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BLASTOMERE CLEAVAGE SYNCHRONICITY IN NONINVASIVE SELECTION OF EUPLOID EMBRYOS WITH HIGH IMPLANTATION POTENTIAL
Introduction:
We have developed a new noninvasive method of euploid embryo selection based on the hypothesis that embryos with synchronously cleaving blastomeres are mostly euploid with greater likelihood of implantation, and that aneuploid embryos tend to cleave asynchronously. It was reported that chromosome segregation during meiosis or mitosis in human does not occur simultaneously and randomly. The time period necessary for
complete chromosome segregation depends on the number of chromosomes; it varies for aneuploid and euploid cells of the same species. We hypothesized that the cell cycle duration also depends on the ploidy of the cells of the same type and same species. Given that aneuploidy of blastomeres leads to embryo mosaicism, we assumed that blastomeres of mosaic embryos do not cleave synchronously due to the different cell cycle duration
of cells with varying number of chromosomes. Blastomere division synchronicity in preimplantation embryos might become an efficient noninvasive criterion for selecting euploid embryos for embryo transfer, partially replacing preimplantation genetic diagnosis (PGD) for aneuploidy. The aim of this study is to prove our hypothesis that embryos with synchronously cleaving blastomeres have higher probabilities to implant and aneuploid embryos cleave mostly asynchronously.
Materials and Methods:
A mathematical model was developed to calculate the probability of implantation for an individual embryo based on the pregnancy outcome of 6032 in vitro fertilization (IVF) cycles with one or two embryos transferred, which took place between 2004 and 2010. Cleavage was deemed synchronous if the embryo had 4 blastomeres on Day 2 and 8 cells on Day 3 of cultivation. We calculated the implantation probability for embryos with 4, 5, 6, 7, 8, 9, 10, and 12 blastomeres on Day 3, as well as the probability of singleton and multiple pregnancies and the
selection of the pair of embryos best for transfer. The cleavage synchronicity rate was calculated for each type of aneuploidy.
Results:
Synchronously cleaving embryos with 8 blastomeres on Day 3 of development had the highest probability to implant (0.366±0.012). The implantation probability of the embryos with 4 cells on Day 3 and synchronous cleavage was 0.301±0.034.
The 6-cell Day 3 embryos with asynchronously cleavage were characterized by the markedly lower probability of implantation (0.197±0.019); embryos with speediest cleavage (attaining 12 blastomeres on Day 3) had the lowest implantation probability (0.118±0.062). PGD for aneuploidy of 278 embryos demonstrated correlation between cell division synchronicity and aneuploidy of embryos; 80% of embryos with aneuploidy detected by PGD
divided asynchronously, whereas 53% of euploid embryos divided synchronously. Thus, PGD has confirmed our hypothesis that embryos with synchronously cleaving blastomeres tend to be euploid with good implantation prognosis. The link between the synchronicity of embryo cleavage and aneuploidy rate provides us with a instrument for noninvasive selection of embryos in order to minimize fetal abnormalities and decrease the
frequency of multiple pregnancies.
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