In GnRH antagonist/rec-FSH stimulated cycles, advanced endometrial maturation on the day of oocyte retrieval correlates with altered gene expression.
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.
Van Vaerenbergh
Inge
I
Department of Pathology, UZ Brussel, Jette, Belgium. ivvaeren@vub.ac.be
Van Lommel
Leentje
L
Ghislain
Vanessa
V
In't Veld
Peter
P
Schuit
Frans
F
Fatemi
Human Mousavi
HM
Devroey
Paul
P
Bourgain
Claire
C
D000328:Adult; D016000:Cluster Analysis; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D054315:Oocyte Retrieval; D010062:Ovulation Induction; D011247:Pregnancy; D011256:Pregnancy Outcome; D011994:Recombinant Proteins / Q000494:pharmacology
D006727:Hormone Antagonists; D011994:Recombinant Proteins; D007987:Gonadotropin-Releasing Hormone; D005640:Follicle Stimulating Hormone; C061018:ganirelix