Pushing the limits of detection: investigation of cell-free DNA for aneuploidy screening in embryos

Abstract

cfDNA is detectable on days 3 and 5, but more accurate on day 5. Although our data suggest moderate concordance rates, PGT-A with the use of cfDNA must be further optimized before clinical implementation.

Outcome of in vitro fertilization cycles with preimplantation genetic testing for aneuploidies: let’s be honest with one another

“…Just as IVF outcomes have improved since the birth of Louise Brown, so will our ability to detect aneuploidy in embryos precisely and non-invasively. The non-invasive collection of cell-free DNA from the culture dish currently looks promising (5). Science, in order to advance, demands a culture of scrutiny of data and skepticism.…”

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

“…The sample size ranged from seven (Shamonki et al, 2016;Liu et al, 2017) to 70 (Hammond et al, 2017) couples undergoing assisted reproductive technology procedures. Gamete fertilization was carried out mainly by intracytoplasmic sperm injection (ICSI) (86.7% [13 out of 15]) (Stigliani et al, 2013;Wu et al, 2015;Shamonki et al, 2016;Xu et al, 2016;Feichtinger et al, 2017;Hammond et al, 2017;Liu et al, 2017;Yang et al, 2017;Capalbo et al, 2018;Ho et al, 2018;Kuznyetsov et al, 2018;Li et al, 2018;Vera-Rodriguez et al, 2018) and the other two studies did not report the fertilization method Galluzzi et al, 2015). In 86.6% (13 out of 15) of studies, Cf-DNA from SCM alone was evaluated (Stigliani et al, 2013;Assou et al, 2014;Galluzzi et al, 2015;Wu et al, 2015;Shamonki et al, 2016;Xu et al, 2016;Feichtinger et al, 2017;Liu et al, 2017;Capalbo et al, 2018;Ho et al, 2018;Vera-Rodriguez et al, 2018), whereas a mixture of SCM and blastocoel fluid was assessed in 26.7% (four out of 15) of them (Hammond et al, 2017;Yang et al, 2017;Kuznyetsov et al, 2018;Li et al, 2018).…”

“…The characteristics of the embryos associated with each SCM sample were also heterogeneous. Specifically, 93.3% (14 out of 15) studies evaluated cf-DNA released from fresh embryos (Stigliani et al, 2013;Galluzzi et al, 2015;Wu et al, 2015;Shamonki et al, 2016;Xu et al, 2016;Hammond et al, 2017;Liu et al, 2017;Yang et al, 2017;Feichtinger et al, 2017;Capalbo et al, 2018;Ho et al, 2018;Kuznyetsov et al, 2018;Li et al, 2018;Vera-Rodriguez et al, 2018), and 20.0% (three out of 15) of studies Kuznyetsov et al, 2018;Ho et al, 2018) assessed cf-DNA secreted from cryopreserved embryos. Moreover, embryo micromanipulation, e.g.…”

“…Moreover, embryo micromanipulation, e.g. assisted hatching and blastocoel collapse or embryo biopsy, was carried out before SCM sampling in 60.0% (nine out of 15) of studies Shamonki et al, 2016;Feichtinger et al, 2017;Hammond et al, 2017;Yang et al, 2017;Ho et al, 2018;Kuznyetsov et al, 2018;Li et al, 2018; Vera-Rodriguez FIGURE 2 Flow chart of search strategy and study inclusion (Moher et al, ). et al, 2018.…”

In vitro fertilisation/intracytoplasmic sperm injection beyond 2020

“…With limited evidence that well studied tools such as time-lapse morphokinetics and metabolomics of spent embryo media improve clinical outcomes, focus is now moving to cell-free DNA (cf-DNA) for aneuploidy screening in embryos. [16][17][18] Despite greater accuracy with cf-DNA from spent culture media (SCM) after day 5 than after day 3, the ploidy concordance rate of cf-DNA of SCM compared with that of trophectoderm biopsy is limited, reported as 65% by Ho et al 19 and 84% by Xu et al 20 It is possible that maternal contamination from the cumulus complex cells and mosaicism might contribute to diagnostic inaccuracy. 19,21 More promisingly, comparison between cf-DNA from blastocoel fluid (BF) aspirated from blastocysts and trophectoderm biopsy reveals a very high ploidy concordance of 97%, 22 although other groups have not reported such high figures.…”