Reproductive Endocrinology Oxford Study (RepOx)

Recruiting

• Conditions: Polycystic Ovary Syndrome
• Interventions: Other: No intervention

• Registration Number: NCT05177562
• Lead Sponsor: University of Oxford

Brief Summary

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.

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 Timeline

• Study Start: 2021-10-21
• Status Verified: 2021-12
• Study First Submitted: 2021-12-15
• Study First Submitted QC: 2021-12-15
• Last Update Submitted: 2021-12-15
• Study First Posted: 2022-01-04
• Last Update Posted: 2022-01-04
• Primary Completion: 2028-09-01
• Study Completion: 2028-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 1175

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
IVF PCOS	No intervention	No intervention
Pregnancy - Intrahepatic cholestasis of pregnancy	No intervention	No intervention
Investigations, fertility PCOS	No intervention	No intervention
Investigations, fertility control	No intervention	No intervention
Surgery control	No intervention	No intervention
PCOS surgery	No intervention	No intervention
Pregnancy - gestational diabetes mellitus	No intervention	No intervention
Pregnancy - control	No intervention	No intervention
PCOS	No intervention	No intervention.
IVF control	No intervention	No intervention

Primary Outcome Measures

Name	Time	Method
Identify the underlying genetic and pathophysiological mechanisms of PCOS and associated phenotypes	one visit	Questionnaire data, imaging analysis, medical records and sample analysis

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Nuffield Department Women's and Reproductive Health; 🇬🇧 Oxford, Oxfordshire, United Kingdom