An endometrial gene expression signature accurately predicts recurrent implantation failure after IVF

Abstract

The primary limiting factor for effective IVF treatment is successful embryo implantation. Recurrent implantation failure (RIF) is a condition whereby couples fail to achieve pregnancy despite consecutive embryo transfers. Here we describe the collection of gene expression profiles from mid-luteal phase endometrial biopsies (n = 115) from women experiencing RIF and healthy controls. Using a signature discovery set (n = 81) we identify a signature containing 303 genes predictive of RIF. Independent validation in 34 samples shows that the gene signature predicts RIF with 100% positive predictive value (PPV). The strength of the RIF associated expression signature also stratifies RIF patients into distinct groups with different subsequent implantation success rates. Exploration of the expression changes suggests that RIF is primarily associated with reduced cellular proliferation. The gene signature will be of value in counselling and guiding further treatment of women who fail to conceive upon IVF and suggests new avenues for developing intervention.

Therapeutic endometrial scratching and implantation after in vitro fertilization: a multicenter randomized controlled trial

“…The subgroup of women with RIF are therefore more likely to have an endometrium-associated implantation failure, in contrast to the subgroup of women with one or two previous implantation failures. This result echoes a recent finding in which RIF patients were reported to have a specific endometrial gene expression profile predictive of RIF when compared with non RIF patients (20). To conclude that endometrial scratching may enhance the clinical pregnancy rate in RIF patients, we compared baseline and cycle characteristics in the subgroups as well (Supplemental Table 3).…”

A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function

“…Based on these GATA2 reporter genes originally derived from the mouse (Fig. 6A, top panel), we then determined the human GATA2 gene activities in individual endometrial tissue of 115 human samples (GSE58144) (Koot et al, 2016). A positive correlation between GATA2 levels and activities in human samples just as in mouse was observed (Fig.…”

Development of the human placenta

“…As they decidualise, the stromal cells secrete a rim of basement membrane proteins, fibronectin and laminin, which provides a scaffold for the EVT to move through (Aplin et al, 1988). Exactly what defines the characteristics of a receptive decidualised endometrium that will support the developing placenta is still unclear (Koot et al, 2016;Young, 2017). This is an important issue because evidence to suggest that defective decidualisation is an antecedent of pregnancy disorders is growing (Conrad et al, 2017;Garrido-Gomez et al, 2017).…”