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Effect of Testosterone Treatment on Embryo Quality

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ClinicalTrials.gov Identifier: NCT01662466
Recruitment Status : Recruiting
First Posted : August 10, 2012
Last Update Posted : June 12, 2018
Sponsor:
Collaborator:
Foundation for Reproductive Medicine
Information provided by (Responsible Party):
Center for Human Reproduction

Tracking Information
First Submitted Date  ICMJE August 2, 2012
First Posted Date  ICMJE August 10, 2012
Last Update Posted Date June 12, 2018
Study Start Date  ICMJE July 2012
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2012)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 9, 2012)
Clinical and Ongoing Pregnancy [ Time Frame: 12 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.
Change History Complete list of historical versions of study NCT01662466 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2012)
  • Measures of Atresia [ Time Frame: 8 weeks after intervention initiation ]
    1. Follicular fluid will be collected separately for the first 5 follicles aspirated that are at least 18mm diameter for each patient.
    2. Granulosa cell counts will be performed on each follicle fluid. Granulosa cell counts of <10,000 per follicle will be considered atretic.
    3. 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Testosterone Treatment on Embryo Quality
Official Title  ICMJE 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
Brief Summary The purpose of this study is to determine the effect of treatment with trans-dermal testosterone cream compared to placebo on measures of ovarian reserve, oocyte and embryo quality, and pregnancy rates among women with evidence of diminished ovarian reserve that have persistently low serum testosterone and free testosterone after completing six previous weeks of DHEA supplementation.
Detailed Description

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Primary Ovarian Insufficiency
  • Female Infertility Due to Diminished Ovarian Reserve
Intervention  ICMJE
  • 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: Testosterone
  • Dietary Supplement: DHEA
    DHEA 25mg tid
    Other Name: Dehydroepiandrosterone
  • Drug: Placebo
    Carrier cream without added testosterone in the identical type of pump
    Other Name: Carrier cream without added testosterone
Study Arms  ICMJE
  • Active Comparator: DHEA+Testosterone
    These patients will be administered the testosterone cream along with standard DHEA supplements
    Interventions:
    • Drug: Testosterone cream (0.5mg per gram)
    • Dietary Supplement: DHEA
  • Placebo Comparator: DHEA+Placebo
    These patients will receive the placebo cream along with her DHEA supplements. In other words, no testosterone will be administered.
    Interventions:
    • Dietary Supplement: DHEA
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 9, 2012)
180
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Women with 38 to 44 years old planning to undergo ovulation induction for IVF who are willing to sign an informed consent.
  • BMI > 18 and <= 30 kg/m^2
  • FSH > 10 mIU/mL
  • AMH =< 1.05 ng/mL
  • Using DHEA for treatment of DOR/POA.
  • Baseline Total Testosterone less than 30 ng per deciliter (1.0 nmol per liter) or serum free testosterone concentrations of less than 3.5 pg per milliliter (12.1 pmol per liter), which are below the median values for normal premenopausal women (Endocrine Sciences, Calabasas Hills, Calif.).

Exclusion Criteria:

  • History of hormone dependent neoplasm
  • History of severe acne or hirsutism.
  • Hyperlipidemia.
  • Pre existing cardiac, renal or hepatic disease
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 38 Years to 44 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jolanta Tapper, MD MS 212 994-4400 ext 4406 jtapper@theCHR.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01662466
Other Study ID Numbers  ICMJE 072312-01
CHR-DHEA-testosterone-2012 ( Other Identifier: Center for Human Reproduction )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Center for Human Reproduction
Study Sponsor  ICMJE Center for Human Reproduction
Collaborators  ICMJE Foundation for Reproductive Medicine
Investigators  ICMJE
Study Chair: Norbert Gleicher, MD Center for Human Reproduction
Principal Investigator: David H Barad, MD, MS Center for Human Reproduction
PRS Account Center for Human Reproduction
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP