Genomic Imprinting and Assisted Reproductive Technologies - Full Text View

Sponsored by:	Assistance Publique - Hôpitaux de Paris
Information provided by:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00773825

Purpose

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.

Condition
Natural Pregnancy Pregnancy After IVF, ICSI, Ovarian Stimulation)

Genetics Home Reference related topics: Angelman syndrome Beckwith-Wiedemann syndrome

U.S. FDA Resources

Study Type:	Observational
Study Design:	Prospective
Official Title:	Assessment of the Risk of Imprinting Defects in Children Born Following Assisted Reproductive Technologies (ART)

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

Assessment of the methylation status at 9 imprinted loci in cord blood collected just after birth. [ Time Frame: At the birth ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Assessment of other epigenetic marks (histone modifications) at imprinted loci and at non imprinted but epigenetically regulated loci. [ Time Frame: At the birth ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Biospecimen Description:

whole blood (serum, ADN) and placenta samples

Estimated Enrollment:	900
Study Start Date:	February 2007
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Groups/Cohorts
1 Pregnancy after ICSI or IVF
2 Pregnancy after ovarian stimulation
3 natural pregnancy

Detailed Description:

Methodology: assessment of the methylation status at 9 different imprinted loci (using Southern blot and methyl-specific quantitative PCR) in 3 groups of patients: 300 children naturally conceived, 300 children conceived after ovarian stimulation but with in vivo fertilization, and 300 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 5 APHP maternity hospitals associated with ART departments ( ANTOINE BECLERE HOSPITAL, Cochin HOSPITAL, Saint-Vincent de Paul HOSPITAL, Jean VERDIER HOSPITAL et Tenon HOSPITAL) during a 3 years period.

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.

Eligibility

Ages Eligible for Study:	26 Years to 40 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Women followed in a participating ART departments

Criteria

Inclusion Criteria:

Mother :

Age: 26 to 40 at conception
Single foetus pregnancy
Signed informed consent
Affiliation to French health benefits
Absence of maternal pathology
Normal foetal karyotype (if available)
Known procedure of ovarian stimulation
ART procedure without sperm or oocyte donation
ART in a participating ART departments
Delivery in a participating hospital Father
Age : 18 to 50 at conception
Signed informed consent

Exclusion Criteria:

Abnormal foetal karyotype (if available)
Delivery before 35 weeks of amenorrhea
Delivery in not participating hospital
Delivery complication leading to the absence of sample collection

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00773825

Contacts

Contact: Yves LE BOUC, Professor

+33(0) 1 44 73 64 47

yves.lebouc@trs.aphp.fr

Locations

France
Trousseau Hospital	Recruiting
Paris, France, 75012
Contact: Yves Le Bouc, Professor yves.lebouc@trs.aphp.fr
Contact: Sylvie Rossignol, PhD, MD sylvie.rossignol@trs.aphp.fr
Principal Investigator: Yves Le Bouc, Professor

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator:

Yves Le BOUC, PUPH

Assistance Publique - Hôpitaux de Paris

More Information

Responsible Party:	Department Clinical Reseach of Developpement ( Christophe Aucan )
Study ID Numbers:	P040440, AOM04019, ENR2006/0205
Study First Received:	October 15, 2008
Last Updated:	October 16, 2008
ClinicalTrials.gov Identifier:	NCT00773825
Health Authority:	France: Direction Générale de la Santé

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Genomic imprinting
Reproductive techniques, assisted
Beckwith-Wiedemann syndrome
Angelman syndrome

Study placed in the following topic categories:

Angelman syndrome
Angelman Syndrome

ClinicalTrials.gov processed this record on January 14, 2009