Embryo assessment strategies and their validation for clinical use: a critical analysis of methodology

A multitude of novel embryo assessment strategies using genomics, transcriptomics, proteomics, and metabolomics approaches are being developed in order to improve upon the currently utilized embryo assessment methods based on morphology and cleavage rate. Although these novel technologies promise significant improvements in clinical outcome for women undergoing infertility treatment with in-vitro fertilization, their validation poses significant challenges. In this review, we discuss the appropriate steps to be taken in clinical validation of an embryo assessment test. We then provide a critical analysis of the studies evaluating embryo assessment strategies from a methodological perspective.

Validation of a novel embryo assessment test requires the determination of appropriate performance parameters (such as sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve), followed by clinical validation using appropriate study design. Finally, benefit from a test, alone or in combination with currently used methods, needs to be tested using a prospective randomized controlled trial study design. Few studies on existing or novel embryo assessment methods provide these parameters.

Validation of a test is a rigorous process that needs to be handled meticulously, using appropriate performance parameters determined by the inherent characteristics of the test and clinical studies with appropriate design.