Reproductive Endocrinology Oxford Study (RepOx) (RepOx)

This is a prospective observational study that aims to identify the underlying mechanisms of PolyCystic Ovarian Syndrome (PCOS) and associated comorbidities such as subfertility, miscarriage; and pregnancy complications such as gestational diabetes mellitus and Intrahepatic cholestasis of pregnancy (ICP). This will be achieved through cross-sectional observation and laboratory analyses.

Study Overview

• Status: Recruiting
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Other: No intervention

Detailed Description

Here we propose a comprehensive program to dissect the underlying disease-causing mechanisms of PCOS and associated comorbidities. We will investigate how the different layers of biological information (ranging from DNA variant genotyping, to RNA sequencing and proteomics), and clinical characteristics are correlated with each other and how this affects PCOS in fat tissue derived cells, as well as ovarian tissue and tissue derived cells by using a combination of big data analysis, a range of "-omics" technologies, of both in-house generated and publicly available data, paired with state of the art statistical and bioinformatics analysis. Out of these mechanisms and pathways we will identify druggable targets for proposals for detailed functional follow up with an aim of development of novel therapeutic options for PCOS.

• Study Type: Observational
• Enrollment (Anticipated): 1175

Contacts and Locations

• Study Contact: Name: RepOx Research Midwife; Phone Number: ++441865 572258; Email: osprea@wrh.ox.ac.uk

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 9DU
      • Recruiting
      • Nuffield Department Women's and Reproductive Health
      • Contact: OSPREA -Study Research Midwives; Phone Number: +44 1865 572258; Email: OSPREA@wrh.ox.ac.uk
      • Principal Investigator: Ingrid Granne, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women with and without OCOS and known associated phenotypes

Description

Inclusion Criteria:

• ● General Criteria for all groups

  • Participant is willing and able to give informed consent for participation in the study.

  • Female, aged between 16 and 45 years of age. As IVF is not undertaken in women less that 18 years, this group will between 18 and 45 years o

    ● PCOS (Group 1, 2 and 3)

  • Currently under investigation for or having diagnosis of PCOS having displayed one or more of the following: Hyperandrogenism, Ovulation Dysfunction and Polycystic ovaries on ultrasound (known as the Rotterdam criteria)

    ● PCOS Controls (Group 4 and 5)

  • Patients under gynaecological investigation or having assisted reproduction

  • Exhibit no features of PCOS

    ● Miscarriage Group (Group 6)

  • Have had at least two previous miscarriages

  • Recruited at any time after their second menstrual cycle following a miscarriage

    ● Miscarriage Controls (Group 7)

  • Patients will have had zero or no more than one miscarriage and having fertility investigations.

    ● Pregnant GDM (Group 8)

  • Pregnant women at least 28 weeks gestation with :
  • 1) A fasting plasma glucose of 5.1mmol/L or above or
  • 2) A 1 hr plasma glucose of 10mmol/L or

  • 3) A 2-hr plasma glucose level of 8.5mmol/L or above

    ● Pregnant ICP (Group 9)

  • Women at least 28 weeks gestation with :
  • Raised ALT or raised bile acids in the context of pruritus with no rash
  • ALT (>32iu/l) and bile acids (>14micromol/l) Pregnant Control (Group 10)
  • Pregnant women at least 28 weeks gestation with no diagnosis of GDM or ICP

Exclusion Criteria:

• For all groups - The participant may not enter the study if ANY of the following apply.

  • Unable to read, or to understand written or spoken English
  • Currently involved in any Clinical Trial of an Investigational Medicinal Product (CTIMP)
  • Undergoing surgery because of a possible cancer diagnosis
  • Diagnosis of other androgen excess disorders such as Congenital Adrenal Hyperplasia (CAH), Androgen Secreting tumours, Cushing syndrome, or Hyperprolactinemia

Study Plan

How is the study designed?

Number of groups / cohorts

10

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PCOS; No intervention.	Other: No intervention; There is no intervention in this study
PCOS surgery; No intervention	Other: No intervention; There is no intervention in this study
Surgery control; No intervention	Other: No intervention; There is no intervention in this study
IVF PCOS; No intervention	Other: No intervention; There is no intervention in this study
IVF control; No intervention	Other: No intervention; There is no intervention in this study
Investigations, fertility PCOS; No intervention	Other: No intervention; There is no intervention in this study
Investigations, fertility control; No intervention	Other: No intervention; There is no intervention in this study
Pregnancy - gestational diabetes mellitus; No intervention	Other: No intervention; There is no intervention in this study
Pregnancy - Intrahepatic cholestasis of pregnancy; No intervention	Other: No intervention; There is no intervention in this study
Pregnancy - control; No intervention	Other: No intervention; There is no intervention in this study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify the underlying genetic and pathophysiological mechanisms of PCOS and associated phenotypes	Questionnaire data, imaging analysis, medical records and sample analysis	one visit

Secondary Outcome Measures

Outcome Measure	Time Frame
To identify novel biomarkers of PCOS and associated comorbidities.	one visit
To identify clinical subgroups of PCOS and associated comorbidities.	one visit
To understand the genetics underlying these conditions and explore the relevant downstream molecular pathways	one visit
To identify novel drug targets, develop models of disease progression and prediction.	one visit

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: Bayer; Li Ka Shing Foundation

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2021
• Primary Completion (Anticipated): September 1, 2028
• Study Completion (Anticipated): September 1, 2028

Study Registration Dates

• First Submitted: December 15, 2021
• First Submitted That Met QC Criteria: December 15, 2021
• First Posted (Actual): January 4, 2022

Study Record Updates

• Last Update Posted (Actual): January 4, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: PCOS
• Additional Relevant MeSH Terms: Neoplasms; Endocrine System Diseases; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome
• Other Study ID Numbers: IRAS302159

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No