The importance of cytoplasmic strings during early human embryonic development

Abstract

Objectives: During human in vitro fertilisation (IVF) treatments, embryologists attempt to select the most viable embryos for embryo transfer (ET). Previously, embryos were evaluated based on light microscopic morphological parameters. However, this is currently accomplished by morphokinetic analysis of time-lapse recordings. This technique provides us the opportunity to observe cytoplasmic strings at the blastocyst stage. The aim of this work was to examine the relationship between the presence of cytoplasmic strings (CS) and the embryo viability in human in vitro fertilised embryos.Study design: Herein, we present an evaluation of the morphokinetic data on the development of embryos obtained during IVF treatments performed at the Division of Assisted Reproduction between December 2020 and March 2021. The dynamics of embryo development, embryo morphology, and morphokinetic scores generated by a time-lapse system were compared between the presence of cytoplasmic strings (CS+) and their absence (CS-) at the blastocyst stage.Results: The development of 208 embryos from 78 patients was examined. Moreover, 81.2% of the embryos had CS in the blastocyst stage; 77% of CS existed in embryos created by conventional IVF, while 86% of CS existed in embryos fertilised by intracytoplasmic sperm injection (ICSI) (p = 0.08). A greater number of CS+ embryos developed into a higher quality blastocyst (52.1% vs. 20.5%, p = 0.02). The morphokinetic score values characterising the development of embryos, such as Known Implantation Data Score (KIDScore) and Intelligent Data Analysis (iDAScore), were higher in CS+ groups (KID: 6.1 ± 2.1 vs. 4.7 ± 2.07; iDA: 8.0 ± 1.9 vs. 6.8 ± 2.3, p < 0.01). The dynamics of the early embryo development were similar between the two groups; however, CS+ embryos reached the blastocyst stage significantly earlier (tB: 103.9 h vs. tB: 107.6 h; p = 0.001).Conclusion: Based on our results, the number of embryos with cytoplasmic strings was higher than that without cytoplasmic strings, and its presence is not related to the fertilisation method. These embryos reached the blastocyst stage earlier, and their morphokinetic (KIDScore and iDAScore) parameters were better. All these results suggest that the presence of CS indicates higher embryo viability. The examination of this feature may help us make decisions about the embryos with higher implantation potential.

Insights into embryonic chromosomal instability: mechanisms of DNA elimination during mammalian preimplantation development

“…However, the study did observe that complex chromosomal abnormalities are more commonly observed in TE cells than the inner cell mass (ICM). For this work, the TE and ICM were separated by biopsy prior to disaggregation into single cells, which can result in cross contamination between cell types due to cytoplasmic strings that connect the ICM to TE cells ( Ebner et al, 2020 ; Joo et al, 2023 ). Thus, additional studies are needed to confirm each lineage by isolating both DNA and RNA from the same individual cell for scDNA-seq and gene expression ( Macaulay et al, 2015 ; Macaulay et al, 2016 ), respectively.…”

Developmental perturbation in human embryos: Clinical and biological significance learned from time‐lapse images

“…“Cytoplasmic strings” that bridge the inner cell mass and TE are commonly present in early blastocysts (approximately 55%–85%) and may withdraw as the blastocyst expands (Video S28 ). 56 , 179 , 180 These strings are suggested to play a role in the direct communication between the mural TE and inner cell mass cells. 181 …”

“…Instead, it is a positive predictor of pregnancy outcomes, although the cytoplasmic strings are associated with increased blastocyst spontaneous collapse. 179 , 180 , 183 , 184 Consequently, the observation of cytoplasmic strings is currently deemed unnecessary for predicting pregnancy outcomes.…”

“…Although recent studies have suggested that strings positively influence blastocyst expansion and post‐implantation development, 180 , 183 , 184 the clinical and biological significance of cytoplasmic strings has yet to be determined. The vesicle‐like structures moving along cytoplasmic strings can be observed, suggesting that the migration of signaling molecules, including FGRR2 and ErbB3, or the exchange of cytoplasmic material occurs through cytoplasmic strings.…”

Editorial: Molecular and cellular mechanisms in preimplantation IVF-embryo development

“…Interestingly, advancements in imaging and specifically time-lapse imaging throughout the culture period of preimplantation embryos, have provided new avenues for morphology studies. For example, several recent reports on the presence of cytoplasmic strings (via time-lapse imaging) in preimplantation embryos conceived via IVF have been published that try to link this morphological structure with blastocyst quality and pregnancy outcomes ( Ma et al, 2022 ; Joo et al, 2023 ). Arguably the most cutting-edge research associated with embryo time-lapse imaging is the application of artificial intelligence (AI) for embryo screening.…”