Follicular Fluid Exosome miRNA During Oocyte Maturation

Study Overview
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Brief Summary
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Folliculogenesis involves the recruitment of primordial follicles into a group of growing follicles in which eventually one follicle is selected, matured and ovulated. Complex endocrine and intra-ovarian paracrine interactions occur to create a changing intra-follicular hormonal milieu suitable for oocyte development. However, this oocyte developmental competence and to undergo fertilization and embryogenesis is impaired in aged women. Diminished ovarian function is generally attributed to decreased quantity and quality of oocytes and their surrounding granulosa cells during ovarian aging, although the underlying mechanisms remain unclear. The aim of the study is to investigate the miRNA in (follicular fluid) FF exosome in young and aged women and their relationship to egg maturation.

Detailed Description
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In recent decades, demographic and socioeconomic factors have resulted in marked changes in human society that include postponement of child bearing and a subsequent rise in mean age at first childbirth. Aged women have more reproductive problems (including menstrual irregulation and decreased ovarian reserve as reflected by reduced anti-mullerian hormone (AMH)) and their oocytes are often of lower quality when compared to younger women. Folliculogenesis involves the recruitment of primordial follicles into a group of growing follicles in which eventually one follicle is selected, matured and ovulated. Complex endocrine and intra-ovarian paracrine interactions occur to create a changing intra-follicular hormonal milieu suitable for oocyte development. However, this oocyte developmental competence, defined as the ability of the oocyte to complete follicular development, and to undergo fertilization and embryogenesis is impaired in aged women. Age-related decline in female fertility is mainly driven by ovarian aging, or diminished ovarian function associated with age. Diminished ovarian function is generally attributed to decreased quantity and quality of oocytes and their surrounding granulosa cells during ovarian aging, although the underlying mechanisms remain unclear. Transcription studies have suggested indirectly that some age-related changes in oocyte gene expression and cell to cell communication may involve epigenetic machinery. Ovarian follicle may be one of the best models in human for exosome study considering the role of the granulosa cells and follicular fluid for oocyte maturation. In the ovarian follicle, follicular fluid (FF) exosome may play an important mediated communication role between the oocyte and surrounding granulosa cells. The aim of the study is to investigate the miRNA in (follicular fluid) FF exosome in young and aged women and their relationship to egg maturation.

Official Title
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Investigation of Follicular Fluid Exosome miRNA in Young and Aged Women During Oocyte Maturation

Conditions
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Oocyte Maturation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 20 to 45; BMI > 19 & < 35; Women who is planning to perform invitro fertilization (IVF) together with intracytoplasmic sperm injection (ICSI) for their fertility problems Exclusion Criteria: Positive pregnancy test before taking study medications; Women with BMI>35 kg/m2; Women with known chromosomal translocation, recurrent abortions or those carrying Fragile X; Women with endometriosis

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RNA-sequencing | 1) To identify for the first time FF exosome miRNAs in mature and immature follicles in young and aged women by RNA-sequencing (RNA-seq). | through study completion, an average of 2 years | 
| quantitative real-time polymerase chain reaction | 2) To verify the identified FF exosome miRNAs in mature and immature follicles in young and aged women and investigate their expression in the corresponding granulosa cells by quantitative real-time polymerase chain reaction (qRT-PCR). | through study completion, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fertilization and pregnancy rate | 3) To observe the effect of the identified specific FF exosome miRNAs on oocyte maturation (by IVM) and assess the association of the miRNAs on fertilization and pregnancy rate. | through study completion, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oocyte maturation, in vitro maturation