Immunogenetic contributions to recurrent pregnancy loss

Abstract

While sporadic pregnancy loss is common, occurring in 15 % of pregnancies, recurrent pregnancy loss (RPL) impacts approximately 5 % of couples. Though multiple causes are known (including structural, hormonal, infectious, autoimmune, and thrombophilic causes), after evaluation, roughly half of all cases remain unexplained. The idiopathic RPL cases pose a challenging therapeutic dilemma in addition to incurring much physical and emotional morbidity. Immunogenetic causes have been postulated to contribute to these cases of RPL. Natural Killer cell, T cell expression pattern changes in the endometrium have both been shown in patients with RPL. Human leukocyte antigen (HLA) and cytokine allelic variations have also been studied as etiologies for RPL. Some of the results have been promising, however the studies are small and have not yet put forth outcomes that would change our current diagnosis and management of RPL. Larger database studies are needed with stricter control criteria before reasonable conclusions can be drawn.

Obesity and recurrent miscarriage: A systematic review and meta‐analysis

“…Several immunological disorders have been discussed as possible causes of idiopathic RPL; these disorders manifested most commonly in the first weeks of pregnancy . Among the main immunological mechanisms studied, the following are of particular importance: hyperactivity of natural killer cells; imbalance of T‐helper 1 (Th1) and Th2 response, with a predominance of Th1 response and low concentration of regulatory T cells, CD4+ CD25+ FoxP3+ …”

“…Obesity is a condition of chronic inflammation, as evidenced by numerous markers, such as high levels of C‐reactive protein (CRP) and interleukin‐6 (IL‐6) . Similarities in the immunological profiles of obese women and women with a history of idiopathic RPL may be the starting point for explaining the high risk of obstetric complications in these groups of women, from the difficulty of embryo implantation to complications in childbirth and in the post‐partum period …”

Maternal recurrent pregnancy loss is associated with an increased risk for long‐term neurological morbidity in offspring

“…Antiphospholipid antibody syndrome is the hallmark of this phenomenon, with a well‐established autoimmune pathogenesis leading to RPLs . Other autoimmune disorders, such as systemic lupus erythematous, inflammatory bowel disease, autoimmune thyroiditis, coeliac disease, and even isolated elevated autoantibodies, were also found to be associated with higher RPL rates . Adequate management, sometimes involving systemic steroids, may control abnormal immune processes and prevent losses .…”

“…25 Other autoimmune disorders, such as systemic lupus erythematous, inflammatory bowel disease, autoimmune thyroiditis, coeliac disease, and even isolated elevated autoantibodies, were also found to be associated with higher RPL rates. 26 Adequate management, sometimes involving systemic steroids, may control abnormal immune processes and prevent losses. 27 However, maternal autoimmunity may also play a role in the neurological development of the offspring, as evident from studies focusing on maternal systemic autoimmune diseases and offspring neurological outcome.…”

Recurrent Pregnancy Loss in Women with Hashimoto's Thyroiditis with Concurrent Non-Endocrine Autoimmune Disorders

“…Autoimmune abnormalities play a relevant role in RPL and represent one of the several accepted causes of miscarriage (7). Among them, an increasing amount of evidence links thyroid autoimmunity with adverse pregnancy outcomes, including miscarriage or preterm deliveries.…”