P-300 Not all DUCs are the same: Impact of DUC type on the blastulation, utilization and ploidy
Authors: Miret Lucio C , Lozano M , Brualla A , Zepeda A , Hickman C , Bergelson N , Escribá M , Benavent M , García A , Crespo J , Teruel J 
Published: June 2023

Abstract

Study question
We have identified six categories of DUCs as identified automatically by CHLOE-EQ. Do these DUC categories differ in embryo competency?

Summary answer
DUC-1, Major chaotic DUC and Fragmented DUC have compromised blastulation, utilization and ploidy, compared to DUC2, minor chaotic DUC and not-direct DUC.

What is known already
CHLOE-EQ (Fairtility, an AI-based support tool) automatically annotates embryo morphokinetics and identifies embryo division anomalies, such as Direct Unequal Cleavage(DUCs). DUCs are defined as less than 5 hours from two cells to three cells. DUCs have been associated with being severely compromised, with lower chance of blastulating, being utilized, euploid, implanting or leading to live birth. In some clinics, DUCs are automatically discarded. Other clinics reported euploids and live births from DUC embryos, raising questions as to whether there are different types of DUCs with different competencies. In this study, we identified 6 types of DUCs and assessed their viability.

Study design, size, duration
Retrospective cohort study that took place between March to July 2022 at a private fertility clinic in Spain. This study included 1032 time-lapse videos of embryos with Direct unequal cleavage (DUCs) as identified by CHLOE-EQ. CHLOE-EQ defines DUCs as (t3-t2)&lt;5 hours. DUCS annotated by CHLOE-EQ were classified into 6 types by embryologists.

Participants/materials, setting, methods
DUC1(direct division from the 1-cell to 3 or more, without a visible 2-cell stage); DUC2 (Direct Division from 2-cells where either cell divides directly from one to three cells); Minor Chaotic DUC (asynchronous irregular divisions: cells still countable); Major chaotic DUC (asynchronous irregular divisions: cells/fragments are too chaotic to count); Fragmented DUC1 (resembles a DUC1, but the third ‘cell’ is a fragment); Not direct DUC (quick division from 1 cell to 2cells to 3cells).

Main results and the role of chance
CHLOE-EQ correctly identified 97.4%(875/898) of 2PN DUCs, based on the definition of DUC (t3-t2&lt;5).
Most DUCs annotated by CHLOE-EQ, were classified by embryologists as minor chaotic [25%(231/921)], followed by DUC 1 [20.3%(187/921)], Not direct DUCs [18.1%(167/921)], major chaotic DUCs [14.6%(135/921)], DUC 2 [14%(129/921)], and lastly, fragmented DUC1 [7.8%(72/921)]. The average t3-t2 time did not differ between the six groups (1.6,1.5,1.5,1.6,1.5,1.6,respectively,p&gt;0.05).
Among DUC embryos, Minor chaotic DUCs [85%(110/129)] and Not direct DUCs [66.9%(109/163)] and DUC2 [57%(73/128)] had similar blastulation rates (p &gt; 0.05) and utilization rates [DUC2:44.2% (57/129), Minor Chaotics: 37.7%(87/231), Not Direct DUCs: 56.3%(94/167), p &gt; 0.05].
These three groups had a higher blastulation rate than DUC1 [20.1% (37/184)], Major chaotic [21.6% (29/134)], Fragmented DUC1 [19.7% (14/71), p &lt; 0.05)] and a higher utilization rate than DUC1 [11.8% (22/187)], Major chaotic [14% (19/135)], Fragmented DUC1 [11.1%(8/72), p &lt; 0.05)].
Type of DUC was not affected by Age(p &gt; 0.05). Four live births from single embryo transfer of DUC embryos were recorded in this dataset.

Limitations, reasons for caution
DUCs were assessed by a single embryologist, further studies will assess intra and inter-operator variation in DUC classification across various clinics. It was particularly challenging to differentiate between fragments and cells. This study is ongoing to further understand implication of DUC types on clinical outcome.

Wider implications of the findings
Given that different DUC types have varied competency levels, the results of this study encourage embryologists not to discard DUC embryos simply because they are DUCs. It is important to assess the type of DUC when determining the fate of the embryo and when managing the expectation of affected patients.

Trial registration number
NOT APPLICABLE