1. Learning Objectives
 To acknowledge the relevance of the endometrial factor
 To learn about the endometrial receptivity array (ERA)
 To discuss the clinical efficiency of personalized embryo transfer
(pET) according to the endometrial status
 To introduce future non-invasive endometrial diagnostic methods

2. Human Endometrium

3. Dating the Endometrial Biopsy1
 Randomized studies
- Interobserver and cycle-to-cycle (60%) variations2
- Endometrial dating is not related to fertility status3
Histological dating is not a valid method for the diagnosis of luteal
phase deficiency neither guidance throughout clinical
management in infertility
1. Noyes, et al. Fertil Steril 1950
2. Murray, et al. Fertil Steril 2004
3. Coutifaris, et al. Fertil Steril 2004

4. The Age of -OMICS
Transcriptome Proteome Metabolome
TRANSCRIPTION TRANSDUCTION
DNA RNA mRNA Protein METABOLITES
Transcription
regulation
Alternative
splicing
Transduction regulation

5. Gene Expression Profiling During the WOI
in Natural Versus COH
EXPERIMENTAL DESIGN
AFFIMETRIX
HG-133A
>22,000 genes
50 WOMEN
LH Day 1 2 3 4 5 6 7 8 9
hCG Day 1 2 3 4 5 6 7 8 9
Caucasian
Fertile women with normal cycles
23–39 years
body mass index: 19-25 kg/m2
PRE-RECEPTIVE RECEPTIVE
n=5
n=5
n=5
n=5
n=5
n=5
n=5
n=5
n=5
n=5
NATURAL
COH
Horcajadas JA/ Simon C. JCEM 2008

6. Endometrial Receptivity Array (ERA)
Customized microarray
Bioinformatic analysis of data obtained by
the customized microarray
Classification and prediction from gene expression.
Predictors: Characterization of RECEPTIVITY transcriptome

7. NATURAL CYCLE
Endometrial biopsy must be taken on the 7th day after the LH surge (LH+7) (urine or serum
preferible).
HORMONE REPLACEMENT THERAPY CYCLE
Endometrial biopsy must be taken on day P+5, after proper E2 priming
E : 6 mg/day
2
P : 800 mg/day
4
Endometrial Receptivity Array (ERA)
Timing of the biopsy

8. Endometrial Receptivity Array (ERA)
INTERPRETATION OF RESULTS
Receptive (R):
The gene expression profile corresponds to a normal receptive endometrium.
It is recomended to proceed with the embryo transfer at the
indicated WOI
Non Receptive (NR):
The gene expression profile does not correspond to a normal receptive endometrium.
It is not recomended to proceed with the embryo transfer at
the indicated WOI and a personalization of the WOI is advised.

9. Conclusions
 ERA test diagnose the timing of the endometrial WOI.
 The reproductive outcome in RIF patients with receptive ERA is
comparable to the general ART population.
 NR ERA patients have the WOI displaced and personalized Embryo
Transfer (pET) improve clinical results.
WE ARE WORKING ON THE CLINICAL VALIDATION OF THE ERA TEST IN
an International Multicenter RCT