Early embryo development anomalies identified by time-lapse system: prevalence and impacting factors To be published in: Reproductive BioMedicine Online

Abstract Research question What are the prevalence of embryo abnormal early cleavages (AC) identified by time-lapse and patient- and treatment- related factors that explain AC occurrence? Design This project was a single-center, retrospective cohort study (Reproductive Department, AP-HP, Paris). We collected data on all IVF cycles for which embryos were observed in the EmbryoScope® from December 2015 to August 2017. Only diploid zygotes cleaved on Day-2 were included. The study included 318 cycles , (250 couples and 1343 embryos). Embryo videos were retrospectively analyzed for AC. The prevalence of each type of AC was recorded. The influence of clinical factors (whether they were intrinsic to patients or specific to IVF treatment) on AC occurrence was analyzed in multivariate multilevel mixed-effect logistic regression analysis. Results A high prevalence of AC was observed: 37.6% (505/1343) of embryos presented at least one AC, 22.8% (306/1343) a trichotomous mitosis (TM), 25.8% (347/1343) a rapid cleavage (RaC), 6.7% (90/1343) a cell fusion (CF), and ≥ 2 AC (mAC, 16.1%). Part of the variation (12 to 25%) in AC occurrence could be explained by embryo origin. TM and mAC phenotypes were less likely to occur in women with endometriosis or tubal pathology and tubal pathology alone, respectively. No factor related to IVF cycles was found to be statistically associated with AC occurrence. Conclusions Our findings emphasize the importance of considering embryo origin when interpreting studies focusing on embryo characteristics and factors that could impact their quality. The present study is limited by a small sample size of known embryo implantations and monocentric criterion.