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Le Blanc-Mesnil, France

Menezo Y.,Laboratoire Clement | Lichtblau I.,Clinique de la Muette | Elder K.,Bourn Hall Clinic
Journal of Assisted Reproduction and Genetics | Year: 2013

The metabolism of pre-implantation embryos is far from being understood. In human embryos, the two major obstacles are the scarcity of material, for obvious ethical reasons, and complete absence of a relevant in vivo control model. Over-extrapolation from animal species to human systems adds to the complexity of the problem. Removal of some metabolites from media has been proposed, such as glucose and essential amino acids, on the basis of their pseudo "toxicity". In contrast, addition of some compounds such as growth factors has been proposed in order to decrease apoptosis, which is a natural physiologic process. These suggestions reflect the absence of global knowledge, and in consequence mask reality. Some aspects of metabolism have been ignored, such as lipid metabolism. Others are seriously underestimated, such as oxidative stress and its relationship to imprinting/methylation, of paramount importance for genetic regulation and chromosomal stability. It has become increasingly obvious that more studies are essential, especially in view of the major extension of ART activities worldwide. © 2013 Springer Science+Business Media New York.

Ferfouri F.,Poissy Medical Center | Ferfouri F.,University of Versailles | Boitrelle F.,Poissy Medical Center | Boitrelle F.,University of Versailles | And 7 more authors.
Molecular Human Reproduction | Year: 2013

Individuals with two independent chromosome rearrangements are rare and meiotic segregation studies are few. Two brothers (P1 and P2) and a cousin (P3) were karyotyped and found to have the same familial reciprocal translocation between the long arm of chromosome 8 and the short arm of chromosome 9: 46,XY,t(8;9)(q24.3;p24). In addition, one brother also had a different de novo reciprocal translocation between the long arm of chromosome 1 and the short arm of chromosome 16: 46,XY,t(1;16)(q21;p11.2)dn,t(8;9)(q24.3;p24)mat. Using locus-specific probes for segments involved in the translocations and for other chromosomes, sperm-FISH analysis was used to investigate the products of meiotic segregation of the translocations and the possibility of an interchromosomal effect (ICE). Sperm nucleus fragmentation was also evaluated. For the t(8;9) translocation, the proportion of unbalanced products was higher for P1 (66.3%, P < 0.0001) than P2 (51.9%) and P3 (50.4%), and the proportion consistent with each meiosis I segregation mode was also different for P1. In addition, for P1, 61.6% of the products of the t(1;16) were unbalanced, and 85.6% of spermatozoa overall included both translocations. No evidence of an ICE was found and sperm nucleus fragmentation rates were similar. Our study suggests that co-segregation of the t(8;9) and the t(1;16) resulted in modifying the proportions of t(8;9) meiotic segregation products found in spermatozoa. This could be due to selection associated with meiotic checkpoints and germ cell death. © The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.

Gurgan T.,Hacettepe University | Montjean D.,Service de Medecine et Biologie de la Reproduction | Demirol A.,Gurgan Clinic | Menezo Y.J.R.,Laboratoire Clement
Journal of Assisted Reproduction and Genetics | Year: 2014

FSH is a key hormone in the regulation of follicular development. Together with the EGF network, these molecules mediate oocyte maturation and competence in preparation for the action of LH. FSH isoforms regulate distinct biological pathways and have specific effects on granulosa cell function and maturation of the ovarian follicle. Their dynamic interactions occur during the follicular cycle; short-living forms are predominant in the pre-ovulatory phase, whereas long-acting molecules characterize the luteal-follicular transition. Recombinant FSH (rFSH) molecules have a reduced number of isoforms and are less acidic, with a shorter half-life. We have investigated sequential stimulation, comparing hFSH + rFSH, vs. rFSH alone and hFSH alone for the entire stimulation phase. Sequential stimulation leads to an E2 per MII oocyte ratio that is much lower than is seen during treatment with the two drugs individually. Although there is a positive tendency in favor of the sequential treatment, there was no significant difference in pregnancy rates, even taking frozen embryos into consideration. The cumulus cell transcriptome varies considerably between the treatments, although with no clear significance. When comparing pregnant vs. non-pregnant patients, in general a decrease in mRNA expression can be observed in the pregnant patients, especially in expression of folic acid receptor 1 and ovostatin 2. This indicates that material has been transferred from CC to the oocyte. However, a common observation in the literature is that variations in the transcriptome of the cumulus cells are highly dependent upon the patient genotype; the potential for applying this strategy as a basis for selecting embryos is, at the very least, questionable. © 2014 Springer Science+Business Media.

Vialard F.,Obstetrics and Gynaeacology | Vialard F.,TOMA Laboratory | Simoni G.,TOMA Advanced Biomedical Assays S.p.A. | Aboura A.,Obstetrics and Gynaeacology | And 13 more authors.
Prenatal Diagnosis | Year: 2011

Objective: Molecular cytogenetic techniques on uncultured prenatal samples are the sole tests applied in some countries in cases with advanced maternal age (AMA) or increased risk after prenatal screening. Moreover, there is a trend to perform invasive prenatal diagnosis (PD) during the first trimester before ultrasound manifestations, so new rapid and reliable assays are necessary to investigate microdeletions not detectable with the conventional karyotype. We report the validation study of the prenatal bacterial artificial chromosomes-on-Beads™ (BoBs™; CE-IVD), a bead-based multiplex assay detecting chromosomes 13, 18, 21, X/Y aneuploidies and nine microdeletion regions having an overall detection rate of 1/1700. Method: We retrospectively studied 408 selected samples and prospectively tested 212 consecutive samples ascertained for conventional karyotyping. Results: We did not find false-positive results. Triploidies were not detected. Maternal cell contamination of male samples up to 90% was unmasked inspecting gonosome profiles. Mosaic conditions at 20 to 30% were revealed. Failures were due to low amount of DNA. Conclusion: Prenatal BoBs™ is a robust technology for the investigation of fetuses with normal karyotype with or without sonographic abnormalities. Running in parallel with the karyotype analysis, it can be proposed instead of rapid FISH or QF-PCR providing rapid results on common aneuploidies and additional information regarding the microdeletion syndromes. © 2011 John Wiley & Sons, Ltd.

Menezo Y.,Laboratoire Clement | Guerin P.,VetAgro Sup | Elder K.,Bourn Hall Clinic
Reproductive BioMedicine Online | Year: 2015

The oviduct has long been considered a 'pipeline', a tube allowing transit of spermatozoa and embryos; this perspective has been reinforced by the success of human IVF. Evidence accumulated over several decades, however, indicates that embryos can modulate the metabolism of tubal cells in their environment. Human IVF culture media is based on formulations that pass mouse embryo assays as quality control: the requirements of mouse embryos differ from those of human embryos, and therefore conditions for human IVF are far removed from the natural environment of the oviduct. The preimplantation environment, both in vitro and in vivo, is known to affect the health of offspring through mechanisms that influence imprinting. Recent studies also show that male accessory glands act in synergy with the oviduct in providing an optimal environment, and this represents a further perspective on the oviduct's contribution to harmonious embryo development and subsequent long-term health. The metabolism of the human embryo is far from being understood, and a 'return' to in-vivo conditions for preimplantation development is worthy of consideration. Although results obtained in rodents must be interpreted with caution, lessons learned from animal embryo culture must not be neglected. © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

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