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<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta>
      <issn pub-type="ppub">1613-0073</issn>
    </journal-meta>
    <article-meta>
      <title-group>
        <article-title>and External Factors</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Thomas Ebner</string-name>
          <email>Thomas.Ebner@kepleruniklinikum.at</email>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
          <xref ref-type="aff" rid="aff5">5</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          ,
          <addr-line>Magnus Johnsson</addr-line>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Adnane Soulaimani</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>Kepler University Clinic</institution>
          ,
          <addr-line>Linz</addr-line>
          ,
          <country country="AT">Austria</country>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution>Malmö University</institution>
          ,
          <addr-line>Malmö</addr-line>
          ,
          <country country="SE">Sweden</country>
        </aff>
        <aff id="aff4">
          <label>4</label>
          <institution>Malmö University</institution>
          ,
          <addr-line>Malmö</addr-line>
          ,
          <country country="SE">Sweden</country>
        </aff>
        <aff id="aff5">
          <label>5</label>
          <institution>Transformers</institution>
          ,
          <addr-line>Attention Mechanism, Multitask Learning, Transfer Learning, Inception V3, Embryo</addr-line>
        </aff>
      </contrib-group>
      <abstract>
        <p>This study aims to integrate embryo images and environmental laboratory factors to predict embryo quality using a complex machine learning model. A challenge was data misalignment, which was solved by using a Random Forest Regressor to synthesise data for a complete dataset. The fine-tuned Inception V3 model with the added attention mechanisms inherent to transformers was used for multitask learning to predict three diferent scores for embryo quality: cell expansion (EXP), inner cell mass (ICP) and trophectoderm (TE). The model achieved an accuracy and F1 Score of 92.76%, 92.74% for EXP, 72.63%, 59.52% for TE and 63.69%, 10.77% for ICM prediction. These results indicate a great performance for 2 of the three scores and build a basis for a reliable model for prediction of embryo quality.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>CEUR
ceur-ws.org
Quality</p>
    </sec>
    <sec id="sec-2">
      <title>1. Introduction</title>
      <p>
        Choosing embryos with a high quality is an important progress for In-vitro fertilisation (IVF), a
life-changing procedure for individuals and couples trying to have a baby. However, IVF can
be expensive and has a limited amount of attempts, so it is important to investigate diferent
factors that can influence embryo quality [
        <xref ref-type="bibr" rid="ref1 ref2">1, 2</xref>
        ]. The idea of this study was initially introduced
by Khoshkangini et al. (2024) [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ] and the focus is on external environmental factors as well
as embryo images to mitigate negative influences in the future, making IVF more reliable and
afordable.
used since then [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ].
      </p>
      <p>Assessing the quality of embryos in their blastocyst stage can be done by using the Gardner
score. This score was created and evaluated by Gardner et al. in 2000 and has been commonly
†These authors contributed equally.</p>
      <p>
        This research will work with a published embryo image dataset by Kromp et al. (2023) [
        <xref ref-type="bibr" rid="ref5 ref6">5, 6</xref>
        ]
together with external factors from Linz, Austria, which is the city where all images were taken,
and Malmö, Sweden.
      </p>
      <p>The overall approach consists of two main modules: a preprocessing pipeline for data
preparation and a deep learning model for prediction. In the preprocessing stage,
laboratoryspecific environmental factors are synthesized using a Random Forest Regressor trained on
paired external and internal environmental measurements from a reference site. This model
enables the generation of temperature, humidity, and air pressure values for locations where
only external data is available. These synthesized features are then combined with embryo
images and Gardner scores as input to the predictive model. The model architecture itself is
composed of three stages, illustrated in figure 2. In the first stage, tabular features, comprising
environmental factors and Gardner scores, are processed through a feed-forward network. In the
second stage, visual features are extracted from embryo images using a convolutional backbone.
In the final stage, tabular and visual features are fused and passed through a classification head
to predict embryo quality across three binary outcomes: TE, ICM, and EXP.</p>
      <p>This study addresses the following research question:
RQ 1) To what extent can transformer (or attention mechanism) predict embryo quality utilizing
embryo images?
This research question explores whether a machine learning model using the attention
mechanism can accurately assess embryo quality based on images. The aim is to evaluate how
efectively the model can learn from visual and tabular data and make reliable predictions about
embryo quality.</p>
      <p>This study gives a novel approach to predicting embryo quality using the transformers’
attention mechanism and utilising both embryo images and external factors. The results from
this study can be applied to make IVF more eficient and accessible. This will help couples and
individuals who want to have IVF pregnancies, as well as help the medical personal doing these
procedures. Showing that transfer learning performs well in a medical scenario with limited
data is very important. It can be dificult to gather a large amount of data in the medical field
due to its specificity and sensitivity inherent to medical data, so this approach can be applied to
various other medical studies in the future.</p>
    </sec>
    <sec id="sec-3">
      <title>2. Related Works</title>
      <p>
        In-vitro fertilization, IVF, is a process for medically assisted reproduction where previously
collected cumulus-oocyte-complexes are fertilised in a laboratory in a short-time embryo
culture in vitro for up to 6 days. Then, the embryo with the best prognosis will be selected for
intrauterine transfer. Extra embryos can be cryopreserved for subsequent embryo transfers [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ].
      </p>
      <p>
        For a successful IVF process, choosing an embryo with high quality is important. This is
done by using the Gardner score to assess the quality of embryos in their blastocyst stage.
This score was created and evaluated by Gardner et al. in 2000 and has been commonly used
since then [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ]. This score consists of three diferent parts: the blastocyst expansion, inner
cell mass and trophectoderm. The blastocyst expansion is on a scale from 1-6 from blastocyst
development and stage status to hatched out of shell. The inner cell mass and trophectoderm
are both assessed by how many cells the embryo has from A-C or not definable [
        <xref ref-type="bibr" rid="ref6 ref7">7, 6</xref>
        ].
      </p>
      <p>
        The Gardner score focuses on the expansion and development of the embryo, but many other
factors can have an impact on embryo development. Gardner and Kelly (2017) mention oxygen
level, temperature, pH levels, and whether the embryo is alone in the culture or not as such
factors [
        <xref ref-type="bibr" rid="ref8">8</xref>
        ].
      </p>
      <p>
        There is various research analysing the influence of diferent environment factors, but
the potential of modern machine learning models have not been harnessed in this field yet.
Transformer-based models are state-of-the-art and excel at identifying long-term dependencies
in data. A study by Zhao et al. (2023) created a TransFM model based on a CNN and Transformer
hybrid framework. This combination of the two machine learning techniques used both the
attention mechanism from transformers and the CNN’s capabilities at handling images as input
to achieve great results [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ]. Parvaiz et al. (2023) claim that the usage of the global attention
mechanism inherent to transformer models resolve long-range dependencies and can be used
to decipher information in images as well [
        <xref ref-type="bibr" rid="ref10">10</xref>
        ].
      </p>
      <p>Recent research has also explored how diferent transformer architectures can be combined
or adjusted to improve performance in specific contexts. For example, models like Swin
Transformers and DeiT have been tailored for medical imaging tasks where data might be limited
but highly structured. The flexibility of transformers to work with sequences, images, or even
mixed data types makes them very useful in this type of study. This study builds on these
insights by designing and evaluating transformer-based models specifically suited for embryo
quality prediction and environmental impact assessment.</p>
      <p>
        A study done by Kromp et al. (2023) gathered a dataset with images of embryos on the 5th day
in the IVF cycle during the blastocyst stage together with their Gardner scores to have a basis
for research in IVF using machine learning. They also trained their own adapted transformer
models on this dataset. The models were XCeption, Deit transformer and Swin transformer [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ].
A study by Mazroa et al. (2024) created a Computer Vision-Aided Swin transformer model with
Boosted-Dipper-Throated Optimisation to detect embryo development [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ]. A study by Kim
et al. (2024) analysed images from time-lapse videos of embryos and electronic health records
of the parents to predict the embryo variability. To do so, they created their own multimodal
transformer model [
        <xref ref-type="bibr" rid="ref12">12</xref>
        ].
      </p>
      <p>
        Another approach to model training is transfer learning which can produce great results
with only a short training period. This approach uses a pre-trained model and fine-tunes it for
a similar problem. Even with a small amount of data, good performance can be achieved this
way [
        <xref ref-type="bibr" rid="ref13">13</xref>
        ]. One study by Yusuf Abas et al. (2023) compared a CNN model and the fine-tuned
VGG-16 model for classifying the quality of embryos based on their images. They showed that
the model using transfer learning performed better than the CNN model. Due to the small
amount of training data, they performed data augmentation to prevent overfitting and balanced
the dataset for better performance [14].
      </p>
      <p>To summarise, there has been various research analysing the influence of diferent factors
on embryos, as well as using transformer models to classify the embryo quality. There has
also been a study using transfer learning in the prediction of embryo quality. But there has
not yet been a focus on the environmental factors for the quality using transformer’s attention
mechanism and transfer learning. This study will address that gap by combining usage of
the transformer mechanism, transfer learning and the focus on the environmental factors for
embryo quality.</p>
    </sec>
    <sec id="sec-4">
      <title>3. Data Representation</title>
      <p>
        In this section, the datasets used in this study will be further explained. The first dataset was
created by Kromp et al. (2023) and contains images of embryos in their blastocyst stage together
with the Gardner scores. The images were taken from 2018 to 2021 in Linz, Austria. The dataset
is already split into a training and testing dataset containing 2044 and 300 images respectively.
The Gardner score consists of three categories: cell expansion, quality of inner cell mass, and
trophectoderm [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ] and is used to assess the quality of the embryo. To be able to match the
images with the laboratory factors later on, the date when the image was taken was also added.
This dataset is publicly available.
      </p>
      <p>The second dataset consists of time-series environmental measurements recorded by two
internal sensor modules in a laboratory in Malmö. These modules track factors such as
temperature, humidity, CO₂ levels, air pressure, light intensity (lux), motion (PIR), and total volatile
organic compounds (TVOC) across multiple years. The sensor modules are referred to using
general labels for clarity.</p>
      <p>The third data source is from the Swedish Meteorological and Hydrological Institute (SMHI)
and has the data from Malmö city regarding the temperature, humidity and air pressure from
2018 - 2021 [15]. Data published by SMHI was chosen because it is easily accessible, well
documented and from an oficial source, so of a high quality and reliable. Similar to the data
taken from Malmö, the fourth data source is from Linz and also contains information about the
cities temperature, humidity and air pressure in the same time frame as Malmö. This data is
published by GeoSphere Austria, the Federal Institute for Geology, Geophysics, Climatology,
and Meteorology in Austria, so also a reliable data source with good documentation [16]. For
both Malmö and Linz’ environmental factors (temperature, humidity and air pressure), it is
important to only use trusted sources to ensure high data accuracy and quality.</p>
      <p>In all datasets, if multiple sensors contained information, the mean was used to synthesise
the multiple data entries. The mean was also used to resample the data to one daily value to
ensure the same timespans across all datasets used in this study.</p>
    </sec>
    <sec id="sec-5">
      <title>4. Proposed Approach</title>
      <p>Laboratory-specific environmental factors are first synthesized from city-level environmental
data using a Random Forest Regressor trained on paired measurements from a reference site.
These synthesized features are then used as part of the input to the model. The proposed
approach consists of three main stages, illustrated as modules in figure 2. In the first stage, the
environmental tabular features are processed through a feed-forward network. In the second
stage, visual features are extracted from embryo images using a convolutional backbone. In the
third stage, the extracted tabular and image features are fused to perform binary classification
of embryo quality, targeting the TE, ICM, and EXP scores. Each module of the architecture is
detailed in the following sections.</p>
      <sec id="sec-5-1">
        <title>4.1. Synthetic Data Generation</title>
        <p>To generate the laboratory environmental factors for Linz, a machine learning approach was
used because there was no access to real lab sensor data from that location. Instead, this study
relied on data from Malmö, where both weather conditions and corresponding IVF laboratory
factors were available. A Random Forest Regressor, a powerful model that can learn complex
relationships, was trained to understand how Malmö’s weather (temperature, humidity, and
air pressure) influenced laboratory conditions. After training, this model was applied to the
weather data from Linz to predict what the laboratory environment would likely have been
under similar circumstances. The model performed well during validation, achieving a low
mean squared error (MSE) of approximately 1.89, which indicated that it was making accurate
predictions. Because of this strong performance, it can confidently be used to generate realistic
and reliable synthetic laboratory factor data for Linz, allowing the project to move forward
despite the lack of direct lab measurements. In figure 1, the comparison between the laboratory
factors and the city environment factors can be seen for both Malmö and Linz.</p>
      </sec>
      <sec id="sec-5-2">
        <title>4.2. Model Architecture</title>
        <p>The environmental features, including temperature, humidity, and air pressure, are first
processed through a feed-forward neural network designed to encode tabular data. This stage,
referred to as Module 1, applies two fully connected layers, each followed by batch normalization,
ReLU activation, and dropout, to transform the raw environmental inputs into a 64-dimensional
latent representation. This encoding facilitates efective integration with visual features in later
stages, as illustrated in figure 2.</p>
        <p>In parallel, embryo images are processed through a convolutional backbone based on a
simplified InceptionV3 architecture. This component, forming the core of Module 2, captures
multi-scale representations using a combination of 1×1, 3×3, and 5×5 convolutional filters
alongside max pooling. The extracted feature maps are then refined through a feedforward
block composed of fully connected layers, batch normalization, ReLU activation, and dropout,
yielding high-level visual embeddings.</p>
        <p>In Module 3, the environmental and visual embeddings are concatenated and passed through
a fusion layer followed by a self-attention mechanism. The attention block models dependencies
across modalities using a residual structure with a learnable scaling factor. The fused
representation is then processed by a shared multi-layer perceptron to generate binary classification
outputs for EXP, ICM, and TE scores, each using a sigmoid activation function. The overall
fusion and prediction process is shown in figure 2.</p>
        <p>Module 1: Preprocessing</p>
        <p>Environmental Factors</p>
        <p>(Tabular CSV)
InceptionV3 Backbone
(Pretrained CNN)</p>
        <p>MLP for Tabular Data</p>
        <p>FC → BN → ReLU → Dropout → FC → BN → ReLU
1x1 Conv
3x3 Conv
5x5 Conv
3x3 MaxPool</p>
        <p>Image Feature Refinement
FC → BN → ReLU → Dropout</p>
        <p>Env Feature Encoding</p>
        <p>→ 64-dim
Image Features</p>
        <p>Env Features
Module 2: Fusion &amp; Attention</p>
        <p>Fusion Layer
(Concat + FC + Dropout)</p>
        <p>Attention Block
(Self-Attention + Residual + γ)</p>
        <p>Attention-weighted Features
Module 3: Prediction</p>
        <p>Shared MLP
(FC → BN → ReLU → Dropout)</p>
        <p>EXP Output
(Sigmoid, Binary)</p>
        <p>ICM Output
(Sigmoid, Binary)</p>
        <p>TE Output
(Sigmoid, Binary)
with attention mechanism and multiple output heads</p>
      </sec>
    </sec>
    <sec id="sec-6">
      <title>5. Results</title>
      <p>This section will show and explain the results of the fine-tuned Inception V3 model that was
trained for prediction on the cell expansion (EXP), inner cell mass (ICM) and trophectoderm
(TE) into binary classes. The evaluation results can be seen in table 1.</p>
      <p>The high values across all metrics for the cell expansion show that the model performs
excellent for this factor with a high reliability. The trophectoderm prediction is moderate with a
potential for improvement, especially in the precision of the model, so correctly identifying the
positive instances. While EXP and TE are acceptable predictions, the model struggles to predict
the ICM factor for the embryo quality. This can be clearly seen by an accuracy not much better
than guessing and an especially poor performance regarding the precision. This means not a
lot of positive cases, in this case embryos with high quality, were predicted correctly which
could be explained by an imbalance in the data.</p>
      <p>To put these results into context, the same model architecture was used, but this time without
the attention-block. The performance results can be seen in table 2.</p>
      <p>While the cell expansion and inner cell mass have better accuracy without the attention
block, the trophectoderm prediction worsens without the attention block. Looking at the other
metrics, it is interesting to see that using the attention block improves the recall of the model,
especially for TE and ICM predictions, but it worsens the precision notably for ICM prediction.</p>
      <p>Analysing the performance of the proposed model with the attention block, ROC curves
are considered. The ROC curves can be seen in figure 3. For the EXP model, the ROC curve
demonstrates exceptional discriminative ability with an AUC of 0.98. The curve rises steeply at
low false positive rates, indicating the model achieves high true positive rates even with strict
classification thresholds. The TE model’s ROC curve demonstrates good discriminative ability
with an AUC of 0.80. The curve rises at a moderate pace and maintains reasonable distance
from the diagonal reference line. Again, the performance is adequate but can be improved
on. Analysing the ICM model’s performance, the ROC curve shows limited discriminative
ability with an AUC of 0.68. The curve rises gradually and stays relatively close to the diagonal
reference line that represents random guessing.</p>
      <p>Further delving into the ICM prediction with a visualisation of the prediction’s distribution
in figure 4, it becomes clear that the model gives similar scores to both good and poor ICMs.
Most scores cluster around the middle (0.4), showing the model is uncertain.</p>
    </sec>
    <sec id="sec-7">
      <title>6. Conclusion</title>
      <p>With the rising advancement of complex machine learning techniques, models can help identify
embryo quality. This study proposed a complex model architecture based on the CNN Inception
V3 model and an MLP neural network in combination that use the attention mechanism to
predict three diferent scores using a multitask learning approach. This model was used to
predict the quality of embryos in three scores EXP, ICM and TE based on their images and
the environmental factors (temperature, humidity and air pressure) in the laboratory. The
preliminary results show that the model achieved an accuracy of 92.76% for EXP, 72.63% for TE
and 63.69% for ICM. This shows that the model performed excellent for classifying EXP scores,
acceptable for TE score and leaves much room for improvement for ICM scoring. Comparing
the model with and without the attention block shows that utilising the attention mechanism
leads to better recall of the model, indicating a better ability to correctly identify embryos with
a high quality. The reason for the models poor ICM performance should be further analysed
in future work and possible data imbalance problems mitigated to improve performance. This
will help build a reliable model for all three parts of the Gardner score. Replacing the Inception
V3 model with another pre-trained model and comparing the results would also be interesting,
just like utilizing a transformers model trained only for these tasks to widen the attention
mechanism through the whole architecture.</p>
    </sec>
    <sec id="sec-8">
      <title>Acknowledgments</title>
      <p>This ongoing research is conducted as part of the EIVF-AI project funded by Vinnova, the
Swedish Governmental Agency for Innovation Systems (Grant No.2024-00088).</p>
    </sec>
    <sec id="sec-9">
      <title>Declaration on Generative AI</title>
      <p>During the preparation of this work, the authors used ChatGPT (GPT-4) to assist with grammar
and spelling checks and to improve clarity of phrasing in some sections. After using this tool,
the authors reviewed and edited the content as needed and take full responsibility for the
publication’s content.
URL: https://www.sciencedirect.com/science/article/pii/S0208521621001297. doi:https:
//doi.org/10.1016/j.bbe.2021.11.004.
[14] Y. A. Mohamed, U. K. Yusof, I. S. Isa, M. M. Zain, An automated blastocyst grading system
using convolutional neural network and transfer learning, in: 2023 IEEE 13th International
Conference on Control System, Computing and Engineering (ICCSCE), 2023, pp. 202–207.
doi:10.1109/ICCSCE58721.2023.10237105.
[15] SMHI, Data och analyser för väder samt Sveriges klimat och miljö| SMHI — smhi.se,
https://www.smhi.se/data, ???? [Accessed 22-02-2025].
[16] G. Austria, GeoSphere Austria Data Hub — data.hub.geosphere.at, https://data.hub.
geosphere.at/dataset/klima-v2-1m, 2024. [Accessed 22-02-2025].</p>
    </sec>
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