Polycystic Ovary Syndrome, Mitochondrial Dysfunction, Obesity, Insulin Resistance Infertility (POMODORI) Cohort (POMODORI)

Polycystic Ovary Syndrome, Insulin Resistance, Infertility, Obesity, and the Associated Mitochondrial Dysfunction With These Disorders in Hungarian Patients

Enrolling of 150 female patients of fertile age diagnosed with PCOS, insulin resistance, infertility, or mitochondrial disease, and the same number of age- and sex-matched controls are planned.

During the research biomarkers already with mitochondrial dysfunction in the scientific literature and common mtDNA abnormalities (deletions, point mutations, copy number changes, etc.) are examined.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Polycystic Ovary Syndrome; Insulin Resistance; Primary Ovarian Insufficiency; Infertility, Female; Mitochondrial Alteration

Detailed Description

Mitochondrial dysfunction can be involved in the development of clinically heterogeneous diseases affecting multiple tissues and organs and can manifest at any age. Clinical signs are mainly manifested in the most energy-demanding tissues, such as the central nervous system, striated muscles, cardiac musculature, endocrine glands, liver, kidney, and sensory organs.

Polycystic ovarian syndrome (PCOS) is a multifactorial disorder with endocrine dysfunction characterized by ovulatory dysfunction, obesity, insulin resistance (IR), hirsutism, mild persistent inflammation, and ultrasonographically confirmed polycystic ovarian morphology. PCOS affects 5-15% of women of reproductive age. PCOS and IR are also common and treatable causes of infertility. As a result of delaying childbearing until later in life, this problem is affecting more and more couples. In the present study, the investigators hypothesize that PCOS, IR, and infertility associated with these conditions may also be a manifestation of mitochondrial dysfunction, the role of mitochondrial dysfunction in these conditions has been investigated to a limited extent based on the current literature.

Recent literature has shown that mitochondrial dynamics and morphology are two of the major factors in the development of insulin resistance and diabetes mellitus by regulating glucose metabolism. The investigators of this study cohort hypothesize that PCOS and IR may also be a manifestation of a primary mitochondrial pathology, the prevalence of IR and PCOS in primary mitochondrial patients has not yet been investigated based on the current literature. Recent literature suggests that mitochondrial dynamics and morphology are two of the main factors in the development of insulin resistance and diabetes mellitus by regulating glucose metabolism.

In the present experimental design, mitochondrial dynamics, bioenergetics, and autophagy pathways are hypothesized to play a key role in the pathomechanisms of PCOS and IR. A better understanding of the role of mitochondrial pathways in the pathophysiology of PCOS and IR may help to develop new biomarkers or therapeutic targets.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Vera Várhegyi, MD; Phone Number: +36206663493; Email: varhegyi.vera@semmelweis.hu
• Study Contact Backup: Name: Anikó Gál, PhD; Phone Number: +36206632516; Email: gal.aniko@med.semmelweis-univ.hu

Study Locations

• Hungary
  • Budapest, Hungary, 1082
    • Recruiting
    • Semmelweis University
    • Contact: Vera Várhegyi, MD; Phone Number: +36206663493; Email: varhegyi.vera@semmelweis.hu
    • Contact: Anikó Gál, PhD; Phone Number: +36206632516; Email: gal.aniko@med.semmelweis-univ.hu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Female patients of fertile age (between 20-45 years) who are being treated for insulin resistance and/or polycystic ovary syndrome, infertility, multi-organ symptoms, or possible primary ovarian insufficiency.

Description

Inclusion Criteria:

• Presence of polycystic ovary syndrome (PCOS) or insulin resistance (IR) associated with other multisystemic phenotypes, mitochondrial dysfunction
• history of infertility associated with other multisystemic phenotypes, mitochondrial dysfunction
• a known history of mitochondrial dysfunction and PCOS and/or IR
• general health is good and there is no serious general medical condition that would prevent participation would make participation highly risky

Exclusion Criteria:

• poor cooperation
• refusal to participate in the study

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Glucose and Insulin Levels	The serum glucose and insulin levels are calculated by using plasma concentrations of insulin and glucose obtained during 120 min of a standard (75 g glucose) OGTT. Fasting, 1h and 2h glucose and insulin levels are measured	One year
Clinical Pregnancy Rate	Clinical pregnancy rate = the number of clinical pregnancies/the total number of participants in the patient cohort × 100%	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Female Sex Hormone Levels and Thyroid Hormone Levels	Measurement of the baseline female sex hormone: anti-Mullerian hormone (AMH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, progesterone, total testosterone, free testosterone, SHBG) and thyroid hormone levels (thyroid stimulating hormone (TSH), T3, T4 + anti-thyroid peroxidase antibody, anti-thyroglobulin antibody) - in the unit of measurement used for the hormone concerned	One year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Mass Index (BMI)	The body mass index (BMI) is the metric currently in use for defining anthropometric height/weight characteristics in adults and classifying (categorizing) them into groups (expressed in kg/m2).	One year
Metformin dose	Daily dose of metformin used (expressed in milligrams)	One year
GLP-1 receptor agonist dose	Daily or weekly dose of the used glucagon-like peptide-1 (GLP-1) agonist depending on the exact type of active substance (expressed in milligrams)	One year

Collaborators and Investigators

• Sponsor: Semmelweis University

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2021
• Primary Completion (Estimated): September 30, 2033
• Study Completion (Estimated): September 30, 2033

Study Registration Dates

• First Submitted: December 3, 2023
• First Submitted That Met QC Criteria: December 3, 2023
• First Posted (Actual): December 12, 2023

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Obesity; Insulin Resistance; Polycystic Ovary Syndrome; Primary Ovarian Insufficiency; Mitochondrial Dysfunction; Female Infertility; Mitochondrial Alteration
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Polycystic Ovary Syndrome; Syndrome; Obesity; Infertility; Insulin Resistance; Primary Ovarian Insufficiency; Menopause, Premature; Infertility, Female
• Other Study ID Numbers: 15672-6/2022/EÜIG

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