Effect of Testosterone Treatment on Embryo Quality

Condition(s) targeted: Primary Ovarian Insufficiency; Female Infertility Due to Diminished Ovarian Reserve

Intervention: Testosterone cream (0.5mg per gram) (Drug); DHEA (Dietary Supplement); Placebo (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: Center for Human Reproduction

Official(s) and/or principal investigator(s):
Norbert Gleicher, MD, Study Chair, Affiliation: Center for Human Reproduction
David H Barad, MD, MS, Principal Investigator, Affiliation: Center for Human Reproduction

Overall contact:
Jolanta Tapper, MD MS, Phone: 212 994-4400, Ext: 4406, Email: jtapper@theCHR.com

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.

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 design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Clinical and Ongoing Pregnancy

Secondary outcome:

Measures of Atresia

Oocytes number

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.

Minimum age: 38 Years. Maximum age: 44 Years. Gender(s): Female.

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

Jolanta Tapper, MD MS, Phone: 212 994-4400, Ext: 4406, Email: jtapper@theCHR.com

Center For Human Reproduction, New York, New York 10021, United States; Recruiting
Jolanta Tapper, Phone: 212-994-4400, Email: jtapper@theCHR.com
David H Barad, MD MS, Principal Investigator
Norbert Gleicher, MD, Principal Investigator
Vitaly Kushnir, MD, Sub-Investigator
Aritro Sen, PhD, Sub-Investigator

Department of Medicine; Division of Endocrinology and Metabolism, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, United States; Active, not recruiting

Center For Human Reproduction Website

Starting date: July 2012
Last updated: July 7, 2015