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

Oligospermia Clinical Trial

— METHYLHOMME  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01239186
• Other study ID #: AOR 08027
• Status: Completed
• Phase: N/A
• First received: October 22, 2010
• Last updated: August 6, 2013
• Start date: June 2009
• Est. completion date: December 2012

Study information

• Verified date: August 2013
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: December 2012
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Oligospermia

Intervention

Other:
• methylation analyses on spermatozoa from infertile men
microarray analysis(www.EPIGENOMICS.com)

Locations

Country	Name	City	State
France	Department of Biology of reproduction (TENON Hospital)	Paris	Ile de France

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (13)

Adami HO, Bergström R, Möhner M, Zatonski W, Storm H, Ekbom A, Tretli S, Teppo L, Ziegler H, Rahu M, et al. Testicular cancer in nine northern European countries. Int J Cancer. 1994 Oct 1;59(1):33-8. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Kaiser J. Developmental biology. Endocrine disrupters trigger fertility problems in multiple generations. Science. 2005 Jun 3;308(5727):1391-2. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bring to light methylation abnormalities of the locus H19 in men's mature sperm cells presenting an unexplained oligozoospermia		1 day	No
Secondary	Determine if these methylation abnormalities of the locus H19 reflect changes in the profile of global methylation of the spermatic DNA		1 day	No
Secondary	Estimate the association between these modifications and the nuclear quality of the sperm cell	by TUNEL analysis	1 day	No
Secondary	Estimate the association between these modifications and the rates of success with In VITRO fertilization		1 day	No