Hippo-Related Competing Endogenous RNA (ceRNA) Network Dysregulation and In Vitro Fertilization (IVF) Outcomes in Women With Diminished Ovarian Reserve
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- Состояния в реестре: Diminished Ovarian Reserve, Female Infertility, In Vitro Fertilization. Базовые параметры: 18 лет — 40 лет · Женщины.
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Официальное название
Investigating the Dysregulation of the Hippo-Related ceRNA Network and Its Impact on IVF Outcomes in Patients With Diminished Ovarian Reserve (DOR)
Обзор
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.
Подробное описание
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.
Первичные конечные точки
- 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). [Срок оценки: At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).]
Вторичные конечные точки (6)
- Association Between NEAT1 and miR-181a-5p Expression [Срок оценки: At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).]
- Association Between miR-181a-5p and Hippo Pathway Components [Срок оценки: At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).]
- Insulin-Like Growth Factor 1 (IGF1) Levels in Follicular Fluid [Срок оценки: At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).]
- Association With IVF Outcomes [Срок оценки: Assessed on the day of oocyte retrieval (approximately 10-14 days after initiation of controlled ovarian stimulation)]
- Association With IVF Outcomes [Срок оценки: Assessed at blastocyst evaluation, 5-6 days after fertilization]
- Association With IVF Outcomes [Срок оценки: Assessed on the day of oocyte retrieval and fertilization assessment (within 0-1 day after oocyte retrieval)]
Критерии участия
Критерии включения
- Women undergoing In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) cycles.
- Infertility duration of at least one year
- Primary or secondary infertility.
Критерии исключения
- 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.
Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.
Здоровые добровольцы: Нет
Дизайн исследования
- Модель наблюдения
- Когортное
Центры проведения
Египет · 1 центр
- Faculty of Medicine, Assiut University — Asyut
Идентификаторы
NCT: NCT07658846 · DOR-Hippo-ceRNA-IVF-2026