Clinical trial NCT03565107: Characterization of Methylation Pattern in Human Germ Cells of Patients Undergoing ICSI Treatment
Official title: Characterization of Methylation Pattern in Human Germ Cells of Patients with the Desire to Have Children Undergoing Intracytoplasmic Sperm Injection Treatment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Female Infertility
Gene Deregulation
Keywords: Epigenetic
Female age
Gene regulation
Methylation pattern
Lead sponsor: Infertility Treatment Center Dortmund
Sponsor class: OTHER
Collaborators: name: University of Wuerzburg
First posted: 2018-06-21
Enrollment: 156
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: female patients seeking ICSI treatment because of male subfertility

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Methylation pattern
timeFrame: 1 day (Directly after oocyte pick-up)
measure: Gene expression
timeFrame: 1 day (Directly after oocyte pick-up)
Secondary outcomes:
Other outcomes:
Locations:
city: Dortmund
country: Germany
facility: Infertility treatment center Dortmund
state: NRW
Study officials:
affiliation: Infertility Treatment Center Dortmund
name: Stefan Dieterle, MD
role: PRINCIPAL_INVESTIGATOR
References: