Blastocyst culture in the Era of PGS and FreezeAlls: Is a ‘C’ a failing grade?

Impact of Day 7 Blastocyst Transfer on Obstetric and Perinatal Outcome of Singletons Born After Vitrified-Warmed Embryo Transfer

“…Day 7 blastocyst could reach maturation with prolonged time after insemination and result in suboptimal ratio of inner cell mass (ICM) and trophectoderm (TE) to some extent (Campbell et al, 2013;Martin et al, 2017), namely increased proportion of inferior morphological grades, which may result in an underlying pathology of worse prognosis concerned with poor embryo quality. Similarly, those growth-retarded blastocysts was also concerned with damaged embryonic euploid viability (Capalbo et al, 2014;Irani et al, 2019), though our study did not found any difference in the risks of PTB, LBW, SGA, and the other adverse perinatal outcome after day 7 blastocysts transfer compared with matched groups of day 3, day 5, or day 6, which indicating that the negative effect of aneuploidy and poor embryo quality may mainly realize in failed implantation and clinical loss, while less resulted in affected babies (Capalbo et al, 2014;Morbeck, 2017;Du et al, 2018;Irani et al, 2019). Above all, in the interest of IVF strategy, in spite of the stage of embryos transferred or the cryopreservation protocols, it is to be remembered that we ultimately aimed for achieving a healthy live baby thus would stand a promising chance to grow into a healthy adult later in life.…”

“…Over the past decades, embryos that do not reach blastulation on day 6 have previously been discarded in the practice of laboratory standard (Shoukir et al, 1998), however, the conventional practice of ceasing embryo culture on day 6 has been challenged by recent studies, which have demonstrated that embryos with delayed blastulation on day 7 can still be clinical viable (Morbeck, 2017;Hammond et al, 2018), reach top morphological grade (Whitney et al, 2019), achieve euploid status (Minasi et al, 2016;Whitney et al, 2019) and result in healthy newborns (Richter et al, 2016;Du et al, 2018). In general, embryos that did not develop into blastocysts on day 5 were considered with higher risk of aneuploidy and impaired viability, which would result in compromised pregnancy outcomes including implantation failure and reduction in live births, especially for day 7 blastocyst (Shapiro et al, 2008;Kovalevsky et al, 2013;Zhao et al, 2015;Richter et al, 2016;Wirleitner et al, 2016;Du et al, 2018;Hernandez-Nieto et al, 2019).…”

Blastocyst score, a blastocyst quality ranking tool, is a predictor of blastocyst ploidy and implantation potential

“…On a cautionary note, these data could be influenced by selection bias, as BL with a ''C'' ICM grade is rarely chosen for transfer in our practice. The lack of data on embryos exhibiting poor ICM grade BL could also affect the statistical significance of the ICM grade (7). Oocyte source, fertilization method, and DUC did not appear to have an impact on BL implantation, confirming that DUC only impacts embryo implantation in early stage but not blastocyst stage (44).…”

“…[2] TE grading is relatively easier compared with ICM, which may lead to fewer variations between observers. The BL grading is subjective and reflected interobserver and intraobserver variance (7). Although the Gardner-based BL grading is widely used, the complexity of grade combinations and the lack of numeric scores with which to assign ranking diminishes its clinical value.…”

“…As aneuploidy is the major cause of implantation failure and pregnancy loss, preimplantation genetic testing for aneuploidy (PGT-A) has also been shown to improve implantation rates and lower miscarriage rates in patients of advanced maternal age (3)(4)(5)(6). With advancing molecular genetic techniques and improved embryo culture methods, current assisted reproductive technology practice is increasingly shifting to the use of BL culture and PGT-A, leading the way toward PGT-A freeze-all cycles (7). Despite the PGT-A randomized controlled trials in the past decades that reported improved ongoing pregnancy outcome, a recently published large Single Embryo TrAnsfeR of Euploid Embryo (STAR) trial (8) failed to find the outcome benefit from PGT-A versus morphology selection in good prognosis patients.…”