The effects of different types of abnormal cleavage and their occurrence periods on the developmental potential of early embryos

Objective This study aims to investigate the effects of abnormal cleavage patterns, with a specific focus on the cell cycle in which they occur, on embryonic developmental potential and clinical outcomes using time-lapse. Methods This retrospective study analyzed 10,144 fertilized (2PN) embryos from 1,321 IVF/ICSI cycles. Embryos were cultured in a time-lapse incubator (Primo Vision) and assessed for abnormal cleavage events: direct cleavage (DC), reverse cleavage (RC), chaotic cleavage (CC), multinucleation (Mn), and mixed patterns. These events were further categorized based on their occurrence in the first (S1), second (S2), or third (S3) division cycle. Embryo quality was assessed on day 3 and 5/6. Clinical pregnancy and implantation rates were analyzed for the transferred embryos. Results The overall incidence of abnormal cleavage was 33.68%, with DC being the most frequent (13.23%), followed by Mn (7.68%), mixed (6.39%), RC (3.90%), and CC (2.47%). The subgroup analysis revealed different distribution patterns across division cycles (e.g., DC-1, 6.15%; DC-2, 6.71%; and DC-3,0.36%). Compared with normal cleavage, all abnormal cleavage types were associated with significantly lower rates of high-quality D3 embryos, blastocyst formation, and high-quality blastocysts. Critically, abnormalities occurring in the first division cycle (S1) had a more profound negative effect on the development potential (e.g., D3 high-quality embryo rate and blastocyst formation rate) than those in S2 or S3 did. Clinically, no pregnancies resulted from embryos with DC in the first cycle (DC-1), a rate that was significantly lower than that of the normal cleavage group. Clinical outcomes trended to decrease in the other abnormal cleavage subgroups, although the difference not always statistically significant. Conclusions The timing of abnormal cleavage is a critical determinant of embryonic potential. Abnormalities occurring in the first cell cycle, particularly direct cleavage (DC-1), are most detrimental, leading to poor development and a high likelihood of implantation failure. These findings emphasize the importance of incorporating the specific type and timing of cleavage anomalies into time-lapse-based embryo selection models to improve clinical pregnancy success. Clinical trial registration: https://www.medicalresearch.org.cn/ , identifier MR-45-23-039336. Registered 1 July 2022