TY - JOUR
T1 - Utilizing FMR1 gene mutations as predictors of treatment success in human in vitro fertilization
AU - Kushnir, Vitaly A.
AU - Yu, Yao
AU - Barad, David H.
AU - Weghofer, Andrea
AU - Himaya, Eric
AU - Lee, Ho Joon
AU - Wu, Yan Guang
AU - Shohat-Tal, Aya
AU - Lazzaroni-Tealdi, Emanuela
AU - Gleicher, Norbert
PY - 2014/7/14
Y1 - 2014/7/14
N2 - 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 (< age 38; in 1st IVF cycles) and 179 donor-recipient cycles, assessed whether the FMR1 gene affects IVF pregnancy chances via oocyte/embryo quality or non-oocyte maternal factors. Interventions: Standardized IVF protocols. Main Outcome Measures: Morphologic embryo quality, ploidy and pregnancy rates. Results: (i) Embryo morphology was reduced in presence of a low FMR1 allele (P = 0.032). In absence of a low allele, the odds ratio (OR) of chance of good (vs. fair/poor) embryos was 1.637. ( ii) FMR1 was not associated with aneuploidy, though aneuploidy increased with female age. (iii) Recipient pregnancy rates were neither associated with donor age or donor FMR1. In absence of a low FMR1 allele, OR of clinical pregnancy (vs. chemical or no pregnancy) was 2.244 in middle-aged infertility patients. Conclusions: A low FMR1 allele (CGG <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.
AB - 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 (< age 38; in 1st IVF cycles) and 179 donor-recipient cycles, assessed whether the FMR1 gene affects IVF pregnancy chances via oocyte/embryo quality or non-oocyte maternal factors. Interventions: Standardized IVF protocols. Main Outcome Measures: Morphologic embryo quality, ploidy and pregnancy rates. Results: (i) Embryo morphology was reduced in presence of a low FMR1 allele (P = 0.032). In absence of a low allele, the odds ratio (OR) of chance of good (vs. fair/poor) embryos was 1.637. ( ii) FMR1 was not associated with aneuploidy, though aneuploidy increased with female age. (iii) Recipient pregnancy rates were neither associated with donor age or donor FMR1. In absence of a low FMR1 allele, OR of clinical pregnancy (vs. chemical or no pregnancy) was 2.244 in middle-aged infertility patients. Conclusions: A low FMR1 allele (CGG <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.
UR - http://www.scopus.com/inward/record.url?scp=84904244462&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0102274
DO - 10.1371/journal.pone.0102274
M3 - Article
C2 - 25019151
AN - SCOPUS:84904244462
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 7
M1 - e102274
ER -