{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T03:27:03Z","timestamp":1790047623123,"version":"4.0.1"},"reference-count":95,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Government Research Training Program (RTP) Scholarship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The dynamic nature of human endometrial tissue presents unique challenges in analysis. Despite extensive research into endometrial disorders such as endometriosis and infertility, recent systematic reviews have highlighted concerning issues with the reproducibility of omics studies attempting to identify biomarkers. This review examines factors contributing to poor reproducibility in endometrial omics research. Hormonal fluctuations in the menstrual cycle lead to widespread molecular changes in the endometrium, most notably in gene expression profiles. In this review, we examine the variability in omics data due to the menstrual cycle and highlight the importance of accurate menstrual cycle dating for effective statistical modelling. The current standards of endometrial dating lack precision and we make the case for using molecular-based modelling methods to estimate menstrual cycle time for endometrium tissue samples. Additionally, we discuss statistical considerations such as confounding and interaction effects, as well as the importance of recording the detailed and accurate clinical information of patients. By addressing these methodological challenges, we aim to establish more robust and reproducible research practises, increasing the reliability of endometrial omics research and biomarker discovery.<\/jats:p>","DOI":"10.3390\/ijms26020857","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T06:53:32Z","timestamp":1737442412000},"page":"857","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Improving Replication in Endometrial Omics: Understanding the Influence of the Menstrual Cycle"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0627-0955","authenticated-orcid":false,"given":"Jessica","family":"Chung","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Melbourne, and Gynaecology Research Centre, Royal Women\u2019s Hospital, Parkville, VIC 3052, Australia"},{"name":"Melbourne Bioinformatics, University of Melbourne, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7399-8997","authenticated-orcid":false,"given":"Peter Adrian","family":"Rogers","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Melbourne, and Gynaecology Research Centre, Royal Women\u2019s Hospital, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"hoac016","DOI":"10.1093\/hropen\/hoac016","article-title":"The Mid-Secretory Endometrial Transcriptomic Landscape in Endometriosis: A Meta-Analysis","volume":"2022","author":"Vargas","year":"2022","journal-title":"Hum. Reprod. Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e220115","DOI":"10.1530\/RAF-22-0115","article-title":"A Systematic Review of Transcriptomic Studies of the Human Endometrium Reveals Inconsistently Reported Differentially Expressed Genes","volume":"4","author":"Walker","year":"2023","journal-title":"Reprod. Fertil."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"dev199577","DOI":"10.1242\/dev.199577","article-title":"Cyclical Endometrial Repair and Regeneration","volume":"148","author":"Salamonsen","year":"2021","journal-title":"Development"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1006\/dbio.2000.9767","article-title":"Embryo Implantation","volume":"223","author":"Carson","year":"2000","journal-title":"Dev. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1093\/molehr\/gaq010","article-title":"Epigenetic Regulation of Endometrium during the Menstrual Cycle","volume":"16","author":"Munro","year":"2010","journal-title":"Mol. Hum. Reprod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.fertnstert.2012.09.013","article-title":"Proteomics of the Human Endometrium and Uterine Fluid: A Pathway to Biomarker Discovery","volume":"99","author":"Salamonsen","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1210\/en.2005-1076","article-title":"Molecular Phenotyping of Human Endometrium Distinguishes Menstrual Cycle Phases and Underlying Biological Processes in Normo-Ovulatory Women","volume":"147","author":"Talbi","year":"2006","journal-title":"Endocrinology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2870","DOI":"10.1210\/en.2003-0043","article-title":"Expression Profiling of Endometrium from Women with Endometriosis Reveals Candidate Genes for Disease-Based Implantation Failure and Infertility","volume":"144","author":"Kao","year":"2003","journal-title":"Endocrinology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Pra\u0161nikar, E., Kunej, T., Gorenjak, M., Poto\u010dnik, U., Kova\u010di\u010d, B., and Knez, J. (2022). Transcriptomics of Receptive Endometrium in Women with Sonographic Features of Adenomyosis. Reprod. Biol. Endocrinol., 20.","DOI":"10.1186\/s12958-021-00871-5"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"gaab027","DOI":"10.1093\/molehr\/gaab027","article-title":"Transcriptional Changes through Menstrual Cycle Reveal a Global Transcriptional Derepression Underlying the Molecular Mechanism Involved in the Window of Implantation","volume":"27","author":"Aleman","year":"2021","journal-title":"Mol. Hum. Reprod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1093\/humrep\/den078","article-title":"Global Gene Analysis of Late Secretory Phase, Eutopic Endometrium Does Not Provide the Basis for a Minimally Invasive Test of Endometriosis","volume":"23","author":"Sherwin","year":"2008","journal-title":"Hum. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"baz062","DOI":"10.1093\/database\/baz062","article-title":"Endometriosis Knowledgebase: A Gene-Based Resource on Endometriosis","volume":"2019","author":"Joseph","year":"2019","journal-title":"Database"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"gaab011","DOI":"10.1093\/molehr\/gaab011","article-title":"Guidelines for Biomarker Discovery in Endometrium: Correcting for Menstrual Cycle Bias Reveals New Genes Associated with Uterine Disorders","volume":"27","author":"Pellicer","year":"2021","journal-title":"Mol. Hum. Reprod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1177\/1535370220903270","article-title":"Challenges in Uncovering Non-Invasive Biomarkers of Endometriosis","volume":"245","author":"Hudson","year":"2020","journal-title":"Exp. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1093\/humrep\/dez116","article-title":"Plasma miRNAs as Biomarkers for Endometriosis","volume":"34","author":"Vanhie","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Open Science Collaboration (2015). Estimating the Reproducibility of Psychological Science. Science, 349, aac4716.","DOI":"10.1126\/science.aac4716"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e71601","DOI":"10.7554\/eLife.71601","article-title":"Investigating the Replicability of Preclinical Cancer Biology","volume":"10","author":"Errington","year":"2021","journal-title":"eLife"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1126\/science.aaf0918","article-title":"Evaluating Replicability of Laboratory Experiments in Economics","volume":"351","author":"Camerer","year":"2016","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1086\/324471","article-title":"Large Upward Bias in Estimation of Locus-Specific Effects from Genomewide Scans","volume":"69","author":"Terwilliger","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ioannidis, J.P.A. (2005). Why Most Published Research Findings Are False. PLoS Med., 2.","DOI":"10.1371\/journal.pmed.0020124"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1093\/jnci\/djh075","article-title":"Assessing the Probability That a Positive Report Is False: An Approach for Molecular Epidemiology Studies","volume":"96","author":"Wacholder","year":"2004","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1097\/EDE.0b013e31821b506e","article-title":"The False-Positive to False-Negative Ratio in Epidemiologic Studies","volume":"22","author":"Ioannidis","year":"2011","journal-title":"Epidemiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jclinepi.2021.05.018","article-title":"Methodology over Metrics: Current Scientific Standards Are a Disservice to Patients and Society","volume":"138","author":"Wynants","year":"2021","journal-title":"J. Clin. Epidemiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1177\/0956797611430953","article-title":"Measuring the Prevalence of Questionable Research Practices With Incentives for Truth Telling","volume":"23","author":"John","year":"2012","journal-title":"Psychol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Fung, J.N., Mortlock, S., Girling, J.E., Holdsworth-Carson, S.J., Teh, W.T., Zhu, Z., Lukowski, S.W., McKinnon, B.D., McRae, A., and Yang, J. (2018). Genetic Regulation of Disease Risk and Endometrial Gene Expression Highlights Potential Target Genes for Endometriosis and Polycystic Ovarian Syndrome. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-29462-y"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1093\/molehr\/gah121","article-title":"Molecular Classification of Human Endometrial Cycle Stages by Transcriptional Profiling","volume":"10","author":"Ponnampalam","year":"2004","journal-title":"Mol. Hum. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6222","DOI":"10.1038\/s41467-023-41979-z","article-title":"A Molecular Staging Model for Accurately Dating the Endometrial Biopsy","volume":"14","author":"Teh","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1038\/s41591-020-1040-z","article-title":"Single-Cell Transcriptomic Atlas of the Human Endometrium during the Menstrual Cycle","volume":"26","author":"Wang","year":"2020","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Leek, J.T., and Storey, J.D. (2007). Capturing Heterogeneity in Gene Expression Studies by Surrogate Variable Analysis. PLOS Genet., 3.","DOI":"10.1371\/journal.pgen.0030161"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3814","DOI":"10.1210\/en.2006-1692","article-title":"Gene Expression Analysis of Endometrium Reveals Progesterone Resistance and Candidate Susceptibility Genes in Women with Endometriosis","volume":"148","author":"Burney","year":"2007","journal-title":"Endocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1002\/stem.2222","article-title":"Loss of Endometrial Plasticity in Recurrent Pregnancy Loss","volume":"34","author":"Lucas","year":"2016","journal-title":"Stem Cells"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0015-0282(16)30062-0","article-title":"Dating the Endometrial Biopsy","volume":"1","author":"Noyes","year":"1950","journal-title":"Fertil. Steril."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1097\/00125480-200311000-00001","article-title":"Hertig and Beyond: A Systematic and Practical Approach to the Endometrial Biopsy","volume":"10","author":"Crum","year":"2003","journal-title":"Adv. Anat. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/j.fertnstert.2003.11.030","article-title":"A Critical Analysis of the Accuracy, Reproducibility, and Clinical Utility of Histologic Endometrial Dating in Fertile Women","volume":"81","author":"Murray","year":"2004","journal-title":"Fertil. Steril."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1080\/00313020126323","article-title":"The Accuracy and Interobserver Reproducibility of Endometrial Dating","volume":"33","author":"Duggan","year":"2001","journal-title":"Pathology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1136\/jcp.2005.029702","article-title":"My Approach to the Interpretation of Endometrial Biopsies and Curettings","volume":"59","author":"McCluggage","year":"2006","journal-title":"J. Clin. Pathol."},{"key":"ref_37","first-page":"325","article-title":"Asynchronous Glands in the Endometrium of Women with Recurrent Reproductive Failure","volume":"46","author":"Russell","year":"2014","journal-title":"Pathol.-J. RCPA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1210\/endo.143.6.8885","article-title":"Global Gene Profiling in Human Endometrium during the Window of Implantation","volume":"143","author":"Kao","year":"2002","journal-title":"Endocrinology"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Rekker, K., Altm\u00e4e, S., Suhorutshenko, M., Peters, M., Martinez-Blanch, J.F., Codo\u00f1er, F.M., Vilella, F., Sim\u00f3n, C., Salumets, A., and Velthut-Meikas, A. (2018). A Two-Cohort RNA-Seq Study Reveals Changes in Endometrial and Blood miRNome in Fertile and Infertile Women. Genes, 9.","DOI":"10.3390\/genes9120574"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1177\/1933719109337165","article-title":"Proteomic Analysis of the Luteal Endometrial Secretome","volume":"16","author":"Scotchie","year":"2009","journal-title":"Reprod. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1210\/jcem-57-4-792","article-title":"Hormonal Dynamics at Midcycle: A Reevaluation","volume":"57","author":"Hoff","year":"1983","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/btm2.10058","article-title":"Detection of Ovulation, a Review of Currently Available Methods","volume":"2","author":"Su","year":"2017","journal-title":"Bioeng. Transl. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.fertnstert.2007.01.045","article-title":"Characteristics of the Urinary Luteinizing Hormone Surge in Young Ovulatory Women","volume":"88","author":"Park","year":"2007","journal-title":"Fertil. Steril."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1016\/j.fertnstert.2004.11.078","article-title":"Prevalence of Premature Urinary Luteinizing Hormone Surges in Women with Regular Menstrual Cycles and Its Effect on Implantation of Frozen-Thawed Embryos","volume":"83","author":"Krotz","year":"2005","journal-title":"Fertil. Steril."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41746-019-0152-7","article-title":"Real-World Menstrual Cycle Characteristics of More than 600,000 Menstrual Cycles","volume":"2","author":"Bull","year":"2019","journal-title":"NPJ Digit. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.fertnstert.2010.04.063","article-title":"A Genomic Diagnostic Tool for Human Endometrial Receptivity Based on the Transcriptomic Signature","volume":"95","author":"Horcajadas","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.fertnstert.2012.09.046","article-title":"The Accuracy and Reproducibility of the Endometrial Receptivity Array Is Superior to Histology as a Diagnostic Method for Endometrial Receptivity","volume":"99","author":"Blesa","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1093\/humrep\/deac006","article-title":"EndoTime: Non-Categorical Timing Estimates for Luteal Endometrium","volume":"37","author":"Lipecki","year":"2022","journal-title":"Hum. Reprod."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1093\/humrep\/dey301","article-title":"Endometrial Receptivity Revisited: Endometrial Transcriptome Adjusted for Tissue Cellular Heterogeneity","volume":"33","author":"Suhorutshenko","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Altm\u00e4e, S., Koel, M., V\u00f5sa, U., Adler, P., Suhorut\u0161enko, M., Laisk-Podar, T., Kukushkina, V., Saare, M., Velthut-Meikas, A., and Krjut\u0161kov, K. (2017). Meta-Signature of Human Endometrial Receptivity: A Meta-Analysis and Validation Study of Transcriptomic Biomarkers. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-10098-3"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e1419","DOI":"10.1210\/clinem\/dgz117","article-title":"Human Endometrial Transcriptome and Progesterone Receptor Cistrome Reveal Important Pathways and Epithelial Regulators","volume":"105","author":"Chi","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e70753","DOI":"10.7554\/eLife.70753","article-title":"Disrupted PGR-B and ESR1 Signaling Underlies Defective Decidualization Linked to Severe Preeclampsia","volume":"10","author":"Cordero","year":"2021","journal-title":"Elife"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Akter, S., Xu, D., Nagel, S.C., Bromfield, J.J., Pelch, K., Wilshire, G.B., and Joshi, T. (2019). Machine Learning Classifiers for Endometriosis Using Transcriptomics and Methylomics Data. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00766"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Mahi, N.A., Najafabadi, M.F., Pilarczyk, M., Kouril, M., and Medvedovic, M. (2019). GREIN: An Interactive Web Platform for Re-Analyzing GEO RNA-Seq Data. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-43935-8"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1093\/humrep\/deaa111","article-title":"Dysregulation of the Interleukin-17A Pathway in Endometrial Tissue from Women with Unexplained Infertility Affects Pregnancy Outcome Following Assisted Reproductive Treatment","volume":"35","author":"Crosby","year":"2020","journal-title":"Hum. Reprod."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Koot, Y.E.M., van Hooff, S.R., Boomsma, C.M., van Leenen, D., Groot Koerkamp, M.J.A., Goddijn, M., Eijkemans, M.J.C., Fauser, B.C.J.M., Holstege, F.C.P., and Macklon, N.S. (2016). An Endometrial Gene Expression Signature Accurately Predicts Recurrent Implantation Failure after IVF. Sci. Rep., 6.","DOI":"10.1038\/srep19411"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1002\/path.2948","article-title":"Specific and Extensive Endometrial Deregulation Is Present before Conception in IVF\/ICSI Repeated Implantation Failures (IF) or Recurrent Miscarriages","volume":"225","author":"Munaut","year":"2011","journal-title":"J. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/0197-2456(88)90046-3","article-title":"Properties of Simple Randomization in Clinical Trials","volume":"9","author":"Lachin","year":"1988","journal-title":"Control. Clin. Trials"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Breheny, P., Stromberg, A., and Lambert, J. (2018). P-Value Histograms: Inference and Diagnostics. High-Throughput, 7.","DOI":"10.3390\/ht7030023"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/sj.ki.5002650","article-title":"Confounding: What It Is and How to Deal with It","volume":"73","author":"Jager","year":"2008","journal-title":"Kidney Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1093\/biomet\/82.4.669","article-title":"Causal Diagrams for Empirical Research","volume":"82","author":"Pearl","year":"1995","journal-title":"Biometrika"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1177\/00491241221099552","article-title":"A Crash Course in Good and Bad Controls","volume":"53","author":"Cinelli","year":"2022","journal-title":"Sociol. Methods Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1136\/bmj.332.7549.1080","article-title":"The Cost of Dichotomising Continuous Variables","volume":"332","author":"Altman","year":"2006","journal-title":"BMJ"},{"key":"ref_64","unstructured":"(2024). R Core Team R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma Powers Differential Expression Analyses for RNA-Sequencing and Microarray Studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor Package for Differential Expression Analysis of Digital Gene Expression Data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated Estimation of Fold Change and Dispersion for RNA-Seq Data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1467-9868.2010.00749.x","article-title":"Fast Stable Restricted Maximum Likelihood and Marginal Likelihood Estimation of Semiparametric Generalized Linear Models","volume":"73","author":"Wood","year":"2011","journal-title":"J. R. Stat. Soc. Ser. B Stat. Methodol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4986","DOI":"10.1210\/en.2014-1490","article-title":"Molecular Classification of Endometriosis and Disease Stage Using High-Dimensional Genomic Data","volume":"155","author":"Tamaresis","year":"2014","journal-title":"Endocrinology"},{"key":"ref_70","unstructured":"Gelman, A., and Loken, E. (2013). The Garden of Forking Paths: Why Multiple Comparisons Can Be a Problem, Even When There Is No \u201cFIshing Expedition\u201d or \u201cp-Hacking\u201d and the Research Hypothesis Was Posited Ahead of Time, Department of Statistics, Columbia University."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Kaplan, R.M., and Irvin, V.L. (2015). Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132382"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1037\/0003-066X.49.12.997","article-title":"The Earth Is Round (p <.05)","volume":"49","author":"Cohen","year":"1994","journal-title":"Am. Psychol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"102296","DOI":"10.1016\/j.cpa.2021.102296","article-title":"Accounting Research and the Significance Test Crisis","volume":"89","author":"Johnstone","year":"2022","journal-title":"Crit. Perspect. Account."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Szucs, D., and Ioannidis, J.P.A. (2017). When Null Hypothesis Significance Testing Is Unsuitable for Research: A Reassessment. Front. Hum. Neurosci., 11.","DOI":"10.3389\/fnhum.2017.00390"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Bruns, S.B., and Ioannidis, J.P.A. (2016). P-Curve and p-Hacking in Observational Research. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149144"},{"key":"ref_76","first-page":"632","article-title":"The Connection Between Varying Treatment Effects and the Crisis of Unreplicable Research: A Bayesian Perspective","volume":"41","author":"Gelman","year":"2015","journal-title":"J. Manag."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v076.i01","article-title":"Stan: A Probabilistic Programming Language","volume":"76","author":"Carpenter","year":"2017","journal-title":"J. Stat. Softw."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"P\u00e4ll, T., Luidalepp, H., Tenson, T., and Maiv\u00e4li, \u00dc. (2021). A Field-Wide Assessment of Differential High Throughput Sequencing Reveals Widespread Bias. PloS Biol., 21.","DOI":"10.1101\/2021.01.04.424681"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s10815-010-9436-1","article-title":"Endometriosis and Infertility","volume":"27","author":"Bulletti","year":"2010","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1038\/ng.2445","article-title":"Genome-Wide Association Meta-Analysis Identifies New Endometriosis Risk Loci","volume":"44","author":"Nyholt","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/ng.731","article-title":"Genome-Wide Association Study Identifies a Locus at 7p15.2 Associated with Endometriosis","volume":"43","author":"Painter","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1093\/humrep\/dey023","article-title":"Asynchronous and Pathological Windows of Implantation: Two Causes of Recurrent Implantation Failure\u2020","volume":"33","author":"Garrido","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1136\/jmg.40.8.553","article-title":"New Approaches to Investigating Heterogeneity in Complex Traits","volume":"40","author":"Bomprezzi","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"579","DOI":"10.5468\/ogs.2017.60.6.579","article-title":"Comorbidity of Gynecological and Non-Gynecological Diseases with Adenomyosis and Endometriosis","volume":"60","author":"Choi","year":"2017","journal-title":"Obs. Gynecol. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Lin, K.Y.-H., Yang, C.-Y., Lam, A., Chang, C.Y.-Y., and Lin, W.-C. (2021). Uterine Leiomyoma Is Associated with the Risk of Developing Endometriosis: A Nationwide Cohort Study Involving 156,195 Women. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0256772"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"803","DOI":"10.3332\/ecancer.2018.803","article-title":"Endometriosis and Endometriosis-Associated Cancers: New Insights into the Molecular Mechanisms of Ovarian Cancer Development","volume":"12","author":"Dawson","year":"2018","journal-title":"Ecancermedicalscience"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"McNamara, H.C., Frawley, H.C., Donoghue, J.F., Readman, E., Healey, M., Ellett, L., Reddington, C., Hicks, L.J., Harlow, K., and Rogers, P.A.W. (2021). Peripheral, Central, and Cross Sensitization in Endometriosis-Associated Pain and Comorbid Pain Syndromes. Front. Reprod. Health, 3.","DOI":"10.3389\/frph.2021.729642"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Uimari, O., Nazri, H., and Tapmeier, T. (2021). Endometriosis and Uterine Fibroids (Leiomyomata): Comorbidity, Risks and Implications. Front. Reprod. Health, 3.","DOI":"10.3389\/frph.2021.750018"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1111\/aogs.14337","article-title":"Prevalence of Endometriosis and Adenomyosis at Transvaginal Ultrasound Examination in Symptomatic Women","volume":"101","author":"Orlov","year":"2022","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.jogc.2019.02.186","article-title":"Is Laparoscopic Visualization Sufficient for the Diagnosis of Endometriosis?","volume":"41","author":"Gratton","year":"2019","journal-title":"J. Obstet. Gynaecol. Can."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.fertnstert.2011.05.090","article-title":"Impact of Endometriosis on Quality of Life and Work Productivity: A Multicenter Study across Ten Countries","volume":"96","author":"Nnoaham","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"319.e1","DOI":"10.1016\/j.ajog.2013.07.017","article-title":"The Impact of Uterine Leiomyomas: A National Survey of Affected Women","volume":"209","author":"Borah","year":"2013","journal-title":"Am. J. Obs. Gynecol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2147\/IJWH.S224891","article-title":"Current Challenges in the Management of Chronic Pelvic Pain in Women: From Bench to Bedside","volume":"14","author":"Conde","year":"2022","journal-title":"Int. J. Womens Health"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/S0015-0282(16)56990-8","article-title":"Prospective, Randomized, Double-Blind, Controlled Trial of Laser Laparoscopy in the Treatment of Pelvic Pain Associated with Minimal, Mild, and Moderate Endometriosis","volume":"62","author":"Sutton","year":"1994","journal-title":"Fertil. Steril."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/j.fertnstert.2004.03.046","article-title":"Laparoscopic Excision of Endometriosis: A Randomized, Placebo-Controlled Trial","volume":"82","author":"Abbott","year":"2004","journal-title":"Fertil. Steril."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/857\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:32:24Z","timestamp":1759919544000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/2\/857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,20]]},"references-count":95,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["ijms26020857"],"URL":"https:\/\/doi.org\/10.3390\/ijms26020857","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,20]]}}}