Development and evaluation of a live birth prediction model for evaluating human blastocysts: a retrospective study

  1. Hang Liu
  2. Zhuoran Zhang
  3. Yifan Gu
  4. Changsheng Dai
  5. Guanqiao Shan
  6. Haocong Song
  7. Daniel Li
  8. Wenyuan Chen
  9. Ge Lin  Is a corresponding author
  10. Yu Sun  Is a corresponding author
  1. University of Toronto, Canada
  2. Chinese University of Hong Kong, Shenzhen, China
  3. Central South University, China

Abstract

Background: In infertility treatment, blastocyst morphological grading is commonly used in clinical practice for blastocyst evaluation and selection, but has shown limited predictive power on live birth outcomes of blastocysts. To improve live birth prediction, a number of artificial intelligence (AI) models have been established. Most existing AI models for blastocyst evaluation only used images for live birth prediction, and the area under the receiver operating characteristic (ROC) curve (AUC) achieved by these models has plateaued at ~0.65.

Methods: This study proposed a multi-modal blastocyst evaluation method using both blastocyst images and patient couple's clinical features (e.g., maternal age, hormone profiles, endometrium thickness, and semen quality) to predict live birth outcomes of human blastocysts. To utilize the multi-modal data, we developed a new AI model consisting of a convolutional neural network (CNN) to process blastocyst images and a multi-layer perceptron to process patient couple's clinical features. The dataset used in this study consists of 17,580 blastocysts with known live birth outcomes, blastocyst images, and patient couple's clinical features.

Results: This study achieved an AUC of 0.77 for live birth prediction, which significantly outperforms related works in the literature. Sixteen out of 103 clinical features were identified to be predictors of live birth outcomes and helped improve live birth prediction. Among these features, maternal age, the day of blastocyst transfer, antral follicle count, retrieved oocyte number, and endometrium thickness measured before transfer are the top five features contributing to live birth prediction. Heatmaps showed that the CNN in the AI model mainly focuses on image regions of inner cell mass and trophectoderm (TE) for live birth prediction, and the contribution of TE-related features was greater in the CNN trained with the inclusion of patient couple's clinical features compared with the CNN trained with blastocyst images alone.

Conclusions: The results suggest that the inclusion of patient couple's clinical features along with blastocyst images increases live birth prediction accuracy.

Funding: Natural Sciences and Engineering Research Council of Canada and the Canada Research Chairs Program.

Data availability

All processed data and code needed to reproduce the findings of the study are made openly available in deidentified form. This can be found in https://github.com/robotVisionHang/LiveBirthPrediction_Data_Code, and attached to this manuscript. All codes and software used to analyze the data can also be accessed through the link. Due to data privacy regulations of patient data, raw data cannot be publicly shared. Interested researchers are welcome to contact the corresponding author with a concise project proposal indicating aims of using the data and how they will use the data. The project proposal will be firstly assessed by Prof. Yu Sun, Prof. Ge Lin, and then by the Ethics Committee of the Reproductive and Genetic Hospital of CITIC-Xiangya. There are no restrictions on who can access the data.

Article and author information

Author details

  1. Hang Liu

    Department of Mechanical Engineering, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7948-4236
  2. Zhuoran Zhang

    School of Science and Engineering, Chinese University of Hong Kong, Shenzhen, Shenzhen, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Yifan Gu

    Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Changsheng Dai

    Department of Mechanical Engineering, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Guanqiao Shan

    Department of Mechanical Engineering, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Haocong Song

    Department of Mechanical Engineering, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  7. Daniel Li

    Department of Mechanical Engineering, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  8. Wenyuan Chen

    Department of Mechanical Engineering, University of Toronto, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  9. Ge Lin

    Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, China
    For correspondence
    linggf@hotmail.com
    Competing interests
    The authors declare that no competing interests exist.
  10. Yu Sun

    Department of Mechanical Engineering, University of Toronto, Toronto, Canada
    For correspondence
    sun@mie.utoronto.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7895-0741

Funding

Natural Sciences and Engineering Research Council of Canada

  • Yu Sun

Canada Research Chairs

  • Yu Sun

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Larisa V. Suturina, Scientific Center for Family Health and Human Reproduction, Russian Federation

Ethics

Human subjects: Informed consent was not necessary because this study used retrospective and fully de-identified data, no medical intervention was performed on the subject, and no biological samples from the patient were collected. This study was approved by the Ethics Committee of the Reproductive and Genetic Hospital of CITIC-Xiangya (approval number: LL-SC-2021-008).

Version history

  1. Received: September 23, 2022
  2. Preprint posted: October 21, 2022 (view preprint)
  3. Accepted: February 20, 2023
  4. Accepted Manuscript published: February 22, 2023 (version 1)
  5. Version of Record published: April 3, 2023 (version 2)

Copyright

© 2023, Liu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,460
    views
  • 249
    downloads
  • 7
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Hang Liu
  2. Zhuoran Zhang
  3. Yifan Gu
  4. Changsheng Dai
  5. Guanqiao Shan
  6. Haocong Song
  7. Daniel Li
  8. Wenyuan Chen
  9. Ge Lin
  10. Yu Sun
(2023)
Development and evaluation of a live birth prediction model for evaluating human blastocysts: a retrospective study
eLife 12:e83662.
https://doi.org/10.7554/eLife.83662

Share this article

https://doi.org/10.7554/eLife.83662

Further reading

    1. Cell Biology
    2. Computational and Systems Biology
    N Suhas Jagannathan, Javier Yu Peng Koh ... Lisa Tucker-Kellogg
    Research Article

    Bats have unique characteristics compared to other mammals, including increased longevity and higher resistance to cancer and infectious disease. While previous studies have analyzed the metabolic requirements for flight, it is still unclear how bat metabolism supports these unique features, and no study has integrated metabolomics, transcriptomics, and proteomics to characterize bat metabolism. In this work, we performed a multi-omics data analysis using a computational model of metabolic fluxes to identify fundamental differences in central metabolism between primary lung fibroblast cell lines from the black flying fox fruit bat (Pteropus alecto) and human. Bat cells showed higher expression levels of Complex I components of electron transport chain (ETC), but, remarkably, a lower rate of oxygen consumption. Computational modeling interpreted these results as indicating that Complex II activity may be low or reversed, similar to an ischemic state. An ischemic-like state of bats was also supported by decreased levels of central metabolites and increased ratios of succinate to fumarate in bat cells. Ischemic states tend to produce reactive oxygen species (ROS), which would be incompatible with the longevity of bats. However, bat cells had higher antioxidant reservoirs (higher total glutathione and higher ratio of NADPH to NADP) despite higher mitochondrial ROS levels. In addition, bat cells were more resistant to glucose deprivation and had increased resistance to ferroptosis, one of the characteristics of which is oxidative stress. Thus, our studies revealed distinct differences in the ETC regulation and metabolic stress responses between human and bat cells.

    1. Computational and Systems Biology
    2. Neuroscience
    Sara Ibañez, Nilapratim Sengupta ... Christina M Weaver
    Research Article

    Normal aging leads to myelin alterations in the rhesus monkey dorsolateral prefrontal cortex (dlPFC), which are positively correlated with degree of cognitive impairment. It is hypothesized that remyelination with shorter and thinner myelin sheaths partially compensates for myelin degradation, but computational modeling has not yet explored these two phenomena together systematically. Here, we used a two-pronged modeling approach to determine how age-related myelin changes affect a core cognitive function: spatial working memory. First, we built a multicompartment pyramidal neuron model fit to monkey dlPFC empirical data, with an axon including myelinated segments having paranodes, juxtaparanodes, internodes, and tight junctions. This model was used to quantify conduction velocity (CV) changes and action potential (AP) failures after demyelination and subsequent remyelination. Next, we incorporated the single neuron results into a spiking neural network model of working memory. While complete remyelination nearly recovered axonal transmission and network function to unperturbed levels, our models predict that biologically plausible levels of myelin dystrophy, if uncompensated by other factors, can account for substantial working memory impairment with aging. The present computational study unites empirical data from ultrastructure up to behavior during normal aging, and has broader implications for many demyelinating conditions, such as multiple sclerosis or schizophrenia.