{"title":"An interpretable artificial intelligence approach to differentiate between blastocysts with similar or same morphological grades.","authors":"Hang Liu,Longbin Chen,Guanqiao Shan,Chen Sun,Changfu Lu,Hongqing Liao,Shuoping Zhang,Shaonan Dong,Xinxin Xu,Qiuyun Yan,Fei Gong,Zhuoran Zhang,Changsheng Dai,Wenyuan Chen,Haocong Song,Lei Chen,Shanshan Wang,Haixiang Sun,Ge Lin,Yu Sun,Yifan Gu","doi":"10.1093/humrep/deaf066","DOIUrl":null,"url":null,"abstract":"STUDY QUESTION\r\nCan a quantitative method be developed to differentiate between blastocysts with similar or same inner cell mass (ICM) and trophectoderm (TE) grades, while also reflecting their potential for live birth?\r\n\r\nSUMMARY ANSWER\r\nWe developed BlastScoringNet, an interpretable deep-learning model that quantifies blastocyst ICM and TE morphology with continuous scores, enabling finer differentiation between blastocysts with similar or same grades, with higher scores significantly correlating with higher live birth rates.\r\n\r\nWHAT IS KNOWN ALREADY\r\nWhile the Gardner grading system is widely used by embryologists worldwide, blastocysts having similar or same ICM and TE grades cause challenges for embryologists in decision-making. Furthermore, human assessment is subjective and inconsistent in predicting which blastocysts have higher potential to result in live birth.\r\n\r\nSTUDY DESIGN, SIZE, DURATION\r\nThe study design consists of three main steps. First, BlastScoringNet was developed using a grading dataset of 2760 blastocysts with majority-voted Gardner grades. Second, the model was applied to a live birth dataset of 15 228 blastocysts with known live birth outcomes to generate blastocyst scores. Finally, the correlation between these scores and live birth outcomes was assessed. The blastocysts were collected from patients who underwent IVF treatments between 2016 and 2018. For external application study, an additional grading dataset of 1455 blastocysts and a live birth dataset of 476 blastocysts were collected from patients who underwent IVF treatments between 2021 and 2023 at an external IVF institution.\r\n\r\nPARTICIPANTS/MATERIALS, SETTING, METHODS\r\nIn this retrospective study, we developed BlastScoringNet, an interpretable deep-learning model which outputs expansion degree grade and continuous scores quantifying a blastocyst's ICM morphology and TE morphology, based on the Gardner grading system. The continuous ICM and TE scores were calculated by weighting each base grade's predicted probability and summing the predicted probabilities. To represent each blastocyst's overall potential for live birth, we combined the ICM and TE scores using their odds ratios (ORs) for live birth. We further assessed the correlation between live birth rates and the ICM score, TE score, and the OR-combined score (adjusted for expansion degree) by applying BlastScoringNet to blastocysts with known live birth outcomes. To test its generalizability, we also applied BlastScoringNet to an external IVF institution, accounting for variations in imaging conditions, live birth rates, and embryologists' experience levels.\r\n\r\nMAIN RESULTS AND THE ROLE OF CHANCE\r\nBlastScoringNet was developed using data from 2760 blastocysts with majority-voted grades for expansion degree, ICM, and TE. The model achieved mean area under the receiver operating characteristic curve values of 0.997 (SD 0.004) for expansion degree, 0.903 (SD 0.031) for ICM, and 0.943 (SD 0.040) for TE, based on predicted probabilities for each base grade. From these predicted probabilities, BlastScoringNet generated continuous ICM and TE scores, as well as expansion degree grades, for an additional 15 228 blastocysts with known live birth outcomes. Higher ICM and TE scores, along with their OR-combined scores, were significantly correlated with increased live birth rates (P < 0.0001). By fine-tuning, BlastScoringNet was applied to an external IVF institution, where higher OR-combined ICM and TE scores also significantly correlated with increased live birth rates (P = 0.00078), demonstrating consistent results across both institutions.\r\n\r\nLIMITATIONS, REASONS FOR CAUTION\r\nThis study is limited by its retrospective nature. Further prospective randomized trials are required to confirm the clinical impact of BlastScoringNet in assisting embryologists in blastocyst selection.\r\n\r\nWIDER IMPLICATIONS OF THE FINDINGS\r\nBlastScoringNet provides an interpretable and quantitative method for evaluating blastocysts, aligned with the widely used Gardner grading system. Higher OR-combined ICM and TE scores, representing each blastocyst's overall potential for live birth, were significantly correlated with increased live birth rates. The model's demonstrated generalizability across two institutions further supports its clinical utility. These findings suggest that BlastScoringNet is a valuable tool for assisting embryologists in selecting blastocysts with the highest potential for live birth. The code and pre-trained models are publicly available to facilitate further research and widespread implementation.\r\n\r\nSTUDY FUNDING/COMPETING INTEREST(S)\r\nThis work was supported by the Vector Institute and the Temerty Faculty of Medicine at the University of Toronto, Toronto, Ontario, Canada, via a Clinical AI Integration Grant, and the Natural Science Foundation of Hunan Province of China (2023JJ30714). The authors declare no competing interests.\r\n\r\nTRIAL REGISTRATION NUMBER\r\nN/A.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"24 1","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human reproduction","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/humrep/deaf066","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
STUDY QUESTION
Can a quantitative method be developed to differentiate between blastocysts with similar or same inner cell mass (ICM) and trophectoderm (TE) grades, while also reflecting their potential for live birth?
SUMMARY ANSWER
We developed BlastScoringNet, an interpretable deep-learning model that quantifies blastocyst ICM and TE morphology with continuous scores, enabling finer differentiation between blastocysts with similar or same grades, with higher scores significantly correlating with higher live birth rates.
WHAT IS KNOWN ALREADY
While the Gardner grading system is widely used by embryologists worldwide, blastocysts having similar or same ICM and TE grades cause challenges for embryologists in decision-making. Furthermore, human assessment is subjective and inconsistent in predicting which blastocysts have higher potential to result in live birth.
STUDY DESIGN, SIZE, DURATION
The study design consists of three main steps. First, BlastScoringNet was developed using a grading dataset of 2760 blastocysts with majority-voted Gardner grades. Second, the model was applied to a live birth dataset of 15 228 blastocysts with known live birth outcomes to generate blastocyst scores. Finally, the correlation between these scores and live birth outcomes was assessed. The blastocysts were collected from patients who underwent IVF treatments between 2016 and 2018. For external application study, an additional grading dataset of 1455 blastocysts and a live birth dataset of 476 blastocysts were collected from patients who underwent IVF treatments between 2021 and 2023 at an external IVF institution.
PARTICIPANTS/MATERIALS, SETTING, METHODS
In this retrospective study, we developed BlastScoringNet, an interpretable deep-learning model which outputs expansion degree grade and continuous scores quantifying a blastocyst's ICM morphology and TE morphology, based on the Gardner grading system. The continuous ICM and TE scores were calculated by weighting each base grade's predicted probability and summing the predicted probabilities. To represent each blastocyst's overall potential for live birth, we combined the ICM and TE scores using their odds ratios (ORs) for live birth. We further assessed the correlation between live birth rates and the ICM score, TE score, and the OR-combined score (adjusted for expansion degree) by applying BlastScoringNet to blastocysts with known live birth outcomes. To test its generalizability, we also applied BlastScoringNet to an external IVF institution, accounting for variations in imaging conditions, live birth rates, and embryologists' experience levels.
MAIN RESULTS AND THE ROLE OF CHANCE
BlastScoringNet was developed using data from 2760 blastocysts with majority-voted grades for expansion degree, ICM, and TE. The model achieved mean area under the receiver operating characteristic curve values of 0.997 (SD 0.004) for expansion degree, 0.903 (SD 0.031) for ICM, and 0.943 (SD 0.040) for TE, based on predicted probabilities for each base grade. From these predicted probabilities, BlastScoringNet generated continuous ICM and TE scores, as well as expansion degree grades, for an additional 15 228 blastocysts with known live birth outcomes. Higher ICM and TE scores, along with their OR-combined scores, were significantly correlated with increased live birth rates (P < 0.0001). By fine-tuning, BlastScoringNet was applied to an external IVF institution, where higher OR-combined ICM and TE scores also significantly correlated with increased live birth rates (P = 0.00078), demonstrating consistent results across both institutions.
LIMITATIONS, REASONS FOR CAUTION
This study is limited by its retrospective nature. Further prospective randomized trials are required to confirm the clinical impact of BlastScoringNet in assisting embryologists in blastocyst selection.
WIDER IMPLICATIONS OF THE FINDINGS
BlastScoringNet provides an interpretable and quantitative method for evaluating blastocysts, aligned with the widely used Gardner grading system. Higher OR-combined ICM and TE scores, representing each blastocyst's overall potential for live birth, were significantly correlated with increased live birth rates. The model's demonstrated generalizability across two institutions further supports its clinical utility. These findings suggest that BlastScoringNet is a valuable tool for assisting embryologists in selecting blastocysts with the highest potential for live birth. The code and pre-trained models are publicly available to facilitate further research and widespread implementation.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by the Vector Institute and the Temerty Faculty of Medicine at the University of Toronto, Toronto, Ontario, Canada, via a Clinical AI Integration Grant, and the Natural Science Foundation of Hunan Province of China (2023JJ30714). The authors declare no competing interests.
TRIAL REGISTRATION NUMBER
N/A.
期刊介绍:
Human Reproduction features full-length, peer-reviewed papers reporting original research, concise clinical case reports, as well as opinions and debates on topical issues.
Papers published cover the clinical science and medical aspects of reproductive physiology, pathology and endocrinology; including andrology, gonad function, gametogenesis, fertilization, embryo development, implantation, early pregnancy, genetics, genetic diagnosis, oncology, infectious disease, surgery, contraception, infertility treatment, psychology, ethics and social issues.