ABSTRACT
INTRODUCTION e main challenge of assisted reproduction technology (ART) has always been to achieve pregnancies resulting in healthy live births for infertile couples and patients. Embryo selection methods have historically been based on microscopically evaluating morphology at dierent time points that have resulted in a signicant improvement in pregnancy rates1,2 and a reduced number of multiple pregnancies. Moreover, using new instruments that provide continuous images of embryos has further improved embryo selection and resulting pregnancy rates.2,3
e addition of new genomic, transcriptomic, proteomic, and metabolomic technologies that supersede traditional morphological methods has led to the proposal of new approaches for improving embryo selection that can provide more information and/or increase the accuracy of selection. For example, by analyzing embryo culture media, the metabolite content can be determined noninvasively, which might be used to assess embryo viability. Nutrients required for embryo development and implantation may change during in vitro embryo culture, and these variations might provide us with information about the metabolic activity of the embryo. Indeed, several retrospective studies have reported associations between the metabolomic prole and clinical outcomes.4-7 e metabolism of embryos cultured for in vitro fertilization (IVF) oen varies because embryos are adapting to the stressful conditions that they are subjected to by the variations in culture conditions.8,9 However, other procedures, such as cryopreservation, are even more demanding on the embryo, and can adversely aect metabolism and development and thus also clinical results. Several reports describe the eects of cryopreservation on embryos or oocytes; for example, Zhao et al. report a reduction in the expression of DNA methyltransferase 1 (Dnmt1) mRNA expression in mouse oocytes.10 At the metabolic level, studies also found eects on the metabolism of murine embryos frozen in late pre-implantation development.11 In humans, Tachataki et al. reported that freezing embryos altered their gene expression proles, and that day 2 frozen embryos contained less mRNA for the tuberous sclerosis gene TSC2 than fresh day 2 embryos. However, several studies report the births of healthy children aer the prior use of dierent vitrication approaches,12 which provide information about the survival, embryonic development, and clinical outcomes
obtained from using vitried oocytes. Nonetheless, there is little evidence in the literature regarding the eects that these techniques may have on early human embryo metabolism.
