Abstract
Infertility presents a substantial challenge for women of reproductive age, exerting profound effects on both individual well-being and healthcare systems. Despite its critical role in folate and homocysteine pathways, the influence of methylenetetrahydrofolate reductase (MTHFR) on the success of assisted reproductive techniques (ART) remains insufficiently understood. This knowledge gap impedes the development of personalized therapeutic strategies. Our study seeks to elucidate the relationship between MTHFR and ART outcomes, exploring potential mediators to enhance treatment efficacy. A cohort of 311 women with infertility was recruited for our study. Multivariate linear models were utilized to evaluate the relationship between the MTHFR 677T allele (a missense mutation resulting in an alanine to valine substitution) and the efficacy of ART, including both treatment outcomes and the number of ART cycles required. Sequential mediation analysis was conducted to elucidate the potential mediators influencing ART efficacy. The MTHFR 677T allele carried by infertile women was associated with a 17-51% reduction in ART efficacy (P < 0.05). This encompassed poorer overall ART outcomes, such as clinical pregnancy and live birth rates, as well as an increased number of ART cycles. Sequential mediation analysis suggested that anti-Müllerian hormone (AMH) and age may act as mediators modulating the impact of the MTHFR 677T allele on ART treatment efficacy. This study has unveiled the intricate connection between MTHFR 677T allele and ART treatment efficacy in infertile women, shedding light on the mediating role of AMH and age.