Clinical, immunologic, and genetic definitions of primary and secondary recurrent spontaneous abortions.

Fifty couples with repeated pregnancy failures were grouped by clinical history as being primary (no children) or secondary (abortions subsequent to having children or stillbirths) aborters. Human leukocyte antigen (HLA) sharing between husband and wife and maternal antipaternal immunity were studied in both groups. Analyses showed significantly more HLA-A, B, and DR locus antigens shared in the primary abortion group than in the secondary abortion group (P = 0.01). The number of couples sharing two to five HLA antigens was higher for those couples with primary abortions than for secondary abortions (P = 0.009). Antipaternal immunity as measured by visual complement-dependent lymphocytotoxicity (CDCE), by 51Cr release (CDC51Cr), and by complement-independent, antibody-dependent cell-mediated cytotoxic (ADCC) assays was different between the two groups. CDCE was not present in the primary aborters' sera but was found in 13 of the 15 secondary aborters' sera (P = 0.0001). Similarly, ADCC was not apparent in primary aborters but was present in 14 of the 15 secondary aborters (P = 0.0001). CDC51Cr was detected in 3 of the 11 primary aborters and in 13 of the 15 secondary aborters (P = 0.008). Such differences in HLA sharing and immune reactivities between these two groups strengthen the idea that either inadequate or inappropriately vigorous maternal antipaternal immunity can be related to spontaneous abortions. These results uphold a central role for immunology in human reproduction and provide further support for the use of immunotherapy to prevent pregnancy losses in certain abortion-prone women.