How to supplement hypo-androgenic women correctly Norbert Gleicher, MD Medical Director and Chief Scientist, Center For Human Reproduction, New York, NY President, Foundation For Reproductive Medicine, New York, NY Guest Investigator, Rockefeller University, New York, NY Professor (Adj), Department Of Obstetrics & Gynecology, Vienna University School Of Medicine, Vienna, Austria FRMC 2018 New York, NY November 15-18, 2018
Conflict Statement Dr. Gleicher is listed as co-inventor on a number of pending patent applications claiming diagnostic and therapeutic benefits from determination of CGG repeat numbers and ovarian FMR1 genotypes and sub-genotypes. Dr. Gleicher is co-inventor of awarded U.S. patents, claiming therapeutic benefits for supplementation of DHEA in women with diminished ovarian reserve, a topic discussed in this talk. Other patent applications in regards to DHEA and other fertility-related claims, with no relationship to this talk, are pending. Dr. Gleicher receives royalties from, and owns shares in Fertility Neutraceuticals, LLC, a distributor of a DHEA product. Dr. Gleicher is co-inventor of three pending patent applications claiming potential therapeutic benefit for anti-müllerian hormone (AMH) in infertile women. Dr. Gleicher owns shares in OvaNova Laboratories, LLC.
FSH and Androgen Receptors Reproductive Biology and Endocrinology 2011, 9:116 doi:10.1186/1477-7827-9-116
DHEA Mimics DHT Effects on Follicular Development Antral Follicle Count Percent of Follicles 20 10 0 FSH FSH + DHEA FSH + DHEA + Flutamide FSH (10ng/ml) DHEA (100nM) Flutamide (100nM) Sen et al; Personal Communication
DHEA in DOR Patients - IVF DHEA 3βHSD Androstenedione CYP19 Estrone 17βHSD Androstenediol 3βHSD 17βHSD Testosterone CYP19 17βHSD Estradiol AR Follicular survival AMH expression FSH sensitivity DHEA AFC Sen et al; Personal Communication # of oocytes retrieved during IVF
The DHEA Story
Egg and Embryo Yields Count 20 18 16 14 12 10 8 6 4 2 0 D H E A Eggs Embryos 1 2 3 4 5 6 7 8 9 Treatment Cycle Gleicher and Barad, Fertil Steril 2005;84(3):756.
Previously Reported Reproductive Benefits of DHEA Improves egg/embryo numbers Improves egg/embryo quality Improves spontaneous pregnancy rates Improves IVF pregnancy rates Improves time to conception Improves cumulative pregnancy rates Casson et al. Hum Reprod 2000 Barad and Gleicher, Hum Reprod 2006 Barad and Gleicher, Fertil Steril 2005 Barad et al, J Assist Reprod Genet 2007
AMH response to DHEA Reprod Biomed Online 2010: 360-365.
Comparison of Miscarriage Rates between DHEA Supplemented Infertility Patients and 2004 National US IVF Outcome Data. 0.6 0.5 0.4 0.3 0.2 National DHEA 0.1 0 <35 35-37 38-40 41-42 >42 Gleicher et al, Reprod Biol Endocrinol 2009;7:108
Gleicher et al., Reprod Biol Endocrinol 2010;8:140. Comparison of Absolute and Percentages of Aneuploidy in DHEA and Control Patients
Androgens, Cortisol and Ratios DOR is an androgen deficiency state Box and whisker plots of serum androgen levels, serum cortisol levels and the ratio of total testosterone concentration over serum cortisol levels for controls, POA/OPOI, and physicologic DOR. The mean is depicted with a dashed line, the median with a solid line, and the normal range for serum androgens with a grey background. (a) Comparison of serum androgen levels: an asterisk denotes significant differences in mean between groups. (b) Shows distribution of serum cortisol levels. (c) Shows the ratio of TT over cortisol levels. Gleicher et al, Hum. Reprod. 2013: 28 (4):1084-1091.
Testosterone Response
Follicle Development from Primordial and Preovulatory Status NEW OLD Broekmans FJ et al, Endocrine Reviews 2009
Summary Preferred supplementation: DHEA Alternative: Testosterone At least 6 weeks before IVF start Preferably controlled by T and SHBG loads Co-supplementation: CoQ10 Per need: HGH, etc.
Side effects DHEA: less than Testosterone Improved libido Oily skin/acne Hair loss CoQ10: None HGH Ankle swelling Joint pains Carpal tunnel/edema
CHR Staff (* Visiting Scientists) David F Albertini, PhD* David H Barad, MS, MD Ali Brivanlou, PhD, MD* Sarah Darmon, PhD, MS* Dieter Egli, PhD* Norbert Gleicher, MD Jianjun Hu, MD, MS Vitaly A Kushnir, MD Emanuela Lazzaroni-Tealdi, MS Aya Shohat-Tal, PhD* Andrea Vidali, MD* Andrea Weghofer, PhD, MS, MBA, MD* Yao Yu, PhD* Affiliates Rockefeller University: Ali Brivanlou, PhD, MD Salk Institute for Biological Studies: Pradeep Reddy, PhD