Hippo-Related Competing Endogenous RNA (ceRNA) Network Dysregulation and In Vitro Fertilization (IVF) Outcomes in Women With Diminished Ovarian Reserve (DOR-HIPPO-IVF)
Investigating the Dysregulation of the Hippo-Related ceRNA Network and Its Impact on IVF Outcomes in Patients With Diminished Ovarian Reserve (DOR)
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.
Descripción general del estudio
Estado
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Abeer Othman Fahmi Mohammed
- Número de teléfono: 01099067741
- Correo electrónico: abeerothman.1995@aun.edu.eg
Ubicaciones de estudio
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Asyut, Egipto
- Faculty of medicine, Assiut university
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Contacto:
- Abeer Othman Fahmi Mohammed
- Número de teléfono: 01099067741
- Correo electrónico: abeerothman.1995@aun.edu.eg
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
Acepta Voluntarios Saludables
Método de muestreo
Población de estudio
Follicular fluid samples will be aspirated during ultrasound-guided oocyte retrieval procedures. Blood-contaminated samples will be excluded. Samples will be centrifuged to separate follicular fluid from cellular pellets.
Supernatants will be stored at -80°C for biochemical analysis. Cellular pellets will undergo ribonucleic acid (RNA) and protein extraction.
Total ribonucleic acid (RNA) extraction will be performed using TRIzol reagent followed by complementary deoxyribonucleic acid (cDNA) synthesis. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) will be used to measure NEAT1, miR-181a-5p, CTGF, and IGF1 expression levels.
YAP1 protein expression will be analyzed using Western blotting.
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
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Group 1: Control Group
Group 1: Control Group Women with normal ovarian reserve undergoing In Vitro Fertilization (IVF) due to non-ovarian causes of infertility such as male factor infertility or tubal factor infertility. |
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Group 2: DOR Group
Group 2: DOR Group Women diagnosed with diminished ovarian reserve according to at least two of the following criteria: Anti-Müllerian Hormone (AMH) ≤1.1 ng/mL Antral Follicle Count (AFC) ≤7 Basal Follicle-Stimulating Hormone (FSH) ≥10 IU/L |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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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).
Periodo de tiempo: At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).
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Assessment of gene and protein expression levels in follicular fluid-derived cells from women with Diminished Ovarian Reserve (DOR) compared with controls.
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At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Association Between NEAT1 and miR-181a-5p Expression
Periodo de tiempo: At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).
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Evaluation of the relationship between NEAT1 and miR-181a-5p expression levels.
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At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).
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Association Between miR-181a-5p and Hippo Pathway Components
Periodo de tiempo: At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).
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Assessment of correlations between miR-181a-5p and YAP1/CTGF expression.
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At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).
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Insulin-Like Growth Factor 1 (IGF1) Levels in Follicular Fluid
Periodo de tiempo: At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).
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Measurement of IGF1 levels and their association with molecular markers.
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At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).
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Association With IVF Outcomes
Periodo de tiempo: Assessed on the day of oocyte retrieval (approximately 10-14 days after initiation of controlled ovarian stimulation)
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Number of retrieved oocytes
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Assessed on the day of oocyte retrieval (approximately 10-14 days after initiation of controlled ovarian stimulation)
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Association With IVF Outcomes
Periodo de tiempo: Assessed at blastocyst evaluation, 5-6 days after fertilization
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Embryo development potential
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Assessed at blastocyst evaluation, 5-6 days after fertilization
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Association With IVF Outcomes
Periodo de tiempo: Assessed on the day of oocyte retrieval and fertilization assessment (within 0-1 day after oocyte retrieval)
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Oocyte quality
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Assessed on the day of oocyte retrieval and fertilization assessment (within 0-1 day after oocyte retrieval)
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- DOR-Hippo-ceRNA-IVF-2026
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
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