Immunologic tests in the evaluation of reproductive disorders: a critical review

The purpose of this study was to evaluate the clinical usefulness of immunologic assays proposed to assist in the diagnosis of alloimmune causes of recurrent spontaneous abortion.

Human leukocyte antigen typing, maternal antipaternal lymphocytotoxic antibody testing, and mixed lymphocyte culture assays were performed on 609 couples with recurrent spontaneous abortion, 92 infertile couples, and 43 fertile couples. The frequency of HLA antigen sharing and the presence of lymphocytotoxic antibodies and mixed lymphocyte culture inhibitors was compared among the populations.

Sharing of two or more HLA-A, HLA-B, HLA-C, or HLA-DR antigens was observed in 41% (252/609) couples with recurrent spontaneous abortion and in 34% (31/92) with infertility compared with 63% (27/43) of fertile couples. The frequency of lymphocytotoxic antibodies to paternal cells was significantly greater in the fertile population (27/143, 63%) (p < 0.0001) than in couples with recurrent spontaneous abortion (160/609, 26%) and in infertile couples (7/92, 8%). Mixed lymphocyte culture inhibitors were also more prevalent in sera from fertile women (19/43, 44%) compared with those with recurrent spontaneous abortion (122/609, 20%) and infertile women (4/92, 4%).

Human leukocyte antigen sharing does not predict pregnancy outcome, and the presence of lymphocytotoxic antibodies and mixed lymphocyte culture inhibitors is a function of the number and duration of pregnancies. More sensitive and specific assays are needed to identify alloimmunologic causes of reproductive disorders.