Molecular Basis of PCOS in Oocytes and Surrounding Cells

Sponsor

Universitair Ziekenhuis Brussel (Other)

Overall Status

Unknown status

CT.gov ID

NCT04493788

Collaborator

(none)

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Polycystic Ovary Syndrome	Other: Blood test, ultrasound and egg retrieval

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

30 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2020

Anticipated Primary Completion Date :

Jul 1, 2021

Anticipated Study Completion Date :

Jul 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
PCOS group	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.
Control group	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.

Arm

Intervention/Treatment

PCOS group

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.

Control group

Other: Blood test, ultrasound and egg retrieval

Outcome Measures

Primary Outcome Measures

DNA methylation profiles in oocytes and cumulus cells [This information is expected to be generated in 24 months]
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.
Gene expression profiles in oocytes and cumulus cells [This information is expected to be generated in 24 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 37 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Universitair Ziekenhuis Brussel

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Universitair Ziekenhuis Brussel

ClinicalTrials.gov Identifier:

NCT04493788

Other Study ID Numbers:

MOLPA-2020253

First Posted:

Jul 30, 2020

Last Update Posted:

Aug 3, 2020

Last Verified:

Jul 1, 2020

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Polycystic Ovary Syndrome

Syndrome

Study Results

No Results Posted as of Aug 3, 2020