Relationship Between Sperm Head Vacuoles and Sperm DNA Alterations in Infertile Men (VATES)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by University Hospital, Rouen
Sponsor:
Information provided by (Responsible Party):
University Hospital, Rouen
ClinicalTrials.gov Identifier:
NCT02006446
First received: November 25, 2013
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

In men presenting sperm alterations, the selection of genetically undamaged spermatozoa need to be improved in order to increase the success of assisted reproduction treatments.

The aim of this study is to determine whether the presence of sperm head vacuoles is associated with sperm DNA alterations.


Condition
Male Infertility

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 1 Day
Official Title: Are Sperm Head Vacuoles Associated With Sperm Nuclear Alterations?

Resource links provided by NLM:


Further study details as provided by University Hospital, Rouen:

Primary Outcome Measures:
  • Correlation coefficient between mean vacuole areas in sperm heads (measured by MSOME) and sperm aneuploidy rates for chromosomes X, Y and 18 (evaluated by FISH) [ Time Frame: up to 30 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Total sperm count [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • Percentage of mobile spermatozoa [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • Percentage of morphologically abnormal spermatozoa [ Time Frame: 1 day ] [ Designated as safety issue: No ]
  • Mean vacuole area threshold (measured with Receiver Operating Characteristic curves) [ Time Frame: up to 30 months ] [ Designated as safety issue: No ]
  • Correlation coefficient between vacuole areas and sperm DNA fragmentation (evaluated by TUNEL analysis) [ Time Frame: up to 30 months ] [ Designated as safety issue: No ]
  • Correlation coefficient between vacuole areas and abnormal chromatin condensation (evaluated by aniline blue staining) [ Time Frame: up to 30 months ] [ Designated as safety issue: No ]
  • Correlation coefficient between vacuole areas and telomere number, distribution and length (evaluated by quantitative FISH) [ Time Frame: up to 30 months ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

spermatozoa


Estimated Enrollment: 200
Study Start Date: December 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
VATES
men with altered spermograms (isolated teratozoospermia or oligo-astheno-teratozoospermia)

Detailed Description:

The use of intracytoplasmic sperm injection (ICSI) has greatly improved the treatment of severe male infertility, especially for men with oligo-astheno-teratozoospermia (OAT). This in vitro fertilization procedure allows the direct injection of a single spermatozoon into an oocyte. The sperm used for ICSI is selected under a microscope at a 400x magnification. Several studies have reported that de novo chromosomal abnormalities are increased in children born from ICSI , thereby raising the question of the genetic quality of spermatozoa used for ICSI.

A method called MSOME (high magnification Motile Sperm Organelle Morphology Examination), which allows the detailed morphological evaluation of motile spermatozoa in real time and under high magnification (6600x), was developed in 2001. With this technique, fine morphological abnormalities - mainly vacuoles in the head of spermatozoa - were detected. The use of MSOME for the detection of morphologically normal sperm for ICSI gave rise to a technique called IMSI (Intracytoplasmic Morphologically Selected sperm Injection). Higher pregnancy rates were obtained with IMSI compared to ICSI and sperm head vacuoles were found to negatively affect assisted reproduction success rates and embryo development. The use of IMSI also decreases the risk of sex chromosome aneuploidy in embryos .

Several authors found that the presence of large vacuoles in the sperm head correlates with several nuclear alterations: DNA fragmentation , abnormal chromatin condensation and aneuploidy . However, these studies are controversial and were performed on few spermatozoa. In order to improve the selection of spermatozoa with a normal chromosomal content, it is essential not only to confirm the existence of a relationship between sperm head vacuoles and altered sperm nuclear quality but also to better characterize these alterations.

The main goal of this study is to investigate the correlation between sperm head vacuole areas and sperm aneuploidy rates in men with isolated teratozoospermia or OAT. Vacuole areas will be measured by MSOME and aneuploidy rates by FISH for chromosomes 18, X and Y. Moreover, the correlation between sperm head vacuole areas and other nuclear alterations (DNA fragmentation, abnormal chromatin condensation, telomere abnormalities) will be evaluated. Semen samples from 200 patients recruited over a 2-year period will be collected, stored and analyzed.

This study involves the collection of relevant medical information. The computer website for the patient database is secure and protected by a password. The information will be entered and only be viewed by the investigators. On-site monitoring visits will be conducted throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

infertile men attending the assisted reproduction units in Rouen and Lille

Criteria

Inclusion Criteria:

  • men
  • 18 years old or more
  • affiliated to social security
  • with isolated teratozoospermia or oligo-astheno-teratozoospermia according to the WHO guidelines (2010):

    • sperm concentration < 15 million per ml or sperm number < 39 million per ejaculate
    • progressive motility < 35%
    • morphologically normal forms < 50% according to the modified David's classification (Auger et al., 2001
    • mobile spermatozoa selected by density gradient centrifugation > 1 million, in previous spermograms
  • with normal constitutional karyotypes (46, XY)
  • signed an informed consent

Exclusion Criteria:

  • with abnormal constitutional karyotypes
  • with a major alteration of sperm parameters, with mobile spermatozoa selected by density gradient centrifugation < 1 million
  • under tutorship or guardianship by court order
  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 ClinicalTrials.gov identifier: NCT02006446

Contacts
Contact: Nathalie Rives, MD., PhD. 33 (0) 2 32 88 82 25 nathalie.rives@chu-rouen.fr

Locations
France
Laboratoire de spermiologie, CHRU de Lille Not yet recruiting
Hôpital Calmette CHRU de Lille, France
Principal Investigator: Valérie MITCHELL, PH         
Laboratoire de Biologie de la Reproduction - CECOS - EA 4308, CHU - Hôpitaux de Rouen Recruiting
Rouen, France, 76031
Contact: Nathalie Rives, MD., PhD.    33 (0) 2 32 88 82 25    nathalie.rives@chu-rouen.fr   
Contact: Nathalie Mousset-Siméon, MD.    33 (0) 2 32 88 89 25    nathalie.mousset-simeon@chu-rouen.fr   
Principal Investigator: Nathalie Rives, MD., PhD.         
Sub-Investigator: Nathalie MOUSSET SIMEON, MD         
Sponsors and Collaborators
University Hospital, Rouen
Investigators
Principal Investigator: Nathalie Rives, MD., PhD. Laboratoire de Biologie de la Reproduction - CECOS - EA 4308, CHU - Hôpitaux de Rouen
  More Information

Publications:

Responsible Party: University Hospital, Rouen
ClinicalTrials.gov Identifier: NCT02006446     History of Changes
Other Study ID Numbers: 2013/005/HP
Study First Received: November 25, 2013
Last Updated: September 5, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by University Hospital, Rouen:
Male infertility
sperm head vacuoles
sperm morphology
aneuploidy
DNA fragmentation
abnormal chromatin condensation
telomere abnormalities

Additional relevant MeSH terms:
Infertility
Infertility, Male
Genital Diseases, Male
Genital Diseases, Female

ClinicalTrials.gov processed this record on September 16, 2014