Molecular Basis of PCOS in Oocytes and Surrounding Cells

Polycystic Ovary Syndrome Clinical Trial

Official title:

Novel Molecular Characterization of Oocytes and Cumulus Cells From Women With Polycystic Ovarian Syndrome (PCOS) Phenotype A

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04493788
• Other study ID #: MOLPA-2020253
• Status: Not yet recruiting
• Start date: July 2020
• Est. completion date: July 2022

Study information

• Verified date: July 2020
• Source: Universitair Ziekenhuis Brussel
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age that is characterized by elevated androgen levels, ovulatory dysfunction and polycystic ovarian morphology (PCOM). Moreover, has been associated to insulin resistance, obesity, type 2 diabetes and infertility.

Women with PCOS are a heterogeneous group, and specific PCOS phenotype could have a substantial impact on oocyte quality and molecular profile. Regarding the Rotterdam criteria for PCOS, four different phenotypes of the syndrome are defined (A, B, C, D). Phenotypic group A is the most frequent and severe subtype of PCOS. It is described that patients with so-called phenotype A exhibit a significantly increased risk of pregnancy complications compared to women with more favorable PCOS phenotypes. Specifically, this clinical-laboratory study will focus on the molecular characterization of PCOS phenotype A.

Epigenetic are external modifications to DNA that affect how cells "read" genes. These external modifications have garnered attention in the pathogenesis of PCOS since epigenetics changes have been reported in various organs in women with the condition. However, remains unknown whether these alterations are also found in the egg and in its surrounding cells.

Further research is needed to understand the PCOS disorder and to design treatments that can ameliorate the symptoms of the disease. In particular, this project aims to generate the molecular profiles of PCOS phenotype A eggs and surrounding cells and compare them with the ones obtained from and healthy controls. This approach involves the aspiration of immature eggs without hormonal stimulation or with stimulation of only a few days.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: July 2022
• Est. primary completion date: July 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 37 Years

Eligibility

Inclusion Criteria:

• women between the ages of 18 and 37

• biochemical hyperandrogenism

• ovulatory dysfunction

• polycystic ovaries)

• BMI > 25.

• normal andro-gen levels

• normal ovarian function

• normal ovarian morphology

• BMI < 29.

Exclusion Criteria:

• congenital adrenal hyperplasia

• Cushing's syndrome

• androgenic-secreting tumor

• high (>grade 2) grade endometriosis

• major uterine or ovarian abnormalities

• pregnant women

• volunteers with metabolic syndrome

Related Conditions & MeSH terms

• Polycystic Ovary Syndrome
• Syndrome

Intervention

Other:
• Blood test, ultrasound and egg retrieval
Blood tests will be performed to determine free testosterone levels, anti-mullerian hormone (AMH) and lipid profile including fasting plasma glucose and insulin. Women from both PCOS and control groups will be minimally stimulated with gonadotrophins and cumulus-oocytes complexes (COCs) will be aspirated from small antral follicles (2-8mm) without any ovulation triggering. Specifically, administration of highly purified human menopausal gonadotropin (HP-hMG) will start on cycle Day 3 of the menstrual period or a withdrawal bleeding. A pelvic ultrasound scan will be performed in the morning of the last stimulation day to schedule the oocyte collection. Cumulus-oocyte complexes retrieved 42 hours after the last gonadotropin injection will be collected, washed, denuded and individually stored for further molecular characterization.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Universitair Ziekenhuis Brussel

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DNA methylation profiles in oocytes and cumulus cells	On of the primary outcome measure of this project will be the generation of DNA methylation profile of PCOS oocytes and paired cumulus cells using single-cell and low-cell parallel sequencing, respectively.	This information is expected to be generated in 24 months
Primary	Gene expression profiles in oocytes and cumulus cells	Another primary outcome measure of this project will be the generation of gene expression profile of PCOS oocytes and paired cumulus cells using single-cell and low-cell parallel sequencing, respectively.	This information is expected to be generated in 24 months