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Anne Delbaere

Publications and source records attributed to Anne Delbaere.

13 recordsLinked to original sources

Biological activity of follistatin isoforms and follistatin-like-3 is dependent on differential cell surface binding and specificity for activin, myostatin, and bone morphogenetic proteins.

Follistatin (FST) and FST-like-3 (FSTL3) are activin-binding and neutralization proteins that also bind myostatin. Three FST isoforms have been described that differ in tissue distribution and cell-surface binding activity, suggesting that the FST isoforms and FSTL3 may have some nonoverlapping biological actions. We produced recombinant FST isoforms and FSTL3 and compared their biochemical and biological properties. Activin-binding affinities and kinetics were comparable between the isoforms and FSTL3, whereas cell-surface binding differed markedly (FST288 > FST303 > FST315 > FSTL3). Inhibition of endogenous activin bioactivity, whether the FST isoforms were administered endogenously or exogenously, correlated closely with surface binding activity, whereas neutralization of exogenous activin when FST and FSTL3 were also exogenous was consistent with their equivalent activin-binding affinities. This difference in activin inhibition was also evident in an in vitro bioassay because FST288 suppressed, whereas FST315 enhanced, activin-dependent TT cell proliferation. Moreover, when FSTL3, which does not associate with cell membranes, was expressed as a membrane-anchored protein, its endogenous activin inhibitory activity was dramatically increased. In competitive binding assays, myostatin was more potent than bone morphogenetic proteins (BMPs) 6 and 7, and BMPs 2 and 4 were inactive in binding to FST isoforms, whereas none of the BMPs tested competed with activin for binding to FSTL3. Neutralization of exogenous BMP or myostatin bioactivity correlated with the relative abilities of the isoforms to bind cell-surface proteoglycans. These results indicate that the differential biological actions among the FST isoforms and FSTL3 are primarily dependent on their relative cell-surface binding ability and ligand specificity.

Activins↗

Ovarian function and spontaneous pregnancy after combined heterotopic and orthotopic cryopreserved ovarian tissue transplantation in a patient previously treated with bone marrow transplantation: case report.

Cryopreservation of ovarian tissue has been proposed for storing gametes of young patients at high risk of premature ovarian failure. Autotransplantation has recently provided some promising results and is still the unique option to restore ovarian function from cryopreserved ovarian tissue in humans. In this article, we analyse data from the combined orthotopic and heterotopic transplantation of cryopreserved ovarian tissue that restored the ovarian function and fertility. Orthotopic transplantation of cryopreserved ovarian tissue at ovarian and peritoneal sites, together with a heterotopic transplantation at the abdominal subcutaneous site, was performed to restore the ovarian function of a 29-year-old woman previously treated with bone marrow transplantation (BMT) for Hodgkin's disease. Ovarian reserve markers progressively suppress within values 5 months after the transplantation (basal FSH 5 mUI/ml and inhibin B 119 ng/ml). Follicular development was observed at all transplantation sites but was predominant at the ovarian site. Six natural cycles were fully documented and analysed. The patient became spontaneously pregnant following the sixth cycle, but unfortunately she later miscarried. Combined orthotopic and heterotopic transplantations succeeded in the restoration of normal spontaneous cycles. Furthermore, this spontaneous pregnancy confirmed the efficiency of this procedure for restoring human fertility.

Abortion, Spontaneous↗

Impact of the assessment of early cleavage in a single embryo transfer policy.

The policy of single embryo transfer (SET) adopted for women <36 years old since 1 July 2003, strongly calls for improvement of embryo selection. A total of 196 cycles in which SET was performed were randomly allocated to two groups. In the first group, early cleavage was assessed (ECA) 25 h after insemination. The embryo with the best score that cleaved early, if present, was selected for transfer. In the second group, early cleavage was not assessed (ECNA) and embryo selection was based solely on the embryo score. Ninety-eight cycles were allocated in the ECA and ECNA group respectively. Early cleavage occurred in 64% of cycles and 32.2% of embryos. Patient population and embryo morphology were similar between the two groups, and similar delivery rates were observed (27.6 versus 24.5% respectively in the ECA and ECNA groups). The assessment of early cleavage as additional parameter did not improve the delivery rate in the single embryo transfer policy.

Adult↗

Embryo-maternal interactive factors regulating the implantation process: implications in assisted reproductive.

The embryo-maternal dialogue that starts very early in the life of the embryo is crucial for its own implantation. A disturbance in this dialogue is the major reason for which 60% of all pregnancies are terminated at the end of the periimplantation period. Many studies have been performed to improve the understanding of the molecular mechanisms involved in this dialogue. Both partners, the mother and the embryo, are equally involved in this exchange of signals. Much progress has been done in understanding the role of (i) chorionic gonadotrophin, (ii) growth factors and cytokines, and (iii) steroid hormones and other mediators, produced either by the embryo, by the mother, or by both, during the peri-implantation period. Today it is clear that their production dictates changes in the endometrium, in the immunological system of the mother and in embryo metabolism, that enable the embryo to implant. Knowledge of the molecular mechanisms involved in the embryo-maternal interaction are reviewed in this article.

Blastocyst↗

Understanding ovarian hyperstimulation syndrome.

The ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of ovarian stimulation treatments. Severe forms are characterized by a massive ovarian enlargement with the formation of multiple ovarian cysts associated with extravascular fluid shifts resulting in the development of ascites, pleural and/or pericardial effusion. The pathophysiology of the syndrome has not been completely elucidated yet. The vascular fluid leakage is thought to result from an increased capillary permeability of mesothelial surfaces under the action of one or several vasoactive ovarian factor(s) produced by the multiple corpora lutea. The paper focuses on the recent identification of mutations in the FSH receptor gene that display an increased sensitivity to hCG and are responsible for the development of spontaneous OHSS occurring during pregnancy. These findings have shed light for the first time on the molecular basis of the pathophysiology of the spontaneous form of the syndrome. As spontaneous and iatrogenic OHSS share similar pathophysiological sequences including massive recruitment and growth of ovarian follicles, extensive luteinization provoked by hCG, and oversecretion of vasogenic molecules by the corpora lutea, they have also opened new research perspectives for the understanding of the much more frequent iatrogenic OHSS.

Corpus Luteum↗

Prediction of severity of symptoms in iatrogenic ovarian hyperstimulation syndrome by follicle-stimulating hormone receptor Ser680Asn polymorphism.

The ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication of ovarian stimulation treatments for in vitro fertilization (i.v.f.). Recently, three different mutations of the FSH receptor (FSHr) have been identified in patients who presented recurrent spontaneous OHSS. This prompted us to study a possible association between coding polymorphisms of the FSHr and the occurrence of iatrogenic OHSS. We sequenced the region of the FSHr gene encompassing the A307T and S680N polymorphisms of exon 10 of FSHr in 37 Caucasian females who developed OHSS after an IVF cycle in our fertility clinic, 130 Caucasian female patients who were treated by i.v.f. but never developed OHSS, and 99 Caucasian female controls. The FSHr allele frequencies in the Caucasian control population were identical to what has already been published (39% S680 61% N680). The control i.v.f. population was enriched in the S680 allele compared with the Caucasian control population (51% S680; 49% N680; P = 0.016). The OHSS population had a even higher enrichment in the S680 allele compared with the Caucasian control population (57% S680; 43% N680; P = 0.010). These results were unexpected, because the frequency of the S680 allele was previously found to be increased among poor responders to FSH stimulation. In a second phase, we studied FSHr allele frequencies according to the severity of OHSS. Interestingly, a significant enrichment in the allele N680 was observed as the severity of OHSS increased (P = 0.034). Bearing in mind the limitations of the small number of patients studied and the possibility of sampling biases, these results suggest that the genotype in position 680 of the FSHr cannot predict which patients will develop OHSS, but could be a predictor of severity of symptoms among OHSS patients.

Adult↗

A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) occurs mainly after excessive stimulation of the ovaries by exogenous gonadotropins administrated in the context of in vitro fertilization procedures (iatrogenic OHSS). Recently, spontaneous and recurrent occurrence of the disease (spontaneous OHSS) was shown in two families to be caused by mutations affecting the follitropin receptor (FSHr). The two mutant FSHr (T449I, D567N) harbor aminoacid substitutions in the serpentine portion of the receptor and display abnormally high sensitivity to the pregnancy hormone hCG, thus providing a satisfactory explanation to the phenotype. In addition, mutant D567N showed also increased sensitivity to thyrotopin (TSH) and displayed increase in basal (ligand-independent) activity. In this report, we describe a new familial case of recurrent OHSS. The affected women were heterozygous for a different mutation involving codon 449, where an alanine was substituted for threonine. Similar to D567N, the T449A FSHr mutant shows an increase of its sensitivity to both hCG and TSH, together with an increase in basal activity. Together with the two previous studies, this report shows that inappropriate stimulation of the FSHr by hCG is a cause of spontaneous OHSS.

Adult↗

A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome (OHSS) occurs mainly after excessive stimulation of the ovaries by exogenous gonadotropins administrated in the context of in vitro fertilization procedures (iatrogenic OHSS). Recently, spontaneous and recurrent occurrence of the disease (spontaneous OHSS) was shown in two families to be caused by mutations affecting the follitropin receptor (FSHr). The two mutant FSHr (T449I, D567N) harbor aminoacid substitutions in the serpentine portion of the receptor and display abnormally high sensitivity to the pregnancy hormone hCG, thus providing a satisfactory explanation to the phenotype. In addition, mutant D567N showed also increased sensitivity to thyrotopin (TSH) and displayed increase in basal (ligand-independent) activity. In this report, we describe a new familial case of recurrent OHSS. The affected women were heterozygous for a different mutation involving codon 449, where an alanine was substituted for threonine. Similar to D567N, the T449A FSHr mutant shows an increase of its sensitivity to both hCG and TSH, together with an increase in basal activity. Together with the two previous studies, this report shows that inappropriate stimulation of the FSHr by hCG is a cause of spontaneous OHSS.

Adult↗

Preliminary experience of ovarian tissue cryopreservation procedure: alternatives, perspectives and feasibility.

Chemotherapy and radiotherapy induce premature ovarian failure in many patients treated for oncological or benign diseases. The present paper reviews the risk of developing premature ovarian failure according to the type of treatment and the different options to preserve fertility, focusing on the cryopreservation of ovarian tissue. This technique constitutes a promising approach to preserve the fertility of young patients and offers the advantage of storing a large number of follicles that could be subsequently transplanted or cultured in vitro to obtain mature oocytes. Based on 34 requests, from which 19 were performed, the feasibility of the ovarian cryopreservation procedure is evaluated. The medical and ethical approaches of this protocol are also discussed. Cryopreservation of ovarian tissue constitutes new hope for many patients, but must still be kept for selected cases, with a significant risk of premature ovarian failure after treatments such as bone marrow transplantation.

Adolescent↗

Similar delivery rates in a selected group of patients, for day 2 and day 5 embryos both cultured in sequential medium: a randomized study.

BACKGROUND: The existence of a real benefit of blastocyst transfer is still a matter of debate. The aim of this study was to compare, in a prospective randomized trial, the outcome of day 2 and day 5 transfer of human embryos cultured in an 'in-house' sequential medium. METHODS: A total of 193 cycles from 171 patients with less than four previous IVF cycles, <39 years old and with four or more zygotes on day 1, were randomly allocated to day 2 (94 cycles) or day 5 (99 cycles) transfer. Zygotes were kept in fertilization medium until 18 h post-fertilization and then placed in a 'glucose-free' cleavage medium. Embryos allocated for day 5 transfer were placed in a blastocyst medium 66 h post-fertilization. Two or three embryos were replaced according to the morphology. RESULTS: A mean (+/- SEM) number of 2.1 +/- 0.4 and 1.9 +/- 0.3 embryos were replaced on day 2 and day 5 (P < 0.001) respectively. Delivery rates per transfer were 44.1 and 37.1% [P = not significant (NS)], implantation rates were 31.4 and 29.4% (NS) and multiple delivery rates 22 and 36% (NS) for day 2 and day 5 groups respectively. Ten patients (10.1%) had no blastocysts available for transfer. CONCLUSIONS: No clear benefits were observed using blastocyst transfer for patients aged <39 years who had had less than four previous IVF cycle attempts.

Adult↗

Medically assisted reproduction in the presence of chronic viral diseases.

Teams practising medically assisted reproduction techniques try to avoid viruses as much as possible. Attitudes towards chronic carriers of viruses are rapidly changing, especially for human immunodeficiency virus (HIV) patients. We focus our attention on the legitimacy of systematic screening before assisted reproductive techniques and the need for specialized approaches including an adapted laboratory for viral hazards as well as the need for a multidisciplinary team. Specificities of HIV, hepatitis C virus (HCV), hepatitis B virus (HBV) carriers and the hypothesis of a reduced fertility potential are discussed. Are male HIV carriers a new indication for assisted reproductive techniques in order to prevent virus transmission? It is largely proven that sperm gradient preparation techniques efficiently decrease viral loads and therefore have a protective effect on contamination risk during assisted reproductive techniques. Although a few thousand assisted reproductive technique cycles were performed in the world for this indication without contamination, it is still too early to demonstrate that this technology is fully safe. Two examples of contaminations during insemination are examined. Many questions remain unresolved, such as the lack of standardized techniques for semen preparation or virus detection or the relative merits of intrauterine insemination or ICSI to prevent HIV contamination during assisted reproductive techniques. The authors plead for well-structured, separate programmes of care linked to research objectives.

Acquired Immunodeficiency Syndrome↗