The reason why direct cleavage and rapid cleavage should be differentiated(第39回ヨーロッパ生殖医学会(ESHRE))
Shinichi Watanabe, Mari Tomida, Shigenori Suzuki, Yukino Matsuda, Kaori Yoshikai,Eiko Nakano, Tomio Sawada
Sawada Women’s Clinic, Nagoya, Japan

Study question
Direct cleavage (DC) and Rapid cleavage (RaC) both appear to be 1 cell divided into 3 (or more) cells, should they be distinguished?

Summary answer
Since blastomeres by RaC had higher developmental potential than blastomeres by DC, and since many RaC embryos had "normal" blastomere, the two should be distinguished.

What is known already
DC, in which one cell divides into three (or more) cells without the two-cell stage, and RaC, in which one or two cells divide rapidly after the short two-cell stage (The former lead to segregation of chromosomes into three cells, while the latter leads to inadequate DNA replication), are both often recorded as "DC", but when classified in detail, there are reports that the blastocyst development rate is higher in RaC embryos. However, the reason for this has not been clarified.

Study design, size, duration
This was a retrospective study of 643 embryos collected and cultured for at least 5 days in 2020 at our clinic. The embryos were time-lapse monitored by EmbryoScope (Vitrolife, Sweden) and classified into three groups according to the style of first division.

Participants/materials, setting, methods
The embryos were classified as follows: DC group: embryos that have divided into three (or more) cells without a two-cell stage; RaC group: embryos that rapidly (<5 hours) divided one (or both) cells after the 2-cell stage; Normal cleavage (NC) group: embryos that had a 2-cell stage for more than 5 hours.
The subsequent development of blastomeres of all embryos was observed and whether they participated in blastocysts or not was recorded.

Main results and the role of chance
Of the embryos, 63 were in the DC group and 199 were in the RaC group (173 of which had one rapidly dividing blastomere and 26 of which had two).
The blastocyst participation rate of blastomeres was 4.4% in the DC group, 19.5% of rapidly dividing blastomeres and 61.6% of normal blastomeres in the RaC group, with significant differences between all groups (p<0.01).
The good blastocyst (4BC or higher in Gardner grade) development rate was 4.8% (3/63) in the DC group, 40.5% (70/173) in the RaC group with one rapidly dividing blastomere (RaC1 group), 19.2% (5/26) in the RaC group with two such blastomeres (RaC2 group), showing a significant difference between the DC and RaC1 groups (P < 0.01).
The live birth rate for single blastocyst transfer was 50% (1/2) in the DC group, 27.8% (5/18) in the RaC1 group, and 100% (1/1) in the RaC2 group.
(Note that there were 381 in the NC group, and the above rates were 76.5%, 63.3% (241/381), and 29.3% (22/75), respectively)

Limitations, reasons for caution
This study examined only the style of first division and did not consider second and subsequent divisions.
In addition, as of 2020, the clinical use of PGT-A is not approved in principle in Japan, and the subject embryos have not undergone chromosome analysis.

Wider implications of the findings
The reason for the higher blastocyst development rate in RaC embryos was indicated by the difference in blastocyst participation rates of the respective blastomeres and the presence of normal blastomeres, but since live births were obtained in both embryos, so these irregular divisions would not completely compromise the blastocyst euploidy.

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