Human Sperm Epigenetics in Embryonic Development.
- Conditions
- Epigenetic DisorderMale Infertility
- Registration Number
- NCT04256668
- Lead Sponsor
- University Hospital, Basel, Switzerland
- 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.
- 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) .
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 60
- Men with a history of infertility. Sperm concentration must be >15 millions per ml.
- No vulnerable persons will be invited to participate.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Differences in chromatin density. 12 months Staining of the nucleus of spermatozoa with the fluorescent dye chromomycin
- Secondary Outcome Measures
Name Time Method Normal and abnormal embryo development after assisted reproduction. 24 months Differences in distribution of epigenetic markers.
Trial Locations
- Locations (1)
University Hospital
🇨🇭Basel, Switzerland
University Hospital🇨🇭Basel, Switzerland