Effect of Testosterone Treatment on Embryo Quality
|Primary Ovarian Insufficiency Female Infertility Due to Diminished Ovarian Reserve||Drug: Testosterone cream (0.5mg per gram) Dietary Supplement: DHEA Drug: Placebo||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized Double Blind Control Trial of Transdermal Testosterone Supplementation vs Placebo on Follicular Development and Atresia, Oocyte and Embryo Quality Among Women With Diminished Ovarian Reserve Undergoing in Vitro Fertilization|
- Clinical and Ongoing Pregnancy [ Time Frame: 8 weeks post treatment initiation ]Clinical pregnancy is defined as the presence of a viable gestational sac visible in the uterus 4 weeks after embryo transfer. Clinical ongoing pregnancy is defined as intrauterine pregnancy with evidence of an active fetal heart at 6 weeks after embryo transfer.
- Measures of Atresia [ Time Frame: 8 weeks after intervention initiation ]
- Follicular fluid will be collected separately for the first 5 follicles aspirated that are at least 18mm diameter for each patient.
- Granulosa cell counts will be performed on each follicle fluid. Granulosa cell counts of <10,000 per follicle will be considered atretic.
- Aliquots of follicular fluid will be analyzed for Testosterone, androstenedoine and estradiol using standard immuno assay. Healthy follicles should be capable of metabolizing testosterone to estradiol and should have a higher concentration estradiol (in nmol/ml) compared to testosterone
- Oocytes number [ Time Frame: 8 weeks after initiation of intervention ]The number of oocytes retrieved at oocyte retrieval for in-vitro fertilization will be compared between the treatment group and placebo.
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||December 2018|
|Estimated Primary Completion Date:||June 2018 (Final data collection date for primary outcome measure)|
Active Comparator: DHEA+Testosterone
These patients will be administered the testosterone cream along with standard DHEA supplements
Drug: Testosterone cream (0.5mg per gram)
Testosterone cream 2 gms per day applied transdermally to the left wrist to deliver 1.mg daily dose with estimated absorption of 100 ug per day testosterone
Other Name: TestosteroneDietary Supplement: DHEA
DHEA 25mg tid
Other Name: Dehydroepiandrosterone
Placebo Comparator: DHEA+Placebo
These patients will receive the placebo cream along with her DHEA supplements. In other words, no testosterone will be administered.
Dietary Supplement: DHEA
DHEA 25mg tid
Other Name: DehydroepiandrosteroneDrug: Placebo
Carrier cream without added testosterone in the identical type of pump
Other Name: Carrier cream without added testosterone
At CHR the investigators have been using DHEA supplementation to improve ovarian response to ovulation induction for in vitro fertilization for about five years (Barad, Brill et al. 2007; Barad, Weghofer et al .2009; Gleicher, Ryan et al. 2009; Gleicher, Weghofer et al. 2010; Gleicher and Barad 2011). Our views on the effect of androgens on the follicular environment have recently been reviewed (Gleicher, Weghofer et al. 2011). A recent analysis of androgen metabolites of DHEA in our patients suggested that women who successfully respond to DHEA supplementation with increased egg production and clinical pregnancy had testosterone above the normal median values for reproductive age women. There also appears to be a cohort of women who did not respond to DHEA and who had very low serum testosterone. The investigators decided to investigate if supplementing those women with testosterone to the normal female range would improve ovarian function and possibly increase pregnancy rates.
Recruitment & Experimental Plan
- A baseline blood draw following completion of 6 weeks of DHEA supplementation will determine eligibility for the study. The baseline blood determinations are part of the standard pre cycle screening at CHR for all patients.
- After signing informed consent subjects will be randomly assigned to either active testosterone cream treatment or placebo.
- Active treatment will consist of a testosterone delivery system that will deliver transdermal testosterone cream(0.5 mg per gram of cream.) The cream and placebo cream will be compounded by Metro Drugs (New York, NY) and dispensed in calibrated pump that will deliver one gram of cream per stroke. Transdermal absorption is about 10% so 2 grams (1.0 mg) per day applied to the skin will deliver about 100 ug per day. In preliminary analysis we have determined that a 2 gram dose of this preparation will raise total testosterone to our target range of between 50 and 100 ng/dL.
- The dose of testosterone cream will be 2 grams of cream per day applied to the left inner forearm. The study medication will continue to be applied for 6 weeks.
- All patients with evidence of diminished ovarian reserve in our practice are treated with DHEA. Thus, patients in this study will be receiving DHEA + testosterone or DHEA + Placebo. Patients who achieve a level of serum testosterone in the desired range using DHEA alone will not be eligible for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01662466
|Contact: Jolanta Tapper, MD MS||212 994-4400 ext 4406||jtapper@theCHR.com|
|United States, New York|
|Center For Human Reproduction||Recruiting|
|New York, New York, United States, 10021|
|Contact: Jolanta Tapper 212-994-4400 jtapper@theCHR.com|
|Principal Investigator: David H Barad, MD MS|
|Principal Investigator: Norbert Gleicher, MD|
|Sub-Investigator: Vitaly Kushnir, MD|
|Sub-Investigator: Aritro Sen, PhD|
|Department of Medicine; Division of Endocrinology and Metabolism, University of Rochester School of Medicine and Dentistry||Active, not recruiting|
|Rochester, New York, United States, 14642|
|Study Chair:||Norbert Gleicher, MD||Center for Human Reproduction|
|Principal Investigator:||David H Barad, MD, MS||Center for Human Reproduction|