BACKGROUND: Recurrent pregnancy loss (RPL) is defined as the occurrence of three or more consecutive miscarriages prior to 20 weeks gestation. Exaggerated maternal immune response to fetal antigens has been proposed to be one of the mechanisms underlying recurrent pregnancy loss. METHOD: A comprehensive literature search was conducted from the websites of the National Library of Medicine (http://www.ncbl.nlm.nih.gov) and Pubmed Central, the US National Library of Medicine's digital archive of life sciences literature (http://www.pubmedcentral.nih.gov/). The data was assessed from books and journals that published relevant articles in this field. RESULT: In normal pregnancy, tolerance of the genetically incompatible fetus by the maternal immune system depends on the interactions of an array of cytokines secreted by maternal and fetal cells at the site of implantation. Earlier research indicated that altered immunity in RPL is dominated by the Th1/Th2 hypothesis, which proposed that the fetus escapes maternal-derived T-cell responses through skewing the Th0 differentiation toward Th2 pathway which dampens pro-inflammatory Th1-type immunity. Recent studies indicate the role of proinflammatory Th17 cells and immunoregulatory Treg cells in RPL in addition to Th1/Th2 interactions. CONCLUSION: Cytokines form a complex regulatory network which maintains homeostasis between the fetal unit and the maternal immune system. If this delicate balance is adversely affected, immunoregulatory mechanisms may be insufficient to restore homeostasis and this may lead to pregnancy failure.
BACKGROUND: Recurrent pregnancy loss (RPL) is defined as the occurrence of three or more consecutive miscarriages prior to 20 weeks gestation. Exaggerated maternal immune response to fetal antigens has been proposed to be one of the mechanisms underlying recurrent pregnancy loss. METHOD: A comprehensive literature search was conducted from the websites of the National Library of Medicine (http://www.ncbl.nlm.nih.gov) and Pubmed Central, the US National Library of Medicine's digital archive of life sciences literature (http://www.pubmedcentral.nih.gov/). The data was assessed from books and journals that published relevant articles in this field. RESULT: In normal pregnancy, tolerance of the genetically incompatible fetus by the maternal immune system depends on the interactions of an array of cytokines secreted by maternal and fetal cells at the site of implantation. Earlier research indicated that altered immunity in RPL is dominated by the Th1/Th2 hypothesis, which proposed that the fetus escapes maternal-derived T-cell responses through skewing the Th0 differentiation toward Th2 pathway which dampens pro-inflammatory Th1-type immunity. Recent studies indicate the role of proinflammatory Th17 cells and immunoregulatory Treg cells in RPL in addition to Th1/Th2 interactions. CONCLUSION: Cytokines form a complex regulatory network which maintains homeostasis between the fetal unit and the maternal immune system. If this delicate balance is adversely affected, immunoregulatory mechanisms may be insufficient to restore homeostasis and this may lead to pregnancy failure.