Key metrics and processes for validating embryo diagnostics

      Embryo diagnostics are somewhat controversial in clinical assisted reproduction technology (ART) practice and remain an active area of investigation. Application of embryo diagnostics holds great potential to raise the standard of clinical care by eliminating futile transfers, allowing highly effective single-embryo transfer, and reducing the probability of clinical loss and ongoing abnormal gestations. These advantages are accompanied by risks, principally the chance that a reproductively competent embryo will be mislabeled and discarded. This would lower the ultimate probability that one or more of the embryos might implant and lead to delivery of a healthy infant. Rigorous validation should be required for embryo diagnostics. Metrics for validation can be divided into three simple areas: analytical validation, determination of clinical predictive values for normal and abnormal test results, and a randomized clinical trial to demonstrate that the selection advantage gained through the diagnostic improves clinical outcomes.

      Key Words

      To read this article in full you will need to make a payment


        • Rosenwaks Z.
        • Handyside A.H.
        • Fiorentino F.
        • Gleicher N.
        • Paulson R.J.
        • Schattman G.L.
        • et al.
        The pros and cons of preimplantation genetic testing for aneuploidy: clinical and laboratory perspectives.
        Fertil Steril. 2018; 110: 353-361
        • Hall S.S.
        A new last chance: there could soon be a baby-boom among women who thought they’d hit an IVF dead end.
        New York Magazine. 2017; (September 18–October 1, 2017)
        • Neal S.R.
        • Morin S.J.
        • Franasiak J.M.
        • Juneau C.R.
        • Forman E.J.
        • Werner M.D.
        • Scott Jr., R.T.
        Preimplantation genetic testing for aneuploidy is cost-effective, shortens treatment time, and reduces the risk of failed embryo transfer and clinical miscarriage.
        Fertil Steril. 2018; 110: 896-904
        • Herrero J.
        • Meseguer M.
        Selection of high potential embryos using time-lapse imaging: the era of morphokinetics.
        Fertil Steril. 2013; 99: 1030-1034
        • Paulson R.J.
        • Reichman D.E.
        • Zaninovic N.
        • Goodman L.R.
        • Racowsky C.
        Time-lapse imaging: clearly useful to both laboratory personnel and patient outcomes versus just because we can doesn’t mean we should.
        Fertil Steril. 2018; 109: 584-591
        • Forman E.J.
        • Hong K.H.
        • Ferry K.M.
        • Tao X.
        • Taylor D.
        • Levy B.
        • et al.
        In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial.
        Fertil Steril. 2013; 100: 100-107.e1
        • Zimmerman R.S.
        • Jalas C.
        • Tao X.
        • Fedick A.M.
        • Kim J.
        • Pepe R.J.
        • et al.
        Development and validation of concurrent preimplantation genetic diagnosis for single gene disorders and comprehensive chromosomal aneuploidy screening without whole-genome amplification.
        Fertil Steril. 2016; 105: 286-294
        • Scott Jr., R.T.
        • Ferry K.M.
        • Su J.
        • Tao X.
        • Scott K.L.
        • Treff N.R.
        Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, non-selection study.
        Fertil Steril. 2012; 97: 870-875
        • National Academies of Sciences, Engineering, and Medicine
        • Health and Medicine Division; Board on Health Care Services
        • Board on the Health of Select Populations
        • Committee on the Evidence Base for Genetic Testing
        Genetic test assessment.
        An evidence framework for genetic testing. National Academies Press, Washington, DC2017 (chapter 3. Available at:)