Human Sperm Epigenetics in Embryonic Development.

Male Infertility Clinical Trial

— EPI  

Official title:

Identification and Characterization of Human Sperm Variation and Its Role in Embryonic Development.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04256668
• Other study ID #: Human Sperm Epigenetic
• Status: Completed
• Phase: N/A
• Start date: April 1, 2020
• Est. completion date: February 29, 2024

Study information

• Verified date: April 2024
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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) .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: February 29, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 28 Years to 39 Years

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• No vulnerable persons will be invited to participate.

Related Conditions & MeSH terms

• Epigenetic Disorder
• Infertility
• Infertility, Male
• Male Infertility

Intervention

Diagnostic Test:
• Obtaining one or semen samples
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.

Locations

Country	Name	City	State
Switzerland	University Hospital	Basel

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Friedrich Miescher Institute for Biomedical Research (FMI)

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in chromatin density.	Staining of the nucleus of spermatozoa with the fluorescent dye chromomycin	12 months
Secondary	Normal and abnormal embryo development after assisted reproduction.	Differences in distribution of epigenetic markers.	24 months