Dehydroepiandrosterone (DHEA) Intervention To Treat Ovarian Aging

Study Overview
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Brief Summary
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To test the hypothesis that supplementation of DHEA for at least twelve weeks prior to and during ovarian stimulation increases oocyte quantity (number of oocytes retrieved) and oocyte quality (clinical pregnancy rates and molecular markers) following IVF and IVF/ICSI treatment. To evaluate the feasibility of conducting a large multicentre trial

Detailed Description
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The purpose of this study is to evaluate the role of DHEA in counteracting the effects of ovarian ageing in an in-vitro fertilization (IVF) model. The study will examine whether the use of DHEA could improve clinical pregnancy rates following IVF treatment in women predicted to have aged ovaries by increasing oocyte quantity (ovarian response to gonadotrophins) and/ or by improving oocyte quality. The oocyte quality will be assessed by morphological and molecular markers. This study will provide a mechanistic framework for translational research on mechanisms of ovarian ageing and drug interventions to slow down the ovarian ageing process and subsequent adverse physical and psychological consequences. Further, the data that will be produced from this research will have the potential to influence clinical practice in fertility clinics worldwide.

Official Title
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Efficacy of Dehydroepiandrosterone to Overcome the Effect of Ovarian Aging - A Pilot Double Blinded Randomised Controlled Trial

Conditions
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Infertility, Ovarian Aging, Diminished Ovarian Reserve (DOR), Predicted Poor-responders

Intervention / Treatment
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* Drug: Dehydroepiandrosterone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged above 23 years with diminished ovarian reserve (predicted to be poor-responder), defined as antral follicle count <10 and/or Anti-Mullerian hormone <5pmol/L Women undergoing IVF and IVF/ICSI treatment Women must have a regular spontaneous menstrual cycle of 21 - 35 days Exclusion Criteria: Women with BMI >35 Kg/M2 Women with a single ovary Women with untreated hydrosalpinx/ submucous fibroid/ endometrial polyp at the start of treatment Women with any history of seizure disorders Women with previous participation in this trial in an earlier treatment cycle Women with any known endocrine disorders such as congenital adrenal hyperplasia, thyroid diseases, hyperprolactinemia Known allergy to DHEA Diabetic women on insulin as insulin lowers DHEA levels and might reduce the effectiveness of DHEA supplements.

Ages Eligible for Study
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Minimum Age: 23 Years
Maximum Age: 48 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DHEA supplementation<br> | Drug: Dehydroepiandrosterone<br>* Dehydroepiandrosterone (DHEA)(St Mary's Pharmaceutical Unit Cardiff and Vale) DHEA 75 mg capsule. 1 capsule taken once daily for at least 12 weeks prior commencing ovarian stimulation protocol : Stimulation protocol standard long down-regulation protocol, using human menopausal gonadotropin (HMG)<br>|
| Placebo Comparator: Control<br> | Drug: Placebo<br>* Matched Placebo containing no active ingredient. 1 capsule taken once daily for at least 12 weeks prior commencing ovarian stimulation protocol : Stimulation protocol standard long down-regulation protocol, using human menopausal gonadotropin (HMG)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of oocytes retrieved | Oocytes retrieved within 15 weeks after DHEA/placebo supplementations. | within 15 weeks after DHEA/Placebo supplementation | 
| Feasibility to conduct a large multicentre randomised controlled trial | Feasibility is evaluated by assessing recruitment rates and compliance of the recruited participants with DHEA/ placebo intake and follow up rates | with in 20 weeks of the research period (per participant) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oocyte quality (clinical and molecular markers) | Clinical pregnancy rates (Pregnancy rate determined at week 5 to 7 after embryo transfer). Molecular markers of oocyte quality as assessed by expression of cumulus cell molecular markers of oocyte competence and also by assessing energy consumption (pyruvate, lactate and glucose utilization) from the media by the oocytes and embryos (nutritional finger printing) | The sample is collected at 14-16 weeks after recruitment and assessment is performed at one year. | 
| Aneuploidy rates in the immature oocytes and unfertilized oocytes using microarray technology |  | The sample is collected at 14-16 weeks after recruitment and assessment is performed at one year. |