Association between maternal MTHFR C677T/A1298C combination polymorphisms and IVF/ICSI outcomes: a retrospective...

Area of Science:

• Reproductive Medicine
• Genetics
• In Vitro Fertilization (IVF)

Background:

• Contradictory findings exist regarding MTHFR polymorphisms and IVF/ICSI outcomes.
• Previous studies often analyzed MTHFR C677T and A1298C separately or had small sample sizes.
• Few studies have systematically investigated the combined effect of MTHFR C677T/A1298C polymorphisms on IVF/ICSI outcomes.

Purpose of the Study:

• To investigate the roles of maternal 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C combination polymorphisms on embryological and clinical outcomes of IVF/ICSI.
• To provide a holistic view of the effect of MTHFR C677T and A1298C polymorphisms on IVF/ICSI outcomes.

Main Methods:

• Retrospective cohort study of 1160 women undergoing IVF/ICSI.
• Classification of women based on combined C677T, A1298C, and C677T/A1298C genotypes.
• Evaluation of embryological and clinical outcomes using generalized linear and log-binomial regression models, adjusted for confounders.

Main Results:

• Lower MTHFR enzyme activity (TT/AA genotype) was associated with a reduced oocyte maturation rate (P=0.007).
• Oocyte maturation rate decreased linearly with declining MTHFR activity (P-trend=0.001).
• Intermediate MTHFR activity (CC/AC, CC/CC&CT/AA, CT/AC genotypes) was linked to a lower transplantable embryo rate.

Conclusions:

• Maternal MTHFR C677T/A1298C polymorphisms significantly affect oocyte maturation and embryo quality in IVF/ICSI.
• Reduced MTHFR activity is linked to decreased oocyte maturation potential.
• Findings can inform personalized folic acid supplementation strategies for women undergoing fertility treatments.