Effects of Dehydroepiandrosterone Supplementation on Cumulus Cells Gene Expression Under Controlled Ovarian Hyper-stimulation in Patients With Diminished Ovarian Reserve

Study Overview
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Brief Summary
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Diminished ovarian reserve (DOR) is one the challenge in the field of artificial reproductive technology (ART) while there is still no effective resolution of this disorder. In patents with DOR, the pregnancy rate is about only 2-4%. Eventually, patients with DOR turn to adapt children instead. In recent studies, dehydroepiandrosterone (DHEAS) supplement might play a role in reverse diminished ovarian reserve and improve the prognosis of ART. Cumulus cells, formed cumulus-oocyte complex (COC) with oocyte, play a important role in folliculogenesis, oocyte maturation, oocyte meiosis and ovulation. Growing evidences disclose there are crosstalks between oocyte and cumulus cells as paracrine regulations. Aberration the crosswalks between oocytes and cumulus cells would be associated with poor prognosis of folliculogenesis and further pregnancy outcomes. In patients under ovarian hyper-stimulation protocol, the assessment of cumulus cells might be reliable indicators of folliculogenesis, embryo development, pregnancy rate and pregnancy outcomes. These genes (indicators), such as Hyaluronan synthase（HAS2), Versican (VCAN), Thrombospondin 1 (THBS1), Runt-related transcription factor 2 (RUNX2), Chromobox homolog 3 (CBX3),Tripartite motif-containing 28 (TRIM28), B-cell lymphoma 2 (BCL2)，BCL2-associated X protein (BAX). This study was assess the gene expressions of cumulus cells after the DHEAS supplement in patients with DOR under ovarian hyper stimulation protocol.

Detailed Description
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This study was designed as a prospective case-control study to assess the gene expression of cumulus cells after DHEAS supplement. Patients with diminished ovarian reserve under ovarian hyper-stimulation protocol were evaluated at Kaoshiung Veteran General Hospital from January 1, 2013 through October 31, 2013. Approval for the study was obtained from the hospital's ethic committee, and informed consent was obtained from all patients (VGHKS13-CT11-17)

Official Title
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Effects of Dehydroepiandrosterone Supplementation on Cumulus Cells Gene Expression Under Controlled Ovarian Hyper-stimulation in Patients With Diminished Ovarian Reserve

Conditions
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Dehydroepiandrosterone, DHEAS, Gene Expression of Cumulus Cells., Ovarian Hyper-stimulation Protocol., Artificial Reproduction Technology.

Intervention / Treatment
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* Drug: Dehydroepiandrosterone (DHEAS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: DOR: antral follicle count (AFC) less than 5, AntiMullerian hormone (AMH) less than 1.0 ng/ml, and previous total retrieved oocyte less than 5. Normal Control: antral follicle count (AFC) equal to or more than 5, AntiMullerian hormone (AMH) equal to or more than 1.0 ng/ml, and previous total retrieved oocyte equal to or more than 5. Patient provided signed informed consent. Exclusion Criteria: Patient who has the allergic history or contraindication to DHEAS usage.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: DHEAS in DOR Group<br>Additional usage of DHEAS supplement in patients with DOR under ovarian hyper-stimulation protocol. | Drug: Dehydroepiandrosterone (DHEAS)<br> <br> * Other names: DHEAS;|
| Active Comparator: Normal Control<br>Patients under ovarian hyper-stimulation protocol. No DHEAS supplement. | Drug: Dehydroepiandrosterone (DHEAS)<br> <br> * Other names: DHEAS;|
| Active Comparator: Shame DOR Group<br>Patients with DOR under ovarian hyper-stimulation protocol. No DHEAS supplement. | Drug: Dehydroepiandrosterone (DHEAS)<br> <br> * Other names: DHEAS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene expressions of culumuls cells under ovarian hyper-stimulation protocol. | Assessment of gene expressions of cumulus cells, including Hyaluronan synthase (HAS2), Versican (VCAN), Thrombospondin 1(THBS1), Runt-related transcription factor 2 (RUNX2), Chromobox homolog 3 (CBX3), Tripartite motif-containing 28 (TRIM28), B-cell lymphoma 2 (BCL2), BCL2-associated X protein (BAX). | The 3 or 5 days after oocyte retrieval. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pregnancy outcomes were compared with diminished ovarian reserve and normal control groups after DHEAS supplement. | The successful pregnancy outcome is defined as intrauterine gestational sac with positive fetal heart activity on the sonogram. | 2 to 4 weeks after embryo transfer. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Artificial reproduction technology., Folliculogenesis., Oocyte maturation., Ovarian hyper-stimulation protocol., Dehydroepiandrosterone, DHEAS, Gene expression of cumulus cells.