The aim of our study was to investigate the effect of maternal and embryo MTHFR C677T and A1298C polymorphisms on embryo aneuploidies and mosaicism and the correlation between these genetic variants in transferred euploid embryos and IVF outcomes. MTHFR genotype was analyzed in 77 women who performed an IVF/ICSI cycle with PGT-A. Moreover, to evaluate the effect of embryo MTHFR polymorphisms on embryo aneuploidies and mosaicism, the MTHFR genotype was analyzed in 191 biopsied embryos from the PGT-A cycles of these patients. Additionally, 218 DNA samples from trophectoderm biopsies belonging to a different group of patients were also genotyped. MTHFR polymorphisms were analyzed in a total amount of 409 trophectoderm samples. The main parameters analyzed were embryo aneuploidy and mosaicism rates. Finally, the IVF outcomes of 241 single euploid embryo transfers were assessed and compared between different MTHFR embryo genotypes. The aneuploidy rates were similar in embryos from homozygous normal women and women with at least one mutated allele (54.7% vs. 30.2% in 677C>T and 37.8% vs. 42.7% in 1298A>C). Furthermore, no differences were observed in the mosaicism rate (24.0% vs. 13.8% in 677C>T and 17.1% vs. 17.3% in 1298A>C). A similar analysis was performed, taking into account the embryo genotype results. No differences in aneuploidy rate were observed between the study groups. The only significant difference was the mosaicism rate among 677C>T genotype (13.5% in 677CC group vs. 5.4% in 677CT/TT; p = 0.019). Implantation rate, biochemical and clinical miscarriage rates, and ongoing pregnancy rate were compared between different embryo genotypes, and no statistically significant differences were found. In conclusion, the maternal MTHFR genotype did not influence embryo chromosomal abnormalities. Moreover, the embryo MTHFR genotype was not associated with embryo aneuploidy or IVF outcomes such as implantation, pregnancy loss, and ongoing pregnancy when euploid embryos were transferred.Abbreviations: MTHFR: methylenetetrahydrofolate reductase; IVF: in vitro fertilization; PGT-A: preimplantation genetic testing for aneuploidies; SAM: S-adenosyl methionine; SNP: single nucleotide polymorphism; SPSS: Statistical Package for Social Sciences; RIF: recurrent implantation failure; RPL: recurrent pregnancy loss; hCG: human chorionic gonadotropin; PBS: phosphate buffered saline; CGH: comparative genomic hybridization; NGS: next generation sequencing.
Keywords: IVF outcomes; MTHFR; aneuploidy; mosaicism; polymorphism.