Identification and Characterization of the Methylation Abnormalities on Whole Genome Among Infertile Men - Full Text View

Purpose

This study will analyse the sperm global methylation status of 62 infertile men before assisted reproductive techniques. Some of these patients (20%) present hypomethylation of H19 locus. A global methylation analysis may reveal others imprinting defects.

Condition	Intervention
Oligospermia	Other: methylation analyses on spermatozoa from infertile men

Study Type:	Observational
Study Design:	Observational Model: Case-Only Time Perspective: Prospective
Official Title:	Identification and Characterization of the Methylation Abnormalities on Whole Genome Among Infertile Men

Resource links provided by NLM:

Genetics Home Reference related topics: CATSPER1-related nonsyndromic male infertility sensorineural deafness and male infertility Y chromosome infertility

MedlinePlus related topics: Infertility

U.S. FDA Resources

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

Primary Outcome Measures:

Bring to light methylation abnormalities of the locus H19 in men's mature sperm cells presenting an unexplained oligozoospermia [ Time Frame: 1 day ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Determine if these methylation abnormalities of the locus H19 reflect changes in the profile of global methylation of the spermatic DNA [ Time Frame: 1 day ] [ Designated as safety issue: No ]
Estimate the association between these modifications and the nuclear quality of the sperm cell [ Time Frame: 1 day ] [ Designated as safety issue: No ]
by TUNEL analysis
Estimate the association between these modifications and the rates of success with In VITRO fertilization [ Time Frame: 1 day ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Sample of sperm collected by automasturbation

Enrollment:	49
Study Start Date:	June 2009
Estimated Study Completion Date:	December 2012
Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Oligozoospermia infertile patients presenting a reduced sperm count (less than 20 Millions of spermatozoa/ml)	Other: methylation analyses on spermatozoa from infertile men microarray analysis(www.EPIGENOMICS.com) Other Name: methylation analyses on spermatozoa from infertile men

Detailed Description:

An increase of the abnormalities of the imprint was brought back at the child's stemming from assisted reproductive techniques. Now abnormalities of methylation could be implied in defects of spermatogenesis and certain abnormalities of development of the male germ cells could be due to modifications abnormal epigenetics.

The objective of this research is to determine the frequency of arisen the abnormalities of methylation at the level of the locus H19 in the sperm cells of barren men presenting an unexplained oligozoospermia and to determine if these changes are a reflection of abnormalities of the profiles of methylation of the whole genome.

The patients will realize a taking of sperm having signed the consent.

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

Men from 18 to 45 years old, presenting an idiopathic oligozoospermia lower than 10 million sperm cells / ml and include in a program of medically assisted conception

Criteria

Inclusion Criteria:

Men from 18 to 45 years old, presenting an idiopathic oligozoospermia lower than 10 million sperm cells / ml and include in a program of medically assisted conception
Patients with social security
Patients having signed the informed consent

Exclusion Criteria:

Infertility with a neoplastic origin: patients subjected to a treatment potentially sterilizing (chemotherapy or radiotherapy).
Infertility with an infectious origin
Infertility with a traumatic origin
Infertility bound to a chromosomal abnormality or a microdeletion of Y
Histories of cryptorchidism, of varicocele

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01239186

Locations

France
Department of Biology of reproduction (TENON Hospital)
Paris, Ile de France, France, 75020

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator:

Célia Ravel, MD

TENON Hospital - APHP

More Information

Publications:

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Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005 Jun 3;308(5727):1466-9. Erratum in: Science. 2010 May 7;328(5979):690.

Auger J, Kunstmann JM, Czyglik F, Jouannet P. Decline in semen quality among fertile men in Paris during the past 20 years. N Engl J Med. 1995 Feb 2;332(5):281-5.

Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992 Sep 12;305(6854):609-13. Review.

Davis TL, Yang GJ, McCarrey JR, Bartolomei MS. The H19 methylation imprint is erased and re-established differentially on the parental alleles during male germ cell development. Hum Mol Genet. 2000 Nov 22;9(19):2885-94.

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. No abstract available.

Hartmann S, Bergmann M, Bohle RM, Weidner W, Steger K. Genetic imprinting during impaired spermatogenesis. Mol Hum Reprod. 2006 Jun;12(6):407-11. Epub 2006 Apr 11.

Kaiser J. Developmental biology. Endocrine disrupters trigger fertility problems in multiple generations. Science. 2005 Jun 3;308(5727):1391-2. No abstract available.

Kobayashi H, Sato A, Otsu E, Hiura H, Tomatsu C, Utsunomiya T, Sasaki H, Yaegashi N, Arima T. Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. Hum Mol Genet. 2007 Nov 1;16(21):2542-51. Epub 2007 Jul 17.

Paulozzi LJ, Erickson JD, Jackson RJ. Hypospadias trends in two US surveillance systems. Pediatrics. 1997 Nov;100(5):831-4.

Preiksa RT, Zilaitiene B, Matulevicius V, Skakkebaek NE, Petersen JH, Jørgensen N, Toppari J. Higher than expected prevalence of congenital cryptorchidism in Lithuania: a study of 1204 boys at birth and 1 year follow-up. Hum Reprod. 2005 Jul;20(7):1928-32. Epub 2005 Apr 28.

Skakkebaek NE, Rajpert-De Meyts E, Main KM. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod. 2001 May;16(5):972-8. Review.

Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, Guillette LJ Jr, Jégou B, Jensen TK, Jouannet P, Keiding N, Leffers H, McLachlan JA, Meyer O, Müller J, Rajpert-De Meyts E, Scheike T, Sharpe R, Sumpter J, Skakkebaek NE. Male reproductive health and environmental xenoestrogens. Environ Health Perspect. 1996 Aug;104 Suppl 4:741-803. Review.

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT01239186 History of Changes
Other Study ID Numbers:	AOR 08027
Study First Received:	October 22, 2010
Last Updated:	November 16, 2012
Health Authority:	France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé

Keywords provided by Assistance Publique - Hôpitaux de Paris:

methylation
micro array
locus H19
male infertility

Additional relevant MeSH terms:

Congenital Abnormalities
Oligospermia
Infertility, Male
Infertility
Genital Diseases, Male

ClinicalTrials.gov processed this record on May 19, 2013

Identification and Characterization of the Methylation Abnormalities on Whole Genome Among Infertile Men (METHYLHOMME)