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Effect of Testosterone Treatment on Embryo Quality

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01662466
Recruitment Status : Recruiting
First Posted : August 10, 2012
Last Update Posted : November 12, 2020
Foundation for Reproductive Medicine
Information provided by (Responsible Party):
Center for Human Reproduction

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.

Condition or disease Intervention/treatment 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

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (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
Study Start Date : July 1, 2012
Estimated Primary Completion Date : June 1, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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 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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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

  2. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   38 Years to 44 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01662466

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Contact: Jolanta Tapper, MD MS 212 994-4400 ext 4406

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United States, New York
Center For Human Reproduction Recruiting
New York, New York, United States, 10021
Contact: Jolanta Tapper    212-994-4400   
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
Center for Human Reproduction
Foundation for Reproductive Medicine
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Study Chair: Norbert Gleicher, MD Center for Human Reproduction
Principal Investigator: David H Barad, MD, MS Center for Human Reproduction
Additional Information:
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Responsible Party: Center for Human Reproduction Identifier: NCT01662466    
Other Study ID Numbers: 072312-01
CHR-DHEA-testosterone-2012 ( Other Identifier: Center for Human Reproduction )
First Posted: August 10, 2012    Key Record Dates
Last Update Posted: November 12, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We do not plan to share IPD
Keywords provided by Center for Human Reproduction:
egg quality
pregnancy rates
Additional relevant MeSH terms:
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Infertility, Female
Primary Ovarian Insufficiency
Menopause, Premature
Ovarian Diseases
Adnexal Diseases
Gonadal Disorders
Endocrine System Diseases
Testosterone undecanoate
Testosterone enanthate
Testosterone 17 beta-cypionate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anabolic Agents
Adjuvants, Immunologic
Immunologic Factors