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Hum. Reprod. Advance Access published online on February 26, 2009
Human Reproduction, doi:10.1093/humrep/dep039
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Gene expression profile of human endometrial receptivity: comparison between natural and stimulated cycles for the same patients

D. Haouzi1,2,3,4, S. Assou1,3,4, K. Mahmoud5, S. Tondeur1,3,4, T. Rème1,3,4, B. Hedon2, J. De Vos1,3,4 and S. Hamamah1,2,3,4,6

1 CHU Montpellier, Institut de Recherche en Biothérapie, Hôpital Saint-Eloi, Montpellier F-34000, France 2 CHU Montpellier, Département de Médecine et Biologie de la Reproduction, Hôpital Arnaud de Villeneuve, Montpellier F-34295, France 3 INSERM U 847, Montpellier F-34000, France 4 Université Montpellier1, UFR de Médecine, Laboratoire ‘Développement embryonnaire précoce et cellules souches embryonnaires humaines’, Montpellier F-34000, France 5 Centre de FIV, Clinique les Jardins, Tunis, Tunisia

6 Correspondence address. ART/PGD Division, Département de Médecine et Biologie de la Reproduction, Hôpital Arnaud de Villeneuve, Montpellier F-34295, France. Tel: +33-04-67-33-64-04; Fax: +33-04-67-33-62-90; E-mail: s-hamamah{at}chu-montpellier.fr

BACKGROUND: The adjunction of exogenous hormones for controlled ovarian stimulation (COS) may alter endometrial receptiveness. In order to identify the genes misregulated under COS, we compared the endometrium gene expression profiles, from the same patients, in a natural cycle and in a subsequent COS cycle.

METHODS: For the same normal-responder patients (n = 21), endometrial biopsies (n = 84) were collected during the pre-receptive (LH + 2) and receptive stages (LH + 7) of a natural cycle and, subsequently, on oocyte retrieval day (hCG + 2) and on transfer day (hCG + 5) of a stimulated cycle. Samples were analyzed using DNA microarrays. Gene expression profiles and biological pathways involved in endometrial receptivity were analyzed.

RESULTS: Although endometrium transition profiles from pre-receptive to receptive phases are similar between patients, COS regimens alter endometrial receptivity in comparison with natural cycle. Under COS conditions, two endometrial profiles were identified and were associated either with a moderately altered receptivity profile for the majority of the patients or a strongly altered profile for a sub-category of patients. The receptive endometrium transcription profile under COS was defective for biological functions such as TGFβ signaling, leukocyte transendothelial migration and the cell cycle.

CONCLUSIONS: Gonadotrophin treatments in COS cycles led to disruptions of the transcriptional activation of genes involved in normal endometrial receptivity. We propose that when the receptiveness of the endometrium is seriously compromised by the COS protocol, fresh embryo replacement should be cancelled, the embryo frozen and thawed embryo replacement should be performed under natural cycles.

Key words: human endometrium/microarray/endometrial receptivity/natural cycle/COS

Submitted on December 15, 2008; resubmitted on January 21, 2009; accepted on January 29, 2009.


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