Do human embryos have the ability of self-correction?
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(2020) 18:98
RESEARCH
Open Access
Do human embryos have the ability of selfcorrection? Raoul Orvieto1,2,3* , Chen Shimon1, Shlomit Rienstein2,4, Anat Jonish-Grossman4, Hagit Shani2,4 and Adva Aizer1,2
Abstract Human embryogenesis frequently coinciding with cell division mistakes contributing to pervasive embryonic aneuploidy/mosaicism. While embryo self-correction was elegantly demonstrated in mouse models, human studies are lacking. Here we are witness to human embryos ability to eliminate/expel abnormal blastomeres as cell debris/ fragments. Each blastocyst and its corresponding debris were separated and underwent whole genome amplification. Seven of the 11 pairs of blastocysts and their corresponding cell debris/fragments revealed discordant results. Of the 9 euploid blastocysts, four showed euploid debris, while in the others, the debris were aneuploid. In the remaining pairs, the debris showed additional aneuploidy to those presented by their corresponding blastocyst. The observed ability of human embryos to self-correction doubts many invasive and non-invasive preimplantation testing for aneuploidy at the blastocyst stage, rendering high rate of false positive (discarding “good” embryos) by identifying the cell-free DNA originated from the expelled cell debris, as aneuploidy/mosaic blastocyst. Keywords: Self-correction, PGT, Human embryo, Blastocyst, Mosaicism
Introduction The first stages of human embryogenesis are characterized by rapid cell proliferation, which frequently coinciding with cell division mistakes, generating changes in chromosome content, e.g. aneuploidy [1–3]. Oocyte meiotic aneuploidies may result from non-disjunction or premature separation of a chromosome into sister chromatids [4], and appears in the whole embryo’s cells [4, 5]. Along with errors in meiosis, mitotic errors during post-zygotic cell division contribute to pervasive aneuploidy in human embryos [6]. Mitotic mistakes are common, with the highest occurrence through the first three cleavages after fertilization [7]. Consequently, the majority of the human preimplantation embryos show aneuploidies that appears mainly as a diploid–aneuploid mosaicism. As with meiotic errors, mitotic mistakes also decrease with embryonic development. This was * Correspondence: [email protected] 1 Infertility and IVF Unit, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center (Tel Hashomer), 56261 Ramat Gan, Israel 2 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel Full list of author information is available at the end of the article
elegantly observed while re-analyzing blastocyst-stage embryos, which were detected as aneuploid at the cleavage stage (Day-3) [8–10]. Mosaicism has been reported in, as high as 50% of cleavage- and blastocyst-stage embryos derived from IVF [11]. Preliminary studies suggest that “mosaic” embryos display low rates of concordance between multiple trophectoderm (TE) biopsies. Moreover, “mosaic” embryos demonstrate increased cell proliferation and cell death in comparis
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