Genomic Imprinting and Assisted Reproductive Technologies

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.

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Key information

Conditions

Natural Pregnancy Abnormalities, Multiple Angelman Syndrome Beckwith-Wiedemann Syndrome Behavior Central Nervous System Diseases Chromosome Disorders Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Helping Behavior Imprinting Disorders Movement Disorders Nervous System Diseases Pregnancy Complications Pregnancy, Ectopic Pregnancy, Ovarian Social Behavior Urogenital Diseases

Age range

26 year–40 year

Sex eligibility

Female

Study type

Observational

Primary location

Trousseau Hospital

Paris, 75012, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

Assessment of the methylation status at 9 imprinted loci in cord blood collected just after birth.

Time frame: At the birth

Secondary outcomes

Assessment of other epigenetic marks (histone modifications) at imprinted loci and at non imprinted but epigenetically regulated loci.

Time frame: At the birth

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study title

Assessment of the Risk of Imprinting Defects in Children Born Following Assisted Reproductive Technologies (ART)

Acronym: EPIGEN

Important dates

Study start: 2007
Primary completion: 2015
Study completion: 2015
First posted: Oct 16, 2008
Registry last updated: Jun 18, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed