Characterization of Methylation Pattern in Human Germ Cells of Patients Undergoing ICSI Treatment

Female Infertility Clinical Trial

Official title:

Characterization of Methylation Pattern in Human Germ Cells of Patients With the Desire to Have Children Undergoing Intracytoplasmic Sperm Injection Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03565107
• Other study ID #: Methylation in Germ cells
• Status: Recruiting
• Start date: July 1, 2018
• Est. completion date: March 30, 2025

Study information

• Verified date: April 2024
• Source: Infertility Treatment Center Dortmund
• Contact: Stefan Dieterle, MD
• Phone: 00492315575450
• Email: dieterle[@]ivf-dortmund.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

There is increasing evidence that exposure to environmental factors in early development is associated with an increased risk of metabolic and other common diseases. These increased disease risks are likely due to environmental-induced epigenetic changes leading to dysregulation of genes and signaling cascades. The best studied epigenetic modification in this context is DNA methylation. Preliminary studies have already shown that an increased father age or intracytoplasmic sperm injection affects methylation pattern in sperm or umbilical cord blood of children. Unlike sperm, less is known about the methylation of human oocytes and their susceptibility to environmental factors. The aim of this study is to analyze the methylation pattern of immature oocytes of women with decreased fertility. Based on the results of a large number of oocytes from different women, risk assessments could be made for individual factors such as the age of the patient, as well as correlations between the occurrence of changes in gene expression and the unfulfilled desire to have children. In addition, the methylation patterns in sperm from 20 patients are to be examined as reference patterns.

Description:

Although more than five million children have been conceived worldwide through Assisted Reproduction Techniques (ARTs), little is known about potential effects of ART in later life. So far, the focus of reproductive research is based on the success rate of infertility treatment. There is increasing evidence that exposure to environmental substances, age of the patient or in vitro culture conditions in early development is associated with a life-long increased risk of metabolic and other common diseases. These increased disease risks are likely due to environmental-induced epigenetic changes leading to dysregulation of genes and signaling cascades. These include Beckwith-Wiedemann and Angelman syndrome.

The best studied epigenetic modification in this context is DNA methylation, which regulates the gene expression in a temporally and highly coordinated manner. Preliminary studies have already shown that an increased father age influences the pattern of methylation in the sperm and umbilical cord blood of children. Moreover, intracytoplasmic sperm injection (ICSI) also leaves epigenetic signatures in umbilical cord blood. Unlike sperm, little is known about the methylation of human oocytes and their susceptibility to environmental factors. The main reason for this is the difficulty of collecting human oocytes in sufficient numbers for genome-wide analysis. The aim of this study is to analyze the methylation pattern of immature oocytes, which are not suitable for further ICSI treatment, of women with decreased fertility. The products of gene expression and also the methylation of the DNA itself can be investigated using newly developed DNA sequencing methods. Based on the results of a large number of oocytes from different women, risk assessments could be made for individual factors such as the age of the patient, as well as correlations between the occurrence of changes in gene expression and the unfulfilled desire to have children. In addition, the methylation patterns in sperms from 20 patients are to be examined as reference.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: March 30, 2025
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• healthy females without sterility factors

Exclusion Criteria:

• Endometriosis

• Polycystic ovary syndrome (PCO)

• Neoplasia (ovary, Uterus, breast)

• Anti-Müllerian hormone (AMH) <1 ng/ml

Related Conditions & MeSH terms

• Female Infertility
• Gene Deregulation
• Infertility
• Infertility, Female

Locations

Country	Name	City	State
Germany	Infertility treatment center Dortmund	Dortmund	NRW

Sponsors (2)

Lead Sponsor	Collaborator
Infertility Treatment Center Dortmund	University of Wuerzburg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Methylation pattern	Analysis of methylation pattern in immature oocytes (not suitable for further ICSI treatment). Methylation will be pointed out as number of methylated gene loci in comparison to the overall amount of analyzed gene loci.	1 day (Directly after oocyte pick-up)
Primary	Gene expression	Analysis of gene expression in immature oocytes (not suitable for further ICSI treatment) will be done by quantification of selected gene transcripts (in picogram).	1 day (Directly after oocyte pick-up)