Clinical trial NCT01915186: Use of Dehydroepiandrosterone (DHEA) in Women With Normal and Poor Ovarian Reserve Undergoing IVF
Official title: A Randomized Controlled Trial on the Effect of Dehydroepiandrosterone (DHEA) Supplementation on Ovarian Reserve Markers, Response to a Standard Low Dose FSH Stimulation and IVF Cycle Outcomes in Patients With Normal and Poor Ovarian Reserve
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Female Infertility Due to Diminished Ovarian Reserve
Keywords: DHEA
Poor ovarian reserve
Normal ovarian reserve
In vitro fertilization treatment
Ovarian response
Pregnancy outcomes
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
First posted: 2013-08-02
Enrollment: 104
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The aim of the study is to evaluate the effect of DHEA supplement on ovarian reserve markers, ovarian response to gonadotrophins and cycle outcomes in patients with normal and poor ovarian reserve.

Study Hypotheses:

1. DHEA supplementation would improve markers of ovarian reserve and ovarian response to low dose FSH stimulation in both normal and poor responders
2. DHEA supplementation would improve IVF cycle outcomes

Detailed description: Consecutive patients attending subfertility clinic at the Department of Obstetrics and Gynaecology, Queen Mary Hospital who are scheduled for in-vitro fertilization (IVF) treatment will be recruited and written consent will be obtained.

Baseline assessment will be performed at early follicular phase (Day 2 or 3) with hormonal tests and ultrasound.

Subjects will be divided into two groups, the normal ovarian reserve group and the poor ovarian reserve group according to AFC. Poor ovarian reserve is defined as an AFC of less than 5, while normal ovarian reserve is defined as an AFC of 5 to 15 based on a previous study showing AFC being a good predictor of ovarian response (Tomas 1997). Subjects with normal ovarian reserve will be further subdivided into \<35 and \>/=35 years old while subjects with poor ovarian reserve will be further subdivided into first or subsequent cycles of IVF for subgroup analysis.

Subjects in both the normal and poor ovarian reserve group will be randomized according to a computer-generated randomization list in sealed envelopes to receive either DHEA at 25mg three times a day or placebo throughout the study period.

Any changes in hormonal profile and ovarian reserve will be assessed by the above-mentioned blood tests and pelvic ultrasound scans which will be repeated at early follicle phase (Day 2 or 3) in the two subsequent cycles.

After two months of DHEA/placebo treatment, the subjects will then be given a standard low dose ovarian stimulation with 75 IU intramuscular human menopausal gonadotrophin (HMG, Menogon®, Ferring Pharmaceuticals) daily for 7 days. Blood tests and pelvic ultrasound scan will be repeated after 7 days of stimulation (ie. on day 10 or 11).

Hormonal profile and ovarian reserve will be repeated in follicular phase (D2 or 3) in the subsequent cycle, where all patients will then be offered a cycle of IVF treatment using antagonist protocol based on our standard departmental regimen. Cycle characteristic and pregnancy outcomes will be compared.

Analysis of ovarian reserve markers, ovarian response and IVF outcomes would be performed.

Eligibility criteria: Inclusion Criteria:

* Indicated for IVF treatment according to our standard department protocol
* Age \< 40
* Regular menstrual cycles (21-35 days with \</= 4 days inter-cycle variation)
* AFC not more than 15

Exclusion Criteria:

* Previous chemotherapy or pelvic irradiation
* Polycystic ovarian syndrome or polycystic ovaries
* On hormonal supplementation for any indication at the time of recruitment (e.g. estrogen, testosterone or DHEA)

Primary outcomes:
measure: Antral follicle count
timeFrame: after 12 weeks of DHEA
Secondary outcomes:
measure: Change in Follicular stimulating hormone (FSH) and anti-Mullerian Hormone (AMH) following DHEA supplementation; post stimulation estradiol level and number of follicles > 10mm, IVF outcomes, hormonal profile of follicular fluid
timeFrame: after 12 weeks of DHEA
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: University of Hong Kong
Study officials:
References:
citation: Gleicher N, Barad DH. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR). Reprod Biol Endocrinol. 2011 May 17;9:67. doi: 10.1186/1477-7827-9-67.
citation: Yeung TW, Chai J, Li RH, Lee VC, Ho PC, Ng EH. A randomized, controlled, pilot trial on the effect of dehydroepiandrosterone on ovarian response markers, ovarian response, and in vitro fertilization outcomes in poor responders. Fertil Steril. 2014 Jul;102(1):108-115.e1. doi: 10.1016/j.fertnstert.2014.03.044. Epub 2014 May 3.