No conflicts of interest were declared.
Specific and extensive endometrial deregulation is present before conception in IVF/ICSI repeated implantation failures (IF) or recurrent miscarriages†
Article first published online: 24 AUG 2011
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 225, Issue 4, pages 554–564, December 2011
How to Cite
Lédée, N., Munaut, C., Aubert, J., Sérazin, V., Rahmati, M., Chaouat, G., Sandra, O. and Foidart, J. M. (2011), Specific and extensive endometrial deregulation is present before conception in IVF/ICSI repeated implantation failures (IF) or recurrent miscarriages. J. Pathol., 225: 554–564. doi: 10.1002/path.2948
- Issue published online: 24 OCT 2011
- Article first published online: 24 AUG 2011
- Accepted manuscript online: 1 JUN 2011 09:24AM EST
- Manuscript Accepted: 25 MAY 2011
- Manuscript Revised: 10 APR 2011
- Manuscript Received: 17 JAN 2011
- uterine receptivity;
- recurrent miscarriages;
- implantation failure;
The objective was to examine if IVF/ICSI repeated implantation failures (IF) or recurrent miscarriages (RM) could be related to preconceptional endometrial deregulations. IF was defined as the absence of pregnancy despite the transfer of at least ten IVF/ICSI good quality embryos, and RM as having at least three unexplained miscarriages. Fertile controls (FC) were women who had given birth at least once. Endometrial biopsy was performed in the mild luteal phase of a non-conceptual cycle (five women were selected in each group). Affymetrix chips (GeneChip Human Genome U133 Plus2.0 Array) were used for hybridization. Data were normalized by the gcRMA method, and raw p values adjusted by the Bonferroni procedure (1%). Differential expression of selected genes was analysed using real-time PCR. Gene networks and biological functions were explored using the Ingenuity Pathways Analysis software. Endometrial gene expression profiles at the time of uterine receptivity differ dramatically in the endometrium among FC, RM, and IF patients. Compared to FC, 2126 and 2477 genes are differentially expressed in IF and RM groups, respectively, and 2363 between IF and RM. In both conditions, differential gene expression referred mainly to DNA transcription and expression. Other main cellular functions deregulated in IF conditions correspond to cell morphology, cellular development, cell cycle, and cellular assembly, while in RM conditions, deregulated cellular functions relate to cell signalling (degradation of cyclic AMP and calcium metabolism) and cellular maintenance. In both conditions, there is an over-representation of deregulations related to the haematological system. In the IF condition, cell-mediated immune response and nervous system development and function are highly deregulated, while in RM patients, main deregulations are in organ and tissue development, humoral immune response, and muscular system development and function. Extensive endometrial deregulations are present before conception in patients who experienced IF or RM with both distinct and common deregulation. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.