Prognostic significance of maternal DR histocompatibility types in Danish women with recurrent miscarriages

In a previous case-control study of women with unexplained recurrent miscarriages we reported that the frequency of women positive for each of the two histocompatibility (HLA) types HLA-DR1, Br and HLA-DR3 was increased in a subset of patients with a history of four or more miscarriages. In the present study we examined whether the increased frequency of the two HLA types in this subset of patients indicated that they would result in a poor pregnancy prognosis. We related pregnancy outcomes to the mothers' HLA-DR type in a prospective study of a well-defined, closely supervised group of 94 women with unexplained recurrent miscarriages who had achieved intra-uterine pregnancy in the course of one of two prospective placebo-controlled trials concerning the efficacy of immunotherapy. Of the patients who were HLA-DR1, Br and/or HLA-DR3 positive 62% miscarried their next pregnancy compared with 29% of the patients negative for the two HLA types [relative risk of miscarriage in the former group = 2.2 (P < 0.002) unadjusted, and 1.8 (P = 0.025) when adjusted for the number of previous miscarriages]. The results suggest that Danish women with unexplained recurrent miscarriages who are positive for HLA-DR1, Br and/or -DR3 display a poorer pregnancy outcome than patients negative for these types.