Diagnosis of Endometrial-Factor Infertility: Current Approaches and New Avenues for Research

Over the last decade, research to improve success rates in reproductive medicine has focused predominantly on the understanding and optimization of embryo quality. However, the emergence of personalized medicine in ovulation induction and embryology has shifted the focus to assessing the individual status of the endometrium. The endometrium is considered receptive during an individually defined period, the window of implantation (WOI), when the mother permits a blastocyst to attach and implant. This individual receptivity status can now be objectively diagnosed using the endometrial receptivity array (ERA) developed in 2011. The ERA, together with a computational algorithm, detects the unique transcriptomic signature of endometrial receptivity by analyzing 238 differentially expressed genes and reliably predicting the WOI. We and others have illustrated the utility of this personalized diagnostic approach to discriminate between individual physiological variation in endometrial receptivity and unknown endometrial pathology, deemed as causal in recurrent implantation failure (RIF). An international randomized controlled trial ("The ERA as a diagnostic guide for personalized embryo transfer." ClinicalTrials.gov Identifier: NCT01954758) is underway to determine the clinical value of this endometrial diagnostic intervention in the work-up for reproductive care. In this review, we analyse the current clinical practice in the diagnosis of the endometrial factor together with new avenues of research.