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Hum. Reprod. Advance Access originally published online on January 27, 2009
Human Reproduction 2009 24(5):1085-1091; doi:10.1093/humrep/den501
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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

In GnRH antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression

Inge Van Vaerenbergh1,4, Leentje Van Lommel2, Vanessa Ghislain1, Peter In't Veld1, Frans Schuit2, Human Mousavi Fatemi3, Paul Devroey3 and Claire Bourgain1

1 Department of Pathology, UZ Brussel, Jette, Belgium 2 Gene Expression Unit, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, Leuven, Belgium 3 Centre for Reproductive Medicine, UZ Brussel, Jette, Belgium

4 Correspondence address. E-mail: ivvaeren{at}vub.ac.be

BACKGROUND: Previously, advanced endometrial maturation on the day of oocyte retrieval in GnRH antagonist and -agonist IVF cycles was observed. In these cycles, endometrial advancement exceeding 3 days between the histological dating and the cycle day never resulted in an ongoing clinical pregnancy. In this study, the gene expression of human endometrium on the day of oocyte retrieval in GnRH antagonist/rec-FSH cycles was analyzed, in correlation with the morphological dating.

METHODS: Biopsies were taken on the day of oocyte retrieval in 47 patients with 1 or 2 embryos replaced on Day 3 in the same cycle. Endometrial dating was performed according to Noyes’ criteria. Biopsies from 11 patients were analyzed for gene expression with the Affymetrix HG U133 Plus 2 microarray. Data analysis, clustering and pathway analysis were performed with GCOS, GeneSpring 7.3 and Ingenuity, respectively.

RESULTS: According to Noyes’ criteria, all endometria taken on the day of oocyte retrieval showed an advanced maturation, ranging from +d2 to +d4. The patients with a subsequent clinical pregnancy all showed a histological dating corresponding to +d2 or +d3. When comparing endometria +d2–3 to +d4, the microarray results showed a differential expression of 2550 probe sets. Significantly up-regulated genes were SERPINB6, FOXO3A, SOX17 and CDC42. Down-regulated genes of interest were NRP1, HOXA10 and OSF2. Principal component analysis and hierarchical clustering demonstrated two distinct clusters.

CONCLUSIONS: In stimulated cycles, endometrial gene expression on the day of oocyte retrieval discriminates between women with and without histologically advanced endometrial maturation exceeding 3 days and supports histological dating results by Noyes’ criteria.

Key words: gene expression/microarray/advanced endometrial maturation/Noyes' criteria/GnRH antagonists

Submitted on October 10, 2008; resubmitted on December 12, 2008; accepted on December 28, 2008.


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