Nick Macklon, M.D., Ph.D.  Fertility and Sterility 

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Presentation transcript:

Recurrent implantation failure is a pathology with a specific transcriptomic signature  Nick Macklon, M.D., Ph.D.  Fertility and Sterility  Volume 108, Issue 1, Pages 9-14 (July 2017) DOI: 10.1016/j.fertnstert.2017.05.028 Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Support vector machine (SVM) classifier results on the (A) signature discovery and (B) validation sets of a 303-gene recurrent implantation failure (RIF) signature. (A) SVM classifier scores for the signature discovery set (RIF patients: red; control subjects: blue). Samples with a score <0.5 are predicted to be control subjects, and those with a score of ≥0.5 are predicted to be RIF patients (the threshold is shown as a dotted line). (B) All samples from the validation set, scored based on the SVM classifier. (C) receiver operating characteristic curves for the results shown in a (blue line) and b (green line). Areas under the receiver operating characteristic curve (AUC) with 95% confidence intervals are shown next to the curves. Reproduced with permission from Koot et al. (22). Fertility and Sterility 2017 108, 9-14DOI: (10.1016/j.fertnstert.2017.05.028) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Gene expression of recurrent implantation failure (RIF) patients compared with control subjects (log2 fold change or M value) and the average expression across all samples (log2 sample intensity). (A–C) Each focus on an example of a gene ontology (GO) term which was found to be significant in gene set enrichment analysis. Genes in the GO term that are up-regulated in RIF patients are shown in yellow, down-regulated in blue. Shown in red are other genes that are part of the 303-gene signature. Genes that are not part of the GO term are shown as a blue density map, where darker blue indicates higher gene density. (D) All of the genes of the gene signature. Reproduced with permission from Koot et al. (22). Fertility and Sterility 2017 108, 9-14DOI: (10.1016/j.fertnstert.2017.05.028) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions

Figure 3 Schematic representation of the possible clinical consequences of dysbalance between the selective and receptive functions of the decidualized endometrium. Whereas excessive receptivity and poor selectivity may result in inappropriate implantation of poorly viable embryos, which may present as recurrent early pregnancy loss, poor-receptivity couples with excessive selectivity may present as recurrent implantation failure. Reproduced with permission from Macklon and Brosens (28). Fertility and Sterility 2017 108, 9-14DOI: (10.1016/j.fertnstert.2017.05.028) Copyright © 2017 American Society for Reproductive Medicine Terms and Conditions