Abstract
BackgroundA 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).Materials and MethodsA 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).ResultsOnly 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.ConclusionWe 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.
Highlights
In vitro fertilization (IVF) is a complex, multistep process
Low implantation rates have prompted physicians to transfer multiple embryos. This strategy increases the likelihood of multiple pregnancy, which constitutes a risk for both the mother and the foetuses [2] and is considered to be the most common adverse outcome associated with in vitro fertilization (IVF)
By using allele-specific polymerase chain reactions, we recently reported, for the first time, that the presence of the TNF-308.A allele was associated with higher implantation, pregnancy and multiple pregnancy rates and a lower miscarriage rate after fresh embryo transfer in patients undergoing IVF for male infertility [26]
Summary
In vitro fertilization (IVF) is a complex, multistep process. Poor control of embryo implantation is still a major obstacle to the achievement of a successful pregnancy. Low implantation rates have prompted physicians to transfer multiple embryos. This strategy increases the likelihood of multiple pregnancy, which constitutes a risk for both the mother and the foetuses [2] and is considered to be the most common adverse outcome associated with IVF. A multiple pregnancy is considered to be the most common adverse outcome associated with in vitro fertilization (IVF). 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. 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). 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)
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