Every pregnancy is unique due to distinct maternal, paternal and fetal factors. Presumably, the immunological response differs between pregnancies, and certain pregnancies could be immunologically more challenging for the mother than others. In the present thesis, pregnancies presumed to be more immunologically challenging were studied. For example, in oocyte donation pregnancies, the fetus is completely allogeneic for the mother. Furthermore, based on findings in pregnancies complicated by pre-eclampsia and chronic intervillositis of unknown etiology (CIUE), it is postulated that the immune system plays a significant role in such pathophysiology. This thesis investigated oocyte donation pregnancies with and without pre-eclampsia and naturally conceived pregnancies complicated by pre-eclampsia or CIUE. Investigating immunologically challenging pregnancies improves our understanding of naturally conceived pregnancies and provides an interesting setting in which to test hypotheses relevant to transplantation immunology and tumour immunology. Henceforth, new discoveries in reproductive immunology could result in novel insights into the dynamics of the immune system. Future research should focus on more continuous study of the fetal-maternal interface during pregnancy and exploit the unique circumstances provided by some of the specific complications of pregnancy, such as FNAIT, ectopic pregnancies and placenta accreta.