An endometrial gene expression signature accurately predicts recurrent implantation failure after IVF

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Koot, Yvonne E M ^a   Van Hooff, Sander R ^a   Boomsma, Carolien M ^a   Van Leenen, Dik ^a   Koerkamp, Marian J A Groot ^a   Goddijn, Mariëtte ^b   Eijkemans, Marinus J C ^a   Fauser, Bart C J M ^a   Holstege, Frank C P ^a   Macklon, Nick S ^a,c  

^a UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^b UNIVERSITY OF AMSTERDAM   (Netherlands)

^c UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CELL PROLIFERATION; COUNSELING; DIAGNOSTIC TEST ACCURACY STUDY; ENDOMETRIUM; ENDOMETRIUM BIOPSY; FEMALE; GENE EXPRESSION; GENE EXPRESSION PROFILING; HUMAN; HUMAN TISSUE; IMPLANTATION; LUTEAL PHASE; MAJOR CLINICAL STUDY; PREDICTIVE VALUE; VALIDATION PROCESS; ADULT; BIOPSY; FEMALE INFERTILITY; GENE EXPRESSION REGULATION; GENETICS; IN VITRO FERTILIZATION; METABOLISM; NIDATION; PATHOLOGY; PREGNANCY; RECURRENT DISEASE; REPRODUCIBILITY;

ADULT; BIOPSY; EMBRYO IMPLANTATION; ENDOMETRIUM; FEMALE; FERTILIZATION IN VITRO; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; HUMANS; INFERTILITY, FEMALE; PREGNANCY; RECURRENCE; REPRODUCIBILITY OF RESULTS;

EID: 84955488988     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep19411     Document Type: Article

References (48)

1. Polanski, L. T. et al. What exactly do we mean by 'recurrent implantation failure'? A systematic review and opinion. Reprod. Biomed. Online 28, 409-423 (2014).
2. Thornhill, A. R. et al. ESHRE PGD Consortium 'Best practice guidelines for clinical preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS)'. Hum. Reprod. Oxf. Engl. 20, 35-48 (2005).
3. Simon, A. & Laufer, N. Repeated implantation failure: clinical approach. Fertil. Steril. 97, 1039-1043 (2012).
4. Koot, Y. E. M., Teklenburg, G., Salker, M. S., Brosens, J. J. & Macklon, N. S. Molecular aspects of implantation failure. Biochim. Biophys. Acta 1822, 1943-1950 (2012).
5. Das, M. & Holzer, H. E. G. Recurrent implantation failure: gamete and embryo factors. Fertil. Steril. 97, 1021-1027 (2012).
6. Simon, A. & Laufer, N. Assessment and treatment of repeated implantation failure (RIF). J. Assist. Reprod. Genet. 29, 1227-1239 (2012).
7. Penzias, A. S. Recurrent IVF failure: other factors. Fertil. Steril. 97, 1033-1038 (2012).
8. Koot, Y. E. M. & Macklon, N. S. Embryo implantation: biology, evaluation, and enhancement. Curr. Opin. Obstet. Gynecol. 25, 274-279 (2013).
9. Urman, B., Yakin, K. & Balaban, B. Recurrent implantation failure in assisted reproduction: how to counsel and manage. B. Treatment options that have not been proven to benefit the couple. Reprod. Biomed. Online 11, 382-391 (2005).
10. Vanneste, E. et al. Chromosome instability is common in human cleavage-stage embryos. Nat. Med. 15, 577-583 (2009).
11. Revel, A. Defective endometrial receptivity. Fertil. Steril. 97, 1028-1032 (2012).
12. Macklon, N. S. & Boomsma, C. M. in Early Pregnancy (Cambridge University Press, 2010) (Date of access:23/10/2015). at
13. Koler, M. et al. Disrupted gene pattern in patients with repeated in vitro fertilization (IVF) failure. Hum. Reprod. 24, 2541-2548 (2009).
14. Ruiz-Alonso, M., Galindo, N., Pellicer, A. & Simón, C. What a difference two days make: 'personalized' embryo transfer (pET) paradigm: a case report and pilot study. Hum. Reprod. Oxf. Engl. 29, 1244-1247 (2014).
15. Brosens, J. J. et al. Uterine selection of human embryos at implantation. Sci. Rep. 4, 3894 (2014).
16. Ruiz-Alonso, M., Blesa, D. & Simón, C. The genomics of the human endometrium. Biochim. Biophys. Acta 1822, 1931-1942 (2012).
17. von Grothusen, C., Lalitkumar, S., Boggavarapu, N. R., Gemzell-Danielsson, K. & Lalitkumar, P. G. Recent advances in understanding endometrial receptivity: molecular basis and clinical applications. Am. J. Reprod. Immunol. N. Y. N 1989 72, 148-157 (2014).
18. Haouzi, D., Dechaud, H., Assou, S., De Vos, J. & Hamamah, S. Insights into human endometrial receptivity from transcriptomic and proteomic data. Reprod. Biomed. Online 24, 23-34 (2012).
19. Kao, L. C. et al. Global gene profiling in human endometrium during the window of implantation. Endocrinology 143, 2119-2138 (2002).
20. Mirkin, S. et al. In search of candidate genes critically expressed in the human endometrium during the window of implantation. Hum. Reprod. Oxf. Engl. 20, 2104-2117 (2005).
21. Riesewijk, A. et al. Gene expression profiling of human endometrial receptivity on days LH+ 2 versus LH+ 7 by microarray technology. Mol. Hum. Reprod. 9, 253-264 (2003).
22. Díaz-Gimeno, P. et al. A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature. Fertil. Steril. 95, 50-60, 60.e1-15 (2011).
23. Haouzi, D. et al. Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients. Hum. Reprod. Oxf. Engl. 24, 1436-1445 (2009).
24. Macklon, N. S., van der Gaast, M. H., Hamilton, A., Fauser, B. C. J. M. & Giudice, L. C. The impact of ovarian stimulation with recombinant FSH in combination with GnRH antagonist on the endometrial transcriptome in the window of implantation. Reprod. Sci. Thousand Oaks Calif 15, 357-365 (2008).
25. Horcajadas, J. A. et al. Controlled ovarian stimulation induces a functional genomic delay of the endometrium with potential clinical implications. J. Clin. Endocrinol. Metab. 93, 4500-4510 (2008).
26. Hauzman, E. E., Garcia-Velasco, J. A. & Pellicer, A. Oocyte donation and endometriosis: What are the lessons? Semin. Reprod. Med. 31, 173-177 (2013).
27. Kao, L. C. et al. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology 144, 2870-2881 (2003).
28. Horcajadas, J. A. et al. Effect of an intrauterine device on the gene expression profile of the endometrium. J. Clin. Endocrinol. Metab. 91, 3199-3207 (2006).
29. Talbi, S. et al. Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women. Endocrinology 147, 1097-1121 (2006).
30. Garrido-Gómez, T. et al. Profiling the gene signature of endometrial receptivity: clinical results. Fertil. Steril. 99, 1078-1085 (2013).
31. Bhagwat, S. R. et al. Endometrial receptivity: a revisit to functional genomics studies on human endometrium and creation of HGEx-ERdb. PloS One 8, e58419 (2013).
32. Ruiz-Alonso, M. et al. The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure. Fertil. Steril. 100, 818-824 (2013).
33. Díaz-Gimeno, P. et al. The accuracy and reproducibility of the endometrial receptivity array is superior to histology as a diagnostic method for endometrial receptivity. Fertil. Steril. 99, 508-517 (2013).
34. Bartosch, C., Lopes, J. M., Beires, J. & Sousa, M. Human endometrium ultrastructure during the implantation window: a new perspective of the epithelium cell types. Reprod. Sci. Thousand Oaks Calif 18, 525-539 (2011).
35. Bourdeau, V. et al. Mechanisms of primary and secondary estrogen target gene regulation in breast cancer cells. Nucleic Acids Res. 36, 76-93 (2008).
36. Georges, A. et al. FOXL2: a central transcription factor of the ovary. J. Mol. Endocrinol. 52, R17-33 (2014).
37. Richards, J. S. & Pangas, S. A. The ovary: basic biology and clinical implications. J. Clin. Invest. 120, 963-972 (2010).
38. Landelijke netwerkrichtlijn subfertiliteit. (2010) (Date of access:23/10/2015). at
39. van Wageningen, S. et al. Functional overlap and regulatory links shape genetic interactions between signaling pathways. Cell 143, 991-1004 (2010).
40. Bolstad, B. M., Irizarry, R. A., Astrand, M. & Speed, T. P. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinforma. Oxf. Engl. 19, 185-193 (2003).
41. Leek, J. T., Johnson, W. E., Parker, H. S., Jaffe, A. E. & Storey, J. D. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinforma. Oxf. Engl. 28, 882-883 (2012).
42. Smyth, G. K. in Bioinformatics and Computational Biology Solutions using R and Bioconductor 397-420 (Springer, 2005).
43. Golub, T. R. et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286, 531-537 (1999).
44. Meyer, D., Dimitriadou, E., Hornik, K., Weingessel, A. & Leisch, F. e1071: Misc Functions of the Department of Statistics (e1071), TU Wien. (2014) (Date of access:23/10/2015). at
45. Robin, X. et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 12, 77 (2011).
46. Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. USA 102, 15545-15550 (2005).
47. Ashburner, M. et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat. Genet. 25, 25-29 (2000).
48. Irizarry, R. A., Wang, C., Zhou, Y. & Speed, T. P. Gene set enrichment analysis made simple. Stat. Methods Med. Res. 18, 565-575 (2009).