Non-invasive pre-implantation genetic testing of human embryos: an emerging concept

Farra, Chantal; Choucair, Fadi; Awwad, Johnny

doi:10.1093/humrep/dey314

Cited by 27 publications

(19 citation statements)

References 33 publications

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“…A less invasive alternative is to analyse genomic DNA from embryo culture medium or blastocyst cavity fluid [9–14]. Culture medium may be a more reliable source because screening of blastocyst cavity fluid often gives results inconsistent with those from embryo biopsy [11–17].…”

Section: Introductionmentioning

confidence: 99%

Chromosome screening using culture medium of embryos fertilised in vitro: a pilot clinical study

et al. 2019

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Background Previous studies from this as well as other research groups suggested that non-invasive chromosome screening (NICS) with embryo culture medium can be used to identify chromosomal ploidy and chromosomal abnormalities. We here report a series of clinical cases utilizing the technology. Methods A total of 45 couples underwent in vitro fertilisation during a period between February 2016 and February 2017. Karyotyping revealed normal chromosomes in both partners in 23 couples, and chromosomal rearrangements in at least one partner in 22 couples. Intracytoplasmic sperm injection (ICSI) was used for fertilization. NICS was carried out using embryo culture medium at the blastocyst stage via multiple annealing and looping-based amplification cycles, whole-genome amplification and next-generation sequencing. Results A total of 413 embryos were obtained; 170 blastocysts were subjected to NICS. The screening showed euploidy in 79 embryos, aneuploidy in 52 embryos, and mosaic ploidy for 33 embryos. The rate of euploidy was comparable in couples with normal karyotype (50.7%; 38/75) vs. chromosomal rearrangement (43.2%; 41/95). A total of 52 euploid embryos (50 oocyte retrieval cycles) were transferred in 43 women. Biochemical pregnancy rate was 72.0% (36/50). Clinical pregnancy rate was 58.0% (29/50). The rate of spontaneous miscarriage was 3/29 (none with chromosomal aneuploidy). A total of 27 healthy babies were delivered. Conclusions NICS could identify embryo chromosomal abnormalities in couples either with or without chromosomal rearrangement, with satisfying clinical outcomes. Electronic supplementary material The online version of this article (10.1186/s12967-019-1827-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Chromosome screening using culture medium of embryos fertilised in vitro: a pilot clinical study

et al. 2019

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“…One of the biggest challenges in the field of PGT is to validate a non-invasive procedure for the genetic diagnosis of in-vitro developing embryos (Kuliev and Rechitsky, 2017;Farra et al, 2018;Munne, 2018), with the aim of improving PGT cost-efficiency and safety ( not affect the embryo development and reproductive potential. Moreover, SCM can be collected at any pre-implantation developmental stage; even cleaved embryos with fewer than six cells at day 3 and early blastocysts can be tested, unlike invasive PGT, which is based on embryo biopsy or blastocentesis.…”

Section: Discussionmentioning

confidence: 99%

Is cell-free DNA in spent embryo culture medium an alternative to embryo biopsy for preimplantation genetic testing? A systematic review

Brouillet

Martinez

Coutton

et al. 2020

Reproductive BioMedicine Online

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Spent culture medium (SCM) represents a possible source of embryonic DNA for non-invasive preimplantation genetic testing (PGT). Before considering routine clinical use, methodologies need to be improved to increase detection of embryo DNA in SCM while preventing contamination by exogenous and maternal DNA. The identification of DNA origin (in particular, maternal versus embryonic) is necessary for improved reliability of SCM-PGT. ABSTRACTPreimplantation genetic testing (PGT) is increasingly used worldwide. It currently entails the use of invasive techniques, i.e. polar body, blastomere, trophectoderm biopsy or blastocentesis, to obtain embryonic DNA, with major technical limitations and ethical issues. Evidence suggests that invasive PGT can lead to genetic misdiagnosis in the case of embryo mosaicism, and, consequently, to the selection of affected embryos for implantation or to the destruction of healthy embryos. Recently, spent culture medium (SCM) has been proposed as an alternative source of embryonic DNA. An increasing number of studies have reported the detection of cell-free DNA in SCM and highlighted the diagnostic potential of non-invasive SCM-based PGT for assessing the genetic status of preimplantation human embryos obtained by IVF. The reliability of this approach for clinical applications, however, needs to be determined. In this systematic review, published evidence on non-invasive SCM-based PGT is presented, and its current benefits and limitations compared with invasive PGT. Then, ways of optimizing and standardizing procedures for non-invasive SCM-based PGT to prevent technical biases and to improve performance in future studies are discussed. Finally, clinical perspectives of non-invasive PGT are presented and its future applications in reproductive medicine highlighted.

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“…Recently, cell‐free DNA has also been detected in blastocyst‐spent culture media but no agreement on concordance rate with the genetic status of embryos has been found . Although both strategies appear to be attractive methods, they are characterized by some limitations including the incomplete representation of the whole embryonic genome, the potential maternal DNA contamination, the poor nucleic acid integrity and the unknown sampling time points to obtain acceptable amplification rates . Well‐designed studies are needed to evaluate the efficacy of cell‐free DNA employment on clinical outcomes.…”

Section: Threatsmentioning

confidence: 99%

Assessment of pre‐implantation genetic testing for embryo aneuploidies: A SWOT analysis

et al. 2019

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The recently re‐named pre‐implantation genetic testing for determining embryo aneuploidies (PGT‐A) is presently very popular although its acceptance by the scientific community is controversial. This approach still encounters drawbacks. This paper uses a SWOT (strengths, weaknesses, opportunities and threats) analysis to discuss salient points to be considered when examining the pre‐implantation genetic testing (PGT‐A) strategy to gather information from a range of perspectives. One of the strengths associated with the procedure is represented by an increase in implantation rate although data from the highest level of evidence do not support an increase in cumulative pregnancy rates. The current difficulty in the management of mosaicisms represents a weakness of PGT‐A. The application of the strategy represents an opportunity to favor the single embryo transfer while other advantages, such as reduction of time to pregnancy and emotional distress are controversial. Potential important threats, at present still undefined, are represented by the biopsy‐related damage to the blastocyst and the impact on neonatal and long‐term outcomes.

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Non-invasive pre-implantation genetic testing of human embryos: an emerging concept

Cited by 27 publications

References 33 publications

Chromosome screening using culture medium of embryos fertilised in vitro: a pilot clinical study

Chromosome screening using culture medium of embryos fertilised in vitro: a pilot clinical study

Is cell-free DNA in spent embryo culture medium an alternative to embryo biopsy for preimplantation genetic testing? A systematic review

Assessment of pre‐implantation genetic testing for embryo aneuploidies: A SWOT analysis

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