P-273 Image-based oocyte model predictive of blastocyst development correlates with ploidy status across a broad spectrum of PGT-A indications, accounting for confounding variables
Authors: Malmsten J , Zaninovic N , Mercuri N , Qi W , Jaberipour M , Nayot D , Rosenwaks Z , Fjeldstad J 
Published: July 2024

Abstract

Study question
Does MAGENTA, an AI assessment of oocyte quality, indicate ploidy potential of the developed blastocysts in the presence of confounding variables?

Summary answer
MAGENTA correlates to oocytes that develop into euploid embryos across diverse demographics, highlighting its robust ability to assess oocyte quality and genetic potential.

What is known already
MAGENTA is a non-invasive AI-image analysis tool that assesses images of mature oocytes and provides a score from 0-10, where higher scores indicate higher chances of developing into a blastocyst. MAGENTA has also displayed a correlation to blastocyst morphological quality. The ploidy status of blastocysts plays a significant role in cycle success and is often utilized for the selection of embryos to transfer. Despite the selection of embryos based on their genetic normality, many transfers are unsuccessful. With most chromosomal errors arising in the oocyte, assessment at the gamete level is critical to improving outcomes.

Study design, size, duration
A retrospective study using CRM Weill Cornell Medicine data included 3,342 mature oocytes that developed into blastocysts and underwent PGT-A in 2021. Blastocysts tested as mosaic (n = 753) or inconclusive (n = 13) were excluded. Images of the oocytes were obtained immediately post-ICSI using EmbryoScope time-lapse incubators (Vitrolife, Sweden). Blastocyst morphological grades were categorized by quality: highest (ICM+TE grade A), high (ICM+TE grade A/B), medium (ICM+TE grade B), or low quality (ICM or TE grade C/D).

Participants/materials, setting, methods
Data was obtained from 629 patients (females 26-45 years old) with an average of 5.3 blastocysts (range 1-20) with PGT-A results per patient. MAGENTA assessed each oocyte image and provided a score (0-10), with higher scores representing a greater potential to develop into a blastocyst embryo. In this dataset, 1827 (55%) blastocysts were tested as euploid and 1515 (45%) were tested as aneuploid. PGT-A was conducted for various specific and non-specific indications in these patients.

Main results and the role of chance
MAGENTA was positively associated with oocytes that developed into blastocysts of increasing quality, with significance between highest and high-quality (7.4 vs 7.0,p&lt;0.05) and medium and low-quality (6.9 vs 6.1,p&lt;0.01).
Of the blastocysts, the MAGENTA score further displayed significant differences between oocytes that developed into euploid (7.0) compared to aneuploid blastocysts (6.6) (p &lt; 0.001;Welch’s t-test).
Although MAGENTA does not predict ploidy, a threshold of 8.8 MAGENTA score was determined to best distinguish between ploidy outcomes with 61% euploidy rate above this threshold compared to 51% below, a significantly different proportion (p &lt; 0.001;Two-Sample Proportions z-test). Therefore, oocytes scored ≥8.8 display a 19.6% relative increase in chance of developing into a euploid blastocyst.
To account for female age, subgroup analysis was conducted and found MAGENTA scores to be significantly different between oocytes that developed into euploid and aneuploid blastocysts for patients &lt;35 years old (7.2 vs 6.6, p &lt; 0.01;Welch’s t-test) and ≥35 years old (6.8 vs. 6.5, p &lt; 0.05;Welch’s t-test).
Blastocyst morphological grade was also investigated as a confounding factor. No significant differences existed between MAGENTA scores of euploid and aneuploid blastocysts among the low, high, or highest-quality. Significantly, differences were only found within medium quality blastocysts (7.0 vs 6.6,p&lt;0.05), which had the greatest sample size (n = 1854).

Limitations, reasons for caution
MAGENTA was not trained to predict euploid embryo development from images of mature oocytes. Further data is required to discern the correlation of MAGENTA to chromosomal ploidy status, apart from blastocyst quality. Additionally, investigation into sperm DNA fragmentation as a potential contributor to ploidy determination is warranted.

Wider implications of the findings
MAGENTA can identify oocytes of better quality that not only have higher chances of blastocyst development and higher morphological grades, but also indicates oocytes that are more likely to become euploid embryos across patients of various PGT-A indications and a broad age demographic.

Trial registration number
not applicable