadotropins purified as to their FSH content in anovulatory sterility presenting a difficult treatment problem]. / L'apport des gonadotrophines de ménopause humaine purifiées en FSH dans les stérilités anovulatoires de traitement difficile.

A preparation of HMG purified to contain only FSH (FSH 75 IU/LH less than 1 IU) was used in 26 patients who had anovulatory sterility because of sclero-polycystic ovaries. It was a selected population in that all the patients had proved to be resistant to Clomiphene Citrate and at risk with HMG therapy. Purified urinary FSH was used and monitored as classical HMG treatment. 44 treatment cycles resulted in 33 ovulatory cycles (75%) and 6 pregnancies (13.6% per cycle). The number of cases of hyperstimulation (13.6%) was low when it is compared to situations at risk when HCG was administered in 2/3 of the treatment cycles. The results obtained in a population with a bad prognosis can be considered to be very encouraging and gives purified urinary FSH a specific place in our therapeutic armamentarium.

[Markers of the periovulatory phase with an eye toward insemination: E2/LH correlations]. / Marqueurs de la phase péri-ovulatoire en vue d'insémination: corrélations E2/LH.

We are investigating the most practical parameters i.e. reliable and with a rapid response, which allow the time of insemination to be determined in women undergoing stimulation because of anovulation. We have already shown the advantage of rapid radio-immunological determinations of 17 beta-oestradiol (E2) to induce the releasing action of chorionic gonadotrophic hormone (hCG). We have carried out our investigations directed towards the rapid-immunological determination of luteotrophic hormone (LH), and have recorded a good temporal correlation between E2 and LH, the rise of E2 preceding by some hours that of LH, and the two summits succeeding each other. Inseminations are followed by fertilization in women who present with the following: a mean oestradiolaemia of about 500 pg/ml in the second part of the follicular phase, maintained after interruption of HMG administration (alone or after clomiphene citrate), which decreases only slowly after administration of hCG; a level of LH increasing from 9-14 ng/ml (mean) in the last two days preceding the summit of LH; the level of LH multiplied at least by 2 after the administration of hCG, whatever the mode of stimulation. Clomiphene citrate, not provoking a constant ovulatory discharge, does not dispense with the administration of hCG in the majority of cases. These considerations result from the study of a group of 22 anovulatory women, in whom stimulation followed by determination of E2 and LH, under echographic control, have allowed 12 pregnancies to be obtained (7 by clomiphene citrate + HMG + hCG; 5 by HMG + hCG), decreasing the mean number of inseminated cycles to 3 per woman thus studied.

[Steroids and the prediction of ovulation]. / Steroides et prediction de l'ovulation.

PIP: Prediction of ovulation is useful in artificial insemination but indispensable in gathering of ovocytes for in vitro fertilization (IVF). IVF programs represent quasi-experimental conditions for correlating hormone levels and sonographic findings with ovulation and ovocyte maturation during spontaneous and induced menstrual cycles. During the follicular phase, only 1 "dominant" follicle is usually selected for ovulation. Under the influence of follicle stimulating hormone (FSH) and luteinizing hormone (LH), the ovocyte develops and transforms androgens secreted by the follicle into estrogens. The plasma at this stage is a poor reflector of the hormonal status of the follicular liquid. The preovulatory LH peak occurs after the level of estradiol (E2) reaches 200 pg/ml for about 50 hours. Increased estrogen secretion is the first notable hormonal variation preceding ovulation, but until a stage near ovulation, hormonal changes in the follicular liquid are not reflected in the plasma. Levels of FSH and LH progressively increase at the beginning of the follicular phase. Beginning in the middle of the follicular phase, around the 6th or 7th cycle day, the plasma concentration of 17 beta estradiol begins to increase rapidly. Plasma levels of several other steroids also increase in the days before the LH peak. The androgens produced throughout the menstrual cycle are not all ovarian origin. Their pulsatile secretion and normal variation make them inappropriate for predicting ovulation. Until recently the urinary levels of estrogens were the only measures routinely available, but their reliability as a measure of the estrogen actually produced depended on several factors. They are still used because of their advantages in cost and practicality. Newer tests of plasma estrogen levels give quick results and are used in numerous clinical situations despite their cost and their technical complexity. Although the increased plasma concentration of estradiol is the first of a series of hormonal events leading to ovulation, great variations in E2 rates from 1 cycle to another mean that it is not a reliable or precise predictor of ovulation. For spontaneous cycles, only repeated measurement of plasma or urinary LH levels allow correct prediction of ovulation in clinical practice. Ovarian stimulation by clomiphene or other substances modifies follicular phenomena. In such cases, monitoring of the estradiol level in association with ultrasound provides useful information about follicular maturation and to some extent ovocyte maturation, both of which are essential for IVF and embryo transfer.^ieng