Clinical trial NCT01662466: Effect of Testosterone Treatment on Embryo Quality
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Primary Ovarian Insufficiency
Female Infertility Due to Diminished Ovarian Reserve
Keywords: testosterone
DHEA
IVF
egg quality
pregnancy rates
Lead sponsor: Center for Human Reproduction
Sponsor class: OTHER
Collaborators: name: Foundation for Reproductive Medicine
First posted: 2012-08-10
Enrollment: 180
Sex: FEMALE
Minimum age (years): 38
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Clinical and Ongoing Pregnancy
timeFrame: 8 weeks post treatment initiation
Secondary outcomes:
measure: Measures of Atresia
timeFrame: 8 weeks after intervention initiation
measure: Oocytes number
timeFrame: 8 weeks after initiation of intervention
Other outcomes:
Locations:
city: New York
country: United States
facility: Center For Human Reproduction
state: New York
city: Rochester
country: United States
facility: Department of Medicine; Division of Endocrinology and Metabolism, University of Rochester School of Medicine and Dentistry
state: New York
Study officials:
affiliation: Center for Human Reproduction
name: Norbert Gleicher, MD
role: STUDY_CHAIR
affiliation: Center for Human Reproduction
name: David H Barad, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: