Premature Ovarian Failure
Conditions
Keywords
DHEA, POF, Pregnancy, Ovarian Failure, Otherwise Unexplained infertility, Ovarian aging
Brief summary
The experimental focus of this project is on the interaction of DHEA treatment on pregnancy in women with open tubes, fertile male partners and evidence of premature ovarian failure.
Detailed description
Recruitment: * New patients presenting for Donor egg cycles * Possible print, magazine or Radio advertisement Experimental plan: 1. Informed consent 2. Baseline studies * Antral follicle counts * Serum FSH, LH, E2, Prog, DHEA, DHEAS, testosterone, AMH, Fragile X 3. Randomization * 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 treatment * Compare antral follicle counts across cycles between groups * Compare possible androgen related effects * Power considerations: * Power assumptions: alpha 0.05; 80% power Spontaneous Pregnancy rate for POF is less than 1% per 3 months Intervention will improve pregnancy rate to 10% per 3 months. Patients will be treated for 3 cycles. Require 100 patients to complete treatment in each group. Allow for 20% dropout will need 120 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 3 months and possible natural continued loss of fertility * Informed consent issues
Interventions
DIETARY_SUPPLEMENTDehydroepiandrosterone
25 mg PO TID
DIETARY_SUPPLEMENTPlacebo
Blinded placebo
Sponsors
David H. Barad
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
* \>= 1 year of infertility * \>21 and \<40 years old * Normal HSG * Normal Semen analysis (Count \>= 20 million/ motility \> 50%/ Kruger morph \> 14%. * Absent menses * Willingness to sign informed consent for study randomization * Willingness to participate in 3 months of treatment.
Exclusion criteria
* Abnormal semen analysis * Abnormal HSG * 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 three months of this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Live Birth | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Endocrine Effects | 12 months |
| Androgen Side Effects | 12 months |
| Clinical Pregnancy | 12 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dehydroepiandrosterone 25 mg Tid po Dehydroepiandrosterone 25 mg tid po | 3 |
| Blinded Placebo Blinded placebo | 2 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Blinded Placebo | Dehydroepiandrosterone 25 mg Tid po | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 5 Participants |
| Age Continuous | 38 years STANDARD_DEVIATION 3 | 38 years STANDARD_DEVIATION 3 | 38 years STANDARD_DEVIATION 3 |
| Region of Enrollment United States | 2 participants | 3 participants | 5 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Live Birth
Time frame: 24 months
Primary
Live Birth
Live Birth outcome compared between DHEA active treatment and Placebo
Time frame: 9 months
Population: This study was closed for futility because of difficulty finding patients willing to undergo randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| DHEA | Live Birth | 0 participants |
| Placebo | Live Birth | 0 participants |
Secondary
Androgen Side Effects
Time frame: 12 months
Secondary
Clinical Pregnancy
Time frame: 12 months
Secondary
Endocrine Effects
Time frame: 12 months