Sperm Phenotype and Differentially Methylated Regions | NCT05461079

Studies
Sperm Phenotype and Differentially Methylated Regions

NCT05461079

Sponsor

University of Basel

Status

Completed

Last Update Posted

Mar 20, 2024Actual

Enrollment

60Actual

Phase

Not provided

Conditions

Infertility, Male

Interventions

obtention of up to three semen samples

Countries

Switzerland

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Mar 2024

Overall Recruitment Status or Expanded Access Status

Completed

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Nov 1, 2017Actual

Primary Completion Date

Jan 30, 2021Actual

Completion Date

Dec 31, 2023Actual

First Submitted Date

Dec 9, 2017

First Submission Date that Met QC Criteria

Jul 12, 2022

First Posted Date

Jul 15, 2022Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Mar 19, 2024

Last Update Posted Date

Mar 20, 2024Actual

Name	Class
University of Geneva, Switzerland	OTHER

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Is FDA Regulated Device

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

Brief 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.

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.

Design Module

Study Type

Observational

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Target Follow-Up Duration

Not provided

Phases

Not provided

Interventional Study Design

Allocation

Not provided

Intervention Model

Biospecimen

Retention

Enrollment

60Actual

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
subfertile men		10 infertile men with shortened AGD (< 40 mm)	Diagnostic Test: obtention of up to three semen samples
fertile semen donors		10 fertile semen donors with normal AGD (>40 mm)	Diagnostic Test: obtention of up to three semen samples

Interventions

Name	Type	Description	Arm Group Labels	Other Names
obtention of up to three semen samples	Diagnostic Test	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
anogenital distance and epigenetics	number of differentially methylated transposable regulatory sequences in the genome of sorted spermatozoa.	6 months

Secondary Outcomes

Measure	Description	Time Frame
sperm phenotype 1	based on conventional semen analysis: concentration of spermatozoa (in mill/ml).	6 months
sperm phenotype 2	based on conventional semen analysis: progressive motility (in %).

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

infertile men with known anogenital distance

Exclusion Criteria:

sperm concentration must be more than 15 million/ml to allow appropriate sorting with flow cytometry...

Accepts Healthy Volunteers

Not provided

Sex

Male

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

20 Years

Maximum Age

55 Years

Standard Ages

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.

Sampling Method

Non-Probability Sample

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Not provided

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Christian De Geyter		Basel		4031	Switzerland

IPD Sharing Statement Module

Plan to Share IPD

Description

Not provided

Types

Not provided

Time Frame

Not provided

Access Criteria

Not provided

URL

Not provided

Condition Browse Module

MeSH Terms

ID	Term
D007248	Infertility, Male

Ancestor Terms

ID	Term
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D007246	Infertility

Browse Leaves

Not provided

Browse Branches

Not provided

Description

Spermatozoa sorted with FACS according to two different staining methods: YoPro1 (apoptosis) and CMA3 (histone content). After sorting, we obtained four different groups: 1. YoPro1 positive and 2. YoPro1 negative, CMA3 positive and CMA3 negative. All sorted samples were stored frozen and sent for analysis of whole genome methylation status.