Jacobs Journal of Genetics

Identifying Genetic Risk Factors for Low Ovarian Response

*Carolyn Coulam
Department Of Genetics, Reproductive Medicine Institute, United States

*Corresponding Author:
Carolyn Coulam
Department Of Genetics, Reproductive Medicine Institute, United States
Email:cbcoulam@aol.com

Published on: 2018-12-21

Abstract

Background: One of the most frustrating problems in the treatment of infertility is that of poor ovarian response to stimulation. It would therefore be advantageous to have a genetic marker that could predict low ovarian reserve at a young age before the impact of low ovarian reserve affects a woman’s fertility. Since both BMP15 and GDF9 gene mutations have been reported in women with premature ovarian failure , the purpose of the present study is to investigate the correlation between low ovarian reserve BMP15 c. A704G( p. Y235C) , BMP15 c.T443C (p.L148P ), GDF9 c.C557A (p. S186Y) ,and GDF9 c. A199C (K67E) polymorphisms .
Methods: Buccal swabs were obtained from 90 women, of whom 50 had a diagnosis of low ovarian reserve and 40 were fertile controls. DNA was extracted from the buccal swabs followed by polymerase chain reaction-sequence based tying (PCR-SBT) amplification to examine the frequencies of BMP15 Y235C , BMP15 L148P , GDF9 S186Y,and missense c.199A>C polymorphisms.
Results: No significant differences were observed when the frequencies between BMP15 Y235C , BMP15 L148P , GDF 9 S186Y,and GDF9 K67E polymorphisms among women with a diagnosis of low ovarian reserve were compared with those of control women.
Conclusion: BMP15 Y235C , BMP15 L148P , GDF9 S186Y,and GDF9 K67E polymorphisms cannot be used as markers of low ovarian reserve.

Keywords

BMP15 Y235C; BMP15 L148P; GDF9 S186Y; and GDF9 K67E polymorphisms; low ovarian reserve

Introduction

One of the most frustrating problems in IVF today is that of poor ovarian response. This event has been called poor ovarian reserve, low ovarian reserve, diminished ovarian reserve, premature ovarian aging, and premature ovarian insufficiency. The number of oocytes retrieved directly influences success rates after in vitro fertilization (IVF) and embryo transfer (ET) [1]. Poor ovarian response reduces the number of embryos generated and results in decreased pregnancy rates in both index and subsequent IVF cycles [2]. Decreased pregnancy rates per cycle of IVF lead to more cycles being performed in an attempt to accomplish the goal of desired family. Poor response to gonadotropin is a significant problem in assisted conception occurring in 9% to 24% of patients and can precede the diagnosis of premature ovarian failure by months to years [3]. Thus, the economic impact of low ovarian reserve is significant. Identification of women with low ovarian reserve would allow consideration of more cost efficient management of infertile patients. Genetic markers are needed so that young women predisposed to low ovarian reserve could be informed and exercise reproductive options early. While antimullerian hormone (AMH) serum concentrations remain an appropriate marker of low ovarian reserve, no significant differences in polymorphisms of the AMH gene and its receptor AMH RII were found when infertile women undergoing IVF with the diagnosis of low ovarian reserve were compared with fertile women [4]. Recent animal studies indicate oocyte-specific genes play important roles in regulation of oogenesis and folliculogenesis [5]. Genetic studies in mice demonstrated critical roles of two key oocyte-derived growth factors belonging to the transforming growth factor-β (TGF-β) superfamily, growth and differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15), in ovarian function [6,7]. The BMP-15 gene, also named GDF9B, is encoded by two exons and maps to the X chromosome in Xp11.2 [8]. The GDF9 gene is also encoded by two exons and maps to chromosome 5 in 5q23.3 [9]. The identification of BMP15 and GDF9 gene mutations as the causal mechanism underlying infertility in several sheep strains in a dosage-sensitive manner also highlighted the crucial role these two genes play in ovarian function [10-12]. Both BMP15 and GDF9 gene mutations have been reported in women with premature ovarian failure [13-20]. The purpose of the current study is to evaluate the association of BMP15 and GDF9 gene mutations including BMP15 c. A704G( p. Y235C) , BMP15 c.T443C (p.L148P ), GDF9 c.C557A (p. S186Y) ,and GDF9 c. A199C (p.K67E) among women with low ovarian reserve and controls.