Fertilized embryo diapause, revisited

Dear Editor,

I read with interest the recent findings of Sandi-Monroy et al. [1] in which they reported a fertilized human zygote with no clear cytokinesis until approximately 107-h post-insemination, and by 113-h post-insemination, inner cell mass and trophectoderm cells could be clearly distinguished, and the blastocyst was completely hatched by 136-h post-insemination.

This finding recalls the earlier study of Greco et al. who showed the developmental arrest in ICSI trials after 96 h of fertilization, and the resultant embryos were cleaved to 3- or 4-cell stages [2]. However, those oocytes that cleaved 96 h after ICSI were cultured in fresh equilibrated B2 medium and examined daily and also failed to develop beyond the 6-cell stage. The delayed oocyte cleavage is probably due to a parthenogenetic activation because parthenogenetic activation is more common in aged or overmature human oocytes [3]. It is also suggested that the injection process itself can contribute to oocyte activation, since mechanical disruption of the oolemma and the aspiration of cytoplasmic contents alone, without injecting spermatozoa, induce parthenogenetic activation in aged human oocytes [4]. On the other hand, mature oocyte zona pellucida and oolemma perforation with a 20-μm injection needle could not parthenogenetically activate the porcine oocytes [5]. Therefore, this phenomenon might be associated with fertilization and could be attributed to a commonly known phenomenon, which is embryonic diapause (ED).

ED is a temporary arrest of embryo development and is characterized by delayed implantation in the uterus [6] and can be induced by interspecies surrogacy such as sheep embryos in mice uterus [7–9]. It occurs in most mammalian species, ranging from bears and badgers to mice and marsupials and even humans. Most of the reported ED was in the blastocyst stages [10, 11], while there is no report from fertilization until cell differentiation. Several studies claimed the external (environmental stress and hormones) or internal factors (cell cycle regulation) are the main controllers of the ED [6, 10, 12].

Therefore, the phenomenon of embryonic diapause still holds many mysteries for scientists to solve, but with the recent tools such as time-lapse imaging, the report of non-cleaved embryos and analysis of these individual exceptional cases will make it possible to understand early ED.

Furthermore, delayed cleavage was also reported and appears not to affect embryo implantation as long as endometrial synchrony is maintained [13]. A comprehensive study of Yang et al. [14] also reported the embryo quiescence but after day 3 embryos and the developmental potential which was affected by this quiescence.

The interesting point of the results of Sandi-Monroy et al. is the quick division and differentiation of the reported case as it showed full development into blastocyst within less than 24 h. This requires further investigation, especially the cell cycles that are related to totipotent and pluripotent stem cells propagation and differentiation into inner cell mass and trophectoderm.

Alongside this finding, I also urge the IVF/ICSI practitioners to report these atypical embryonic developments and share it with the scientific community. Understanding the mechanism of cleavage delay or the early ED might be a tool for prolonging and/or enhancement of embryo culture durations in some patients of infertility.

Compliance with ethical standards

Conflict of interest

The author declares that he has no conflict of interest.