Potential causes of idiopathic infertility include in particular: abnormal function of the endometrium, including implantation disorders and immunological abnormalities, genetic abnormalities and the functioning of reproductive cells and embryos, functional abnormalities of reproductive cells and embryos, dysfunctions and discreet anatomical anomalies of the fallopian tubes transport of reproductive cells and embryos. MedDRA version: 20.0 Level: HLT Classification code 10016471 Term: Fertility
Conditions
Interventions
Trade Name: Glucophage
Product Name: Metformin 500mg
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
Medical Univeristy of Bialystok
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. age =20=40 years. 2. No occurrence of pregnancy for a minimum of 12 months prior to screening. 3. Diagnosed idiopathic infertility. 4. No use of hormonal therapy 30 days prior to screening. 5. No use of any method of contraception 30 days prior to screening and during screening. 6. BMI between 18.5 - 30 kg/m2. 7. Eligibility for an in vitro fertilisation programme. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 180 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Positive pregnancy test result. 2. Patients diagnosed with another infertility factor. 3. Patients with type I or II diabetes. 4. Patients taking metformin or other hypoglycaemic drugs in the last 4 weeks prior to screening. 5. patients with liver dysfunction and abnormal liver function tests (alanine aminotransferase activity and/or aspartate aminotransferase activity (above 3x GGN). 6. patients with an eGFR below 45 ml/ min/1.73m2. 7. Accompanying chronic diseases with poor prognosis. 8. patients with a history of lactic acidosis or other metabolic acidosis. 9. Patients with a history of congestive heart failure NYHA class III/IV. 10. patients with acute myocardial ischaemia. 11. patients with sepsis or severe infection. 12. diseases that, in the opinion of the investigator, constitute an exclusion criterion and preclude the patient's participation in the study. 13. Patients with foreseeable problems with co-operation with the study team.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The aim of the study is to evaluate the effect of metformin on endometrial function in women diagnosed with idiopathic infertility, by proving the use of the proposed therapy to improve fertility in these women.;Secondary Objective: 1. Evaluation of the effect of metformin therapy on endometrial function. It will be tested by assessing the concentration of markers such as: cytokines, IGF, LIF, TGF-a, EGF, HB-EGF, VEGF, histamine, inhibin B, relaxin and insulin receptor in the tissue before and after treatment. 2. Transcriptome analysis of endometrial tissues (NGS) before and after metformin therapy. 3. Intratissue metabolomic profiling of steroids. The study will test whether treatment with metformin affects the intracrine production of steroid hormones in the endometrium. 4. Effect of metformin treatment on the regulation of oxidative stress in the endometrium. Additional information will also be provided by the analysis of the Quality of life (QoL) questionnaire of the patients undergoing the study and the analysis of menus combined with the DXA study.;Primary end point(s): Obtaining a pregnancy during the study.;Timepoint(s) of evaluation of this end point: Ater 57 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): .Evaluation of the effect of metformin therapy on endometrial function. It will be tested by assessing the concentration of markers such as: cytokines (interleukin-1 and 2), insulin-like growth factor (IGF), leukemia inhibitory factor (LIF), transforming growth factor alpha (TGF-a), epidermal growth factor (EGF), heparin-binding EGF-like growth factor (HB-EGF), vascular endothelial growth factor (VEGF), histamine, inhibin B, relaxin, and insulin receptor in tissue before and after treatment. 2. Transcriptome analysis of endometrial tissues using Next Generation Sequencing (NGS) technology before and after metformin therapy. The transcriptome will be examined, including the microRNA profile, which will allow to assess the mechanisms of metformin action and determine whether microRNAs as gene expression regulators can be diagnostic or predictive markers of endometrial dysfunction. 3. Intratissue metabolomic profiling of steroids. The study will test whether treatment with metformin affects the intracrine production of steroid hormones in the endometrium. 4. Effect of metformin treatment on the regulation of oxidative stress in the endometrium. In-depth analysis of molecular and cellular processes using multi-omics combined with clinical data will provide the necessary knowledge about the mechanisms of action of metformin, which may also be clinically applicable to both idiopathic female infertility and other conditions. Additional information will also be provided by the analysis of the Quality of life (QoL) questionnaire of the patients undergoing the study and the analysis of menus combined with the DXA study.;Timepoint(s) of evaluation of this end point: After 57 months | — |
Countries
Poland
Contacts
Public ContactMonika Zbucka-Kretowska
Medical University of Bialystok
Outcome results
None listed