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      A systematic review of noninvasive preimplantation genetic testing for aneuploidy

      , , ,
      Fertility and Sterility
      Elsevier BV

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          Abstract

          Noninvasive and minimally invasive preimplantation genetic testing for aneuploidy (PGT-A) is a tool that may one day become the gold standard for embryonic chromosomal screening. Investigations on this topic have ranged from studying the culture media of embryos to the fluid inside the blastocoel, all in an attempt to find a reliable source of DNA without the need to biopsy the embryo. There is great interest across the board, both from those for and against biopsy, in a reliable test process that would give the patient and provider the same information possible from a biopsy without the risk. We aim to explore the current available research to better understand the utility and accuracy of PGT-A with these new sampling techniques. General concordance rates in comparison with biopsy-based PGT-A are promising, but it is clear that additional research and understanding are needed before adopting noninvasive and minimally invasive PGT-A as a widely used tool with strong clinical utility.

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          Most cited references28

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          Noninvasive preimplantation genetic testing for aneuploidy in spent medium may be more reliable than trophectoderm biopsy

          Preimplantation genetic testing for aneuploidy (PGT-A) with trophectoderm (TE) biopsy is widely applied in in vitro fertilization (IVF) to identify aneuploid embryos. However, potential safety concerns regarding biopsy and restrictions to only those embryos suitable for biopsy pose limitations. In addition, embryo mosaicism gives rise to false positives and false negatives in PGT-A because the inner cell mass (ICM) cells, which give rise to the fetus, are not tested. Here, we report a critical examination of the efficacy of noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) in the spent culture media of human blastocysts by analyzing the cell-free DNA, which reflects ploidy of both the TE and ICM. Fifty-two frozen donated blastocysts with TE biopsy results were thawed; each of their spent culture medium was collected after 24-h culture and analyzed by next-generation sequencing (NGS). niPGT-A and TE-biopsy PGT-A results were compared with the sequencing results of the corresponding embryos, which were taken as true results for aneuploidy reporting. With removal of all corona-cumulus cells, the false-negative rate (FNR) for niPGT-A was found to be zero. By applying an appropriate threshold for mosaicism, both the positive predictive value (PPV) and specificity for niPGT-A were much higher than TE-biopsy PGT-A. Furthermore, the concordance rates for both embryo ploidy and chromosome copy numbers were higher for niPGT-A than TE-biopsy PGT-A. These results suggest that niPGT-A is less prone to errors associated with embryo mosaicism and is more reliable than TE-biopsy PGT-A.
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            Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization.

            Preimplantation genetic screening (PGS) is widely used to select in vitro-fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. Here, we present and validate a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. By using multiple annealing and looping-based amplification cycles (MALBAC) for whole-genome amplification (WGA), we performed next-generation sequencing (NGS) on the spent culture medium used to culture human blastocysts (n = 42) and obtained the ploidy information of all 24 chromosomes. We validated these results by comparing each with their corresponding whole donated embryo and obtained a high correlation for identification of chromosomal abnormalities (sensitivity, 0.882, and specificity, 0.840). With this validated NICS method, we performed chromosome screening on IVF embryos from seven couples with balanced translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved successful clinical pregnancies, and five have already achieved healthy live births thus far. The NICS method avoids the need for embryo biopsy and therefore substantially increases the safety of its use. The method has the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness.
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              Concordance analysis: part 16 of a series on evaluation of scientific publications.

              In this article, we describe qualitative and quantitative methods for assessing the degree of agreement (concordance) between two measuring or rating techniques. An assessment of concordance is particularly important when a new measuring technique is introduced. We give an example to illustrate a number of simple methods of comparing different measuring or rating techniques, and we explain the underlying principle of each method. We also give further illustrative examples from medical research papers that were retrieved by a selective literature search. Methods of comparing different measuring or rating techniques are of two kinds: those with a nominal rating scale and those with a continuous rating scale. We only discuss methods for comparing one measuring or rating technique with another one. Moreover, we point out some common erroneous approaches to concordance analysis. Concordance analysis is needed to establish the validity of a new diagnostic measuring or rating technique or to demonstrate the near-equivalence of multiple measuring or rating techniques. Erroneous approaches to concordance analysis can lead to false conclusions.
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                Author and article information

                Journal
                Fertility and Sterility
                Fertility and Sterility
                Elsevier BV
                00150282
                August 2023
                August 2023
                : 120
                : 2
                : 235-239
                Article
                10.1016/j.fertnstert.2023.06.013
                37356468
                bd5c6c9a-b9aa-4230-a4dc-bbd6c8a7b171
                © 2023

                https://www.elsevier.com/tdm/userlicense/1.0/

                http://creativecommons.org/licenses/by-nc-nd/4.0/

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