Chromothripsis

Brittany L. Daughtry, Shawn L. Chavez, Daughtry, Brittany L., Chavez, Shawn L.

The use of time-lapse microscopic imaging has proven to be a powerful tool for the study of mitotic divisions and other cellular processes across diverse species and cell types. Although time-lapse monitoring (TLM) of human preimplantation development was first introduced to the in vitro fertilization (IVF) community several decades ago, it was not until relatively recently that TLM systems were commercialized for clinical embryology purposes. Traditionally, human IVF embryos are assessed by successful progression and morphology under a stereomicroscope at distinct time points prior to selection for transfer. Due to the high frequency of aneuploidy, embryos may also be biopsied at the cleavage or blastocyst stage for preimplantation genetic screening (PGS) of whole and/or partial chromosomal abnormalities. However, embryo biopsy is invasive and can hinder subsequent development, and there are additional concerns over chromosomal mosaicism and resolution with PGS. Moreover, embryos are typically outside of the incubator in suboptimal culture conditions for extended periods of time during these procedures. With TLM systems, embryos remain in the stable microenvironment of an incubator and are simultaneously imaged for noninvasive embryo evaluation using a fraction of the light exposure as compared to a stereomicroscope. Each image is then compiled into a time-lapse movie, the information from which can be extrapolated to correlate morphological, spatial, and temporal parameters with embryo quality and copy number status. Here, we describe the various TLM systems available for clinical and/or research use in detail and provide step-by-step instructions on how the measurement of specific timing intervals and certain morphological criteria can be implemented into IVF protocols to enhance embryo assessment and avoid the selection of aneuploid embryos. We also discuss the biological significance of processes unique to mitotically dividing embryos and the likelihood that complex chromosomal events such as chromothripsis occur during preimplantation development in humans and other mammals, particularly nonhuman primates.