Is there an androgen level threshold for aneuploidy risk in infertile women?

Norbert Gleicher,David H Mcculloh,Nandita Ganguly,James A Grifo,Mark M Kushnir,David F Albertini,Vitaly A Kushnir,David H Barad,Kara N Goldman

doi:10.1186/s12958-015-0034-z

Abstract

BackgroundLow functional ovarian reserve (LFOR) has been associated with hypoandrogenemia and increased embryo aneuploidy, while androgen supplementation has been reported to improve aneuploidy rates. We, therefore, assessed whether in infertile women undergoing in vitro fertilization (IVF) androgen concentrations are associated with aneuploidy rates.MethodsThis study was performed in 2 academically affiliated fertility centers in New York City and an academically affiliated steroid chemistry laboratory in Utah. Androgen concentrations were measured in blinded fashion from 84 infertile women (age 40.3 +/− 2.4 years) at New York University (NYU), using a validated LC-MS/MS method, in cryopreserved serum samples of patients who had undergone IVF with concomitant preimplantation genetic screening (PGS), utilizing a 24-chromosome platform. The Center for Human Reproduction (CHR) provided plasma samples of 100 historical controls (ages 38.6+/−5.0 years) undergoing IVF without PGS. Statistical comparisons were made of androgen concentrations, and of associations between androgen concentrations and embryo aneuploidy.ResultsWomen undergoing IVF + PGS at NYU revealed no association between embryo aneuploidy and androgen concentrations but demonstrated significantly lower androgen concentrations than the 100 control patients from CHR,ConclusionsThough this study revealed no association between androgen levels and embryo ploidy, the extremely low androgen levels in the NYU study group raise the possibility of a threshold effect below which testosterone no longer affects aneuploidy. Before an androgen effect on embryo ploidy can be completely ruled out, a patient population with more normal androgen levels has to be investigated.

Highlights

Low functional ovarian reserve (LFOR) has been associated with hypoandrogenemia and increased embryo aneuploidy, while androgen supplementation has been reported to improve aneuploidy rates
Study population Women were identified who presented to New York University (NYU) between 2013 and 2014 for in vitro fertilization (IVF) with 24-chromosome preimplantation genetic screening (PGS)
We in this study attempted to investigate whether androgen levels statistically related to embryo aneuploidy

Summary

Introduction

Low functional ovarian reserve (LFOR) has been associated with hypoandrogenemia and increased embryo aneuploidy, while androgen supplementation has been reported to improve aneuploidy rates. Though even young women at peak fertility produce a large number of aneuploid embryos, rates of aneuploidy increase with advancing female age [3]. Recent animal [4] and human data [5] suggest that loss of functional ovarian reserve (FOR), in itself, may be associated with increased embryo aneuploidy. What causes the high rate of aneuploidy in human oocytes and embryos is so far only partially understood [1]. Been suggested to reduce aneuploidy rates [7]. Whether caused by physiologic female aging or POA, low functional ovarian reserve (LFOR) has, almost universally, been associated with relative hypoandrogenemia [9]

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Conclusion