Associations between maternal MTHFR polymorphisms and embryological outcomes in Korean patients with infertility undergoing IVF/ICSI cycles.

Objective: Methylenetetrahydrofolatereductase (MTHFR) is important for folate metabolism, which is involved in DNA synthesis and cell growth. However, the relationship between Maternal MTHFR polymorphisms and outcomes in assisted reproduction remains controversial. This is the first study to explore the effect of MTHFR polymorphisms on the embryological outcomes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles in Korean patients with infertility.

Materials and methods: This retrospective cohort study included 173 women who underwent MTHFR genotyping between July, 2021 and June, 2022. The embryologic outcomes of 301 IVF/ICSI cycles were compared between groups according to MTHFR polymorphisms using ANOVA and Chi-square test.

Results: Oocyte maturation rates were 80.0%, 75.0%, and 71.4% for MTHFR 677CC, 677CT, and 677TT, respectively. Cleaved embryo formation and transplantable embryo rates were comparable across various maternal MTHFR 677 genotypes. Good-quality embryo (GQE) rate was higher for MTHFR 677CT than those for 677CC and 677TT (40.0% vs. 29.4%, p = 0.001 and 40.0% vs. 33.3%, p = 0.025, respectively). When analyzing the combined MTHFR genotypes, the oocyte maturation rate was significantly lower in 677TT than in 677CC 1298AA/677CC 1298AC and 677CC 1298CC/677CT 1298AA/677CT 1298AC (71.4% vs. 76.7%, p = 0.012 and 71.4% vs. 75.7%, p = 0.029, respectively). The MTHFR 677CC/1298CC, 677CT/1298AA, and 677CT/1298AC genotypes had the highest GQE rates.

Conclusions: MTHFR 677TT genotype, which had the lowest enzymatic activity, had the lowest oocyte maturation rate. The combined MTHFR 677CC/1298CC, 677CT/1298AA, and 677CT/1298AC genotypes with intermediate enzyme activities had higher GQE rates. However, no differences were observed in the transplantable embryo rate between MTHFR genotypes.