Utilizing FMR1 gene mutations as predictors of treatment success in human in vitro fertilization

Abstract

Context: Mutations of the fragile X mental retardation 1 (FMR1) gene are associated with distinct ovarian aging patterns. Objective: To confirm in human in vitro fertilization (IVF) that FMR1 affects outcomes, and to determine whether this reflects differences in ovarian aging between FMR1 mutations, egg/embryo quality or an effect on implantation. Design, Setting, Patients: IVF outcomes were investigated in a private infertility center in reference to patients' FMR1 mutations based on a normal range of CGGn = 26-34 and sub-genotypes high (CGGn>34) and low (CGG<26). The study included 3 distinct sections and study populations: (i) A generalized mixed-effects model of morphology (777 embryos, 168 IVF cycles, 125 infertile women at all ages) investigated whether embryo quality is associated with FMR1; (ii) 1041 embryos in 149 IVF cycles in presumed fertile women assessed whether the FMR1 gene is associated with aneuploidy; (iii) 352 infertile patients ( <26) is associated with significantly poorer morphologic embryo quality and pregnancy chance. As women age, low FMR1 alleles affect IVF pregnancy chances by reducing egg/embryo quality by mechanisms other than embryo aneuploidy. © 2014 Kushnir et al.