Human Sperm Epigenetics in Embryonic Development.

NCT04256668 | Completed

• 1 other identifier: Human Sperm Epigenetic
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Male Infertility; Epigenetic Disorder

Keywords

assisted reproductive technology; DNA fragmentation; histone; protamine; blastocyst

Outcome Measures

Primary Outcomes (1)

• Differences in chromatin density.

  Staining of the nucleus of spermatozoa with the fluorescent dye chromomycin

  12 months

Secondary Outcomes (1)

• Normal and abnormal embryo development after assisted reproduction.

  24 months

Study Arms (3)

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%).

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).

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).

Diagnostic Test: Obtaining one or semen samples

Interventions

Obtaining one or semen samples DIAGNOSTIC_TEST

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.

Also known as: Semen analysis

good embryo development in assisted reproduction; natural conception; poor embryo development in assisted reproduction

Eligibility Criteria

• Age: 28 Years - 39 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Men with a history of infertility. Sperm concentration must be \>15 millions per ml.

You may not qualify if:

• No vulnerable persons will be invited to participate.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Friedrich Miescher Institute for Biomedical Research (FMI): collaborator

Study Sites (1)

University Hospital

Basel, 4031, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 40375809 DERIVED

MeSH Terms

Conditions

Infertility, Male

Interventions

Semen Analysis

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Infertility; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Christian De Geyter, MD

  University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Sperm samples will be collected, processed and stained at the hospital site (RME). Slides generated for imaging will be assigned an anonymous code, removing all possible patient identifiable features. Then the slides will be sent to the research laboratory (FMI) for further analysis.
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: January 27, 2020
• First Posted: February 5, 2020
• Study Start: April 1, 2020
• Primary Completion: December 31, 2023
• Study Completion: February 29, 2024
• Last Updated: April 8, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)