No abstract

The majority of embryos created through in vitro fertilization (IVF) do not implant. It seems plausible that rates of implantation would improve if we had a better understanding of molecular factors affecting embryo competence. Currently, the process of selecting an embryo for uterine transfer uses an ad hoc combination of morphological criteria, the kinetics of development, and genetic testing for aneuploidy. However, no single criterion can ensure selection of a viable embryo. In contrast, RNA-sequencing (RNA-seq) of embryos could yield high-dimensional data, which may provide additional insight and illuminate the discrepancies among current selection criteria. Recent advances enabling the production of RNAseq libraries from single cells have facilitated the application of this technique to the study of transcriptional events in early human development. However, these studies have not assessed the quality of their constituent embryos relative to commonly used embryological criteria. Here, we perform proof-of-principle advancement to embryo selection procedures by generating RNA-seq libraries from a trophectoderm biopsy as well as the remaining whole embryo. We combine state-of-the-art embryological methods with low-input RNA-seq to develop the first transcriptome-wide approach for assessing embryo competence. Specifically, we show the capacity of RNA-seq as a promising tool in preimplantation screening by showing that biopsies of an embryo can capture valuable information available in the whole embryo from which they are derived. Furthermore, we show that this technique can be used to generate a RNA-based digital karyotype and to identify candidate competence-associated genes. Together, these data establish the foundation for a future RNA-based diagnostic in IVF.

With increasing rates of diagnosis of childhood cancers and the evolution of more effective treatment options resulting in prolonged life spans, fertility preservation counseling is an integral component of the discussion at the time of diagnosis of childhood cancers. The primary fertility preservation option that exists for prepubertal girls is ovarian tissue cryopreservation. Although ovarian tissue cryopreservation is still considered to be experimental in nature, live births have resulted from orthotopic tissue transplantation. Fertility preservation should be offered to all prepubertal girls at high-risk for premature ovarian failure as a result of gonadotoxic treatment. Ethical and legal questions surrounding these issues must be considered as more and more pediatric patients pursue fertility preservation.