O-067 Artificial intelligence system detects “goldilocks” morphokinetic zone for embryos transferred or frozen in time-lapse videos
Authors: Castilla J A , Almunia N , Brualla A , Jiménez R , Villaquirán A M , Har-vardi I , Ben-Meir A , Gomez E 
Published: June 2022

Abstract

Study question
Are there specific morphokinetic time points which can be used to determine whether an embryo should be discarded?

Summary answer
Morphokinetic ranges where embryos will be discarded rather than transferred or cryopreserved, can be defined using time-lapse annotations automatically generated with artificial intelligence (AI).

What is known already
Time-lapse incubation has changed the way embryos are selected. Instead of static daily observations, continuous monitoring of embryos allows for generation of morphokinetic parameters which quantify the pace of development. However, annotations by humans have been shown to incur operator variations and are time-consuming to perform. AI can automatically annotate embryos with equivalence in accuracy to experienced embryologists. Although most embryo selection methods are designed to identify the embryo with the highest chance of becoming a healthy live birth baby, the ability to identify embryos that will not be suitable for treatment is equally important for clinical decision making.

Study design, size, duration
This is a prospective, observational, cohort study. Time-lapse videos from 142 embryos from a private fertility clinic in Spain were automatically annotated using CHLOE (Fairtility), an AI-based software. CHLOE automatically generated the following morphokinetic parameters: tPNa, tPNf, t2, t3, t4, t5, t6, t7, t8, t9+, tM, tSB, tB, tEB.

Participants/materials, setting, methods
Embryos analysed were from donor and own oocyte’s treatments. Selected embryos were analysed using CHLOE, to automatically identify morphokinetic parameters. The distribution for each morphokinetic parameter was compared between fates (data presented for transferred + frozen vs discarded as mean+-standard deviation, 2-sided t-test). Each continuous morphokinetic parameter was categorised according to the ranges where embryo utilisation was futile (&lt;1%), optimal (maximum utilisation rate) or reduced utilisation rate (between optimal and futile).

Main results and the role of chance
For every morphokinetic parameter the difference in event time between frozen+transferred vs discarded embryos was statistically significant(p &lt; 0.003). The results detail the time point in hours for each morphokinetic feature to occur (mean(SD) frozen+transferred vs discarded, p-value):
tPNa (7.68(2.03)vs22.04(27.15),p&lt;0.0001),
tPNf (21.71(2.86)vs34.63(24.11),p&lt;0.0001),
t2 (24.92(2.71)vs33.78(16.17),p&lt;0.0001),
t3 (34.62(4.03)vs42.58(22),p=0.0024),
t4 (37.29(4.31)vs48.29(20.29,p&lt;0.0001),
t5 (47.03(6.47)vs55.32(22.63),p=0029),
t6 (49.54(5.63)vs60.56(22.20),p&lt;0.0001),
t7 (53.1(7.86)vs69.13(24.54),p&lt;0.0001),
t8 (57.78(9.78)vs77.33(25.79),p&lt;0.0001),
t9+ (69.14(7.39)vs81.9(21.96),p&lt;0.0001),
tM (83.9(8.72)vs96.08(16.88),p&lt;0.0001),
tSB (97.89(7.55)vs105.38(11.38),p=0.0005),
tB (105.74(7)vs113.25(15.53),p=0.0002),
eEB (110.65(7.58)vs120.47(11.36),p=0.0031).
When looking at the exact distribution of these embryos according to time, it became apparent that a goldilocks zone appeared whereby the proportion of embryos transferred or frozen peaked, and the number discarded was at its minimum. The converse was true when looking at the more extreme values of a particular parameter. Thus, we were able to determine the (optimal vs futile time ranges): tPNa (4.4-8.8 hours, where the utilization rate was at its maximum vs &lt; 4.4 or &gt; 13.7, where the utilization rate was at its minimum), tPNf (19.1-23.2vs&lt;9.4,&gt;28.9), t2 (23.-36.4vs&lt;19.9,&gt;33.6), t3 (32.1-37.4vs&gt;24.6,&gt;43), t4 (34-40.2vs&lt;29.5,&gt;55), t5 (42.7-52vs&lt;33.7, &gt;63.5), t6 (45-4-54.2vs&lt;36.10,&gt;63.70), t7 (47.8-56.7vs&lt;42.8,&gt;77.5), t8 (49.2-64.5 vs &lt;44.5,&gt;82.5), t9+ (64.1-74.2vs&lt;57,&gt;90), tM (76.6-92.6 vs &lt;64.7,&gt;104.2), tSB (91.2-105vs&lt;81.3,&gt;113.8), tB(97.2-111.2 vs &lt;92,&gt;118.7), tEB (103.4-116.7,&lt;94.7,&gt;122.5).
A 60% of the embryos were in the futile range in at least 1 parameter, from which only 1 in 3 were utilised.

Limitations, reasons for caution
This is a single centre study. Further work will (i) test the limits across different clinics, with different geographical demographic variations, and varied clinical practices, to understand how these factors affect the limits between futile and optimal ranges of morphokinetics, and (ii) assess clinical outputs (implantation, ploidy, live birth).

Wider implications of the findings
Identifying objective ranges for determining when an embryo is not suitable for treatment will help reduce variation between and within embryologists and clinics; will avoid overly optimistic decisions which waste time and resources and increase patient’s emotional burden, and increase professional confidence when selecting embryos for discarding, transfer or freezing

Trial registration number
not applicable