P-265 Should we divide two types of direct cleavage at the first division in human embryos observed by time-lapse imaging?
Authors: Doi K , Kumeta C , Narumiya Y , Mizuta S , Matsubayashi H , Takeuchi T , Ishikawa T 
Published: July 2024

Abstract

Study question
Are there any differences on clinical outcomes between two types of direct cleavage at the first division (DC1) in human embryos observed by time-lapse imaging?

Summary answer
Blastocyst development of DC1 without any two-cell stage was lower than DC1 with momentary two-cell stage. Once they became blastocysts, they didn’t affect pregnancy outcomes.

What is known already
In recent years, time-lapse imaging (TLI) has been used to analyze dynamics on embryo development. It clarified that some embryo showed direct cleavage, where one cell divided into three or more cells directly (DC1). It has been reported that DC1 embryos showed chromosomal abnormalities and negative effect on the embryonic development compared to normal cleavage without DC1. Some reports revealed that once embryos with DC1 became blastocysts, they didn’t affect pregnancy outcomes compared to normal cleavage without DC1. No study has been published to date that categorizes DC1 into two types: DC1 embryos with or without momentary two-cell stage.

Study design, size, duration
This study included patients whose oocytes had been retrieved between January 2020 to December 2022. A retrospective study was conducted on 11,366 cleavage embryos derived from 2PN2PB in 2,735 cycles using time-lapse imaging (Geri®, Genea BIOMEDX, Australia, 5-minute intervals, 9 slices) after intracytoplasmic sperm injection (ICSI) with ejaculated spermatozoa. We focused on DC1 only and analyzed pregnancy outcomes on 248 cycles with single blastocyst transfer obtained from this study.

Participants/materials, setting, methods
Among 1,817 cycles where DC1 was observed by TLI, DC1 were classified into two types: DC1 embryos without any two-cell stage (DC1A) and with momentary two-cell stage (DC1B). We comparatively analyzed for blastocyst developmental rates, good-quality blastocyst (Grade 3BB or more by the Gardner’s classification) rates and pregnancy outcomes with single blastocyst transfer (clinical pregnancy rate, CPR; live birth rate, LBR). Statistical analysis was performed using student t-test and chi-square test.

Main results and the role of chance
Among 2,735 cycles where ICSI was performed, female age was 39.3 ± 4.8 years (mean ± SD), previous ART cycles were 4.6 ± 5.5 times, and number of retrieved oocytes was 10.0 ± 8.7. DC1 embryos were found in 32.2% (3,663/11,366). Blastocyst development and good-quality blastocyst rates were 28.3% (826/2,921) and 14.6% (427/2,921) in DC1 embryos, whereas 67.5% (3,512/5,204) and 41.4% (2,157/5,204) in embryos without direct cleavage (non-DC), respectively. The former was significantly lower than the latter (P &lt; 0.001). Among DC1 embryos, we confirmed DC1A was relatively fewer (21.2%) than DC1B (78.8%). Blastocyst development and good blastocyst rates were 11.7% and 2.1% in DC1A embryos, whereas 32.7% and 11.0% in DC1B embryos, respectively. The former was significantly lower than the latter (P &lt; 0.001). CPRs, miscarriage rates and LBRs per single blastocyst transfer of DC1A were 44.4% (4/9), 11.1% (1/9), and 33.3% (3/9), while those of DC1B were 33.8% (47/139), 12.2% (17/139), and 21.6% (30/139), respectively. On the other hand, those of non-DC were 44.7% (232/519), 13.1% (68/519), and 30.6% (159/519). Both embryos with DC1A and DC1B produced healthy babies, except for one case with congenital hydronephrosis from DC1B.

Limitations, reasons for caution
We excluded embryos with direct cleavage in the second division (DC2) in this study, because we focused on DC1 only. DC2 embryos may have complex effects besides DC1. The number of blastocysts from DC1A embryos may not be sufficient for comparison of pregnancy outcomes.

Wider implications of the findings
Since blastocyst development and good-quality blastocyst rates were of DC1A was significantly lower than those of DC1B, it may be necessary to categorizes DC1 into two types: DC1 embryos with or without momentary two-cell stage. However, once they became blastocysts, they didn’t affect pregnancy outcomes.

Trial registration number
not applicable