Genetic factors in fetal losses.

When all known causes of fetal losses are ruled out, there remains a small population of women (0.5-1.0%) who have recurrent fetal losses of unknown etiology. A significant proportion of these recurrent spontaneous abortions may be due to primarily genetic causes. The critical characteristic of couples experiencing such fetal losses is the sharing of HLA antigens between husband and wife. The hypothesis developed here states that the sharing of HLA antigens indicates the sharing of recessive lethal genes linked to the major histocompatibility antigens (MHC) and that the sharing of the antigens per se is not significant. These recessive lethal genes could act alone to cause fetal death, or they could act epistatically with lethal genes on other chromosomes. Several models of such genetic mechanisms and the observations from studies in experimental animals and from studies in humans to support these models are presented.