Male InfertilityEPINCT04256668
Human Sperm Epigenetics in Embryonic Development.
A study testing Obtaining one or semen samples in people with Male Infertility and Epigenetic Disorder, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
A total of 60 men (40 with a history of infertility and treatment with assisted reproduction and 20 infertile controls achieving conception naturally) will be asked to provide at least one semen sample each for conventional semen analysis including measurement of DNA-fragmentation and semen preparation with swim-up. Read more about this study
- Who is it for?
- Ages 28 to 39 years, men only
- Conditions the study is for
- Male Infertility, Epigenetic Disorder
- What is being tested?
- Obtaining one or semen samples
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Apr 2020to 29 Feb 2024
- Phase
- Interventional
- 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 28 to 39 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Men with a history of infertility. Sperm concentration must be >15 millions per ml.
Who cannot join
- No vulnerable persons will be invited to participate.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Identification and Characterization of Human Sperm Variation and Its Role in Embryonic Development.
A total of 60 men (40 with a history of infertility and treatment with assisted reproduction and 20 infertile controls achieving conception naturally) will be asked to provide at least one semen sample each for conventional semen analysis including measurement of DNA-fragmentation and semen preparation with swim-up. The prepared semen sample will then analyzed by comprehensive microscopy analyses aiming at identifying distinct subpopulations of spermatozoa based on chromatin density and composition, mitochondrial and acrosome function and epigenetic markers. In addition, spermatozoa samples of selected individuals will be subjected to comprehensive analyses of the chromatin and RNA expression status using epigenomic approaches.
Read the detailed description
Hitherto male infertility has been defined by conventional semen analysis only, which mainly consists of determining concentration, progressive mobility and morphology of spermatozoa. However, the diagnostic accuracy of conventional semen analysis is poor and has very limited relationship with the outcome of assisted reproductive medicine. Preliminary data suggest that differences in chromatin density and epigenetic status of sperm may be more relevant, in particular with respect to the growth and differentiation of early embryos.
Chromatin density, morphology, mitochondrial status and epigenetic state in sperm of infertile men with disturbances of early embryo development in vitro will be compared with those of infertile men with normal embryo development and with fertile controls.
Primary outcome:
Features of chromatin density will be determined through staining of large numbers of spermatozoa. Differences in the staining results will be compared with known fertility outcome.
Secondary outcome:
Development of significant staining parameters towards the selection against sperm with reduced embryonic competence and/or in favor of sperm supporting embryonic development after assisted reproduction, thereby using flow cytometry and sorting (FACS) .
- Conditions
- Male Infertility, Epigenetic Disorder
- Being tested
- Obtaining one or semen samples
- Keywords
- assisted reproductive technology, DNA fragmentation, histone, protamine, blastocyst
- Medical subject headings
- Infertility, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Obtaining one or semen samplesDiagnostic test
Also called Semen analysis
Through staining of semen samples with sets of dyes to measure features of chromatin density, nuclear morphology and mitochondrial status in large numbers of single spermatozoa and to compare differences in the staining results with known fertility outcome. Through comprehensive comparative epigenetic studies we anticipate to explain different efficiencies of sperm from men with seemingly normal semen quality in driving embryonic development.
| Study group | Role | What they receive |
|---|---|---|
| good embryo development in assisted reproduction | Active comparator | 20 infertile men treated with assisted reproduction with normal embryo development in vitro, as demonstrated in a previous treatment with assisted reproductive technology (defined by normal fertilization rate >50% and normal blastocyst development rate >50%). Receives: Diagnostic Test: Obtaining one or semen samples |
| poor embryo development in assisted reproduction | Active comparator | 20 infertile men treated with assisted reproduction with poor embryo development in vitro, as demonstrated in a previous treatment with assisted reproductive technology (defined by normal or slightly reduced fertilization rate <50% and low or absent blastocyst development (0 or only 1 blastocyst). Receives: Diagnostic Test: Obtaining one or semen samples |
| natural conception | Placebo comparator | 20 previously infertile men, normal history, normal genital status, normal sperm count, DNA fragmentation rate <20% (as given by TUNEL) and achieving pregnancy naturally (without medical intervention). Receives: Diagnostic Test: Obtaining one or semen samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in chromatin density.
Staining of the nucleus of spermatozoa with the fluorescent dye chromomycin
Measured: 12 months
Secondary outcomes (1)
Normal and abnormal embryo development after assisted reproduction.
Differences in distribution of epigenetic markers.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start1 Apr 2020
- Primary completion31 Dec 2023
- Study completion29 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Male InfertilityStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 20 infertile men treated with assisted reproduction with normal embryo development in vitro, as demonstrated in a previous treatment with assisted reproductive technology (defined by normal fertilization rate \>50% and normal blastocyst development rate \>50%). 20 infertile men treated with assisted reproduction with poor embryo development in vitro, as demonstrated in a previous treatment with assisted reproductive technology (defined by normal or slightly reduced fertilization rate \<50% and low or absent blastocyst development (0 or only 1 blastocyst). 20 previously infertile men, normal history, normal genital status, normal sperm count, DNA fragmentation rate \<20% (as given by TUNEL) and achieving pregnancy naturally (without medical intervention).
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Friedrich Miescher Institute for Biomedical Research (FMI)
- Responsible party
- Sponsor
- Investigators
- Christian De Geyter, MD, Principal investigator, University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04256668
- Sponsor's protocol ID
- Human Sperm Epigenetic
- Acronym
- EPI
- Status last verified
- Apr 2024
- First submitted
- 27 Jan 2020
- Last updated
- 8 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gill ME, Fischer M, De Geyter C, Peters AHFM. Normozoospermic infertile men possess subpopulations of sperm varying in DNA accessibility, relating to differing reproductive outcomes. Hum Reprod. 2025 Jul 1;40(7):1266-1281. doi: 10.1093/humrep/deaf081.
PubMed 40375809
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification and Characterization of Human Sperm Variation and Its Role in Embryonic Development.
- ClinicalTrials.gov ID
- NCT04256668
- Acronym / sponsor ID
- EPI / Human Sperm Epigenetic
- Conditions
- Male Infertility, Epigenetic Disorder
- Keywords
- assisted reproductive technology, DNA fragmentation, histone, protamine, blastocyst
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- Friedrich Miescher Institute for Biomedical Research (FMI)
- Study start
- 1 Apr 2020 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 29 Feb 2024 (actual)
- First posted
- 5 Feb 2020 (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.
A total of 60 men (40 with a history of infertility and treatment with assisted reproduction and 20 infertile controls achieving conception naturally) will be asked to provide at least one semen sample each for conventional semen analysis including measurement of DNA-fragmentation and semen preparation with swim-up. The prepared semen sample will then analyzed by comprehensive microscopy analyses aiming at identifying distinct subpopulations of spermatozoa based on chromatin density and composition, mitochondrial and acrosome function and epigenetic markers. In addition, spermatozoa samples of selected individuals will be subjected to comprehensive analyses of the chromatin and RNA expression status using epigenomic approaches.
Detailed description
Hitherto male infertility has been defined by conventional semen analysis only, which mainly consists of determining concentration, progressive mobility and morphology of spermatozoa. However, the diagnostic accuracy of conventional semen analysis is poor and has very limited relationship with the outcome of assisted reproductive medicine. Preliminary data suggest that differences in chromatin density and epigenetic status of sperm may be more relevant, in particular with respect to the growth and differentiation of early embryos.
Chromatin density, morphology, mitochondrial status and epigenetic state in sperm of infertile men with disturbances of early embryo development in vitro will be compared with those of infertile men with normal embryo development and with fertile controls.
Primary outcome:
Features of chromatin density will be determined through staining of large numbers of spermatozoa. Differences in the staining results will be compared with known fertility outcome.
Secondary outcome:
Development of significant staining parameters towards the selection against sperm with reduced embryonic competence and/or in favor of sperm supporting embryonic development after assisted reproduction, thereby using flow cytometry and sorting (FACS) .
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- 20 infertile men treated with assisted reproduction with normal embryo development in vitro, as demonstrated in a previous treatment with assisted reproductive technology (defined by normal fertilization rate >50% and normal blastocyst development rate >50%). 20 infertile men treated with assisted reproduction with poor embryo development in vitro, as demonstrated in a previous treatment with assisted reproductive technology (defined by normal or slightly reduced fertilization rate <50% and low or absent blastocyst development (0 or only 1 blastocyst). 20 previously infertile men, normal history, normal genital status, normal sperm count, DNA fragmentation rate <20% (as given by TUNEL) and achieving pregnancy naturally (without medical intervention).
| Arm | Type | Receives |
|---|---|---|
| good embryo development in assisted reproduction | Active comparator | Diagnostic Test: Obtaining one or semen samples20 infertile men treated with assisted reproduction with normal embryo development in vitro, as demonstrated in a previous treatment with assisted reproductive technology (defined by normal fertilization rate >50% and normal blastocyst development rate >50%). |
| poor embryo development in assisted reproduction | Active comparator | Diagnostic Test: Obtaining one or semen samples20 infertile men treated with assisted reproduction with poor embryo development in vitro, as demonstrated in a previous treatment with assisted reproductive technology (defined by normal or slightly reduced fertilization rate <50% and low or absent blastocyst development (0 or only 1 blastocyst). |
| natural conception | Placebo comparator | Diagnostic Test: Obtaining one or semen samples20 previously infertile men, normal history, normal genital status, normal sperm count, DNA fragmentation rate <20% (as given by TUNEL) and achieving pregnancy naturally (without medical intervention). |
Who may qualify
- Ages
- 28 to 39 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Men with a history of infertility. Sperm concentration must be >15 millions per ml.
Key exclusion criteria (1 listed)
- No vulnerable persons will be invited to participate.
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 |
|---|---|---|
| Obtaining one or semen samplesAlso: Semen analysisThrough staining of semen samples with sets of dyes to measure features of chromatin density, nuclear morphology and mitochondrial status in large numbers of single spermatozoa and to compare differences in the staining results with known fertility outcome. Through comprehensive comparative epigenetic studies we anticipate to explain different efficiencies of sperm from men with seemingly normal semen quality in driving embryonic development. | Diagnostic test | good embryo development in assisted reproduction, natural conception, poor embryo development in assisted reproduction |
Primary outcome
Differences in chromatin density.
Time frame: 12 months
Staining of the nucleus of spermatozoa with the fluorescent dye chromomycin
1 secondary outcome
Normal and abnormal embryo development after assisted reproduction.
Time frame: 24 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 8 Apr 2024.
- Derived from this study: PubMed 40375809Gill ME, Fischer M, De Geyter C, Peters AHFM. Normozoospermic infertile men possess subpopulations of sperm varying in DNA accessibility, relating to differing reproductive outcomes. Hum Reprod. 2025 Jul 1;40(7):1266-1281. doi: 10.1093/humrep/deaf081.
- 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.
Christian De Geyter, MD principal investigator
University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Obtaining one or semen samples in people with Male Infertility and Epigenetic Disorder, run by University Hospital, Basel, Switzerland 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 8 Apr 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. Some participants in this study may receive a placebo. 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?
Differences in chromatin density. (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04256668, which also lists 1 linked publication.
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 8 Apr 2024.