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

June 17, 2026 updated by: Abeer Othman Fahmi Mohammed, Assiut University

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.

Study Overview

Status

Not yet recruiting

Conditions

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.

Study Type

Observational

Enrollment (Estimated)

70

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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.
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Assessment of gene and protein expression levels in follicular fluid-derived cells from women with Diminished Ovarian Reserve (DOR) compared with controls.
At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Evaluation of the relationship between NEAT1 and miR-181a-5p expression levels.
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).
Assessment of correlations between miR-181a-5p and YAP1/CTGF expression.
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).
Measurement of IGF1 levels and their association with molecular markers.
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)
Number of retrieved oocytes
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
Embryo development potential
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)
Oocyte quality
Assessed on the day of oocyte retrieval and fertilization assessment (within 0-1 day after oocyte retrieval)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2026

Primary Completion (Estimated)

February 1, 2028

Study Completion (Estimated)

October 1, 2028

Study Registration Dates

First Submitted

June 13, 2026

First Submitted That Met QC Criteria

June 17, 2026

First Posted (Actual)

June 22, 2026

Study Record Updates

Last Update Posted (Actual)

June 22, 2026

Last Update Submitted That Met QC Criteria

June 17, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DOR-Hippo-ceRNA-IVF-2026

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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