ERA
Endometrial
Receptivity
Array
When to
perform the
embryo
transfer
The blastocyst transfer should be performed in the same type of cycle
and on the same day on which a receptive result was obtained. A
receptive result implies that this is the day on which the blastocyst
transfer (D5-6) should be performed. If a day 3 embryo is going to be
transferred then the transfer should be performed 2 days earlier.
Embryo
Embryo
D-3
Day-3 embryo transfer timing
Endometrium
D-5
Continued
development
Pre-Receptive
Patient Receptive at P+4
Day-5 embryo transfer timing
Receptive
P+0
P+1
P+2
P+3
P+4
Post-Receptive
P+5
P+6
P+7
P+8
P+9
P+6
P+7
P+8
P+9
P+...
P+...
Start
Progesterone
Patient Receptive at P+5
P+0
P+1
P+2
P+3
P+4
P+5
Start
Progesterone
Patient Receptive at P+7
P+0
P+1
P+2
P+3
P+4
P+5
P+6
P+7
P+8
P+9
P+...
P+...
The patient continues
progesterone intake
according to the
treatment protocol
Start
Progesterone
Comparison of
clinical results
2455
patients
CLINICAL OUTCOME
ET
pET
Number of patients
Source of oocytes
Age
Ovum donation
40.7 ± 4.7 (32-49)
1.8± 0.4
1.7± 0.5
Implantation rate
12.9% (4/31)
34.5% (10/29)
Pregnancy rate
23.5% (4/17)
52.9% (9/17)
Number of embryos transferred
First attempt
17
0% (0/4)
66.7% (6/9)
Clinical abortion
100% (4/4)
0% (0/9)
Biochemical pregnancy
0.0% (0/4)
33.3% (3/9)
Ongoing pregnancy rate
Data from a pilot study done with patients
undergoing embryo transfer (ET) before their first
ERA test (on a day later diagnosed as
non-receptive by the ERA) who subsequently did
a 2nd biopsy and ERA test and received
personalized embryo transfer (pET) on a day
which the ERA gave a receptive diagnosis.
Ruiz-Alonso et al. Human Reproduction 2014 Jun; 29(6): 1244-7
Classification
of ERA patients
according
to their
endometrial
receptivity
24%
of patients are
non-receptive
Endometrial biopsy
1877
receptive
578
non-receptive
20%
post-receptive
80%
pre-receptive
2nd Endometrial
biopsy
• 87.3 % Receptive
• 11.8 % ‘Out of phase’ but with the
possibility of finding the moment of
receptivity between both biopsies.
• 0.9 % have the same result as the
one obtained with the first biopsy.
www.igenomix.com
ERA
Endometrial
Receptivity
Array
ENDOMETRIAL
RECEPTIVITY ARRAY
www.igenomix.com
is the
1 What
ERA test?
The Endometrial Receptivity Array (ERA) is
an endometrial evaluation test designed,
developed
and
patented
(PCT/ES2009/000386) by IGENOMIX. This
molecular diagnostic tool allows to analyze
the level of expression of 238 genes related
with the status of endometrial receptivity. It
consists of a personalized microarray with
probes for these 238 genes onto which an
RNA sample obtained from endometrial
tissue is hybridized. After the hybridization,
the intensities of the signals are scanned and
the ERA predictor classifies the samples into
receptive or non-receptive depending on the
expression profile.
The ERA test has been proven in patients who have
experienced implantation failures with good quality
embryos (at least 3 implantation failures in young
women or 2 in patients 37 years-old or more). A
displaced window of implantation is detected in
approximately 25 % of these patients.
This test is indicated for patients with an apparently
normal uterus and with an endometrium with a
normal thickness (6 mm or more).
Advantages of
the ERA test
is the purpose
2 What
of the ERA test?
The ERA test is used to evaluate the stage of an
endometrium and to determine if it presented a receptive or
non-receptive genetic profile when the biopsy was taken. In
the case that the stage is non-receptive, the test allows us to
find a personalized window of implantation for each patient.
P+0= First day of progesterone intake
LH+0= The day of LH surge
HRT
Natural
P+0
LH+0
120 hrs.
P+5
168 hrs.
LH+7
6
4
The classical method of endometrial dating is based on
histological criteria. However it has been proven that these
criteria do not discriminate between fertile and infertile
patients and are highly subjective, meaning that they have
not clinical application. The ERA test has been shown to be
highly sensitive and specific in the detection of genetic
expression profiles associated with receptivity. It allows the
personalized window of implantation to be detected before
the patient starts using assisted reproduction techniques.
extraction
5 Sample
and shipment
Menstruation
Sample extraction
Methodology
3
Who should
use the ERA
test and why?
An endometrial biopsy taken from the uterine fundus must be
immediately introduced into an ERA cryotube and preserved in a
refrigerator (4-8ºC) for at least 4 hours.
Shipment to our laboratory, at room temperature, should not take
longer than 72-96 hours and the sample should not be allowed to
reach more than 35˚C.
MAIN STAGES OF THE ASSAY
Receptivo
MESSENGER RNA
(mRNA)
IS OBTAINED
THE QUALITY OF THE
EXTRACTED mRNA
IS DETERMINED
SAMPLE LABELING
AND
PURIFICATION
HYBRIDIZATION OF THE
LABELED mRNA WITH
THE ERA ARRAY
WASHING AND
SCANNING OF THE
ARRAY
THE SIGNAL INTENSITY IS
MEASURED AND IS CLASSIFIED
BY THE PREDICTOR COMPUTER
REPORT
7. Limits of the technique. The ERA test has a specificity of 0.8857 and a sensitivity of 0.9975 for receptivity profile classification. The
biopsy procedure, though simple, has a risk (less than 5%) of not obtaining a sufficient quantity and/or quality of endometrial tissue, in
which case it is impossible to perform the test and a new sample extraction would be required.
Díaz-Gimeno P, Horcajadas JA, Martínez-Conejero
JA, Esteban FJ, Alamá P, Pellicer A, Simón C. A
Genomic Diagnostic Tool for Human Endometrial
Receptivity based on the Transcriptomic Signature.
Fertil Steril.2011 Jan; 95(1)pp: 50-60, 60.e1-15.
Díaz-Gimeno P, Ruiz-Alonso M, Blesa D, Bosch N,
Martínez-Conejero JA, Alamá P, Garrido N, Pellicer A,
Simón C. The accuracy and reproducibility of the
endometrial receptivity array is superior to histology as
a diagnostic method for endometrial receptivity. Fertil
Steril. 2013 Feb;99(2):508-17.
Ruiz-Alonso M, Blesa D, Díaz-Gimeno P, Gómez E,
Fernández-Sánchez M, Carranza F, Carrera J, Vilella F,
Pellicer A, Simón C. The endometrial receptivity array for
diagnosis and personalized embryo transfer as a
treatment for patients with repeated implantation failure.
Fertil Steril. 2013 Sep;100(3):818-24.
Ruiz-Alonso M, Galindo N, Pellicer A, Simón C. What a
difference two days make personalized embryo transfer
(pET) paradigm: A case report and pilot study. Hum
Reprod. 2014 Apr 15.In press.
www.igenomix.com