Sharing of human leukocyte antigens in couples with unexplained infertility affects the success of in vitro fertilization and tubal embryo transfer

OBJECTIVE: The purpose was to test further our hypothesis that genes, or genetic defects, linked to the major histocompatibility complex affect reproduction by correlating human leukocyte antigen sharing with the success or failure of in vitro fertilization and tubal embryo transfer in couples having unexplained infertility. STUDY DESIGN: Seventy-six couples with unexplained infertility who failed superovulation and intrauterine insemination at least three times were typed for human leukocyte antigens and treated by in vitro fertilization and tubal embryo transfer. The results were correlated with the sharing of human leukocyte antigens in the couples. RESULTS: Thirty-four of the women had successful pregnancies, 36 did not become pregnant, and six became pregnant but aborted shortly thereafter. There was a highly significant excess of human leukocyte antigen sharing in the couples who failed treatment: three of the A, B, DR, and DQ antigens (p = 0.015) or two of the B, DR, and DQ antigens (p = 0.015). No specific human leukocyte antigen alleles were present in excess. CONCLUSIONS: Genes, or genetic defects, linked to the major histocompatibility complex significantly affect the success of in vitro fertilization and tubal embryo transfer just as they affect the prevalence of recurrent spontaneous abortion, cancer, and congenital anomalies. It appears as if the critical genes, or genetic defects, are located in the B-DR-DQ region of the major histocompatibility complex. (AM J OBSTET GYNECOL 1994;170:63-71.)