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Utilizing FMR1 Gene Mutations as Predictors of Treatment Success in Human In Vitro Fertilization (Jul 2014)

plos one
Title:
Utilizing FMR1 Gene Mutations as Predictors of Treatment Success in Human In Vitro Fertilization
Journal:
PLoS One. 2014 Jul 14;9(7)
Author(s):
Vitaly A. Kushnir, Yao Yu, David H. Barad, Andrea Weghofer, Eric Himaya, Ho-Joon Lee, Yan-Guang Wu, Aya Shohat-Tal, Emanuela Lazzaroni-Tealdi, Norbert Gleicher
 

 

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Link to the journal
 

 

Abstract taken from PubMed

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, Settings, Patients:
IVF outcomes were investigated in a private infertility center in reference to patients' FMR1 mutations based on a normal range of CGG(n = 26-34) and sub-genotypes high (CGG(n>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.
Link to the paper on PubMed
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