About this Research Topic
Advances in Preimplantation Genetic Testing for Aneuploidy (PGT-A), with improvements and implementation of new technologies, make it feasible to reliably detect mosaicism, intermediate chromosomal copy number changes in biopsy samples of preimplantation embryos. This has brought to light the biological phenomenon of mosaicism, the coexistence of cells with distinct chromosomal content within an embryo. The clinical management of in-vitro fertilization (IVF) cycles utilizing PGT-A was challenged with the reports of healthy babies after mosaic embryo transfers. In spite of continuous debate on the biological and clinical significance of mosaicism (including ethical constraints), current professional associations recommend considering mosaic (euploid-aneuploid) embryos for transfer. Personalized IVF treatment with the selection of the most developmentally competent embryo for transfer requires precise assessment and consideration of the complexities surrounding preimplantation testing of embryos and critical evaluation of clinical outcomes.
Over the last several years there has been a continuous increase in the volume and diversity of indications for PGT-A testing in assisted reproductive technologies (ART), evolving into a near-routine test used to select against aneuploidy in embryos and improve transfer outcomes. Approximately 15% of all tested embryos are diagnosed as mosaic - a percentage that has been shown to vary between genetic testing labs and IVF laboratories. There is a noted discrepancy in the utilization of mosaicism in the PGT-A reports, further increasing the gap to personalized patient care. Next generation sequencing (NGS) technologies and/or improved data analysis algorithms used in PGT-A now produce enhanced information, including the origin of aneuploidy detected (meiotic/meiotic), higher resolution and sensitivity in detection of copy number variants (CNV) from whole chromosome (chr) aneuploidy and small segmental chr deletions/duplications, as well as polyploidy and haploidy. On average, mosaic embryos have reduced developmental potential with an increased chance of no implantation or miscarriage compared to euploid embryos. While many mosaic embryo transfers have resulted in babies, the selection of mosaic embryos for transfer is a significant clinical problem as the management and counselling of patients is empirical and based on limited outcome data. Systematic and detailed follow-up studies on pregnancies, neonatal and long-term development from such embryos are needed especially to evaluate the impact of “level” (percentage of abnormal cells) of mosaicism, type (segmental or whole chromosome), and influence of specific chromosome involved in the aberration. Compelling data from single-cell analysis of human embryos utilizing new technical and bioinformatic tools offer unprecedented genomic and multiomic insight at these early stages of development, elucidating the mechanisms that ensure proper cell division and differentiation.
The goal of this Topic on embryo mosaicism is to gather the leading and multifaceted expertise of scientists working in this field, share their knowledge and experience, and advance this field of Reproductive Genetics. Papers are sought that expand the knowledge on mosaicism in human embryos covering the origin and biological concepts underlying mosaicism, especially with data from experimental studies on preimplantation and post-implantation embryos, and data from prenatal assessment of placenta and foetuses. The advancements in diagnostic technologies and data analysis, especially with the new prospect of adopting multiomics in embryo assessment and utilization of non-invasive assessment, allow for a multidimensional view of mosaicism to understand its origin and mechanisms behind observed clinical outcomes. In addition, it is necessary to integrate the aspect of IVF, culturing, and embryo manipulation as contributing factors in the occurrence of mosaicism. While long-term follow-up data on the health of IVF-conceived individuals is very limited, accumulating clinical experience of mosaic embryo transfers, pregnancy, and neonatal follow-up studies, including genetic counselling and ethical considerations, should be systematically and critically evaluated.
Svetlana Madjunkova is employed by CReATe Fertility Centre. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
Over the last several years there has been a continuous increase in the volume and diversity of indications for PGT-A testing in assisted reproductive technologies (ART), evolving into a near-routine test used to select against aneuploidy in embryos and improve transfer outcomes. Approximately 15% of all tested embryos are diagnosed as mosaic - a percentage that has been shown to vary between genetic testing labs and IVF laboratories. There is a noted discrepancy in the utilization of mosaicism in the PGT-A reports, further increasing the gap to personalized patient care. Next generation sequencing (NGS) technologies and/or improved data analysis algorithms used in PGT-A now produce enhanced information, including the origin of aneuploidy detected (meiotic/meiotic), higher resolution and sensitivity in detection of copy number variants (CNV) from whole chromosome (chr) aneuploidy and small segmental chr deletions/duplications, as well as polyploidy and haploidy. On average, mosaic embryos have reduced developmental potential with an increased chance of no implantation or miscarriage compared to euploid embryos. While many mosaic embryo transfers have resulted in babies, the selection of mosaic embryos for transfer is a significant clinical problem as the management and counselling of patients is empirical and based on limited outcome data. Systematic and detailed follow-up studies on pregnancies, neonatal and long-term development from such embryos are needed especially to evaluate the impact of “level” (percentage of abnormal cells) of mosaicism, type (segmental or whole chromosome), and influence of specific chromosome involved in the aberration. Compelling data from single-cell analysis of human embryos utilizing new technical and bioinformatic tools offer unprecedented genomic and multiomic insight at these early stages of development, elucidating the mechanisms that ensure proper cell division and differentiation.
The goal of this Topic on embryo mosaicism is to gather the leading and multifaceted expertise of scientists working in this field, share their knowledge and experience, and advance this field of Reproductive Genetics. Papers are sought that expand the knowledge on mosaicism in human embryos covering the origin and biological concepts underlying mosaicism, especially with data from experimental studies on preimplantation and post-implantation embryos, and data from prenatal assessment of placenta and foetuses. The advancements in diagnostic technologies and data analysis, especially with the new prospect of adopting multiomics in embryo assessment and utilization of non-invasive assessment, allow for a multidimensional view of mosaicism to understand its origin and mechanisms behind observed clinical outcomes. In addition, it is necessary to integrate the aspect of IVF, culturing, and embryo manipulation as contributing factors in the occurrence of mosaicism. While long-term follow-up data on the health of IVF-conceived individuals is very limited, accumulating clinical experience of mosaic embryo transfers, pregnancy, and neonatal follow-up studies, including genetic counselling and ethical considerations, should be systematically and critically evaluated.
Svetlana Madjunkova is employed by CReATe Fertility Centre. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
Keywords: Mosaicism, PGT-A, CNV, aneuploidy, euploidy, pregnancy outcomes, mitotic errors, next generation sequencing, technical error, trophectoderm biopsy, NiPGT, multiomic assessment of embryos, single-cell analysis
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