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

January 19, 2017 updated by: University Hospital, Rouen

Are Sperm Head Vacuoles Associated With Sperm Nuclear Alterations?

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Hôpital Calmette CHRU de Lille, France
        • Laboratoire de spermiologie, CHRU de Lille
      • Rouen, France, 76031
        • Laboratoire de Biologie de la Reproduction - CECOS - EA 4308, CHU - Hôpitaux de Rouen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Sampling Method

Probability Sample

Study Population

infertile men attending the assisted reproduction units in Rouen and Lille

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
VATES
men with altered spermograms (isolated teratozoospermia or oligo-astheno-teratozoospermia)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
up to 30 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Total sperm count
Time Frame: 1 day
1 day
Percentage of mobile spermatozoa
Time Frame: 1 day
1 day
Percentage of morphologically abnormal spermatozoa
Time Frame: 1 day
1 day
Mean vacuole area threshold (measured with Receiver Operating Characteristic curves)
Time Frame: up to 30 months
up to 30 months
Correlation coefficient between vacuole areas and sperm DNA fragmentation (evaluated by TUNEL analysis)
Time Frame: up to 30 months
up to 30 months
Correlation coefficient between vacuole areas and abnormal chromatin condensation (evaluated by aniline blue staining)
Time Frame: up to 30 months
up to 30 months
Correlation coefficient between vacuole areas and telomere number, distribution and length (evaluated by quantitative FISH)
Time Frame: up to 30 months
up to 30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Rouen

Investigators

  • Principal Investigator: Nathalie Rives, MD., PhD., Laboratoire de Biologie de la Reproduction - CECOS - EA 4308, CHU - Hôpitaux de Rouen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 1, 2013

Primary Completion (ACTUAL)

December 1, 2016

Study Completion (ACTUAL)

January 1, 2017

Study Registration Dates

First Submitted

November 25, 2013

First Submitted That Met QC Criteria

December 4, 2013

First Posted (ESTIMATE)

December 10, 2013

Study Record Updates

Last Update Posted (ESTIMATE)

January 20, 2017

Last Update Submitted That Met QC Criteria

January 19, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2013/005/HP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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