Biomedical subjects

J N Hugues

Publications and source records attributed to J N Hugues.

At least 19 recordsLinked to original sources

PubMed2000

Effectiveness of low dose of gonadotropin releasing hormone agonist on hormonal flare-up.

PURPOSE: The hormonal response (flare-up) following administration of a standard dose (100 micrograms) or a low dose (25 micrograms) of gonadotropin releasing hormone agonist (GnRH-a) (Triptorelin) was compared in patients prior to an in vitro fertilization (IVF) cycle and during the early follicular phase of a short-term IVF protocol. METHODS: The gonadotroph (FSH, LH) and steroid [estradiol (E2) and progesterone (P)] flare-up was studied on two consecutive cycles in 30 normo-ovulatory women. Patients were randomized to receive either 25 or 100 micrograms of triptorelin for three days at the beginning of the first cycle. Then doses were switched according to a crossing over design in the second cycle. RESULTS: No significant difference in the magnitude of FSH and E2 release could be observed following administration of the two doses of agonist whereas maximal plasma LH level was significantly reduced after injection of 25 micrograms of triptorelin. CONCLUSIONS: As compared to a standard dose, using a low dose of GnRH-a induces an hormonal flare-up which seems adequate for an optimal follicular recruitment.

Adult↗

PubMed2000

Consequences on gonadotrophin secretion of an early discontinuation of gonadotrophin-releasing hormone agonist administration in short-term protocol for in-vitro fertilization.

Administration of gonadotrophin-releasing hormone (GnRHa) agonists, used in IVF short-term protocols to initiate follicular recruitment, may be restricted to the early follicular phase without any further risk of LH surge. However, consequences of an early discontinuation upon residual endogenous gonadotrophin secretion are still unknown. Here, the effects of early cessation of GnRH agonist upon gonadotrophin secretion and ovarian parameters of IVF cycles were investigated. A total of 230 normo-ovulatory women were prospectively allocated to one of the two regimens: decapeptyl-GnRH (100 microgram) was daily injected either from day 1 to the triggering of ovulation (group 1) or for the first 7 days (group 2). Exogenous gonadotrophins (150 IU) were administered on day 4 and 5 with a subsequent adjustment. Detections of free alpha subunit and dimeric LH were performed by highly specific 'two site' monoclonal immunoradiometric assays. The results show that early discontinuation of GnRH agonist administration was associated with a sharp decrease in both plasma free alpha subunit and dimeric LH concentrations while plasma oestradiol response to exogenous gonadotrophins was reduced. Other ovarian parameters and pregnancy rate were unchanged. These data indicate that endogenous LH secretion is maintained by a daily administration of GnRH agonist and may contribute to the final follicular maturation.

Adult↗

PubMed1999

Pregnancies, growth and development of children conceived by subzonal injection of spermatozoa.

Subzonal injection of spermatozoa (SUZI) was one of the first micromanipulation techniques efficient in treating male factor infertility and unexplained in-vitro fertilization failures. The aim of this retrospective study was to evaluate the in-vitro development of embryos conceived by SUZI, the obstetric outcome, the rate of congenital malformations and subsequent follow-up in children. Fifty-five pregnancies were obtained between 1991 and 1994 (54 after fresh embryos were transferred and one after cryopreserved embryos were transferred). Among the 50 clinical pregnancies, there were seven miscarriages (14%) and two ectopic pregnancies (4%). Among the 41 resulting evolutive pregnancies, the discovery of one anencephaly led to a medical abortion. Forty deliveries including six twin pregnancies occurred, leading to the births of 45 live neonates and one stillbirth. The gender distribution of the offspring included 17 males and 29 females (ratio 0.59:1). Birth weight, length and head circumference were within the expected ranges. Two children presented a malformation: the first one had one thumb with congenital shelf and the second a polymalformative neurological syndrome. Growth curves were normal for all these children except one (weight above the 2 SD curve). Medical follow-up detected no pathological features in these children apart from a physical disability in one girl. In this small series a 4.2% rate of malformation was observed, particularly affecting the neural tube, in SUZI offspring. However, no firm conclusions can be drawn since the study was carried out on a small cohort. SUZI is no longer performed but these observations suggest that it is necessary to collect extensive data about children conceived by microfertilization.

Abortion, Spontaneous↗

PubMed1998

Chromosome 21 detection in human oocyte fluorescence in situ hybridization: possible effect of maternal age.

PURPOSE: The purpose of this study was to evaluate, among 100 uncleaved oocytes, the incidence of numerical and structural chromosome 21 and X abnormalities and to analyze the influence of various factors, such as in vitro (IVF) indications, follicle stimulation protocols, and women's age. METHODS: We investigated 150 uncleaved oocytes from 128 patients after an IVF attempt. After cytogenetic analysis (Giemsa) 100 oocytes (66%) were selected for fluorescence in situ hybridization (FISH). Fluorescent probes for human chromosomes X and 21 were used simultaneously according to standard procedures for their hybridization and detection. RESULTS AND CONCLUSIONS: We analyzed by the FISH protocol 100 metaphase II oocytes with 22 to 25 chromosomes. Our results demonstrate a high rate of disomy for chromosome 21 in human oocytes. Among them, eight were disomic (8%) and three were nullosomic (3%) for chromosome 21. Only one disomy of chromosome X was noted. The various indications of IVF and the different folliculogenesis stimulating protocols did not seem to influence the results but suggested a correlation between the maternal age and the aneuploidy rate of chromosome 21.

Adult↗

PubMed1998

A comparative prospective study of a chronic low dose versus a conventional ovulation stimulation regimen using recombinant human follicle stimulating hormone in anovulatory infertile women.

The efficacy and safety of a chronic low dose (group A) and a conventional (group B) stimulation regimen of recombinant human follicle stimulating hormone (r-HFSH) were compared in 103 WHO Group II infertile women with clomiphene citrate-resistant anovulation. Mono- or bifollicular development was induced in 88.1% of patients in group A compared with 76.1% in group B. Ovulation and pregnancy rates were higher in group A (71.4% and 33.3%, respectively) than in group B (63.0% and 20%), but these differences were not statistically significant. Additionally, the total number of follicles that were >10 mm diameter was lower in group A than group B (3.0+/-2.6 versus 6.3+/-6.5; P < 0.0001), as was the oestradiol concentration (504+/-477 pg/ml versus 988+/-740 pg/ml; P < 0.03). The median dose of FSH (75 IU ampoules) used per cycle was 11 ampoules in group A and 12.5 in group B. In terms of the incidence of ovarian hyperstimulation syndrome, no differences were recorded between the two groups. The results demonstrated that r-HFSH is effective and safe in both these treatment protocols. The chronic low dose regimen was associated with a trend towards a higher rate of mono- or bifollicular development, without jeopardizing the incidence of pregnancy.

Adult↗

PubMed1998

["Step protocols"].

Within the last decade, induction of ovulation with gonadotrophins, specially for patients with polycystic ovary syndrome, has been extensively revisited. On the basis of physiological concepts as the FSH threshold, the FSH window and the hypersensitivity to FSH of selected dominant follicle, news protocols have been described: step-up protocol, step-down, sequential protocol. In this article, their efficacy and safety are discussed. It is presumed that these new protocols would open a new way in the management of ovulation induction.

Clinical Protocols↗

PubMed1998

[Immunohistochemical characterization of the inflammatory infiltrate in the human endometrium prior to in vitro fertilization and embryo transfer].

UNLABELLED: Infiltrating leukocyte population appears at the time of implantation in the endometrium of human and other mammals with hemochorial placentation. This leukocyte population is mainly composed of macrophages and typical granular lymphocytes CD56+ CD16-. 63 endometrial samples were studied using immunocytochemistry, before IVF and embryo transfer. We evaluated the sensibility for the assessment of immunological relevant infiltrating cells, of classical histopathologic examination compared with quantitation of leukocyte-common-antigen antibody immunostaining. 21 samples were thoroughly studied during proliferative phase. RESULTS: The sensibility of classical histologic analysis for the semi-quantitative assessment of leukocyte population, even when performed by an experienced histopathologist, is only 62%. When leukocyte population during proliferative phase is dense, it is mainly composed of macrophages and CD56+ CD16- lymphocytes. CONCLUSION: Immunological reaction already reported around the time of implantation may occur at other period of the menstrual cycle. Close mechanisms of the control and functions of this characteristic reaction remain to clarify.

Adult↗

PubMed1997

[GnRH analog protocols revisited I--advantages and doubts].

During the last decade, the introduction of GnRH analogs in ovarian stimulati on protocols has greatly improved the outcome of IVF cycles. Through a suppressive effect of hypophyseal secretion, GnRH analogs have allowed to prevent cycle cancellation related to endogenous LH surge and/or premature luteinization. Nevertheless, apart from this beneficial effect, little information has been done about consequences of their administration on residual gonadotroph secretion, ovarian responsiveness to gonadotrophins, quality of oocyte and conceptus, endometrial receptivity. The extreme diversity of long-term and short-term protocols used in clinical practice makes this analysis more difficult. In the first part of this review, the authors examine the several ways of GnRH analogs prescription in order to separate their specific effects on each reproductive function component.

Clinical Protocols↗

PubMed1997

[Revisiting GnRH analog protocols II. Strategy for poor responders].

In the first part of this review, we analyzed protocols for ovarian hyperstimulation with GnRH analogs and stressed both their diversity and uncertainty for mechanisms which lead to improve the outcome of IVF cycles. Apart from their beneficial effects on prevention of endogenous LH surges and premature luteinization, other adverse effects have been reported: need of higher amount of exogenous gonadotrophins, direct negative action on ovarian function and conceptus quality. They must be considered before defining a strategy for poor responders to IVF protocols using GnRH analogs. The recent trend for reducing GnRH doses must be evaluated.

Animals↗

PubMed1996

Effects of growth hormone releasing hormone on rat ovarian steroidogenesis.

During the last decade, it has been shown that each part of the somatotrophic axis can influence granulosa cell function. Growth hormone releasing hormone (GHRH) may be effective through the release of hypophyseal growth hormone (GH) and the subsequent increase of insulin-like growth factors (IGF). There is also some evidence that GHRH could act directly on ovarian function. The aim of this study was to determine the mechanism through which GHRH affects granulosa cell steroidogenesis in the ovary. Granulosa cells were obtained from immature, oestrogen- treated rats supplemented with or without follicle stimulating hormone (FSH) in vivo and were cultured for 48 h to evaluate steroid production. GHRH was administered either in vivo at the same time as FSH, or in vitro in the presence or absence of testosterone and FSH. Our results show that co-treatment with GHRH and FSH in vivo induced significant increases in plasma IGF-I concentrations and steroid production by cultured granulosa cells. The addition of GHRH to culture medium did not significantly alter steroid production by either non-differentiated (no FSH in vivo) or differentiated (FSH in vivo granulosa cells. In contrast, treatment in vitro with IGF-I significantly increased steroidogenesis in both cases. Our results suggest that any physiologically significant effect of GHRH on ovarian function is probably to be exerted via activation of the somatotrophic axis and the subsequent amplification of ovarian FSH responsiveness by IGF-I.

Animals↗

PubMed1996

Sequential step-up and step-down dose regimen: an alternative method for ovulation induction with follicle-stimulating hormone in polycystic ovarian syndrome.

This study was designed to compare both the effectiveness and safety of two low-dose gonadotrophin regimens (step-up versus sequential step-up and step-down) for ovulation induction in polycystic ovarian syndrome (PCOS) patients. In all, 56 infertile clomiphene citrate-resistant PCOS patients were included in this prospective randomized study. A total of 38 cycles were conducted with a classic step-up protocol, whereas for 35 cycles the follicle-stimulating hormone (FSH) threshold dose was reduced by half when the leading follicle reached 14 mm in diameter (sequential protocol). Serum oestradiol, progesterone and luteinizing hormone concentrations and follicular growth rate were evaluated during the cycle. At the time of human chorionic gonadotrophin administration, cycles treated with sequential protocol exhibited significantly lower oestradiol concentrations [434 +/- 45 versus 593 +/- 67 pg/ml (mean +/- SEM)] and the number of medium-sized (14-15 mm) follicles was significantly reduced (0.3 +/- 0.1 versus 0.8 +/- 0.2) compared with cycles treated with the classic step-up protocol. Moreover, in these cycles serum luteal oestradiol concentrations were decreased significantly (350 +/- 77 versus 657 +/- 104 pg/ ml) compared with the classic step-up protocol. A sequential step-up and step-down protocol seems to be a safe and effective regimen for ovulation induction in PCOS patients. Decreasing the FSH dose following step-up follicular selection may be an alternative method to avoid multifollicular development.

Adult↗

PubMed1996

The hormonal flare-up following gonadotrophin-releasing hormone agonist administration is influenced by a progestogen pretreatment.

In a short-term protocol, the influence of progestogen pretreatment upon the oestradiol flare-up (delta E2) induced by gonadotrophin-releasing hormone agonist (GnRHa) was assessed in relation to in-vitro fertilization (IVF) outcome in 90 cycles programmed (n = 52) or not (n = 38) by norethisterone (10 mg/day for 12-20 days). Patients pretreated by progestogen had a significantly lower delta E2 value than patients without pretreatment (delta E2 = 26 +/- 5 versus 61 +/- 8 pg/ml, P = 0.003). It could be related to a lower gonadotrophic response for luteinizing hormone (LH) (delta LH = 9 +/- 0.8 versus 14.5 +/- 2.2 IU/l, P = 0.01). The IVF outcome (final oestradiol, number of oocytes or embryos) was similar in both groups and delta E2 was well correlated with these final parameters in each group. A significant rise in serum progesterone was observed only in patients without pretreatment (delta P = 1.1 +/- 0.2 versus 0.1 +/- 0.1 ng/ml, P < 0.0001). Thus norethisterone pretreatment decreases the oestradiol flare-up and prevents the early increase of progesterone (by avoiding some rescue of the corpus luteum or some luteinization of small developing follicles) but does not influence the outcome of the IVF cycle. In clinical practice, evaluation of the hormonal flare-up for predicting IVF outcome must take into account any pretreatment prescription.

Adult↗

PubMed1996

[Evaluation of ovarian sensitivity to gonadotrophins: role of ovarian reserve tests].

Among several parameters involved in the age-dependent reduction in conception rate, intra-ovarian factors, specially the follicular oocyte complex, play a major role. The aim of endocrine challenge tests is to assess ovarian follicular reserve. Basal serum FSH determination on day 3 of the cycle is easily measurable, inexpensive. Its sensitivity is increased with a clomiphene citrate challenge test. Both GnRH agonist stimulation test and exogenous FSH test allow to evaluate more directly the ovarian function. However they are more invasive, expensive and need further standardisation.

Clomiphene↗

PubMed1995

Chromosome 18 analysis by fluorescence in situ hybridization (FISH) in human blastomeres of abnormal embryos after in vitro fertilization (IVF) attempt.

We performed fluorescence in situ hybridization (FISH) with a chromosome 18-specific probe on human abnormal cleaved embryos, fertilized either by two spermatozoa and exhibiting three pronuclei (3 PN) or normally fertilized and exhibiting two pronuclei (2 PN) with subsequent severe fragmentation and/or blocking. The aim of the study was to evaluate the incidence of chromosome 18 anomalies among these embryos in order to evaluate the FISH efficiency on such material and to obtain more precise and complete data than those obtained with classical cytogenetic analysis. For the 3 PN cleaved embryos, FISH confirmed the frequent regulation towards diploidy (25 per cent) and the high frequency of mosaics (53 per cent). For the 2 PN blocked or damaged embryos, FISH permitted chromosome evaluation, which was otherwise impossible with classical cytogenetic techniques: we also found a high mosaic frequency (45 per cent) with these embryos. If this frequency were the same for normally developing embryos, it would be a major obstacle to the reliability of either chromosomal or genetic preimplantation diagnosis.

Blastomeres↗

PubMed1995

Risk of thromboembolism in relation to an in-vitro fertilization programme: three case reports.

Severe thrombotic events following ovarian stimulation for in-vitro fertilization (IVF) procedures in three women are reported. None of these patients presented any concomitant clinical sign of ovarian hyperstimulation syndrome. Coagulation inhibitors were in the normal range but cardiovascular risk factors were present. It is postulated that early thrombosis could be favoured by high endogenous plasma oestrogen concentrations subsequent to ovarian stimulation when associated with another risk factor. Our data are discussed in relation to previous publications. It is suggested that risk factors must be considered individually before each IVF attempt. In patients at high risk, clinical management of the post-transfer period is recommended.

Adult↗

PubMed1995

Progestogen pretreatment in the short-term protocol does not affect the prognostic value of the oestradiol flare-up in response to a GnRH agonist.

The prognostic value of the oestradiol flare-up in response to gonadotrophin-releasing hormone (GnRH) agonist was evaluated in 140 in-vitro fertilization (IVF) cycles programmed by progestogen pretreatment. Three days after the end of administration of norethisterone, a routinely used short-term DTRP6 GnRH agonist protocol was started (designated day 1), gonadotrophins being introduced from day 4. Serum oestradiol flare-up values were evaluated on days 1, 2 and 3 to study their relationship with the subsequent IVF outcome. On day 2, 87.9% of the cycles exhibited a significant rise in serum oestradiol concentration from baseline (delta E2 > or = 5 pg/ml). Compared to cycles without any significant oestradiol increase, they had a higher pregnancy rate per transfer (33.3 versus 9.1%, P = 0.02), although the number of transferred embryos did not differ significantly. Taking into account the previously described cut-off value (doubling from baseline), we found that less than half of the cycles (45.7%) involved a doubling of oestradiol values during flare-up, and we did not observe any significant difference in IVF outcome in these cycles compared to those without doubling. In conclusion, progestogen pretreatment, by inducing ovarian quiescence, may lower the oestradiol cut-off value that is predictive of the subsequent pregnancy rate. Nevertheless, determination of the absolute oestradiol response (delta E2) to GnRH agonist after progestogen pretreatment could allow a further adaptation of the protocol to achieve an optimum response in each cycle. Another alternative for patients with a lower delta E2 could be the suppression of progestogen pretreatment.

Adult↗

PubMed1995

Efficacy and safety of recombinant follicle stimulating hormone (Puregon) in infertile women pituitary-suppressed with triptorelin undergoing in-vitro fertilization: a prospective, randomized, assessor-blind, multicentre trial.

The objective of this study was to compare the efficacy and safety of a recombinant follicle stimulating hormone (FSH) preparation (Org 32489, Puregon) with a urinary FSH preparation (Metrodin) in infertile women undergoing in-vitro fertilization (IVF and embryo transfer and who were pituitary-suppressed with triptorelin. In an assessor-blind, group-comparative, multicentre study, 60 women were randomized to Org 32489 and 39 to urinary FSH. An evaluation of the main parameter, the mean total number of oocytes recovered, indicated a similar efficacy for the two preparations: 9.7 with Org 32489 versus 8.9 with urinary FSH. In addition, there were no significant between-group differences with respect to other efficacy variables such as the total dose used, the duration of the treatment, the number of follicles > or = 17 mm in diameter and embryo quality. The ongoing pregnancy rates per attempt (30.2 versus 17.4%) and per transfer (34.0 versus 18.8%) were higher with Org 32489, but this difference was not statistically significant. No clinically relevant differences between Org 32489 and urinary FSH were seen with respect to safety variables. Serum antibodies were not detected in any of the subjects. It is concluded that Org 32489 compares favourably with urinary FSH in the treatment of infertile pituitary-suppressed women undergoing IVF and embryo transfer.

Abdominal Pain↗

PubMed1994

Presence in mouse Sertoli cell-conditioned medium of a factor that expresses AVP-like inhibition of steroidogenesis by mouse Leydig cells in long-term culture.

The influence of spent medium from immature mouse Sertoli cells (SCM) on testosterone production by purified Leydig cells was investigated and compared to that of AVP, a potent local modulator of Leydig cell steroidogenesis. SCM inhibited in a dose-dependent manner the hCG-stimulated testosterone production, but was ineffective in basal conditions. As is known for AVP, (i) a lag period of 72 h was prerequisite for SCM to inhibit Leydig cell function; (ii) the main effect of SCM was located at a step beyond the receptor-adenylate cyclase system, since the hCG- and 8-bromo-cAMP-stimulated testosterone productions were similarly affected. The possibility that the effect of SCM may be related to AVP-like molecule(s) is also supported by the observations that at maximal concentrations the inhibitory effects of AVP and SCM were not additive and that the inhibition of testosterone production was largely (65%) reversed by the presence of [(beta-mercapto-beta, beta-cyclopentamethylenepropionyl, O-Me-Tyr2,Arg8)-vasopressin], a selective vasopressor antagonist. These data indicate that Sertoli cells produce in vitro potent inhibitory factors of Leydig cell steroidogenesis. They provide additional evidence that one of these bioactive factors has an effect on Leydig cell function similar to that of AVP.

8-Bromo Cyclic Adenosine Monophosphate↗