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

Abstract

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.

Zusammenfassung

Die Verbesserung der Erfolgsraten der assistierten Reproduktion hat sich bisher vor allem auf das Verständnis sowie die Optimierung der Embryoqualität konzentriert. Erst durch die Einführung der personalisierten Medizin im Rahmen der Ovulationsinduktion und in der Embryologie hat sich der Fokus auch auf den individuellen Status des Endometriums erweitert. Die endometriale Rezeptivität definiert den persönlichen Zeitraum, in dem sich der im Blastozystenstadium befindliche Embryo an das hormonell regulierte Endometrium einer Frau anheften und einnisten kann. Durch den 2011 patentierten Endometrial Receptivity Array (ERA) steht erstmals ein objektiver diagnostischer Test zur Bestimmung der rezeptiven Phase des Endometriums zur Verfügung. ERA identifiziert das transkriptomische Profil des Endometriums anhand der Signatur von 238 unterschiedlich exprimierten Genen in Verbindung mit einem computerbasierten Prädiktor und klassifiziert darauf beruhend den rezeptiven Status der Patientin. Die Bedeutung dieser personalisierten Untersuchung des Endometriums, die zwischen individueller physiologischer Variabilität der endometrialen Rezeptivität und unbekannter Pathologie des Endometriums unterscheiden kann, konnte sowohl durch uns als auch durch andere Gruppen bisher bei Patientinnen mit rezidivierendem Implantationsversagen (RIF) gezeigt werden. Auf diesen Ergebnissen aufbauend, wird der Nutzen von ERA in der Routinediagnostik bei unerfülltem Kinderwunsch aktuell in einer internationalen, randomisierten, kontrollierten Studie („The ERA as a diagnostic guide for personalized embryo transfer.“ ClinicalTrials.gov Identifier: NCT01954758) untersucht.

Key words

endometrial receptivity array (ERA) - microRNA - window of implantation - implantation failure - assisted reproduction

Schlüsselwörter

endometriale Rezeptivität - Implantationsfenster (WOI) - assistierte Reproduktionstechniken (ART) - micro-Ribonucleinsäure (RNA)

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