REPRODUCTIVE FAILURE AND THE MAJOR HISTOCOMPATIBILITY COMPLEX

The association between HLA sharing and recurrent spontaneous abortion (RSA) was tested in 123 couples and the association between HLA shari ng, and the outcome of treatment for unexplained infertility by in vit ro fertilization (IVF) was tested in 76 couples, by using a new shared -allele test in order to identify more precisely the region of the maj or histocompatibility complex (MHC) influencing these reproductive def ects. The shared-allele test circumvents the problem of rare alleles a t HLA loci and at the same time provides a substantial gain in power o ver the simple chi(2) test. Two statistical methods, a corrected homog eneity test and a bootstrap approach, were developed to compare the al lele frequencies at each of the HLA-A, HLA-B, HLA-DR, and HLA-DQ loci; they were not statistically different among the three patient groups and the control group. There was a significant excess of HLA-DR sharin g in couples with RSA and a significant excess of HLA-DQ sharing in co uples with unexplained infertility who failed treatment by IVF. These findings indicate that genes located in different parts of the class I I region of the MHC affect different aspects of reproduction and stron gly suggest that the sharing of HLA antigens per se is not the mechani sm involved in the reproductive defects. The segment of the MHC that h as genes affecting reproduction also has genes associated with differe nt autoimmune diseases, and this juxtaposition may explain the associa tion between reproductive defects and autoimmune diseases.