found that maternal carriage of HLA class II alleles that restrict anti-HY antigen responses reduces the chances of a live birth in secondary RM patients with a firstborn boy compared high throughput screening compounds with a firstborn girl (OR = 0·17; 95% CI = 0·1–0·4; P = 0·0001) [6]. In another study, the prevalence of a 14 base pair insertion in exon 8 of the HLA-G

gene was found to be increased significantly in secondary RM patients, compared with controls. These studies provide evidence that particular HLA polymorphisms characterize secondary RM [5-7]. Huge heterogeneity between eight randomized placebo-controlled trials of IVIg to patients with RM has been observed, with live birth rates in placebo groups ranging from 29 to 79% [8-15]. The differences in live birth rates observed between these studies raises questions as

to whether the patient categories are the same. Differences in IVIg treatment response in patients further supports the notion that primary and secondary RM patients should be investigated separately. Hutton et al., in a meta-analysis of placebo-controlled trials of IVIg in RM, found that the OR of achieving a live birth in primary and secondary RM was 0·66 and 2·71, respectively, suggesting Alectinib that IVIg may be effective in secondary RM patients, but not primary RM patients [16]. A recent meta-analysis of five placebo-controlled studies (Christiansen et al., unpublished data) found that the OR for an unsuccessful pregnancy in secondary RM patients was 0·74 (95% CI = 0·53–1·03, P = 0·07), suggesting that IVIg may be

beneficial for this patient subset. Currently, the efficacy of IVIg treatment in RM has not been determined conclusively. However, evaluation of randomized control trials indicates that IVIg may be a promising treatment for secondary RM. Previously conducted studies have been small and heterogeneous. Furthermore, the borderline significance observed in our meta-analysis indicates that further studies should be conducted to determine the efficacy of IVIg treatment in secondary RM. In addition to the heterogeneity observed in the patient population studied, IVIg treatment doses and intervals also varied in different studies, from 20 g every 3 weeks to 55 g every week [10-12, 15]. Furthermore, treatment initiation Edoxaban varied between studies, with several trials beginning after gestational week 6/7, when most of the ‘risk time’ had elapsed. The trials were also very heterogeneous with regard to the intensity of treatment; in some trials only two infusions of 20 g were given in the first trimester, whereas in other trials seven infusions of 55 g IVIg were administered, which may partly explain the very different results [10, 12]. Larger randomized controlled trials are needed to provide more definitive conclusions on the efficacy of IVIg treatment. The largest double-blind, randomized, placebo-controlled trial of IVIg (Privigen®) in 82 women with secondary RM conducted over a period of 5 years will be published in 2014.