Diminished Ovarian ReserveDOR-HIPPO-IVFNCT07658846
Hippo-Related Competing Endogenous RNA (ceRNA) Network Dysregulation and In Vitro Fertilization (IVF) Outcomes in Women With Diminished Ovarian Reserve
An observational study of Diminished Ovarian Reserve and Female Infertility, run by Assiut University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Diminished Ovarian Reserve, Female Infertility, In Vitro Fertilization
- How many people
- 70 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Aug 2026to 1 Oct 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
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.
Who may be able to join
- Women undergoing In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) cycles.
- Infertility duration of at least one year
- Primary or secondary infertility.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Egypt1 site
Faculty of Medicine, Assiut University
Asyut
Abeer Othman Fahmi Mohammed, 01099067741, abeerothman.1995@aun.edu.eg
About this study
Official title: 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.
Read the 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.
- 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
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Evaluation of the relationship between NEAT1 and miR-181a-5p expression levels.
Measured: 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
Assessment of correlations between miR-181a-5p and YAP1/CTGF expression.
Measured: 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
Measurement of IGF1 levels and their association with molecular markers.
Measured: At oocyte retrieval during the participant's IVF cycle (approximately 10-14 days after initiation of controlled ovarian stimulation).
Association With IVF Outcomes
Number of retrieved oocytes
Measured: Assessed on the day of oocyte retrieval (approximately 10-14 days after initiation of controlled ovarian stimulation)
Association With IVF Outcomes
Embryo development potential
Measured: Assessed at blastocyst evaluation, 5-6 days after fertilization
Association With IVF Outcomes
Oocyte quality
Measured: Assessed on the day of oocyte retrieval and fertilization assessment (within 0-1 day after oocyte retrieval)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2026
- Study start1 Aug 2026 (estimated)
- Primary completion1 Feb 2028 (estimated)
- Study completion1 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diminished Ovarian ReserveStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Abeer Othman Fahmi Mohammed, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07658846
- Sponsor's protocol ID
- DOR-Hippo-ceRNA-IVF-2026
- Acronym
- DOR-HIPPO-IVF
- Status last verified
- Jun 2026
- First submitted
- 13 Jun 2026
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Dysregulation of the Hippo-Related ceRNA Network and Its Impact on IVF Outcomes in Patients With Diminished Ovarian Reserve (DOR)
- ClinicalTrials.gov ID
- NCT07658846
- Acronym / sponsor ID
- DOR-HIPPO-IVF / DOR-Hippo-ceRNA-IVF-2026
- 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)
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Aug 2026 (estimated)
- Primary completion
- 1 Feb 2028 (estimated)
- Study completion
- 1 Oct 2028 (estimated)
- First posted
- 22 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (3 listed)
- Women undergoing In Vitro Fertilization (IVF) or Intracytoplasmic Sperm Injection (ICSI) cycles.
- Infertility duration of at least one year
- Primary or secondary infertility.
Key exclusion criteria (8 listed)
- Polycystic Ovary Syndrome (PCOS)
- Endometriosis.
- Ovarian tumors or malignancy.
- Severe systemic diseases affecting fertility.
- Metabolic syndrome.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
6 secondary outcomes
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Diminished Ovarian Reserve and Female Infertility, run by Assiut University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Abeer Othman Fahmi Mohammed (01099067741, abeerothman.1995@aun.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2026.