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Association between homocysteine level and unexplained recurrent pregnancy loss: a meta-analysis
1Center of Reproductive Medicine, First Affiliated Hospital, Naval Medical University, Shanghai, China.
Frontiers in Endocrinology
|July 3, 2026
Summary
Hyperhomocysteinemia (HHcy) is linked to unexplained recurrent pregnancy loss (uRPL). This meta-analysis confirms HHcy as a significant risk indicator, though further research is needed.
Area of Science:
- Reproductive Medicine
- Clinical Biochemistry
- Epidemiology
Background:
- Unexplained recurrent pregnancy loss (uRPL) affects many women, presenting a significant clinical challenge.
- Emerging evidence suggests a potential link between hyperhomocysteinemia (HHcy) and the pathogenesis of uRPL.
- Inconsistent findings across individual studies necessitate a comprehensive meta-analysis to clarify this association.
Purpose of the Study:
- To systematically evaluate the association between elevated homocysteine (Hcy) levels and unexplained recurrent pregnancy loss (uRPL).
- To synthesize findings from observational studies using meta-analysis to provide a pooled estimate of the risk.
Main Methods:
- A systematic literature search was conducted across PubMed, Embase, and Web of Science databases.
- Observational studies investigating the relationship between Hcy levels and uRPL were included.
- Pooled odds ratios (ORs) were calculated using a random-effects model to account for heterogeneity.
Main Results:
- Thirteen case-control studies involving 1,473 women with uRPL and 1,605 controls were analyzed.
- A significant association was found between HHcy and uRPL (OR 3.46, 95% CI 2.33-5.14).
- Subgroup analyses revealed consistent associations across different geographic regions and were influenced by Hcy cutoff definitions and measurement methods.
Conclusions:
- Elevated Hcy levels are significantly associated with an increased risk of uRPL.
- Variations in Hcy cutoff criteria contribute to heterogeneity in study findings.
- HHcy is supported as a potential risk indicator for uRPL, underscoring the need for prospective investigations.
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