A FRESH LOOK AT THE CAUSES AND TREATMENTS OF RECURRENT MISCARRIAGE, ESPECIALLY ITS IMMUNOLOGICAL ASPECTS

The scientific basis for many traditionally accepted causes of recurre nt miscarriage (RM) is weak, A significant proportion of RM cases with relatively few miscarriages can presumably be attributed to the rando m occurrence of consecutive chromosomally abnormal conceptions, New in sights in the immunological interactions taking place at the fete-mate rnal interface provide us with the opportunity to propose detailed pat hophysiological models for immunologically mediated RM, Scientific sup port for the theory that RM is a consequence of graft rejection-like a llo-immune reactions against paternal human leukocyte antigens on the fetus is sparse. Conversely, there is considerable evidence that decid ual natural killer cells play a role in the implantation and early inv asion of the trophoblast and in the pathogenesis of RM, T helper (T-h) cells from women with RM react against trophoblast antigens in vitro with the secretion of mainly interleukin-2 and interferon-gamma (a so- called T(h)1 response), which are known to inhibit trophoblast growth, The predisposition to a T(h)1 response against a given antigen may be determined by an individual's class II histocompatibility genes, In a ccordance with this, case-control, prospective and family studies indi cate that maternal histocompatibility haplotypes comprising DR1 and DR 3 alleles confer susceptibility to RM, The frequent occurrence of auto antibodies in women with RM is compatible with the theory of a T(h)1 r esponse against trophoblast as a cause of the syndrome, but the autoan tibodies themselves probably do not cause RM.