title: Associations between Individual and Combined Polymorphisms of the TNF and VEGF Genes and the Embryo Implantation Rate in Patients Undergoing In Vitro Fertilization (IVF) Programs.
abstract: BACKGROUND
  A multiple pregnancy is now considered to be the most common adverse outcome associated with in vitro fertilization (IVF). As a consequence, the identification of women with the best chances of embryo implantation is a challenge in IVF program, in which the objective is to offer elective single-embryo transfer (eSET) without decreasing the pregnancy rate. To date, a range of hormonal and clinical parameters have been used to optimize eSET but none have significant predictive value. This variability could be due to genetic predispositions related to single-nucleotide polymorphisms (SNPs). Here, we assessed the individual and combined impacts of thirteen SNPs that reportedly influence the outcome of in vitro fertilisation (IVF) on the embryo implantation rate for patients undergoing intracytoplasmic sperm injection program (ICSI).
  
  
  METHODS
  A 13 gene polymorphisms: FSHR(Asn680Ser), p53(Arg72Pro), AMH(Ile49Ser), ESR2(+1730G>A), ESR1(-397T>C), BMP15(-9C>G), MTHFR1(677C>T), MTHFR2(1298A>C), HLA-G(-725C>G), VEGF(+405G>C), TNFα(-308A>G), AMHR(-482A>G), PAI-1(4G/5G), multiplex PCR assay was designed to genotype women undergoing ICSI program. We analyzed the total patients population (n = 428) and a subgroup with homogeneous characteristics (n = 112).
  
  
  RESULTS
  Only the VEGF(+405G>C) and TNFα(-308A>G) polymorphisms impacted fertilization, embryo implantation and pregnancy rates. Moreover, the combined VEGF+405.GG and TNFα-308.AG or AA genotype occurred significantly more frequently in women with high implantation potential. In contrast, the VEGF+405.CC and TNFα-308.GG combination was associated with a low implantation rate.
  
  
  CONCLUSIONS
  We identified associations between VEGF(+405G>C) and TNFα(-308A>G) polymorphisms (when considered singly or as combinations) and the embryo implantation rate. These associations may be predictive of embryo implantation and could help to define populations in which elective single-embryo transfer should be recommended (or, conversely, ruled out). However, the mechanism underlying the function of these polymorphisms in embryo implantation remains to be determined and the associations observed here must be confirmed in a larger, more heterogeneous cohort.
authors.affiliation: Department of Reproductive Biology, Genetics, Gynaecology and Obstetrics, Poissy Saint Germain Medical Centre, Poissy, France; EA 2493, Versailles Saint Quentin University, Versailles, France.
authors.forename: Radia
authors.initials: R
authors.lastname: Boudjenah
authors.affiliation: Department of Reproductive Biology, Genetics, Gynaecology and Obstetrics, Poissy Saint Germain Medical Centre, Poissy, France; EA 2493, Versailles Saint Quentin University, Versailles, France.
authors.forename: Denise
authors.initials: D
authors.lastname: Molina-Gomes
authors.affiliation: Department of Reproductive Biology, Genetics, Gynaecology and Obstetrics, Poissy Saint Germain Medical Centre, Poissy, France; EA 2493, Versailles Saint Quentin University, Versailles, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Torre
authors.affiliation: Department of Reproductive Biology, Genetics, Gynaecology and Obstetrics, Poissy Saint Germain Medical Centre, Poissy, France; EA 2493, Versailles Saint Quentin University, Versailles, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Boitrelle
authors.affiliation: EA 2493, Versailles Saint Quentin University, Versailles, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Taieb
authors.affiliation: EA 2493, Versailles Saint Quentin University, Versailles, France.
authors.forename: Esther
authors.initials: E
authors.lastname: Dos Santos
authors.affiliation: Department of Reproductive Biology, Genetics, Gynaecology and Obstetrics, Poissy Saint Germain Medical Centre, Poissy, France; EA 2493, Versailles Saint Quentin University, Versailles, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Wainer
authors.affiliation: EA 2493, Versailles Saint Quentin University, Versailles, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: de Mazancourt
authors.affiliation: Department of Reproductive Biology, Genetics, Gynaecology and Obstetrics, Poissy Saint Germain Medical Centre, Poissy, France; EA 2493, Versailles Saint Quentin University, Versailles, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Selva
authors.affiliation: Department of Reproductive Biology, Genetics, Gynaecology and Obstetrics, Poissy Saint Germain Medical Centre, Poissy, France; EA 2493, Versailles Saint Quentin University, Versailles, France.
authors.forename: François
authors.initials: F
authors.lastname: Vialard
mesh_terms: D000328:Adult; D000483:Alleles; D010064:Embryo Implantation / Q000235:genetics* / Q000502:physiology; D004624:Embryo Transfer; D005260:Female; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D018873:Pregnancy Rate; D011272:Pregnancy, Multiple / Q000235:genetics; D020554:Sperm Injections, Intracytoplasmic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A