Infertility, MaleEpigeneticsNCT05461079
Sperm Phenotype and Differentially Methylated Regions
An observational study of Infertility, Male, run by University of Basel at 1 site in Switzerland.
Trial summary
Testicular dysgenesis syndrome (TDS) is known to cause epigenetic abnormalities in spermatozoa. Anogenital distance (AGD) is considered to be a suitable clinical marker of TDS, but the direct link between AGD and epigenetic abnormalities is still missing. Read more about this study
- Who is it for?
- Ages 20 to 55 years, men only
- Conditions the study is for
- Infertility, Male
- What is being tested?
- obtention of up to three semen samples
- How many people
- 60 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Nov 2017to 31 Dec 2023
- 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 20 to 55 years
- Men only
- Adult
Study population: Both the 10 infertile men with shortened AGD and the fertile control men (semen donors) will be recruited and examined in the infertility consultation of the Clinic of Gyn. Endocrinology and Reproductive Medicine.
Who may be able to join
- infertile men with known anogenital distance
Who cannot join
- sperm concentration must be more than 15 million/ml to allow appropriate sorting with flow cytometry...
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Association Between Anogenital Distance, Sperm Phenotype and Epigenetics in Infertile Men.
Testicular dysgenesis syndrome (TDS) is known to cause epigenetic abnormalities in spermatozoa. Anogenital distance (AGD) is considered to be a suitable clinical marker of TDS, but the direct link between AGD and epigenetic abnormalities is still missing.
Infertile men (n=10) presenting with shortened AGD and a control group of normal semen donors (n=10) with normal AGD will then be asked to provide one semen sample each. Using a flow cytometer and sorter (FACS) their spermatozoa will be sorted into populations of spermatozoa with/without DNA fragmentation or with/without chromatin decondensation. These sorted populations of spermatozoa will then be examined for differences in epigenetic imprinting differences using whole genome expression analysis. Whereas the sorting of spermatozoa will be carried out in Basel, the epigenetic analysis will be carried at the University of Geneva.
Read the detailed description
A subset of 10 men with shortened AGD (together with a control group of 10 fertile donors with normal AGD) will be asked to provide up to three semen samples, each of which then will be sorted with FACS into subpopulations with/without DNA fragmentation and into subpopulations with/without chromatin decondensation.
Spermatozoa with fragmented DNA will be separated through FACS-sorting of spermatozoa with intact DNA using the YoPro 1-dye, which has been shown to correlate significantly with the degree of DNA fragmentation in the nuclei of sperm.
In addition, spermatozoa with abnormal chromatin remodelling will be separated through sorting from spermatozoa with condensed chromatin using the fluorochrome chromomycin A3 (CMA3), which competes for protamin for binding to the minor groove of DNA thereby correlating with the persistence of histones in the sperm nuclei. Pilot experiments have demonstrated the highly significant and close correlation of CMA3 with anilin blue staining. Anilin blue staining is not suitable for the sorting experiment, because it requires fixation of the spermatozoa. Sorting based on CMA3 can be carried out with living spermatozoa.
The sorted and anonymized samples will then be sent frozen in dry ice to a laboratory at the University of Geneva for the assessment of differences in the epigenetic imprinting of the DNA using whole genome expression studies.
- Conditions
- Infertility, Male
- Being tested
- obtention of up to three semen samples
- Medical subject headings
- Infertility, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
obtention of up to three semen samplesDiagnostic test
Also called conventional semen analysis followed by sorting
sorting of spermatozoa with flow cytometry. In the presence of insufficient numbers of spermatozoa after sorting (<15 mill), up to three semen samples will be collected.
| Study group | Role | What they receive |
|---|---|---|
| subfertile men | 10 infertile men with shortened AGD (< 40 mm) Receives: Diagnostic Test: obtention of up to three semen samples | |
| fertile semen donors | 10 fertile semen donors with normal AGD (>40 mm) Receives: Diagnostic Test: obtention of up to three semen samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
anogenital distance and epigenetics
number of differentially methylated transposable regulatory sequences in the genome of sorted spermatozoa.
Measured: 6 months
Secondary outcomes (5)
sperm phenotype 1
based on conventional semen analysis: concentration of spermatozoa (in mill/ml).
Measured: 6 months
sperm phenotype 2
based on conventional semen analysis: progressive motility (in %).
Measured: 6 months
sperm phenotype 3
based on conventional semen analysis: normal morphology (in %), staining).
Measured: 6 months
sperm phenotype 4
chromatin decondensation (as given by % of CMA3 staining).
Measured: 6 months
sperm phenotype 5
DNA fragmentation (% of YoPro 1-staining).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2022
- Study start1 Nov 2017
- Primary completion30 Jan 2021
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infertility, MaleStudies of the same condition, open and under way.
- 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
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Basel
- Sponsor type
- University, hospital or other
- Collaborators
- University of Geneva, Switzerland
- Responsible party
- Principal investigator, Christian De Geyter, University of Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05461079
- Sponsor's protocol ID
- RME12072017
- Acronym
- Epigenetics
- Status last verified
- Mar 2024
- First submitted
- 9 Dec 2017
- Last updated
- 20 Mar 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Association Between Anogenital Distance, Sperm Phenotype and Epigenetics in Infertile Men.
- ClinicalTrials.gov ID
- NCT05461079
- Acronym / sponsor ID
- Epigenetics / RME12072017
- Conditions
- Infertility, Male
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of BaselUniversity, hospital or other
- Collaborators
- University of Geneva, Switzerland
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 30 Jan 2021 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 15 Jul 2022 (actual)
- 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.
Testicular dysgenesis syndrome (TDS) is known to cause epigenetic abnormalities in spermatozoa. Anogenital distance (AGD) is considered to be a suitable clinical marker of TDS, but the direct link between AGD and epigenetic abnormalities is still missing.
Infertile men (n=10) presenting with shortened AGD and a control group of normal semen donors (n=10) with normal AGD will then be asked to provide one semen sample each. Using a flow cytometer and sorter (FACS) their spermatozoa will be sorted into populations of spermatozoa with/without DNA fragmentation or with/without chromatin decondensation. These sorted populations of spermatozoa will then be examined for differences in epigenetic imprinting differences using whole genome expression analysis. Whereas the sorting of spermatozoa will be carried out in Basel, the epigenetic analysis will be carried at the University of Geneva.
Detailed description
A subset of 10 men with shortened AGD (together with a control group of 10 fertile donors with normal AGD) will be asked to provide up to three semen samples, each of which then will be sorted with FACS into subpopulations with/without DNA fragmentation and into subpopulations with/without chromatin decondensation.
Spermatozoa with fragmented DNA will be separated through FACS-sorting of spermatozoa with intact DNA using the YoPro 1-dye, which has been shown to correlate significantly with the degree of DNA fragmentation in the nuclei of sperm.
In addition, spermatozoa with abnormal chromatin remodelling will be separated through sorting from spermatozoa with condensed chromatin using the fluorochrome chromomycin A3 (CMA3), which competes for protamin for binding to the minor groove of DNA thereby correlating with the persistence of histones in the sperm nuclei. Pilot experiments have demonstrated the highly significant and close correlation of CMA3 with anilin blue staining. Anilin blue staining is not suitable for the sorting experiment, because it requires fixation of the spermatozoa. Sorting based on CMA3 can be carried out with living spermatozoa.
The sorted and anonymized samples will then be sent frozen in dry ice to a laboratory at the University of Geneva for the assessment of differences in the epigenetic imprinting of the DNA using whole genome expression studies.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| subfertile men | – | Diagnostic Test: obtention of up to three semen samples10 infertile men with shortened AGD (< 40 mm) |
| fertile semen donors | – | Diagnostic Test: obtention of up to three semen samples10 fertile semen donors with normal AGD (>40 mm) |
Who may qualify
- Ages
- 20 to 55 years
- Sex
- Male only
- Age groups
- Adult
- Study population
- Both the 10 infertile men with shortened AGD and the fertile control men (semen donors) will be recruited and examined in the infertility consultation of the Clinic of Gyn. Endocrinology and Reproductive Medicine.
Key inclusion criteria (1 listed)
- infertile men with known anogenital distance
Key exclusion criteria (1 listed)
- sperm concentration must be more than 15 million/ml to allow appropriate sorting with flow cytometry...
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| obtention of up to three semen samplesAlso: conventional semen analysis followed by sortingsorting of spermatozoa with flow cytometry. In the presence of insufficient numbers of spermatozoa after sorting (<15 mill), up to three semen samples will be collected. | Diagnostic test | fertile semen donors, subfertile men |
Primary outcome
anogenital distance and epigenetics
Time frame: 6 months
number of differentially methylated transposable regulatory sequences in the genome of sorted spermatozoa.
5 secondary outcomes
sperm phenotype 1
Time frame: 6 months
sperm phenotype 2
Time frame: 6 months
sperm phenotype 3
Time frame: 6 months
sperm phenotype 4
Time frame: 6 months
sperm phenotype 5
Time frame: 6 months
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 20 Mar 2024.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Infertility, Male, run by University of Basel at 1 site in Switzerland.
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 1 inclusion and 1 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 20 Mar 2024. 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 Switzerland. 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?
anogenital distance and epigenetics (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Mar 2024.