Clinical Trial: Genomic Imprinting and Assisted Reproductive Technologies
Study Status: Completed
Recruit Status: Completed
Study Type: Observational
Official Title: Assessment of the Risk of Imprinting Defects in Children Born Following Assisted Reproductive Technologies (ART)
Brief Summary: Genomic imprinting, referring to an epigenetic marking resulting in monoallelic gene expression, plays a critical role in development. Recently, various imprinting diseases were reported in animals (Large Offspring syndrome (LOS)) and humans (Beckwith-Wiedemann syndrome (BWS) and Angelman syndrome (AS)) born after ART. In all cases, an imprinting defect was involved (loss of methylation at ICR2 in BWS, at SNRPN in AS and at IGF2R DMR2 in LOS). These data suggest that ART procedures may impair the establishment or the maintenance (following fertilization) of methylation marks at maternally imprinted loci. In view of these data, the aim of this study is to determine if children born following ART exhibit an increased risk of imprinting defects. If the answer is yes, the second objective is to identify the problematic step in the ART procedure and thus to suppress or modify this step.
Detailed Summary:
Methodology: assessment of the methylation status at 9 different imprinted loci (using Southern blot and methyl-specific quantitative PCR) in 3 groups of patients: 150 children naturally conceived, 150 children conceived after ovarian stimulation but with in vivo fertilization, and 150 children conceived after ovarian stimulation and in VITRO fertilization. These analyses will be performed on cord blood. Fragments of placental tissue will also be collected for further analyses. Patients will be selected in maternity hospitals associated with ART departments ( ANTOINE BECLERE HOSPITAL, Cochin HOSPITAL, Saint-Vincent de Paul HOSPITAL, Jean VERDIER HOSPITAL, Tenon HOSPITAL and Dijon Hospital).
This work is also a unique opportunity to establish a DNA, RNA and tissue collection allowing further investigation regarding other epigenetic modifications than DNA methylation, not only at imprinted loci, but also in other genomic regions regulated by epigenetic modifications.
Sponsor: Assistance Publique - Hôpitaux de Paris
Current Primary Outcome: Assessment of the methylation status at 9 imprinted loci in cord blood collected just after birth. [ Time Frame: At the birth ]
Original Primary Outcome: Same as current
Current Secondary Outcome: Assessment of other epigenetic marks (histone modifications) at imprinted loci and at non imprinted but epigenetically regulated loci. [ Time Frame: At the birth ]
Original Secondary Outcome: Same as current
Information By: Assistance Publique - Hôpitaux de Paris
Dates:
Date Received: October 15, 2008
Date Started: February 2007
Date Completion:
Last Updated: June 17, 2015
Last Verified: June 2015
