Current topic: HLA and reproduction: lessons from studies in the Hutterites.

The paradoxical observation that maternal-fetal incompatibility with respect to human leucocyte antigen (HLA) genes was not associated with spontaneous abortion, stillbirths or developmental abnormalities led to the hypothesis that fetuses with paternally-derived HLA that differ from maternal HLA may enjoy a selective advantage during pregnancy. If true, then couples who share HLA should experience poorer reproductive outcome than couples not sharing HLA. Numerous, retrospective studies of parental HLA sharing and fetal wastage in humans have yielded conflicting results and discrepancies are difficult to reconcile because of methodological differences among studies and potential heterogeneity among subjects. To explore the hypothesis that maternal-fetal HLA compatibility is deleterious in human pregnancy, we initiated prospective and population-based studies in the Hutterites, a religious isolate that lives communally and proscribes contraception. Our data suggest that HLA-DR-linked genes may affect fertilization or implantation and HLA-B-linked genes may contribute toward recognized fetal loss. Discrepant results among retrospective studies of outbred couples may be due to the fact that more than one HLA region influences reproductive outcome and that the genes influencing fertility may not be HLA genes per se, but loci in linkage disequilibrium with HLA-B and HLA-DR.