Natural PregnancyEPIGENNCT00773825
Genomic Imprinting and Assisted Reproductive Technologies
An observational study of Natural Pregnancy and Pregnancy, Ovarian, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 26 to 40 years, women only
- Conditions the study is for
- Natural Pregnancy, Pregnancy, Ovarian
- How many people
- 542 participants
- Where
- 1 siteFrance
- Study dates
- Feb 2007to Jun 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 26 to 40 years
- Women only
- No healthy volunteers
- Adult
Study population: Women followed in a participating ART departments
Who may be able to join
- Mother :
- Age: 26 to 40 at conception
- Single foetus pregnancy
- Signed informed consent
- Affiliation to French health benefits
- Absence of maternal pathology
Show all 14Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessment of the Risk of Imprinting Defects in Children Born Following Assisted Reproductive Technologies (ART)
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.
Read the 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.
- Conditions
- Natural Pregnancy, Pregnancy, Ovarian
- Keywords
- Genomic imprinting, Reproductive techniques, assisted, Beckwith-Wiedemann syndrome, Angelman syndrome
- Medical subject headings
- Pregnancy, Ovarian, Helping Behavior, Beckwith-Wiedemann Syndrome, Angelman Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Pregnancy after ICSI or IVF | |
| 2 | Pregnancy after ovarian stimulation | |
| 3 | natural pregnancy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the methylation status at 9 imprinted loci in cord blood collected just after birth.
Measured: At the birth
Secondary outcomes (1)
Assessment of other epigenetic marks (histone modifications) at imprinted loci and at non imprinted but epigenetically regulated loci.
Measured: At the birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2008 (estimated)
- Study startFeb 2007
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Natural PregnancyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 542 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yves Le BOUC, PUPH, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00773825
- Sponsor's protocol ID
- P040440
- Acronym
- EPIGEN
- Status last verified
- Jun 2015
- First submitted
- 15 Oct 2008
- Last updated
- 18 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 18279777Rossignol 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.
PubMed 16825435Gicquel 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.
PubMed 12772698Gaston 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.
PubMed 11436121
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of the Risk of Imprinting Defects in Children Born Following Assisted Reproductive Technologies (ART)
- ClinicalTrials.gov ID
- NCT00773825
- Acronym / sponsor ID
- EPIGEN / P040440
- Conditions
- Natural Pregnancy, Pregnancy, Ovarian
- Keywords
- Genomic imprinting, Reproductive techniques, assisted, Beckwith-Wiedemann syndrome, Angelman syndrome
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 542 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Feb 2007
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 16 Oct 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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.
Study design
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Pregnancy after ICSI or IVF |
| 2 | – | –Pregnancy after ovarian stimulation |
| 3 | – | –natural pregnancy |
Who may qualify
- Ages
- 26 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Women followed in a participating ART departments
Key inclusion criteria (14 listed)
- Age: 26 to 40 at conception
- Single foetus pregnancy
- Signed informed consent
- Affiliation to French health benefits
- Absence of maternal pathology
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Assessment of the methylation status at 9 imprinted loci in cord blood collected just after birth.
Time frame: At the birth
1 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2015.
- Background: PubMed 18279777Gicquel 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.
- Background: PubMed 16825435Rossignol 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.
- Background: PubMed 12772698Gicquel 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.
- Background: PubMed 11436121Gaston 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yves Le BOUC, PUPH principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Natural Pregnancy and Pregnancy, Ovarian, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of the methylation status at 9 imprinted loci in cord blood collected just after birth. (time frame: At the birth). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00773825, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2015.