Genomic Imprinting and Assisted Reproductive Technologies

NCT00773825 | Completed

• 1 other identifier: P040440
• Study Type: observational
• Target: 542
• Locations: 1 country
• Sites: 1

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.

Conditions

Natural Pregnancy; Pregnancy, Ovarian

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  At the birth

Secondary Outcomes (1)

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

  At the birth

Study Arms (3)

1

Pregnancy after ICSI or IVF

2

Pregnancy after ovarian stimulation

3

natural pregnancy

Eligibility Criteria

• Age: 26 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Women followed in a participating ART departments

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Trousseau Hospital

Paris, 75012, France

Location

Related Publications (4)

• Gicquel C, El-Osta A, Le Bouc Y. Epigenetic regulation and fetal programming. Best Pract Res Clin Endocrinol Metab. 2008 Feb;22(1):1-16. doi: 10.1016/j.beem.2007.07.009.

  PMID: 18279777 BACKGROUND

• Rossignol S, Steunou V, Chalas C, Kerjean A, Rigolet M, Viegas-Pequignot E, Jouannet P, Le Bouc Y, Gicquel C. The epigenetic imprinting defect of patients with Beckwith-Wiedemann syndrome born after assisted reproductive technology is not restricted to the 11p15 region. J Med Genet. 2006 Dec;43(12):902-7. doi: 10.1136/jmg.2006.042135. Epub 2006 Jul 6.

  PMID: 16825435 BACKGROUND

• Gicquel C, Gaston V, Mandelbaum J, Siffroi JP, Flahault A, Le Bouc Y. In vitro fertilization may increase the risk of Beckwith-Wiedemann syndrome related to the abnormal imprinting of the KCN1OT gene. Am J Hum Genet. 2003 May;72(5):1338-41. doi: 10.1086/374824. No abstract available.

  PMID: 12772698 BACKGROUND

• Gaston V, Le Bouc Y, Soupre V, Burglen L, Donadieu J, Oro H, Audry G, Vazquez MP, Gicquel C. Analysis of the methylation status of the KCNQ1OT and H19 genes in leukocyte DNA for the diagnosis and prognosis of Beckwith-Wiedemann syndrome. Eur J Hum Genet. 2001 Jun;9(6):409-18. doi: 10.1038/sj.ejhg.5200649.

  PMID: 11436121 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

whole blood (serum, ADN) and placenta samples

MeSH Terms

Conditions

Pregnancy, Ovarian; Helping Behavior; Beckwith-Wiedemann Syndrome; Angelman Syndrome

Condition Hierarchy (Ancestors)

Pregnancy, Ectopic; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Social Behavior; Behavior; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Imprinting Disorders; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Yves Le BOUC, PUPH

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2008
• First Posted: October 16, 2008
• Study Start: February 1, 2007
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 18, 2015

Record last verified: 2015-06

Locations

FR (1)