New Frontiers in Embryo Selection
Glatstein et al., Journal of Assisted Reproduction and Genetics (JARG), 2023
Abstract
Human infertility is a major global public health issue estimated to affect one out of six couples, while the number of assisted reproduction cycles grows impressively year over year. Efforts to alleviate infertility using advanced technology are gaining traction rapidly as infertility has an enormous impact on couples and the potential to destabilize entire societies if replacement birthrates are not achieved.
Artificial intelligence (AI) technologies, leveraged by the highly advanced assisted reproductive technology (ART) industry, are a promising addition to the armamentarium of tools available to combat global infertility. This review provides a background for current methodologies in embryo selection, which is a manual, time-consuming, and poorly reproducible task. AI has the potential to improve this process (among many others) in both the clinician’s office and the IVF laboratory. Embryo selection is evolving through digital methodologies into an automated procedure, with superior reliability and reproducibility, that is likely to result in higher pregnancy rates for patients. There is an emerging body of data demonstrating the utility of AI applications in multiple areas in the IVF laboratory. AI platforms have been developed to evaluate individual embryologist performance; to provide quality assurance for culture systems; to correlate embryologist’s assessments and AI systems; to predict embryo ploidy, implantation, fetal heartbeat, and live birth outcome; and to replace the current “analogue” system of embryo selection with a digital paradigm. AI capability will distinguish high performing, high profit margin, low-cost, and highly successful IVF clinic business models. We think it will become the standard, “new normal” in IVF labs, as rapidly and thoroughly as vitrification, blastocyst culture, and intracytoplasmic sperm injection replaced their predecessor technologies. At the time of this review, the AI technology to automate embryo evaluation and selection has robustly matured, and therefore, it is the main focus of this review.
KEY WORDSArtificial intelligence • Machine Learning • Embryo Selection • Embryo Ranking
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Ahlström A, et al. Trophectoderm morphology: an important parameter for predicting live birth after single blastocyst transfer. Hum Reprod. 2011;26(12):3289-3296.
Gardner DK, et al. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000;73(6):1155-1158.
Bormann CL, et al. Consistency and objectivity of automated embryo assessments using deep neural networks. Fertil Steril. 2020;113(4):781-787.e1.
Curchoe C. Development of a mobile competency assessment platform for IVF laboratory quality management systems. J Assist Reprod Genet. 2018;35:2087-2106.
Morbeck D, Hammond E, Kit AMF, Curchoe CL. Assuring quality in embryology decision making: blastocyst grading agreement assessed via a smartphone application. Hum Reprod. 2021;36. doi:10.1093/humrep/deab130.166.
Curchoe CL. Smartphone applications for reproduction: from rigorously validated and clinically relevant to potentially harmful. EMJ Reprod Health. 2020;6(1):85-91.
Montag M, Toth B, Strowitzki T. New approaches to embryo selection. Reprod Biomed Online. 2013;27(5):539-546.
Meseguer M, et al. The use of morphokinetics as a predictor of embryo implantation. Hum Reprod. 2011;26(10):2658-2671.
Kermack AJ, Fesenko I, Christensen DR, Parry KL, Lowen P, Wellstead SJ, Harris SF, Calder PC, Macklon NS, Houghton FD. Incubator type affects human blastocyst formation and embryo metabolism: a randomized controlled trial. Hum Reprod. 2022;37(12):2757-2767. doi:10.1093/humrep/deac233.
Carrasco B, et al. Selecting embryos with the highest implantation potential using data mining and decision tree based on classical embryo morphology and morphokinetics. J Assist Reprod Genet. 2017;34(8):983-990.
Armstrong S, et al. Time-lapse systems for embryo incubation and assessment in assisted reproduction. Cochrane Database Syst Rev. 2018;5:CD011320.
Hosny A, et al. Artificial intelligence in radiology. Nat Rev Cancer. 2018;18(8):500-510.
Ting DSW, et al. Artificial intelligence and deep learning in ophthalmology. Br J Ophthalmol. 2019;103(2):167-175.
Topol EJ. High-performance medicine: the convergence of human and artificial intelligence. Nat Med. 2019;25(1):44-56.
Krittanawong C, et al. Artificial intelligence in precision cardiovascular medicine. J Am Coll Cardiol. 2017;69(21):2657-2664.
Benjamens S, Dhunnoo P, Mesko B. The state of artificial intelligence-based FDA-approved medical devices and algorithms: an online database. NPJ Digit Med. 2020;3:118.
Curchoe CL, Bormann CL. Artificial intelligence and machine learning for human reproduction and embryology presented at ASRM and ESHRE 2018. J Assist Reprod Genet. 2019;36(4):591-600.
Corani G, et al. A Bayesian network model for predicting pregnancy after in vitro fertilization. Comput Biol Med. 2013;43(11):1783-1792.
Uyar A, Bener A, Ciray HN. Predictive modeling of implantation outcome in an in vitro fertilization setting: an application of machine learning methods. Med Decis Making. 2015;35(6):714-725.
Hernandez-Gonzalez J, et al. Fitting the data from embryo implantation prediction: learning from label proportions. Stat Methods Med Res. 2018;27(4):1056-1066.
Ratna MB, et al. A systematic review of the quality of clinical prediction models in in vitro fertilisation. Hum Reprod. 2020;35(1):100-116.
Simopoulou M, et al. Are computational applications the “crystal ball” in the IVF laboratory? The evolution from mathematics to artificial intelligence. J Assist Reprod Genet. 2018;35(9):1545-1557.
Swain J, et al. AI in the treatment of fertility: key considerations. J Assist Reprod Genet. 2020;37(11):2817-2824.
Fernandez EI, et al. Artificial intelligence in the IVF laboratory: overview through the application of different types of algorithms for the classification of reproductive data. J Assist Reprod Genet. 2020;37(10):2359-2376.
Milewski R, et al. How much information about embryo implantation potential is included in morphokinetic data? A prediction model based on artificial neural networks and principal component analysis. Adv Med Sci. 2017;62(1):202-206.
Blank C, et al. Prediction of implantation after blastocyst transfer in in vitro fertilization: a machine-learning perspective. Fertil Steril. 2019;111(2):318-326.
Santos Filho E, et al. A method for semi-automatic grading of human blastocyst microscope images. Hum Reprod. 2012;27(9):2641-2648.
Manna C, et al. Artificial intelligence techniques for embryo and oocyte classification. Reprod Biomed Online. 2013;26(1):42-49.
Tran D, et al. Deep learning as a predictive tool for fetal heart pregnancy following time-lapse incubation and blastocyst transfer. Hum Reprod. 2019;34(6):1011-1018.
Berntsen J, Rimestad J, Lassen JT, Tran D, Kragh MF. Robust and generalizable embryo selection based on artificial intelligence and time-lapse image sequences. PLoS One. 2022;17(2):e0262661. doi:10.1371/journal.pone.0262661.
Reignier A, et al. Performance of Day 5 KIDScore morphokinetic prediction models of implantation and live birth after single blastocyst transfer. J Assist Reprod Genet. 2019;36(11):2279-2285.
Kragh MF, et al. Automatic grading of human blastocysts from time-lapse imaging. Comput Biol Med. 2019;115:103494.
Miyagi Y, Miyake T. Potential of artificial intelligence for estimating Japanese fetal weights. Acta Med Okayama. 2020;74(6):483-493.
Raudonis V, et al. Towards the automation of early-stage human embryo development detection. Biomed Eng Online. 2019;18(1):120.
Khosravi P, et al. Deep learning enables robust assessment and selection of human blastocysts after in vitro fertilization. NPJ Digit Med. 2019;2:21.
VerMilyea M, et al. Development of an artificial intelligence-based assessment model for prediction of embryo viability using static images captured by optical light microscopy during IVF. Hum Reprod. 2020;35(4):770-784.
Bori L, et al. Novel and conventional embryo parameters as input data for artificial neural networks: an artificial intelligence model applied for prediction of the implantation potential. Fertil Steril. 2020;114(6):1232-1241.
Bori L, et al. An artificial intelligence model based on the proteomic profile of euploid embryos and blastocyst morphology: a preliminary study. Reprod Biomed Online. 2021;42(2):340-350.
Fitz VW, et al. Should there be an “AI” in TEAM? Embryologists selection of high implantation potential embryos improves with the aid of an artificial intelligence algorithm. J Assist Reprod Genet. 2021;38(10):2663-2670.
Chavez-Badiola A, et al. Predicting pregnancy test results after embryo transfer by image feature extraction and analysis using machine learning. Sci Rep. 2020;10(1):4394.
Chavez-Badiola A, et al. Embryo Ranking Intelligent Classification Algorithm (ERICA): artificial intelligence clinical assistant predicting embryo ploidy and implantation. Reprod Biomed Online. 2020;41(4):585-593.
Go KJ. Beauty (quality) is in the eye of the convoluted neural network. Fertil Steril. 2020;113(4):756-757.
He J, et al. The practical implementation of artificial intelligence technologies in medicine. Nat Med. 2019;25(1):30-36.
Doshi-Velez F, Perlis RH. Evaluating machine learning articles. JAMA. 2019;322(18):1777-1779.
Mahadevaiah G, et al. Artificial intelligence-based clinical decision support in modern medical physics: selection, acceptance, commissioning, and quality assurance. Med Phys. 2020;47(5):e228-e235.
Curchoe CL, et al. Predictive modeling in reproductive medicine: where will the future of artificial intelligence research take us? Fertil Steril. 2020;114(5):934-940.
Sanson-Fisher RW, et al. Limitations of the randomized controlled trial in evaluating population-based health interventions. Am J Prev Med. 2007;33(2):155-161.
Eaneff S, Obermeyer Z, Butte AJ. The case for algorithmic stewardship for artificial intelligence and machine learning technologies. JAMA. 2020;324(14):1397-1398.
Perrault R, Shoham Y, Brynjolfsson E, Clark J, Etchemendy J, Grosz B, Lyons T, Manyika J, Mishra S, Niebles JC. The AI Index 2019 Annual Report. Stanford, CA: AI Index Steering Committee; 2019. Available from: https://hai.stanford.edu/sites/default/files/ai_index_2019_report.pdf.