P–202 Past embryo viability is not always a good predictor of future pregnancy: dynamic viability suggests video has limited benefit over static images for AI assessment

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J M M Hall ◽  
M A Dakka ◽  
D Perugini ◽  
S Diakiw ◽  
T Nguyen ◽  
...  

Abstract Study question Does embryo quality/viability change over time, suggesting the use of video for AI-based embryo quality assessment has limited benefit over single point-in-time images? Summary answer AI assessment of single static embryo images at multiple time-points indicates embryo viability is dynamic, and past viability is a limited predictor of future pregnancy. What is known already Artificial Intelligence (AI) has been applied to the problem of embryo quality (viability) assessment using either video or single static images. However, whether historical data within video provide an additional advantage over single static images of embryos (at the time of transfer) for assessing embryo viability is not known. This applies to both manual and AI-based embryo assessment. If embryo viability changes over time prior to transfer, then the implication is that the assessment of future pregnancy using historical embryo data from videos would provide limited additional value over single static images taken immediately prior to transfer. Study design, size, duration Retrospective dataset of single embryo images taken at up-to three time-points prior to transfer: Early Day 5, Late Day 5 (8 hours later), and Early Day 6 (16 hours later), with corresponding fetal heartbeat (pregnancy) outcomes. The AI assessed the viability of each embryo at its available timepoints. Viability prediction was compared with pregnancy outcome to assess viability predictiveness at each timepoint prior to transfer, and assess the variability of viability over time. Participants/materials, setting, methods Single static images of 173 embryos were taken using time-lapse incubators from a single IVF clinic. 116 embryos were viable (led to a pregnancy) and 57 were non-viable (did not lead to a pregnancy). The AI was trained on thousands of Day 5 static embryo images taken from multiple IVF laboratories and countries, but was not trained on data from this clinic. Main results and the role of chance When embryos were assessed as viable by the AI immediately prior to transfer (no delay), the AI accuracy (sensitivity) in predicting pregnancy was 88.1% (59/67) for Early Day 5, 84.8% (28/33) for Late Day 5 and 87.5% (14/16) for Early Day 6. When the delay between AI assessment and transfer is 8 hours, 16 hours and 24 hours, the the accuracy drops to 66.7% (22/33), 31.3% (5/16) and 12.5% (2/16), respectively. These results indicate that the viability of the embryo is dynamic, and therefore time series analysis, i.e. using video, may not be well suited for embryo viability assessment because past viability is not necessarily a good predictor of future viability or pregnancy outcome. The viability of the embryo immediately prior to transfer, from a single static image, is a reliable predictor of viability. This is consistent with the current clinical practice of using Gardner score end-point assessment for embryo quality. Results also suggest significant benefits from using time-lapse with AI, where AI continually assesses embryo viability over time using static images. The time point at which the embryo should be transferred to maximize pregnancy outcome is when the embryo has the greatest AI viability score. Limitations, reasons for caution Although evidence suggests past embryo viability is a limited predictor of future pregnancy, a side-by-side comparison of video versus single static image AI assessment would further verify that the historical or change in embryo development or viability has minimal impact on embryo viability assessment at the time prior to transfer. Wider implications of the findings: Time-lapse and AI can beneficially change the way embryos are assessed. Continual AI monitoring of embryos enables optimization of which embryo to transfer and when, to ultimately improve pregnancy outcomes for patients. The findings also suggest that static end-point AI assessment is sufficient for predicting embryo implantation potential. Trial registration number Not applicable

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S Diakiw ◽  
M VerMilyea ◽  
J M M Hall ◽  
K Sorby ◽  
T Nguyen ◽  
...  

Abstract Study question Do artificial intelligence (AI) models used to assess embryo viability (based on pregnancy outcomes) also correlate with known embryo quality measures such as Gardner score? Summary answer An AI for embryo viability assessment also correlated with Gardner score, further substantiating the use of AI for assessment and selection of good quality embryos. What is known already The Gardner score consists of three separate components of embryo morphology that are graded individually, then combined to give a final score describing Day 5 embryo (blastocyst) quality. Evidence suggests the Gardner score has some correlation with clinical pregnancy. We hypothesized that an AI model trained to evaluate likelihood of clinical pregnancy based on fetal heartbeat (in clinical use globally) would also correlate with components of the Gardner score itself. We also compared the ability of the AI and Gardner score to predict pregnancy outcomes. Study design, size, duration This study involved analysis of a prospectively collected dataset of single static Day 5 embryo images with associated Gardner scores and AI viability scores. The dataset comprised time-lapse images of 1,485 embryos (EmbryoScope) from 638 patients treated at a single in vitro fertilization (IVF) clinic between November 2019 and December 2020. The AI model was not trained on data from this clinic. Participants/materials, setting, methods Average patient age was 35.4 years. Embryologists manually graded each embryo using the Gardner method, then subsequently used the AI to obtain a score between 0 (predicted non-viable, unlikely to lead to a pregnancy) and 10 (predicted viable, likely to lead to a pregnancy). Correlation between the AI viability score and Gardner score was then assessed. Main results and the role of chance The average AI score was significantly correlated with the three components of the Gardner score: expansion grade, inner cell mass (ICM) grade, and trophectoderm grade. Average AI score generally increased with advancing blastocyst developmental stage. Blastocysts with expansion grades of ≥ 3 are generally considered suitable for transfer. This study showed that embryos with expansion grade 3 had lower AI scores than those with grades 4-6, consistent with a reduced pregnancy rate. AI correlation with trophectoderm grade was more significant than with ICM grade, consistent with studies demonstrating that trophectoderm grade is more important than ICM in determining clinical pregnancy likelihood. The AI predicted Gardner scores of ≥ 2BB with an accuracy of 71.7% (sensitivity 75.1%, specificity 45.9%), and an AUC of 0.68. However, when used to predict pregnancy outcome, the AI performed 27.9% better than the Gardner score (accuracies of 49.8% and 39.0% respectively). Even though the AI was highly correlated with the Gardner score, the improved efficacy for predicting pregnancy suggests that a) the AI provides an advantage in standardization of scoring over the manual and subjective Gardner method, and b) the AI is likely identifying and evaluating morphological features of embryo quality that are not captured by the Gardner method. Limitations, reasons for caution The Gardner score is not a linear score, creating challenges with setting a suitable threshold relating to the prediction of pregnancy. The 2BB treshold was chosen based on literature (Munné et al 2019) and verified by experienced embryologists. This correlative study may also require additional confirmatory studies on independent datasets. Wider implications of the findings The correlation between AI scores and known features of embryo quality (Gardner score) substantiates the use of the AI for embryo assessment. The AI score provides further insight into components of the Gardner score, and may detect morphological features related to clinical pregnancy beyond those evaluated by the Gardner method. Trial registration number Not applicable


2012 ◽  
Vol 24 (1) ◽  
pp. 162
Author(s):  
C. Pribenszky ◽  
M. Cornea ◽  
T. Jando ◽  
E. Losonczi ◽  
Z. Lang

Assessing embryo quality has been relying on morphological evaluation of embryos at a few time points during their in vitro culture. Consequently, definitive events (e.g. fragmentations, blastocoel pulsation, synchrony of divisions) were often not noticed and important time points (e.g. cleavages, length of interphases) could not be detected. Thus, morphologically sound embryos selected for transfer often carry reduced competence, resulting in reduced pregnancy and increased abortion rates. Our previous study described the predictive value of the 2nd and 3rd cleavage times and the high rate of false diagnosis at routine morphological assessment (Pribenszky et al. 2010 Reprod. Biomed. Online). Previous literature and our experience reveal that blastocyst pulsation and the event of hatching both happen in vivo as well. Our present study examines the contraction dynamics of in vivo-produced blastocysts and shows its correlation to embryo quality and the probability of hatching. NMRI mouse embryos were flushed at 3.5 days post-coitus and expanded blastocysts were selected. They were distributed to 3 groups: (1) vitrified/warmed, (2) stressed with lethal hydrostatic pressure stress (HP) and (3) untreated. Embryos were transferred individually to the microwells of a well of the well (WOW) culture dish and cultured in groups, under mineral oil at 37°C, 6% CO2 and 90% humidity in air for 2 days, on the stages of compact digital inverted microscopes designed to be used inside of the incubator, exhibiting automated time-lapse analysis (Primo Vision time-lapse embryo monitoring system, Cryo-Innovation Technologies, Budapest, Hungary). Imaging frequency was set to 10 min. Measured parameters were diameter of the embryo when it reached a local minimum or maximum during pulsation and the relevant time for the given size. The number of measurements per embryo, pulsation frequency, speed of collapses and re-expansion, the time of the hatching and hatched statuses and the beginning of necrosis were recorded. Altogether, 117 embryos were used, in 5 replicates; data were analysed by the Cox regression model. Both HP stress and vitrification reduced the probability of hatching compared with untreated control (61, 80 and 64%, respectively). However, descriptive factors that are characteristic for these statuses were the same in all of the groups. The number of pulsations, the maximal size, the extent of expansions per pulsation and the extent of collapse per pulsation were all significant predictors for the event of hatching. Relative hazard coefficients for the unit increments of these factors were 1.39, 1.03, 1.04 and 0.96, respectively. Data showed that the way a blastocyst contracts is correlated with its quality and to its probability of hatching. Moreover, similar pulsation patterns preceded hatching, independent of the treatment of the blastocyst. The time-lapse system used was capable of detecting these events routinely in our laboratory, while not affecting culture conditions.


2016 ◽  
Vol 31 (11) ◽  
pp. 2450-2457 ◽  
Author(s):  
Dorit C. Kieslinger ◽  
Stefanie De Gheselle ◽  
Cornelis B. Lambalk ◽  
Petra De Sutter ◽  
E. Hanna Kostelijk ◽  
...  

2020 ◽  
Vol 114 (3) ◽  
pp. e556-e557
Author(s):  
Alex C. Varghese ◽  
Maria Teresita Lao ◽  
Nnenna Maduabum ◽  
Essam S.N. Michael ◽  
Kannamannadiar Jayaprakasan

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M VerMilyea ◽  
S Diakiw ◽  
J Hall ◽  
M Dakka ◽  
T Nguyen ◽  
...  

Abstract Study question Do AI models used to assess embryo viability (based on pregnancy outcome) also correlate with known embryo quality measures such as ploidy status? Summary answer An AI for embryo viability assessment correlated with ploidy status, and with karyotypic features of aneuploidy, supporting its use for embryo selection. What is known already One factor that can influence pregnancy success is the genetic status of the embryo. PGT-A is commonly used to test for embryo ploidy, with the aim of identifying karyotypically normal embryos (euploid embryos), for preferential transfer. There is evidence suggesting that transfer of euploid embryos produces favorable clinical outcomes over aneuploid embryos. Given the AI model was trained to evaluate clinical pregnancy, it was hypothesized that the score might also correlate with ploidy status, and with different types of aneuploidies. Little is known about morphological correlations with embryo ploidy status, so we also sought to explore this relationship. Study design, size, duration This study involved analysis of a retrospective dataset of single static Day 5 embryo (blastocyst) images with associated PGT-A results and AI viability scores. The dataset comprised images of 5,469 embryos from 2,615 consecutive patients treated at five US IVF clinics between February 2015 and April 2020. The AI was trained on thousands of Day 5 embryo images from multiple IVF laboratories in multiple countries, but was not trained on data used in this study. Participants/materials, setting, methods Average patient age was 36.2 years, and average embryo cohort size was 2.1/patient. PGT-A analysis was performed on embryos at time of evaluation. The dataset comprised 3,251 (59.4%) euploid embryos, 1,815 (33.2%) aneuploid embryos, and 403 (7.4%) mosaic embryos. The AI was retrospectively used to provide a score between 0 (predicted non-viable) and 10 (predicted viable) for each image. Correlation between the AI viability score and euploid, mosaic and aneuploid embryos was then assessed. Main results and the role of chance Results showed a statistically significant correlation between AI viability score and PGT-A outcome, consistent with a relationship between pregnancy outcome and ploidy status. The average score for euploid embryos was 8.20, which was significantly higher than the average score for aneuploid embryos of 7.80 (p < 0.0001). There was a significant linear increase in confidence score from full aneuploid embryos, through mosaic embryos (average score 7.97), to full euploid embryos (mosaic threshold of 20–80%). High mosaic embryos tended to have a lower average score (7.60) than low mosaic embryos (7.96), consistent with correlation of viability (pregnancy outcome) with the degree of mosaicism. AI viability score also correlated with ploidy features believed to affect pregnancy outcomes. Trisomic changes had higher average scores than monosomic changes. Segmental changes had higher average scores than full gain or loss. The AI score differentiated euploid from aneuploid status more efficiently in embryos with poorer morphology than those with good morphology. Whilst there was an evident correlation between pregnancy outcome and ploidy status, the AI was only weakly predictive of euploidy, with an accuracy of 57.3% using an AI viability score threshold of 7.5/10.This suggests pregnancy-related morphological features are somewhat correlated with embryo ploidy, but not completely. Limitations, reasons for caution The PGT-A technique is held to have some limitations for evaluating ploidy status, therefore it would be of benefit to perform additional confirmatory studies on independent datasets. It would be of interest to conduct prospective studies evaluating correlations between the AI’s evaluation of morphology and pregnancy outcome with ploidy status. Wider implications of the findings: The AI score correlated with genetic features of embryos that are known to correlate with pregnancy, which further supports the efficacy and use of AI for embryo viability assessment. The AI identified morphological features that are somewhat predictive of ploidy status, with potential application to embryos of poorer Gardner score. Trial registration number none


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
V Venkatappa ◽  
S S Vasan ◽  
S K Adiga ◽  
S R Varsha ◽  
V Prata. Kumar ◽  
...  

Abstract Study question Whether embryo-secreted ubiquitin could serve as a predictive biomarker for embryo development and viability for assessing pregnancy outcome? Summary answer Embryo-secreted ubiquitin concentrations showed positive correlations with (a) developing embryonic stages, (b) implantation rates, (iii) live-birth rates. Their altered levels were associated with miscarriages. What is known already Human infertility affects 15–20% couple and is mitigated by ART approaches. Poor biological-viability of in vitro developed embryos contributes to implantation failure and low birth rates(LBR). The current morphology-based embryo selection approach has shortcomings in identifying biologically-viable embryos capable of producing live-births. Earlier studies have identified ubiquitin as a biomarker for embryo developmental competence. However, there have been no studies on estimations of ubiquitin in embryo-spent medium samples (E-SMs) and their correlative analysis with embryo-quality score and pregnancy outcome. Hence, such studies are required to establish whether or not ubiquitin could be a biomarker predicting pregnancy outcome. Study design, size, duration This was a retrospective, multi-centric study performed between July 2018 and September 2020. A total of 574 E-SMs (from 574 individual embryos), from 325 infertile women, were analysed for ubiquitin levels. Frozen E-SMs post-thaw were subjected to sandwich ELISA (Mybiosource, USA). Correlation analysis was performed on ubiquitin levels with developing embryonic stages and their scores, implantation rates (IRs) and pregnancy outcomes in terms of LBR. Participants/materials, setting, methods We measured ubiquitin levels in E-SMs obtained from three embryonic stages i.e., cleavage-stage (2–10-cells; n = 182), morulae (n = 102) and blastocysts (n = 290). Ubiquitin concentrations among three developmental stages were compared and analysed using the Student’s t-test/ANOVA (P ≤ 0.05), followed by Tukey posthoc test. Levels of ubiquitin were correlated (using Pearson/Spearman analysis) with (a) developing embryonic stages, (b) embryo morphology, (c) IRs, and (d) pregnancy outcomes in terms of LBR. Main results and the role of chance Of 574 E-SMs analysed, 540 (94.07%) had detectable ubiquitin levels (pg/ml) and they varied in an increasing manner across developing embryonic stages and, across the three clinics. We observed a significantly different (p < 0.0001) levels of ubiquitin in three sets of secretors i.e low (153.1 ± 5.4; n = 219), medium (498.9 ± 15.7) & high (1615 ± 46.5) secretors. Levels of ubiquitin among three developmental stages were significantly (p < 0.05) different under FET, but not with fresh-ET categories. Ubiquitin levels were independent of cleavage-stage morphology score but showed a positive correlation with blastocyst grades. Also, we observed a significant (p < 0.05) positive correlation of ubiquitin levels with implantation rates. Importantly, ubiquitin levels were higher in E-SMs of embryos which gave live-births vis-à-vis those with no-births. Moreover, altered levels (very high low) were associated with those embryos which resulted in miscarriages. This is the first report which measured ubiquitin in individual hE-SMs from three developing embryos and showed a development stage-wise positive correlations as well as a significant association (p < 0.0001) of ubiquitin levels with implantation and live-birth rates. Limitations, reasons for caution Observed variations in levels of ubiquitin across clinics could be attributed to (i) oocyte/sperm donors’ variation and their infertility status (i) IVF-ET protocol differences. A large multi-centric cohort studies are required to establish the predictive value of ubiquitin for assessing embryo-viability and pregnancy outcome in term of live-births. Wider implications of the findings: For the first time, our multi-centric study showed developmental stage-specific changes in ubiquitin levels. It could be a valuable biomarker of embryo-viability and to predict IR and live-births. Ubiquitin, as a biomarker, could be a valuable adjunct to currently practicing embryo score system for selecting transferable quality embryos. Trial registration number Not applicable


2019 ◽  
Author(s):  
Vince Polito ◽  
Amanda Barnier ◽  
Erik Woody

Building on Hilgard’s (1965) classic work, the domain of hypnosis has been conceptualised by Barnier, Dienes, and Mitchell (2008) as comprising three levels: (1) classic hypnotic items, (2) responding between and within items, and (3) state and trait. The current experiment investigates sense of agency across each of these three levels. Forty-six high hypnotisable participants completed an ideomotor (arm levitation), a challenge (arm rigidity) and a cognitive (anosmia) item either following a hypnotic induction (hypnosis condition) or without a hypnotic induction (wake condition). In a postexperimental inquiry, participants rated their feelings of control at three time points for each item: during the suggestion, test and cancellation phases. They also completed the Sense of Agency Rating Scale (Polito, Barnier, & Woody, 2013) for each item. Pass rates, control ratings, and agency scores fluctuated across the different types of items and for the three phases of each item; also, control ratings and agency scores often differed across participants who passed versus failed each item. Interestingly, whereas a hypnotic induction influenced the likelihood of passing items, it had no direct effect on agentive experiences. These results suggest that altered sense of agency is not a unidimensional or static quality “switched on” by hypnotic induction, but a dynamic multidimensional construct that varies across items, over time and according to whether individuals pass or fail suggestions.


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