Clinical trial NCT00650754: Study of Oral Dehydroepiandrosterone(DHEA) to Treat Previously Unexplained Infertility
Official title: A Randomized Double Blinded Trail of DHEA Supplementation for Treatment of Couples With Normal Hysterosalpingogram and Normal Semen Analysis and Evidence of Premature Ovarian Aging (POA).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Primary Ovarian Insufficiency
Unexplained Infertility
Keywords: DHEA
Pregnancy
Lead sponsor: Center for Human Reproduction
Sponsor class: OTHER
First posted: 2008-04-02
Enrollment: 35
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 37
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The experimental focus of this project is on the interaction of DHEA treatment on pregnancy in women with otherwise unexplained infertility and evidence of premature ovarian aging (POA).

Detailed description: Recruitment:

Eligible patients will be recruited by advertising on the web and in newspaper. We will screen women under 38 years old with regular menstrual cycles and more than one year of infertility.

Experimental plan:

1. Informed consent
2. Baseline studies

   * Antral follicle counts on Day 2 - 3 of cycle
   * Day 3 Serum FSH, LH, E2, Prog, DHEA, DHEAS, testosterone, AMH, Fragile X
3. Randomization for pretreatment

   * Group A: DHEA (25 mg three times per day)
   * Group B: Placebo
4. Monitoring during treatment

   * All participants will have:
   * USG for follicle measurement
   * Repeat serum, FSH, E2, DHEA, DHEAS, testosterone, AMH monthly during treatment.
   * Physical examination
   * Completion of study questionnaire regarding possible androgen effects of treatment
5. Analysis plan:

   * Primary Outcome
   * Pregnancy
   * Pregnancy rates will be compared using logistic regression with age and pre-treatment AMH as covariates.
   * Secondary Outcomes
   * Endocrine Factors
   * Androgen side effects
   * Primary analysis. We will perform a factorial ANOVA for the two pretreatment factors DHEA and Placebo. Baseline AMH and age as main covariates
   * Secondary analysis.
   * Examine rate of change of estradiol and other endocrine response over the four cycles of pretreatment
   * Compare antral follicle counts across pretreatment cycles between groups
   * Compare possible androgen related effects
   * Power considerations:
   * Power assumptions: alpha 0.05; 80% power
   * Pregnancy rate for unexplained infertility is 2% per cycle.
   * Intervention will improve pregnancy rate to 5% per cycle.
   * Patients will be treated for 8 cycles.
   * Cumulative pregnancy rate for control patients - 13%
   * Cumulative pregnancy rate for Treated patients - 30%
   * Require 91 patients to complete treatment in each group.
   * Allow for 20% dropout ( 91\* 1.2) will need 109 patients randomized to each group.
   * Randomization:

Randomization will be by permuted blocks in order to maintain an even distribution among the groups (because of the small numbers of participants)

* Human subjects issues
* Potential risks associated with DHEA use
* Potential risk of delay of treatment for 8 months and possible natural continued loss of fertility
* Informed consent issues

Eligibility criteria: Inclusion Criteria:

* \>= 1 year of infertility
* \< 38 years old
* Normal HSG
* Normal Semen analysis (Count \>= 20 million/ motility \> 50%/ Kruger morph \> 14%.
* Regular menses
* Willingness to sign informed consent for study randomization
* Willingness to participate in 8 months of non-IVF will he him treatment.

Exclusion Criteria:

* Abnormal semen analysis
* Abnormal HSG
* Baseline FSH/E2 within normal age specific criteria
* Medical condition that would contraindicate pregnancy, ovulation induction or general anesthesia
* Family history of significant genetic disease, or factor V leiden thrombophilia
* Inability to present for monitoring visits
* Inability to follow medication instruction
* Desire to undergo other fertility treatments before completing eight months of this trial

Primary outcomes:
measure: Live Birth
timeFrame: 24 months
Secondary outcomes:
measure: Endocrine effects
timeFrame: 12 months
measure: Androgen side effects
timeFrame: 12 months
measure: Clinical Pregnancy
timeFrame: 12 months
Other outcomes:
Locations:
city: New York
country: United States
facility: Center for Human Reproduction
state: New York
Study officials:
affiliation: Center for Human Reproduction
name: David Barad, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for Human Reproduction
name: Norbert Gleicher, MD
role: STUDY_CHAIR
References: