Abstract
Applications and indications of assisted reproduction technology are expanding, but every new approach is under scrutiny and thorough consideration. Recently, groups of assisted reproduction experts have presented data that support the clinical use of mosaic preimplantation embryos at the blastocyst stage, previously excluded from transfer. In the light of published contemporary studies, with or without clinical outcomes, there is growing evidence that mosaic embryos have the capacity for further in utero development and live birth. Our in-depth discussion will enable readers to better comprehend current developments. This expansion into the spectrum of ART practices requires further evidence and further theoretical documentation, basic research, and ethical support. Therefore, if strict criteria for selecting competent mosaic preimplantation embryos for further transfer, implantation, fetal growth, and healthy birth are applied, fewer embryos will be excluded, and more live births will be achieved. Our review aims to discuss the recent literature on the transfer of mosaic preimplantation embryos. It also highlights controversies as far as the clinical utilization of preimplantation embryos concerns. Finally, it provides the appropriate background to elucidate and highlight cellular and genetic aspects of this novel direction.
Highlights
It is widely accepted, based on single-cell studies, that the clonal cell expansion throughout development and differentiation allows individual cells to deviate—within certain limits of uncertainty—in replication proofreading, recombination, point mutation generation, methylation maintenance, histone modification, and cell cycle control [1,2]
We focus on the deviations which are relevant to the transfer of mosaic preimplantation embryos
In 2009, the assisted reproductive technology (ART) scientific community was overwhelmed when Vanneste et al, 2009 in their work published in Nature, claimed that one of the most prominent hallmarks of tumorigenesis, namely the chromosome instability, is a common phenomenon in the cleavage-stage human embryos derived from normal fertile women, but not in the preceding premeiotic or meiotic cell cycle stages [12]
Summary
It is widely accepted, based on single-cell studies, that the clonal cell expansion throughout development and differentiation allows individual cells to deviate—within certain limits of uncertainty—in replication proofreading, recombination, point mutation generation, methylation maintenance, histone modification, and cell cycle control [1,2]. We still do not know the impact of each particular intervention on each gamete or each embryo generated by the ART process. This is due to the fact that we cannot have a spontaneous control for each ART case. The possibility of recombination outnumbers by far the number of humans on earth, which currently amounts to approximately 7,340,000,000 This is the measure of diversity with all potential recombination modes, which is a complex and diverse process implicating at least three main mechanisms: homologous, non-homologous and replicative recombination. As a matter of fact, recombinations are as high as 50% in the oocyte than in the sperm These differences draw a striking picture of chances within the embryo and between cells [9]. Two of the most recent and disputed interventions, namely the spindle transfer for oocyte-inherited mitochondrial diseases as well as germline and embryo gene therapies, still have a long way to go until concordance—concerning the ethical and biological issues—is reached [11]
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