Clinical value of research in chronic spontaneous abortion.

We have focused on comparisons of abnormal with normal pregnancies. Humoral and cellular aspects were studied in 50 couples with unexplained consecutive pregnancy failures and compared with 15 fertile couples. The results show that spontaneous aborters generally fall into two groups: Primary spontaneous aborters are those women who, by the same husband, never have carried a pregnancy beyond 20 weeks; secondary spontaneous aborters have had, by the same husband, either a normal pregnancy or a pregnancy failure beyond the 20th week. Primary spontaneous aborting couples tend to share a significantly greater number of HLA antigens than do secondary aborters or normally fertile mates. Secondary spontaneous aborters manifest cytotoxic non-HLA-dependent antibody to husbands' lymphocytes in complement-dependent assays; these are antibodies to trophoblast-lymphocyte cross-reactive (TLX) antigens. Secondary but not primary aborters have complement-independent antibody-dependent cell-mediated cytotoxicity reactions to their husbands' lymphocytes. Both exhibit diminished mixed lymphocyte culture reactions between mating partners if the tests are done in autologous plasma; only primary aborters show poor reactions if the assays are done in control sera. Immunotherapy with nonhusband lymphocytes in more than 20 primary spontaneous aborters has resulted in greater than 90% successful subsequent pregnancies. Leukocyte immunotherapy has not been useful for secondary aborters, but two of three women have had normal pregnancies following daily subcutaneous injections of heparin. The clinical relevance of these findings will be discussed.