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Hippo-Related Competing Endogenous RNA (ceRNA) Network Dysregulation and In Vitro Fertilization (IVF) Outcomes in Women With Diminished Ovarian Reserve

Observational Diminished Ovarian Reserve Female Infertility In Vitro Fertilization

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
This is an observational study: the protocol does not assign a study treatment.
Who it may be relevant to
Registry conditions: Diminished Ovarian Reserve, Female Infertility, In Vitro Fertilization. Basic parameters: 18 years — 40 years · Female.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Egypt
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

Investigating the Dysregulation of the Hippo-Related ceRNA Network and Its Impact on IVF Outcomes in Patients With Diminished Ovarian Reserve (DOR)

Overview

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.

Primary outcome measures

  • 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). [Time frame: At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).]
Secondary outcome measures (6)
  • Association Between NEAT1 and miR-181a-5p Expression [Time frame: 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 [Time frame: 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 [Time frame: At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).]
  • Association With IVF Outcomes [Time frame: Assessed on the day of oocyte retrieval (approximately 10-14 days after initiation of controlled ovarian stimulation)]
  • Association With IVF Outcomes [Time frame: Assessed at blastocyst evaluation, 5-6 days after fertilization]
  • Association With IVF Outcomes [Time frame: Assessed on the day of oocyte retrieval and fertilization assessment (within 0-1 day after oocyte retrieval)]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model
Cohort

Study locations

Egypt · 1 center
  • Faculty of Medicine, Assiut University — Asyut

Identifiers

NCT: NCT07658846 · DOR-Hippo-ceRNA-IVF-2026

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗