Objective:

To evaluate the association between elevated homocysteine (Hcy) levels and unexplained recurrent pregnancy loss (uRPL) using categorical exposure definitions and to explore potential sources of heterogeneity.

Approach:

Key Findings:

• Thirteencase–controlstudiescomprising1,473womenwithuRPLand1,605controlswereincluded.Overall,HHcywassignificantlyassociatedwithuRPL(OR3.46,95%CI2.33–5.14;I²=57%).Subgroupanalysesshowedconsistentassociationsacrossgeographicregions,withpooledORsof4.41inAsia,2.96inEurope,and2.59inAfrica/MiddleEast.TheassociationwasstrongerinstudieswithHcycutoff>12μmol/L(OR4.02)comparedto≤12μmol/L(OR2.00).Meta-regressionidentifiedHcycutoffasasignificantcontributortoheterogeneity.

Interpretation:

Elevated Hcy levels are associated with increased odds of uRPL, with variations in Hcy cutoff definitions potentially explaining between-study heterogeneity.

Limitations:

• The study is limited by the observational nature of included studies.
• Variability in Hcy measurement methods and cutoff definitions may affect the results.
• Further prospective studies are warranted to confirm these findings.

Conclusion:

These findings support HHcy as a potential risk indicator in uRPL.

Sources:

• Systematic Review Registration
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