Clinical trial NCT01572025: Dehydroepiandrosterone (DHEA) Intervention To Treat Ovarian Aging
Official title: Efficacy of Dehydroepiandrosterone to Overcome the Effect of Ovarian Aging - A Pilot Double Blinded Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infertility
Ovarian Aging
Diminished Ovarian Reserve (DOR)
Predicted Poor-responders
Lead sponsor: University of Nottingham
Sponsor class: OTHER
First posted: 2012-04-05
Enrollment: 60
Sex: FEMALE
Minimum age (years): 23
Maximum age (years): 48
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: * 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of oocytes retrieved
timeFrame: within 15 weeks after DHEA/Placebo supplementation
measure: Feasibility to conduct a large multicentre randomised controlled trial
timeFrame: with in 20 weeks of the research period (per participant)
Secondary outcomes:
measure: Oocyte quality (clinical and molecular markers)
timeFrame: The sample is collected at 14-16 weeks after recruitment and assessment is performed at one year.
measure: Aneuploidy rates in the immature oocytes and unfertilized oocytes using microarray technology
timeFrame: The sample is collected at 14-16 weeks after recruitment and assessment is performed at one year.
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham University Research and Treatment Unit in Reproduction (NURTURE)
state: Nottinghamshire
Study officials:
affiliation: Division of Obstetrics and Gynaecology, School of Clinical Sciences, University of Nottingham
name: Kannamannadiar Jayaprakasan, MRCOG,PhD.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nottingham
name: Bruce Campbell, PhD, DSc
role: STUDY_DIRECTOR
affiliation: University of Nottingham
name: Nick Raine-Fenning, MRCOG, PhD
role: STUDY_DIRECTOR
References:
citation: Jayaprakasan K, Narkwichean A, Maalouf WE, Campbell BK. Efficacy of dehydroepiandrosterone to overcome the effect of ovarian ageing (DITTO): a proof of principle randomised controlled trial protocol. BMJ Open. 2014 Oct 8;4(10):e005767. doi: 10.1136/bmjopen-2014-005767.