Infertility Caused by hCG Autoantibody

An anti-hCG autoantibody was found in a patient with a 9-yr history of secondary infertility. Although the patient had regular menstrual cycles, had conceived spontaneously, and had good hormonal and follicular responses to gonadotropic stimulation regimens during the in vitro fertilization work-up, she presented with apparent recurrent pregnancy loss associated with prolonged raised hCG levels. Initially the presence of a high mol wt hCG complex was demonstrated in the serum by gel chromatography. The binding of [(125)I]recombinant hCG to a serum sample and subsequently to the affinity-purified IgG from the same sample revealed the presence of an hCG antibody. The antiserum was shown to be specific, with a low affinity (K(a), 1.4 x 10(6) liters/mol), but a high capacity (418 nmol/liter), for hCG. Cross-reaction with recombinant human FSH, recombinant human LH, hCG alpha, and hCG beta were low (<0.019%, 0.021%, 0.039%, and 0.006%, respectively). In addition, heat-inactivated serum and the affinity-purified IgG were shown to inhibit the action of hCG in an in vitro bioassay. We suggest that the persisting titer of the antibody to be responsible for the patient's infertility.