Associations between Individual and Combined Polymorphisms of the TNF and VEGF Genes and the Embryo Implantation Rate in Patients Undergoing <i>In Vitro</i> Fertilization (IVF) Programs

<div><p>Background</p><p>A multiple pregnancy is now considered to be the most common adverse outcome associated with <i>in vitro</i> 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).</p><p>Materials and Methods</p><p>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).</p><p>Results</p><p>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.</p><p>Conclusion</p><p>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.</p></div

VEGF alleles in the total patient population: description and ART results.

<p>VEGF alleles in the total patient population: description and ART results.</p

TNFα/VEGF alleles in the selected subgroup: description and ART results.

a<p>: TNFAA+AG-VEGF GG+GC vs. TNFGG-VEGF GG+GC.</p>b<p>: TNFAA+AG-VEGF.GG+GC vs. TNFGG-VEGFCC.</p>c<p>: TNFGG-VEGF GG+GC vs. TNFGG-VEGFCC.</p><p>TNFα/VEGF alleles in the selected subgroup: description and ART results.</p

VEGF alleles in the selected subgroup: description and ART results.

<p>VEGF alleles in the selected subgroup: description and ART results.</p

Table S2 from Association of <i>FOXD1</i> variants with adverse pregnancy outcomes in mice and humans

Primer sequence

Table S2 from Association of <i>FOXD1</i> variants with adverse pregnancy outcomes in mice and humans

Primer sequence

Table S1 from Association of <i>FOXD1</i> variants with adverse pregnancy outcomes in mice and humans

Number of FKHD binding sites in the promoters of modified gene

Figure S1 from Association of <i>FOXD1</i> variants with adverse pregnancy outcomes in mice and humans

FKHD binding sites are more abundant in placenta down-regulated genes in the 66H-Chr13 strai