peri-IMplantation Profile of Endometrial Transcription

Implantation failure constitutes the major limiting step in in-vitro
fertilization (IVF) success rates and it is a considerable cause of frustration
to patients and clinicians. The endometrium becomes receptive in preparation
for embryo implantation during a restricted period, which is referred to as a
*window* of receptivity and takes place from approximately day 19-24 in a
normal menstrual cycle. Up to now, no individual factors have been identified
to be crucial for implantation in the human. However, given the complexity of
the process of implantation and its crucial role in human survival, it is
unlikely that a single marker of great clinical significance will be
identified. Microarray analysis enables an approach from a global genomic
perspective. Our study (06/101/K) provided a comparison of endometrial gene
expression during the window of implantation in women with recurrent
implantation failure (RIF) and controls. The study reports the biggest set of
microarray data on endometrial gene expression in women with implantation
failure to date. We have shown that the expression profile of several promising
genes are predictive of the recurrent implantation failure. Above a certain
cut-off the predictive accuracy to correctly determine whether the endometrial
sample is taken from a good receptive endometrium or from women with recurrent
implantation failure is 94%.

In order to confirm and externally validate the novel panel of genes identified
in our study (06/101/K) to be significantly predictive of recurrent
implantation failure, we will recruit 50 additional subjects treated by IVF who
have undergone at least 3 consecutive fresh good quality embryo transfers
without achieving pregnancy, 50 controls, defined according to the same
criteria as in the development study cohort, i.e.: who were formerly treated by
ICSI for severe male factor infertility only and who achieved a healthy live
birth after the first or second treatment cycle and 50 references; patients who
conceived and gave birth to a healthy child within 3 IVF attempts.
This additional recruitment is necessary to confirm and extent our initial
findings of a molecular signature which can be distinguish between good
receptive and less-receptive endometrial tissue.

The study design is a patientcontrol study (comparison of endometrial
receptivity markers of patients with RIF vs. controls vs. references).

Women who attended our Clinic for IVF or ICSI treatment with recurrent
implantation failure, women who achieved a healthy live birth after ICSI
treatment for severe male infertility and women conceived and gave birth to a
healthy child within three IVF attempts will be asked to participate in our
study. Patients will be asked to give written informed consent for the
endometrail biopsie and the storage of samples for research purposes.

Women who attend the study will perform at home ovulation predictor tests in
urine from cycleday 10 till a positive test. Six or seven days after a positive
test the endometrial biopsy is sheduled. Analysis of endometrial gene
expression profiles in the endometrial tissue will be performed by microarray
and PCR and protein expression by Western blotting.

The study includes an endometrial biopsy. This is a minimal invasive method
with minimal risks. The most common (temporary) complain is abdominal pain or
discomfort. Rare is dizziness, infection, bleeding or very rare a perforation
of the uterus. No negative effect on pregnancy rate from this intervention in
following cycles has been reported.