Miscarriage and Its Associations

Stephen Brown, M.D.


Semin Reprod Med. 2008;26(5):391-400. 

In This Article


The idea that allele sharing of HLA antigens between mothers and fathers can disrupt the normal maternal immune response to the fetal "allograft" and thereby cause miscarriage has been active for many years.[48,49] This theory led to the idea that immunization of women experiencing recurrent abortion with lymphocytes from their partners could help prevent "alloimmune-mediated" pregnancy loss.[50,51] Over the ensuing years, there were many publications purporting to show efficacy of this type of treatment[52] whereas others disputed it.[53] Most recently, a large and methodologically sound randomized controlled trial failed to show any benefit to immunotherapy with paternal lymphocytes,[54] effectively ending the practice of immunizing mothers with their partners' lymphocytes.

Interestingly, the concept that allele sharing at the human lymphocyte antigen (HLA) locus has a role in miscarriage may still be correct. Ober et al have shown that in a highly inbred population, sharing of HLA loci is associated with an increased risk of pregnancy loss.[55] Although statistically significant, the effect was modest, and the authors note that it may not be immunologically mediated. Overall, it seems safe to conclude that immune-mediated pregnancy loss, while it may exist, is not a major contributor to the overall problem of pregnancy loss.


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