Association between HLA-DR1 and -DR3 antigens and unexplained repeated miscarriage

Few, mostly small, studies have investigated the distribution of HLA class II antigens among women with unexplained recurrent miscarriage. Although some studies have reported statistically significant associations between this syndrome and certain HLA-DR antigens--especially the -DR1 and -DR3 antigens--other studies have been unable to demonstrate such associations. For the present meta-analysis, 18 cross-sectional or case-control studies (published or unpublished) reporting on frequencies of HLA-DR1 and -DR3 antigens among Caucasian women with unexplained repeated miscarriage were identified by searching literature databases (MEDLINE and EMBASE), reading the references of identified studies, and by contacting researchers within the field. The studies comprised a total of 1508 patients. The methodological quality of most of the studies was low, especially because of small numbers of patients and because patients with only two miscarriages were included in many studies; this is defined as repeated miscarriage. The odds ratios of repeated miscarriage for the HLA-DR1 and -DR3 antigens were calculated for the individual studies and subsequently the pooled odds ratios for the studies were calculated. The combined odds ratio for HLA-DR1 was 1.29 [95% confidence interval (CI) = 1.05-1.58] (17 studies) which is statistically significant (P <0.05). The combined odds ratio for HLA-DR3 was 1.00 (95% CI 0.80-1.24) (18 studies), which is not significant. The results of the meta-analysis suggest that the HLA-DR antigen DR1 is associated with an increased susceptibility to unexplained repeated miscarriage.