The Effect of a Higher Dose of Dehydroepiandrosterone (DHEA) Supplementation in Poor Responders (DHEA)

November 16, 2015 updated by: ShangHai Ji Ai Genetics & IVF Institute

The Effect of a Higher Dose of Dehydroepiandrosterone (DHEA) Supplementation on the Number of Oocytes Obtained During IVF in Poor Ovarian Responders

The supplementation of Dehydroepiandrosterone (DHEA) has been used in some centers for patients with previous poor ovarian reserve and response in an attempt to improve pregnancy outcomes. However, there still has controversy on the clinical effect on the 75mg/d for the use,especially in Asian people. Whether the double dosage of DHEA in patients with poor ovarian reserve and response in China can improve the IVF outcome with little side effect is unknown.

The aim of this randomized controlled study is to compare the effect of a higher dose (150mg daily) and a standard dose (75mg daily) of DHEA on the number of oocytes obtained in poor ovarian responders. The effect of DHEA action on the cumulus cells will be examined.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Consecutive infertile women attending the subfertility clinic at Shang Hai Ji Ai Genetics &IVF Institute for IVF treatment will be approached. Those fulfilling the selection criteria stated below would be recruited and a written consent will be obtained after detailed explanation and counseling.

Poor ovarian responders are defined according to the Bologna criteria fulfilling 2 out of 3 of the following:

(i) Advanced maternal age (>/= 40) or any other genetic or acquired risk factor for poor ovarian response(POR); (ii) Previous poor ovarian response (POR) (</= 3 oocytes with a conventional stimulation protocol using at least 150 international units (IU) gonadotrophins per day) (iii) Abnormal ovarian reserve test [i.e. antral follicle count (AFC) < 5-7 or antimüllerian hormone (AMH) < 0.5 - 1.1ng/ml]

Alternatively, two episodes of POR after maximal stimulation are sufficient to define a patient as poor responder in the absence of advanced maternal age or abnormal ovarian reserve test(ORT).

Baseline assessment will be performed at early follicular phase (Day 2 or 3) at recruitment. Patient characteristics including age, Body Mass Index (BMI), and smoking status would be recorded and blood test including follicular stimulating hormone (FSH), estradiol (E2), testosterone, DHEA-S, full blood count, renal and liver function test would be checked. Pelvic scan will be performed to assess the total AFC and total ovarian volume.

Subjects will be randomized divided into two groups:

  1. Standard dose group: Subjects will take DHEA (Lab Hercules™) 25mg three times a day for 12 weeks prior to the start of IVF treatment till the day of egg collection.
  2. High dose group: Subjects will taking DHEA (Lab Hercules™) 50mg three times a day for 12 weeks prior to the start of IVF treatment till the day of egg collection.

Hormonal profile, ultrasound assessment, full blood count, renal and liver function test will be repeated in follicular phase (D2 or 3) of every month or cycle followed by a IVF treatment using antagonist protocol based on our standard departmental regimen. The human menopausal gonadotropin (hMG) injections were started at 300 international units (IU) for 2 days followed by 300 international units (IU) daily. Improvement of ovarian reserve markers would be assessed by the change in serum AMH between the time of recruitment and that after 6 and 12 weeks of DHEA. Cycle characteristics including the dose of gonadotrophins use, duration of stimulation, number of oocytes obtained, number of fertilized embryos and good quality embryos will be recorded and follicular fluid will be saved for hormonal profiles.

Statistics

  1. Statistical tests

    Statistical comparisons will be performed according to the intention to treat principle by Student t test or Fisher's exact tests for normally distributed data and Mann-Whitney test for skewed data. Chi-square test would be used for binary variables. Statistical analyses will be performed using the Statistical Package for (the) Social Sciences (SPSS) software and a P-value of 0.05 would be considered statistically significant. Linear regression analysis / logistic regression analysis curve would be used to evaluate the age, BMI, smoking, FSH, E2, AMH, testosterone, DHEA-S, AFC, ovarian volume and duration of DHEA use for the prediction of improved ovarian reserve after DHEA supplementation.

  2. Sample size estimation

The number of oocytes retrieved will be used as the primary outcome of the study. Based on our own database for patients undergoing IVF treatment, the mean oocytes obtained was 2.7 with a standard deviation (SD) of 1.4. Assuming an increase of oocytes obtained by 1.0 to be clinically significant, 18 subjects in each arm would be required to achieve a test of significance of 0.05 and a power of 0.8. Considering possible dropouts, we aim at recruiting 18 patients in each arm, i.e. 36 patients.

In order to compare one of the secondary outcome -- AMH (which has more relevance on the effect of ovarian response) with adequate power, based on our own database for patients undergoing IVF treatment, the mean AMH of the group with poor ovarian reserve is 0.8 with a SD of 0.6. Assuming an increase of number of oocyte retrieved by 0.5 to be clinically significant, 25 subjects in each arm would be required to achieve a test of significance of 0.01 and a power of 0.9. Totally 50 patients.

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shang Hai, Shanghai, China, 200011
        • Ji Ai Genetics and IVF center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

22 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. age<45 years,
  2. subfertility >1 year, and
  3. A previous POR (≤3 oocytes with a conventional stimulation protocol of at least 150 IU FSH per day); or
  4. An abnormal ovarian reserve test (i.e. AFC ≤5-7 follicles or AMH ≤0.5-1.1 ng/ml).

Exclusion Criteria:

Patients were excluded if they:

  1. had a history of ovarian cystectomy or oophorectomy,
  2. had received cytotoxic chemotherapy,
  3. had received pelvic irradiation, or
  4. had a history of taking testosterone or DHEA supplementation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: High dose group
dehydroepiandrosterone,DHEA,capsule, 50mg/capsule, one capsule t.i.d..
Drug: dehydroepiandrosterone
high dose group treatment represent for 50mg t.i.d and standard dose group represents for normal treatment with 25mg t.i.d. Each patients in these two group will take one capsule each time and three times a day for three months before entering into IVF cycles.
Other Names:
  • DHEA (Lab Hercules™)
Experimental: Standard dose group
dehydroepiandrosterone,DHEA, capsule, 25mg/capsule, one capsule t.i.d.
Drug: dehydroepiandrosterone
high dose group treatment represent for 50mg t.i.d and standard dose group represents for normal treatment with 25mg t.i.d. Each patients in these two group will take one capsule each time and three times a day for three months before entering into IVF cycles.
Other Names:
  • DHEA (Lab Hercules™)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of oocytes obtained
Time Frame: up to 12 weeks
After 12 weeks treatment,the change of the number of oocytes obtained from the IVF cycle will be detected among the higher dose group ,normal dose group and placebo group
up to 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Antral follicle count (AFC)
Time Frame: baseline and 12 weeks
9-10mm follicles
baseline and 12 weeks
Follicle stimulating hormone (FSH) levels
Time Frame: baseline and 12 weeks
The change of FSH levels in the three groups.
baseline and 12 weeks
Estrogen 2 (E2)
Time Frame: baseline and 12 weeks
Serum and follicular E2 levels
baseline and 12 weeks
The number of follicles>10mm
Time Frame: up to 12 weeeks
The number of follicles>10mm represent for the ovarian reserve and response
up to 12 weeeks
Antimüllerian hormone ( AMH ) level
Time Frame: baseline and 12 weeks
The change of AMH levels in serum and follicular fluid
baseline and 12 weeks
testosterone
Time Frame: baseline and 12 weeks
baseline and 12 weeks
Dehydroepiandrosterone-Sulfide (DHEA-S)
Time Frame: baseline and 12 weeks
baseline and 12 weeks
insulin-like growth factor-1 (IGF-1)
Time Frame: baseline and 12 weeks
baseline and 12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of mature oocytes obtained
Time Frame: up to 12 weeks
up to 12 weeks
Pregnancy rate
Time Frame: 2 weeks after transfer
The rate of clinical pregnancy and ongoing pregnancy
2 weeks after transfer
the numbers of fertilized embryos
Time Frame: up to 12 weeks
up to 12 weeks
the numbers of cleaved embryos
Time Frame: up to 12 weeks
up to 12 weeks
the numbers of transferred embryos
Time Frame: up to 12 weeks
up to 12 weeks
the numbers of top-quality embryos.
Time Frame: up to 12 weeks
top-quality embryos are represented for >7cell on Day 3 and the fragments <20%
up to 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ShangHai Ji Ai Genetics & IVF Institute

Investigators

  • Study Chair: Xiao Xi Sun, PHD,MD, Shang Hai JIAi Genetics & IVF center
  • Principal Investigator: Jing Fu, MD, Shang Hai JIAi Genetics & IVF center
  • Study Director: Ying Su Liu, PHD,MD, Shang Hai JIAi Genetics & IVF center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2014

Primary Completion (Anticipated)

December 1, 2015

Study Completion (Anticipated)

December 1, 2016

Study Registration Dates

First Submitted

January 17, 2015

First Submitted That Met QC Criteria

February 2, 2015

First Posted (Estimate)

February 6, 2015

Study Record Updates

Last Update Posted (Estimate)

November 17, 2015

Last Update Submitted That Met QC Criteria

November 16, 2015

Last Verified

November 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JIAIE2014-03

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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