Recurrent Spontaneous Abortion

Recurrent spontaneous abortion (RSA) is defined as the occurrence of three or more spontaneous abortions and occurs in about 2-4% of women.1 About 50% of RSA cases can be attributed to chromosomal anomalies, endocrine disorders, or anatomical abnormalities.7,37'73 Immunological explanations have been sought to explain the remaining 50% unexplained RSA. Recent evidence in humans suggests that perturbations in the balance of pro- and anti-inflammatory cytokine expression is associated with RSA. Women with a history of RSA exhibit decreased IL-10 expression in peripheral blood mononuclear cells (PBMC).45,66,67 However, these observations are accumulated in response to PBMC activation by polyclonal or recall antigens and do not address the status of local IL-10 production. Our recent work clearly demonstrated a lack of IL-10 production in decidual and placental tissue from patients with spontaneous abortion.64 In addition, serum cytokine levels of IL-10 appear lower in women suffering from RSA than women experiencing normal pregnancy.46

It may be expected that IL-10 promoter polymorphisms may influence pregnancy outcomes, with low-production phenotypes perhaps associated with increased risk of pregnancy abnormalities. Several studies have investigated this potential role in the etiology of RSA, yielding conflicting results.4,12 However, it should be understood that cytokines often influence and modulate the expression and functions of other cytokines. Pro- and anti-inflammatory cytokines counter-regulate each other such that the balance between their expression is crucial, not their individual expression levels. Women with IL-10 high-production promoter haplotypes that experience RSA may also have high-production promoter haplotypes of pro-inflammatory cytokine promoters or are otherwise prone to severe inflammation. The converse may be true for women with low IL-10-production promoter haplotypes that experience normal pregnancies.

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