{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:13:20Z","timestamp":1783487600383,"version":"3.55.0"},"reference-count":70,"publisher":"The Royal Society","issue":"182","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HD092550-01"],"award-info":[{"award-number":["R01HD092550-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HD104969-01"],"award-info":[{"award-number":["R01HD104969-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["royalsocietypublishing.org"],"crossmark-restriction":true},"short-container-title":["J. R. Soc. Interface."],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:p>\n            Macroscopic, phenomenological models are useful as concise framings of our understandings in fields from statistical physics to finance to biology. Constructing a phenomenological model for development would provide a framework for understanding the complicated, regulatory nature of oogenesis and embryogenesis. Here, we use a data-driven approach to infer quantitative, precise models of human oocyte maturation and pre-implantation embryo development, by analysing clinical\n            <jats:italic>in-vitro<\/jats:italic>\n            fertilization (IVF) data on 7399 IVF cycles resulting in 57 827 embryos. Surprisingly, we find that both oocyte maturation and early embryo development are quantitatively described by simple models with minimal interactions. This simplicity suggests that oogenesis and embryogenesis are composed of modular processes that are relatively siloed from one another. In particular, our analysis provides strong evidence that (i) pre-antral follicles produce anti-M\u00fcllerian hormone independently of effects from other follicles, (ii) oocytes mature to metaphase-II independently of the woman\u2019s age, her BMI and other factors, (iii) early embryo development is memoryless for the variables assessed here, in that the probability of an embryo transitioning from its current developmental stage to the next is independent of its previous stage. Our results both provide insight into the fundamentals of oogenesis and embryogenesis and have implications for the clinical IVF.\n          <\/jats:p>","DOI":"10.1098\/rsif.2021.0475","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T07:13:23Z","timestamp":1631085203000},"page":"20210475","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Inferring simple but precise quantitative models of human oocyte and early embryo development"],"prefix":"10.1098","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0070-0985","authenticated-orcid":true,"given":"Brian D.","family":"Leahy","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA"},{"name":"SEAS, Harvard University, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Racowsky","sequence":"additional","affiliation":[{"name":"Brigham Women\u2019s Hospital, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Needleman","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA"},{"name":"SEAS, Harvard University, Cambridge, MA, USA"},{"name":"Center for Computational Biology, Flatiron Institute, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.11.003"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3602"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2020.05.007"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biophys-070816-033602"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.07.010"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-021920-110200"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3643"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aax0164"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.017178"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.05.013"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/35066065"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.060426"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034102"},{"key":"e_1_3_6_15_2","volume-title":"Statistical mechanics: entropy, order parameters, and complexity","author":"Sethna J","year":"2006","unstructured":"Sethna J. 2006 Statistical mechanics: entropy, order parameters, and complexity, vol. 14. Oxford, UK: Oxford University Press."},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511753893"},{"key":"e_1_3_6_17_2","volume-title":"Biophysics: searching for principles","author":"Bialek W","year":"2012","unstructured":"Bialek W. 2012 Biophysics: searching for principles. Princeton, NJ: Princeton University Press."},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2017.48"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.202100062"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.07.038"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2014.12.009"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2016.02.004"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.11.063"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gah015"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dep210"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1530\/rep.0.1240601"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmp036"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.11.004"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2014.10.014"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.01.017"},{"key":"e_1_3_6_31_2","volume-title":"In-vitro fertilization","author":"Elder K","year":"2020","unstructured":"Elder K, Dale B. 2020 In-vitro fertilization. Cambridge, UK: Cambridge University Press."},{"key":"e_1_3_6_32_2","volume-title":"Information theory, inference and learning algorithms","author":"MacKay DJ","year":"2003","unstructured":"MacKay DJ, Mac Kay DJ. 2003 Information theory, inference and learning algorithms. Cambridge, UK: Cambridge University Press."},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1162\/neco.1992.4.3.415"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1089\/106652700750050961"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511803161"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-statistics-022513-115545"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094068"},{"key":"e_1_3_6_38_2","volume-title":"Pattern recognition and machine learning","author":"Bishop CM","year":"2006","unstructured":"Bishop CM. 2006 Pattern recognition and machine learning. Berlin, Germany: Springer."},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1530\/REP-09-0415"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1978.tb01896.x"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1136\/jms.9.1.2"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav7321"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa9529"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2016.09.002"},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.08.051"},{"key":"e_1_3_6_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.06.057"},{"key":"e_1_3_6_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gap007"},{"key":"e_1_3_6_48_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.113.112151"},{"key":"e_1_3_6_49_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh682"},{"key":"e_1_3_6_50_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/16.8.1676"},{"key":"e_1_3_6_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3012"},{"key":"e_1_3_6_52_2","volume-title":"Statistical analysis with missing data","author":"Little RJ","year":"2019","unstructured":"Little RJ, Rubin DB. 2019 Statistical analysis with missing data, vol. 793. New York, NY: John Wiley & Sons."},{"key":"e_1_3_6_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.02.009"},{"key":"e_1_3_6_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.02.008"},{"key":"e_1_3_6_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaw057"},{"key":"e_1_3_6_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/332459a0"},{"key":"e_1_3_6_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2014.09.012"},{"key":"e_1_3_6_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew183"},{"key":"e_1_3_6_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2013.02.006"},{"key":"e_1_3_6_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmu023"},{"key":"e_1_3_6_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2012.12.003"},{"key":"e_1_3_6_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der325"},{"key":"e_1_3_6_63_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2005-0015"},{"key":"e_1_3_6_64_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00285341"},{"key":"e_1_3_6_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(81)84800-X"},{"key":"e_1_3_6_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/0025-5564(88)90072-7"},{"key":"e_1_3_6_67_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu276"},{"key":"e_1_3_6_68_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/den190"},{"key":"e_1_3_6_69_2","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0590357"},{"key":"e_1_3_6_70_2","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0710607"},{"key":"e_1_3_6_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/35011540"}],"container-title":["Journal of The Royal Society Interface"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsif.2021.0475","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/full-xml\/10.1098\/rsif.2021.0475","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/royalsocietypublishing.org\/doi\/pdf\/10.1098\/rsif.2021.0475","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T07:15:10Z","timestamp":1631085310000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/doi\/10.1098\/rsif.2021.0475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":70,"journal-issue":{"issue":"182","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1098\/rsif.2021.0475"],"URL":"https:\/\/doi.org\/10.1098\/rsif.2021.0475","relation":{},"ISSN":["1742-5662"],"issn-type":[{"value":"1742-5662","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9]]},"assertion":[{"value":"2021-06-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}