Importance: Methylenetetrahydrofolate reductase syndrome is the lack of an enzyme that is crucial to folate metabolism, preventing the body from converting folate into usable material and helping reduce homocysteine levels. Many women diagnosed with methylenetetrahydrofolate reductase syndrome experience recurring pregnancy loss, defined as 2 or more unsuccessful pregnancies.

Objective: This secondary research study aims to evaluate the efficacy of various medication types in preventing recurring pregnancy loss in women with methylenetetrahydrofolate reductase syndrome.

Evidence Review: Secondary research from 2010–2025 was gathered from PubMed, Scopus, and Google Scholar. Included studies focused on MTHFR-related pregnancy complications and assessed low-dose aspirin, LMWH, folic acid, or methylfolate. Articles without clear efficacy data or relevance to MTHFR-related pregnancy loss were excluded. Twenty-nine articles were thematically analyzed.

Findings: Results indicate no significant benefit in using low molecular weight heparin, low-dose aspirin, folic acid, or methylfolate individually, with no one medication leading to more successful pregnancies. Some studies included secondary reports of combination therapy use in high-risk or fertility settings, with improved full-term pregnancy rates compared to monotherapy or standard care.

Conclusions and Relevance: Findings show that no single therapy significantly improved outcomes; however, studies reporting combined use of low-dose aspirin, LMWH, folic acid, and methylfolate showed higher successful full-term pregnancy rates, supporting further research on combination therapy as a promising intervention for improving pregnancy outcomes in women with MTHFR-related pregnancy loss.