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

17 июня 2026 г. обновлено: 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.

Обзор исследования

Статус

Еще не набирают

Условия

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.

Тип исследования

Наблюдательный

Регистрация (Оцененный)

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Контакты исследования

Имя: Abeer Othman Fahmi Mohammed
Номер телефона: 01099067741
Электронная почта: abeerothman.1995@aun.edu.eg

Места учебы

Египет
- - Asyut, Египет
    - Faculty of medicine, Assiut university
    - Контакт:
      
      Abeer Othman Fahmi Mohammed
      
      Номер телефона: 01099067741
      
      Электронная почта: abeerothman.1995@aun.edu.eg

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

Взрослый

Принимает здоровых добровольцев

Нет

Метод выборки

Невероятностная выборка

Исследуемая популяция

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.

Описание

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.

Учебный план

В этом разделе представлена подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

Количество групп / когорт

Когорты и вмешательства

Группа / когорта
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

Что измеряет исследование?

Первичные показатели результатов

Мера результата	Мера Описание	Временное ограничение
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). Временное ограничение: 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).

Вторичные показатели результатов

Мера результата	Мера Описание	Временное ограничение
Association Between NEAT1 and miR-181a-5p Expression Временное ограничение: 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 Временное ограничение: 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 Временное ограничение: 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 Временное ограничение: 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 Временное ограничение: 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 Временное ограничение: 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)

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Assiut University

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Оцененный)

1 августа 2026 г.

Первичное завершение (Оцененный)

1 февраля 2028 г.

Завершение исследования (Оцененный)

1 октября 2028 г.

Даты регистрации исследования

Первый отправленный

13 июня 2026 г.

Впервые представлено, что соответствует критериям контроля качества

17 июня 2026 г.

Первый опубликованный (Действительный)

22 июня 2026 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)