The role of hyperhomocysteinemia in the pathogenesis of recurrent spontaneous abortion: A review

Objective To investigate the role of hyperhomocysteinemia (HHcy) in the pathogenesis of recurrent spontaneous abortion (RSA) and its clinical significance.Methods Recent studies on the relationship between homocysteine (Hcy) metabolism and RSA were reviewed. The molecular mechanisms of Hcy elevation, related gene polymorphisms, and nutritional and lifestyle influences were analyzed. The effects of folate and vitamin B12 supplementation on reducing Hcy levels and improving pregnancy outcomes were also summarized.Results RSA, defined as two or more consecutive or non-consecutive pregnancy losses before 20–28 gestational weeks, affects approximately 2～5% of women of reproductive age. Elevated Hcy can induce endothelial dysfunction, oxidative stress, thrombosis, and trophoblast apoptosis, resulting in placental hypoperfusion and pregnancy loss. Polymorphisms in genes such as MTHFR C677T, MTRR A66G, and CBS 844ins68, especially under folate or vitamin B12 deficiency, aggravate HHcy. Unhealthy lifestyle factors, including malnutrition, obesity, and smoking, further increase Hcy levels. Clinical studies have shown significantly higher serum Hcy levels in RSA patients than in women with normal pregnancies, while supplementation with folate and vitamin B12 effectively lowers Hcy levels and reduces miscarriage risk.Conclusions HHcy may be an important but underestimated risk factor for RSA. Early screening and targeted nutritional interventions may improve reproductive outcomes. Large-scale prospective studies integrating genetic, metabolic, and epigenetic approaches are needed to clarify the causal mechanisms and guide individualized prevention and treatment strategies.