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

NCT07658846 | Not Yet Recruiting

• 1 other identifier: DOR-Hippo-ceRNA-IVF-2026
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Diminished Ovarian Reserve; Female Infertility; In Vitro Fertilization

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

Outcome Measures

Primary Outcomes (1)

• 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).

  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 Outcomes (6)

• 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).

• 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).

• 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).

• Association With IVF Outcomes

  Assessed on the day of oocyte retrieval (approximately 10-14 days after initiation of controlled ovarian stimulation)

• Association With IVF Outcomes

  Assessed at blastocyst evaluation, 5-6 days after fertilization

Study Arms (2)

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

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

• Women undergoing In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) cycles.
• Infertility duration of at least one year
• Primary or secondary infertility.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Assiut University: lead

Study Sites (1)

Faculty of Medicine, Assiut University

Asyut, Egypt

Location

Biospecimen

Retention: SAMPLES WITH DNA

Follicular fluid samples and follicular fluid-derived cellular pellets collected during oocyte retrieval procedures for molecular analysis.

MeSH Terms

Conditions

Infertility, Female

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Central Study Contacts

Abeer Othman Fahmi Mohammed

CONTACT

01099067741; abeerothman.1995@aun.edu.eg

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Lecturer of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University

Study Record Dates

• First Submitted: June 13, 2026
• First Posted: June 22, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): October 1, 2028
• Last Updated: June 22, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)