Early irregular division of human embryos changes in style between the first and second divisions(第39回ヨーロッパ生殖医学会(ESHRE))
Mari Tomida, Shinichi Watanabe, Shigenori Suzuki, Yukino Matsuda, Kaori Yoshikai,
Eiko Nakano, Tomio Sawada
Sawada Women’s Clinic, Nagoya, Japan

Study question
Is there a difference in irregular division kinetics between first and second division of human embryos?

Summary answer
The incidence of rapid cleavage was reduced in the second division, but the developmental potential of the blastomeres by this dynamics was unexpectedly low.

What is known already
The styles of irregular division of early human embryos are known: direct cleavage (DC), in which one cell becomes three (or more) cells without a two-cell phase, and rapid cleavage (RaC), in which one (or both) cells dividing rapidly after two-cell phase, both of which reduces the embryonic developmental potential. However, there are no reports that have examined in detail whether these division styles occur similarly in the first and second divisions, and how these dynamics affect the potential.

Study design, size, duration
This is a retrospective study of 635 embryos collected in 2020 at our clinic and cultured for at least 5 days. The embryos were time-lapse monitored by EmbryoScope (Vitrolife, Sweden) to observe the first and second divisions, and the blastomeres of each embryo were classified according to their style of division.

Participants/materials, setting, methods
It was observed whether there was a DC (division into 3 cells without a 2-cell phase) or RaC (One or two blastomeres divide within 5 hours after the 2-cell phase) at the first division. First dividing normal embryos were observed for the presence of a DC or RaC at the second division. Blastomeres by DC or RaC were observed for subsequent development and whether they participated in blastocysts or not was recorded.

Main results and the role of chance
Among the subject embryos, 63 embryos had DC and 199 embryos had RaC in the first division, and their blastomeres were classified into the DC1 and RaC1 groups, respectively. Of the 373 first division normal embryos, 39 had DC and 23 had RaC (there were 4 embryos with both DC and RaC) in the second division, and their blastomeres were classified into DC2 and RaC2 groups. The blastomeres blastocyst participation rate was 4.4% in the DC1 group and 19.5% in the RaC1 group, respectively, the former was significantly lower (P<0.01), however, in the DC2 and RaC2 groups, 23.3% and 4.2%, respectively, the latter was significantly lower (P<0.01). The incidence of DC was similar in the first (9.9%) and second (10.5%) divisions, but the incidence of RaC was 31.3% in the first division and 6.2% in the second division, the latter was significantly lower (P<0.01). The development rate of good blastocysts (≥4BC in Gardner grade) was 4.8% in embryos with DC1 and 19.5% in embryos with RaC1, with the former significantly lower (P<0.01), 37.0% in embryos with DC2, and 26.3% in embryos with RaC2, with no significant difference.

Limitations, reasons for caution
As of 2020, the clinical use of PGT-A is not approved in principle in Japan, and the subject embryos have not been chromosomally analyzed.

Wider implications of the findings
RaC would lead to inadequate DNA proliferation, but the incidence of this and the prognosis of the blastomeres were different in the first and second divisions. In human embryos, the mechanisms that control blastomeres from dividing may change as development progresses, but further studies are needed to elucidate this.

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