Eravani and S. Alizadeh (Pasteur Institute of Iran). Special thanks to Dr Nariman Aghaei Bandbon Balenga (Medical University of Graz) for helpful

discussion on neutrophil isolation. Financial support was Pirfenidone order provided by Iran Ministry of Health and Pasteur Institute of Iran. “
“Recurrent miscarriage (RM) is the occurrence of three or more consecutive miscarriages before gestational week 20 and is a condition that affects 1–3% of women [1]. RM can be classified into two categories: primary RM (no prior live birth) or secondary RM (three or more consecutive miscarriages following a live birth). In addition to genetic and anatomical factors causing RM, many studies have suggested that signs of autoimmunity and dysregulation of natural killer (NK) cell immunity characterize women with RM. Approximately 25 years ago, the first pilot studies on the use of intravenous immunoglobulin (IVIg) for the treatment of RM were conducted and reported a live birth rate of 80–82% [2, 3], which provided support to warrant further investigation in placebo-controlled trials. In 2006, a Cochrane review Selleck Panobinostat of IVIg treatment for RM in

eight placebo-controlled trials with 303 RM patients was conducted, concluding that IVIg did not increase live birth rates when compared to placebo [odds ratio (OR) = 0·98; 95% confidence interval (CI) = 0·61–1·58] [4]. However, this review did not differentiate between primary and secondary RM patients. Separate analysis of these two subsets of RM patients may be necessary, as several studies have observed that secondary RM is a condition dominated by immunological risk factors when compared to primary RM, suggesting large heterogeneity between these two subgroups. Tumour necrosis factor (TNF)-α is a cytokine involved in the immune system’s inflammatory response. Piosik et al. analysed peripheral blood samples of RM patients taken at gestational week 5, and found that TNF-α levels were increased significantly in secondary RM patients compared to primary RM patients (P = 0·042) [1]. This indicates that Nintedanib (BIBF 1120) secondary RM is a condition with an increased proinflammatory

response in early pregnancy. More evidence of the role of immunological factors in secondary RM has been reported in studies that have shown associations between secondary RM patients with specific maternal human leucocyte antigen (HLA) polymorphisms. Kruse et al. found that there was a significantly higher prevalence of the HLA-DRB1*03 allele in secondary RM patients compared with controls (OR = 1·8; 95% CI = 1·3–2·5) [5], whereas the allele was not increased in patients with primary RM. A previous pregnancy with a boy can be a risk factor for secondary RM. In general, maternal immune recognition of male-specific minor histocompatibility (HY) antigens expressed in male fetal and trophoblast cells is well tolerated, resulting in a live birth. However, pregnancy with a boy may prime the mother’s HY immunity.