Know Your DUCs: Direct Unequal Cleavage Subtypes Are Associated with Distinct Preimplantation Developmental Patterns

Background/Objectives: Direct unequal cleavage (DUC) is generally considered a marker of poor embryo competence. However, increasing evidence suggests that DUC represents a heterogeneous group of developmental abnormalities rather than a single biological entity. This study aimed to characterize developmental differences among individual DUC subtypes and to descriptively explore implantation and live-birth outcomes in the subset of transferred embryos. Methods: This retrospective study included 1381 DUC embryos from 505 patients and 532 treatment cycles, cultured in a single IVF centre between March 2022 and February 2023 using time-lapse imaging (EmbryoScope+™). DUC embryos were automatically identified by the CHLOE-EQ artificial intelligence platform and classified into six DUC subtypes by experienced embryologists. Developmental kinetics and AI-derived quality and blastulation scores were compared among DUC subtypes, and clinical outcomes were described. Results: DUC subtype was significantly associated with blastulation after accounting for the clustering of embryos within patients (Wald χ2(5) = 118.00, p < 0.001). DUC1 (83/227, 36.6%) and Major Chaotic DUC (76/203, 37.4%) embryos showed the lowest blastulation rates, lower AI-derived embryo quality scores, and lower predicted blastulation potential. DUC2, Indirect DUC, and Minor Chaotic DUC embryos showed blastulation rates of approximately 67–72%. Clinical outcomes were available for 37 deferred single-embryo transfers and are reported descriptively: implantation occurred in 27/37 (73.0%; exact 95% CI 55.9–86.2%) and live birth in 20/37 (54.1%; exact 95% CI 36.9–70.5%). CHLOE-Blast showed moderate to good discrimination for observed blastulation (AUC = 0.769; 95% CI 0.741–0.796), although the calibration slope of 0.585 indicated that predictions were more extreme than the observed outcomes. Morphokinetic analysis identified overall differences in early developmental intervals among DUC subtypes, whereas no significant differences were detected at later developmental stages among the embryos that reached them. Conclusions: DUC subtypes were associated with distinct blastulation rates and developmental patterns. DUC1 and Major Chaotic DUC were associated with the lowest blastulation rates and the lowest AI-derived scores, even after adjustment for the clustering of embryos within patients. Live births occurred following transfer of selected embryos from several DUC subtypes; however, the limited and highly selected clinical sample precludes comparisons of reproductive potential between subtypes. These findings support a more differentiated assessment of DUC embryos, while larger studies are required to establish their clinical prognosis.