Diminished Ovarian Reserve, Female Infertility, In Vitro Fertilization
Conditions
Keywords
Diminished Ovarian Reserve (DOR), In Vitro Fertilization (IVF), Hippo Signaling Pathway, Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), microRNA-181a-5p, Yes-Associated Protein 1 (YAP1), Connective Tissue Growth Factor (CTGF), Insulin-Like Growth Factor 1 (IGF1), Follicular Fluid
Brief summary
Diminished Ovarian Reserve (DOR) is an important cause of female infertility and is associated with poor ovarian response and lower pregnancy rates during In Vitro Fertilization (IVF). The molecular mechanisms underlying impaired follicular development in DOR remain incompletely understood. Increasing evidence suggests that non-coding RNAs and components of the Hippo signaling pathway play important roles in granulosa cell proliferation, apoptosis, and follicular development. This prospective observational cohort study aims to investigate the expression of the long non-coding RNA (lncRNA) Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), microRNA (miRNA)-181a-5p, Hippo pathway components including Yes-Associated Protein 1 (YAP1) and Connective Tissue Growth Factor (CTGF), and Insulin-Like Growth Factor 1 (IGF1) in follicular fluid-derived cells from women with DOR undergoing IVF compared with women with normal ovarian reserve. The study will also evaluate relationships among these molecular markers and IVF outcomes, including oocyte quality, number of retrieved oocytes, and embryo developmental potential.
Detailed description
Infertility affects a significant proportion of reproductive-aged couples worldwide, and female infertility contributes substantially to these cases. Diminished ovarian reserve (DOR) is characterized by reduced quantity and quality of ovarian follicles and is associated with impaired oocyte competence and reduced success rates during assisted reproductive technologies. Recent evidence highlights the importance of the Hippo signaling pathway in ovarian physiology and folliculogenesis. Yes-Associated Protein 1 (YAP1), a major downstream effector of Hippo signaling, regulates granulosa cell proliferation and survival. Dysregulation of YAP1 and its downstream target Connective Tissue Growth Factor (CTGF) may contribute to abnormal follicular development and ovarian dysfunction. Non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have emerged as important regulators of ovarian function. Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) has been implicated in granulosa cell proliferation and ovarian disorders through its function as a competing endogenous RNA (ceRNA). miR-181a-5p has been shown to regulate cell proliferation and apoptosis and may target YAP1 expression. This study will investigate the proposed NEAT1/miR-181a-5p/Hippo signaling regulatory axis in women with DOR undergoing IVF treatment. Follicular fluid-derived cells and follicular fluid samples will be analyzed for expression of NEAT1, miR-181a-5p, YAP1, CTGF, and IGF1. Associations between these biomarkers and IVF outcomes will also be evaluated.
Interventions
None listed
Sponsors
Assiut University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Women undergoing In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) cycles. * Infertility duration of at least one year * Primary or secondary infertility.
Exclusion criteria
* Polycystic Ovary Syndrome (PCOS) * Endometriosis. * Ovarian tumors or malignancy. * Severe systemic diseases affecting fertility. * Metabolic syndrome. * Connective tissue disorders. * Hormonal therapy within the last three months. * Refusal to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Expression levels of Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), microRNA-181a-5p (miR-181a-5p), Yes-Associated Protein 1 (YAP1), and Connective Tissue Growth Factor (CTGF). | At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation). | Assessment of gene and protein expression levels in follicular fluid-derived cells from women with Diminished Ovarian Reserve (DOR) compared with controls. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Association Between NEAT1 and miR-181a-5p Expression | At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation). | Evaluation of the relationship between NEAT1 and miR-181a-5p expression levels. |
| Association Between miR-181a-5p and Hippo Pathway Components | At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation). | Assessment of correlations between miR-181a-5p and YAP1/CTGF expression. |
| Insulin-Like Growth Factor 1 (IGF1) Levels in Follicular Fluid | At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation). | Measurement of IGF1 levels and their association with molecular markers. |
| Association With IVF Outcomes | Assessed on the day of oocyte retrieval (approximately 10-14 days after initiation of controlled ovarian stimulation) | Number of retrieved oocytes |
Countries
Egypt
Contacts
CONTACTAbeer Othman Fahmi Mohammed
Outcome results
None listed