This site became the new on June 19th. Learn more.
Show more Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more... Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more... Menu
Give us feedback

Genomic Imprinting and Assisted Reproductive Technologies (EPIGEN)

This study has been completed.
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris Identifier:
First received: October 15, 2008
Last updated: June 17, 2015
Last verified: June 2015
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.

Natural Pregnancy Pregnancy, Ovarian

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

Resource links provided by NLM:

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 ]

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 ]

Biospecimen Retention:   Samples With DNA
whole blood (serum, ADN) and placenta samples

Enrollment: 542
Study Start Date: February 2007
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Pregnancy after ICSI or IVF
Pregnancy after ovarian stimulation
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: 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.


Ages Eligible for Study:   26 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Women followed in a participating ART departments

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


  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00773825

Trousseau Hospital
Paris, France, 75012
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Principal Investigator: Yves Le BOUC, PUPH Assistance Publique - Hôpitaux de Paris
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris Identifier: NCT00773825     History of Changes
Other Study ID Numbers: P040440
Study First Received: October 15, 2008
Last Updated: June 17, 2015

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Genomic imprinting
Reproductive techniques, assisted
Beckwith-Wiedemann syndrome
Angelman syndrome

Additional relevant MeSH terms:
Pregnancy, Ovarian
Pregnancy, Ectopic
Pregnancy Complications processed this record on September 21, 2017