Influence of Histocompatibility Antigens in Recurrent Spontaneous Abortion Couples and on Their Reproductive Performances

Abstract

The results suggest that gene(s) disadvantageous for reproduction may exist between the HLA-B and -DR chromosomal region which influences the pregnancy outcome in RSA couples, and that HLA-antigen sharing itself does not influence the outcome.

Immunotherapy with Paternal Lymphocytes for Recurrent Miscarriages and Unsuccessful in vitro Fertilization Treatment

“…Therefore, the original hypothesis of a strong HLA compatibility as a cause of RA [26,27] cannot be corroborated with our data [9,28,29].…”

Alloimmune Causes of Recurrent Pregnancy Loss

“…10,16 Some investigators have found increased HLA sharing in all regions of the MHC, 6,10,[17][18][19][20] especially in the HLA-B and HLA-DR loci. [21][22][23][24][25][26][27] Others have found no difference in HLA sharing between couples with recurrent pregnancy loss and fertile controls. 8,28-34 Some investigators have reported an association between spe-cific HLA haplotypes and alleles and an increased risk for pregnancy loss.…”

“…24,[35][36][37][38][39][40] However, others have found no association between recurrent pregnancy loss and specific HLA types. 26,27,34,41 There are several possible explanations for the confusing and sometimes conflicting data regarding HLA sharing in couples with recurrent pregnancy loss. Studies differ with regard to HLA alleles tested, methods of HLA typing, definitions of recurrent pregnancy loss, the type of controls used, and the heterogeneity of ethnic groups included.…”

“…Only one study tested abortus specimens and liveborn infants as well as fathers and reported fewer cases of HLA-DQA1 compatible liveborn children than expected. 42 Very few studies have been prospective and most, 9,20,25,27 but not all, 42 report an increased risk of subsequent pregnancy loss in couples with increased HLA sharing. Interestingly, in two studies the risk of spontaneous abortion was not increased when more than one (as opposed to one) HLA antigen was shared by parents, suggesting that HLA sharing is not directly responsible for miscarriage.…”

“…Interestingly, in two studies the risk of spontaneous abortion was not increased when more than one (as opposed to one) HLA antigen was shared by parents, suggesting that HLA sharing is not directly responsible for miscarriage. 9,27 Instead, the association between HLA sharing and pregnancy loss may be due to sharing of genes linked to the HLA region that influence reproductive outcome. 26,27 In the 10-year prospective study of HLA sharing and RPL in 111 Hutterite couples, Ober et al 20 reported that matching for the entire 16-locus haplotype was associated with RPL.…”