Effect of Testosterone Treatment on Embryo Quality

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Center for Human Reproduction
Sponsor:
Collaborator:
Foundation for Reproductive Medicine
Information provided by (Responsible Party):
David H. Barad, Center for Human Reproduction
ClinicalTrials.gov Identifier:
NCT01662466
First received: August 2, 2012
Last updated: September 18, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
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 Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Center for Human Reproduction:

Primary Outcome Measures:
  • Clinical and Ongoing Pregnancy [ Time Frame: 8 weeks post treatment initiation ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Measures of Atresia [ Time Frame: 8 weeks after intervention initiation ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The number of oocytes retrieved at oocyte retrieval for in-vitro fertilization will be compared between the treatment group and placebo.


Estimated Enrollment: 180
Study Start Date: July 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Testosterone
Dietary 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: Dehydroepiandrosterone
Drug: Placebo
Carrier cream without added testosterone in the identical type of pump
Other Name: Carrier cream without added testosterone

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.
  Eligibility

Ages Eligible for Study:   38 Years to 44 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01662466

Contacts
Contact: Jolanta Tapper, MD MS 212 994-4400 ext 4406 jtapper@theCHR.com

Locations
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
Sponsors and Collaborators
David H. Barad
Foundation for Reproductive Medicine
Investigators
Study Chair: Norbert Gleicher, MD Center for Human Reproduction
Principal Investigator: David H Barad, MD, MS Center for Human Reproduction
  More Information

Additional Information:
No publications provided

Responsible Party: David H. Barad, Director of Clinical Research, Center for Human Reproduction
ClinicalTrials.gov Identifier: NCT01662466     History of Changes
Other Study ID Numbers: 072312-01, CHR-DHEA-testosterone-2012
Study First Received: August 2, 2012
Last Updated: September 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Center for Human Reproduction:
testosterone
DHEA
IVF
egg quality
pregnancy rates

Additional relevant MeSH terms:
Primary Ovarian Insufficiency
Gonadal Dysgenesis
Turner Syndrome
Infertility
Infertility, Female
Menopause, Premature
Genital Diseases, Male
Genital Diseases, Female
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Sex Chromosome Disorders of Sex Development
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Sex Chromosome Disorders
Chromosome Disorders
Genetic Diseases, Inborn
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Dehydroepiandrosterone
Androgens

ClinicalTrials.gov processed this record on October 01, 2014