Failure to recruit designed nuimebrt of subjects

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).

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

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