Protection of sperm from isoimmune attack in vivo by pretreatment with antisperm Fab: fertility trials in the immune rabbit model.

We tested the hypothesis that binding of rabbit isoimmune antisperm Fab fragments to rabbit sperm prior to artificial insemination could protect the sperm from isoimmune attack in vivo and lead to normal pregnancy and healthy offspring in isoimmune does. Twenty-four female rabbits and 4 males were used. Twelve does were immunized with rabbit sperm to induce isoimmunity and 12 does immunized with adjuvant/saline served as controls. Following 5 immunizations, the immune serum IgG fraction and its Fab fragments were prepared. The does from the control group and isoimmune group were artificially inseminated following the 6th and 7th immunization with untreated sperm or sperm pretreated with antisperm IgG or Fab in quadruplicates and allowed to complete a pregnancy. Three fertility trials were performed to investigate the therapeutic efficacy of Fab-coated sperm to restore fertility in isoimmune does. In the 3 fertility trials, none of the isoimmune does inseminated with untreated sperm had a successful pregnancy. By contrast, in 3 cases, rabbit sperm pretreated with antisperm Fab were able to fertilize in vivo with successful pregnancy in a control and isoimmune doe resulting in normal offspring. These results demonstrate that in vitro treatment of sperm with antisperm Fab fragments had a protective effect from isoimmune attack in vivo. The successful use of Fab fragments for reversal of antisperm antibody-mediated infertility observed in the isoimmune rabbit model offers the prospect of a new means of restoring fertility in some isoimmune women.