why are we still not convinced with era

1. Why are we still
not convinced with
ERA
Dr Kaberi Banerjee

2. • 133 ERA Patients vs 353 non ERA Patient
• No difference in the pregnancy , miscarriage , or live birth rate
• No difference in pregnancy rate where PET was performed.

3. • 75% undergoing first ET
,therefore not about Recurrant
IVF Failures
• Slight benefit of ERA only
when couples were undergoing
multiple transfers over a year

4. ASSISTED REPRODUCTION TECHNOLOGIES
Evaluation of the endometrial receptivity assay
and the preimplantation genetic test for aneuploidy
in overcoming recurrent implantation failure
Mauro Cozzolino1,2,3
& Patricia Diaz-Gimeno1
& Antonio Pellicer1,4,5
& Nicolas Garrido1
Received: 4 June 2020 /Accepted: 13 September 2020
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
Purpose To evaluate the clinical usefulness of the endometrial receptivity array (ERA) and the preimplantation genetic test for
aneuploidy (PGT-A) in patients with severe and moderate recurrent implantation failure (RIF).
Design A retrospective multicenter cohort study was conducted in patients who failed to achieve implantation following transfer of
3 or more or 5 or more embryos in at least three single embryo transfers; patients were classified as moderate or severe RIF,
respectively. Patients with previous RIF were compared based on the testing they received: PGT-A, ERA, or PGT-A+ERA versus a
control group with no testing. Mean implantation rate and ongoing pregnancy rates per embryo transfer were considered primary
outcomes. Multiple logistic regression analysis was performed and adjusted ORs were calculated to control possible bias.
Results Of the 2110 patients belonging to the moderate RIF group, those who underwent transfer of euploid embryos after PGT-A had
a higher implantation rate than those who did not. Additionally, the PGT-A group had a significantly higher rate of ongoing pregnancy.
The same outcomes measured for the 488 patients in the severe RIF group did not reveal any statistically significant improvements. The
use of the ERA test did not appear to significantly improve outcomes in either group.
Conclusions PGT-A may be beneficial for patients with moderate recurrent implantation failure but not for severe cases. At its
current level of development, ERA does not appear to be clinically useful for patients with RIF.
Keywords Recurrent implantation failure . Endometrial receptivity . Window of implantation . PGT-A . Infertility . Embryo
transfer . ERA test . Pregnancy . Implantation rate . Ongoing pregnancy rate . IVF cycles
https://doi.org/10.1007/s10815-020-01948-7
Received: 4 June 2020 /Accepted: 13 September 2020
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
Purpose To evaluate the clinical usefulness of the endometrial receptivity array (ERA) and the preimplantation genetic test for
aneuploidy (PGT-A) in patients with severe and moderate recurrent implantation failure (RIF).
Design A retrospective multicenter cohort study was conducted in patients who failed to achieve implantation following transfer of
3 or more or 5 or more embryos in at least three single embryo transfers; patients were classified as moderate or severe RIF,
respectively. Patients with previous RIF were compared based on the testing they received: PGT-A, ERA, or PGT-A+ERA versus a
control group with no testing. Mean implantation rate and ongoing pregnancy rates per embryo transfer were considered primary
outcomes. Multiple logistic regression analysis was performed and adjusted ORs were calculated to control possible bias.
Results Of the 2110 patients belonging to the moderate RIF group, those who underwent transfer of euploid embryos after PGT-A had
a higher implantation rate than those who did not. Additionally, the PGT-A group had a significantly higher rate of ongoing pregnancy.
The same outcomes measured for the 488 patients in the severe RIF group did not reveal any statistically significant improvements. The
use of the ERA test did not appear to significantly improve outcomes in either group.
Conclusions PGT-A may be beneficial for patients with moderate recurrent implantation failure but not for severe cases. At its
current level of development, ERA does not appear to be clinically useful for patients with RIF.
Keywords Recurrent implantation failure . Endometrial receptivity . Window of implantation . PGT-A . Infertility . Embryo
transfer . ERA test . Pregnancy . Implantation rate . Ongoing pregnancy rate . IVF cycles

5. LETTER
Intra-patient variability in the endometrial receptivity assay (ERA) test
Kristy Cho1
& SeangLin Tan2,3
& William Buckett2
& Michael H. Dahan2,3
Received: 14 January 2018 /Accepted: 18 January 2018 /Published online: 29 January 2018
# Springer Science+Business Media, LLC, part of Springer Nature 2018
Many correctable factors have been attributed to repeated
implantation failure (RIF). These include endometrial
polyps, submucosal fibroids, intrauterine synechiae, endo-
metriosis, and embryo aneuploidy [1, 2]. However, unex-
plained RIF can be a significant challenge for the clinician
and couple. The use of endometrial genomic expression to
identify a personalized transfer timeframe and optimize
embryo-endometrial synchrony has significant appeal as
a possible management of RIF [3]. One such test is the
endometrial receptivity assay (ERA), performed by
Igenomix.
An endometrial biopsy is performed at the expectant time
of embryo transfer as part of an estrogen and progesterone
supported cycle or natural cycle. The ERA analyses the
endometrial biopsy sample using next-generation sequenc-
ing to identify the expression of 238 genes [1]. Then, a
computed prediction model uses this information to esti-
mate the receptivity of the endometrium [1]. An embryo
transfer synchronized with a Breceptive^ endometrium is
said to be associated with a pregnancy rate of 50% and
found to more closely predict cycle dates based on serum
LH peaks compared to histologic features [4]. Furthermore,
seven of these samples were compared to repeat endometri-
al biopsies, collected on average 3 years later, from the re-
spective patients on the same cycle day [4]. These samples
were found to have identical endometrial receptivity classi-
fications compared to the earlier samples [4]. Despite the
initially promising results, the sample size is small and it is
also unclear whether the results from oocyte donors are ap-
plicable to the RIF population, as the genomic expression in
RIF patients may be downregulated compared to the fertile
counterparts [5]. For a test to be of clinical value, ideally, it
should be reproducible in the same patient. Therefore, the
following small study presents evidence highlighting an is-
sue noted with the ERA.
A 44-year-old healthy post-menopausal woman failed the
transfer of two high-quality donor oocyte blastocysts. When
all standard causes of failure were ruled out, an ERA test was
performed. After 10 days of oral estradiol valerate
(Duchesnay, Canada) 2 mg three times daily, she commenced
Journal of Assisted Reproduction and Genetics (2018) 35:929–930
https://doi.org/10.1007/s10815-018-1125-5
ERA test than others? Some of the issues with the ERA in-
clude that it is expensive and there is limited ability for inde-
pendent centers to study outcomes. Therefore, there may be a
bias in the ERA literature presently available.
Perhaps independent groups should be able to perform
studies on the ERA test. Although this study is based on a
single patient, the lack of consistency is intriguing.
Hopefully, this report may lead to more researchers without
a direct financial benefit to publish their experience with the
ERA test.
Compliance with ethical standards
References
1. Valdes CT, Schutt A, Simon C. Imp
origin: it is not pathology, but our fa
oping embryo with a receptive endom
15–8.
2. Fox C, Morin S, Jeong JW, Scott RT,
factors and implantation: what is
2016;105:873–84.
3. Lessey BA. Detection of the smaller w
timing isn't everything. Fertil Steril. 2
4. Díaz-Gimeno P, Ruiz-Alonso M, B
Conejero JA, Alamá P, et al. The a
the endometrial receptivity array is s
nostic method for endometrial recepti
17.
(days) (days) (hours) when biopsy
was performed
classification
#1 N/A N/A 106 Pre-receptive Repeat endometrial
biopsy
#2 42 42 194 Post-receptive Repeat endometrial
biopsy
#3 38 80 170 Post-receptive Perform embryo transfe
#4 33 113 148 Receptive Perform embryo transfe
N/A not applicable, P4 progesterone

6. Case Report
Clinical Obstetrics, Gynecology and Reproductive Medicine
ISSN: 2059-4828
A non -receptive ERA test result in an HRT cycle may not
be replicable in a natural cycle: A case report
Upma Shanker1
*, Francisco Ruiz1
, Barbara Lawrenz3,4
and Human M Fatemi1,2,3
1
IVI Middle East Clinic, Muscat
2
IVI Middle East Clinic, Dubai
3
IVI Middle East Clinic, Abu Dhabi
4
Women´s university hospital Tuebingen, Germany
Abstract
Background: Implantation of an embryo in Artificial Reproductive Techniques is a complex process. With the advent of ERA, a diagnostic tool was supposedly
developed to identify a receptive endometrium based on the array of 238 genes which are expressed at different times in a cycle.
Case: The current case describes a patient with three previously failed IVF cycles, who underwent an ERA testing in an HRT cycle, with diagnosis of a post receptive
endometrium.However,an embryo transfer was performed on day 5 after progesterone rise in a natural cycle,resulting in successful achievement of pregnancy,despite
timing the embryo transfer outside the assumed window of implantation as diagnosed by ERA.
• The current case describes a patient with three previously failed IVF cycles,
who underwent an ERA testing in an HRT cycle, with diagnosis of a post
receptive endometrium. However, an embryo transfer was performed on day 5
after progesterone rise in a natural cycle, resulting in successful achievement
of pregnancy, despite timing the embryo transfer outside the assumed window
of implantation as diagnosed by ERA. Conclusion: This puts into perspective
the question whether ERA can be regarded as the ultimate tool of endometrial
receptivity assessment.

7. • This article addresses the limitations of the
endometrial receptivity array (ERA) methodology to
increase implantation. Such limitations vary from the
assumed inconsistency of the endometrial biopsy, the
variable number of genes found to be dysregulated in
endometrium samples without the embryonal-induced
effect, the failure to account for the simultaneous serum
progesterone level, and the expected low percentage of
patients who may need this add-on procedure, to the
difficulties in synchronising the endometrium with
hormone replacements in successive cycles and the
inherent perinatal risks associated with routine
cryopreservation of embryos. Without a gold standard
to compare, the claim that the window of implantation
(WOI) might be off by ±12 h only requires a good
argument for the advantage it provides to human
procreation, knowing that embryos can linger for days
before actual embedding starts and that the window is
actually a few days. The intra-patient variations in the
test need to be addressed. In summary, like all other
add-ons, it is doubtful whether the ERA test use can
significantly enhance implantation success rates.
Endometrial Receptivity Analysis
(ERA) test: an unproven technology
Zion Ben Rafael *
Adelson School of Medicine, Ariel, University, Israel
*Correspondence address. Adelson School of Medicine, Ariel, University, Israel. E-mail: Zion@ben-rafael.com https://orcid.org/0000-
0003-3606-9475
Submitted on September 29, 2020; resubmitted on December 2, 2020; editorial decision on February 23, 2021
ABSTRACT: This article addresses the limitations of the endometrial receptivity array (ERA) methodology to increase implantation. Such
limitations vary from the assumed inconsistency of the endometrial biopsy, the variable number of genes found to be dysregulated in
endometrium samples without the embryonal-induced effect, the failure to account for the simultaneous serum progesterone level, and
the expected low percentage of patients who may need this add-on procedure, to the difficulties in synchronising the endometrium with
hormone replacements in successive cycles and the inherent perinatal risks associated with routine cryopreservation of embryos. Without
a gold standard to compare, the claim that the window of implantation (WOI) might be off by §12 h only requires a good argument for
the advantage it provides to human procreation, knowing that embryos can linger for days before actual embedding starts and that the
window is actually a few days. The intra-patient variations in the test need to be addressed. In summary, like all other add-ons, it is doubt-
ful whether the ERA test use can significantly enhance implantation success rates.
Human Reproduction Open, Vol.00, No.0, pp. 1–6, 2021
doi:10.1093/hropen/hoab010
DEBATE
Downloaded
from
https://academic.oup.com/hrop

8. ASSISTED REPRODUCTION TECHNOLOGIES
Does the endometrial receptivity array really provide personalized
embryo transfer?
Rawad Bassil1
& Robert Casper1,2
& Nivin Samara1
& Tzu-Bou Hsieh1
& Eran Barzilay3
& Raoul Orvieto3,4
& Jigal Haas1,3
Received: 31 January 2018 /Accepted: 13 April 2018 /Published online: 8 May 2018
# Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
Purpose The aim of the present study was to determine the percentage of infertility patients who are diagnosed with a non-
receptive endometrium according to the endometrial receptivity array (ERA) test and to examine whether adjusting the embryo
transfer day according to the proposed shift in the window of implantation improves the pregnancy rate compared to non-ERA-
tested patients.
Methods A single-center retrospective cohort study, including 53 consecutive good prognosis patients (0–2 previous frozen
embryo transfers) admitted to our IVF unit for a mock cycle prior to their frozen day-5 embryo (blastocyst) transfer cycle. The
mock cycle included an endometrial biopsy for both the ERA test and histological assessment by the Noyes criteria (study group).
The next cycle frozen embryo transfer (FET) in the study group was adjusted according to the ERA results. The control group
consisted of patients who underwent FETcycles at our clinic during the same period, without performing the endometrial biopsy
and ERA testing.
Results During the study period, 503 patients (control group) underwent FET cycles without performing the ERA testing and 41
Journal of Assisted Reproduction and Genetics (2018) 35:1301–1305
https://doi.org/10.1007/s10815-018-1190-9
ASSISTED REPRODUCTION TECHNOLOGIES
Does the endometrial receptivity array really provide personalized
embryo transfer?
Rawad Bassil1
& Robert Casper1,2
& Nivin Samara1
& Tzu-Bou Hsieh1
& Eran Barzilay3
& Raoul Orvieto3,4
& Jigal Haas1,3
Received: 31 January 2018 /Accepted: 13 April 2018 /Published online: 8 May 2018
# Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
Purpose The aim of the present study was to determine the percentage of infertility patients who are diagnosed with a non-
receptive endometrium according to the endometrial receptivity array (ERA) test and to examine whether adjusting the embryo
transfer day according to the proposed shift in the window of implantation improves the pregnancy rate compared to non-ERA-
tested patients.
Methods A single-center retrospective cohort study, including 53 consecutive good prognosis patients (0–2 previous frozen
embryo transfers) admitted to our IVF unit for a mock cycle prior to their frozen day-5 embryo (blastocyst) transfer cycle. The
mock cycle included an endometrial biopsy for both the ERA test and histological assessment by the Noyes criteria (study group).
The next cycle frozen embryo transfer (FET) in the study group was adjusted according to the ERA results. The control group
consisted of patients who underwent FETcycles at our clinic during the same period, without performing the endometrial biopsy
and ERA testing.
Results During the study period, 503 patients (control group) underwent FET cycles without performing the ERA testing and 41
patients had FET following an ERA test. There were no between-group differences in patients’ age, number of previous transfers,
endometrial thickness, number of transferred embryos, and ongoing pregnancy rates (35.2 vs. 39%, respectively, p = NS). Out of
the 53 patients who performed the ERA test before their first or second FET, five endometrial samples (9.4%) were found to be
post-receptive, 29 (54.7%) pre-receptive, and only 19 samples (35.8%) were receptive. Women in the study group with pre- or
post-receptive endometrium on ERA testing, the appropriate adjustment in timing of FET according to the ERA test resulted in a
33.3% pregnancy rate, which is comparable to the 35.2% background ongoing pregnancy rate of the control group.
Conclusions Performing the ERA test in a mock cycle prior to a FET does not seem to improve the ongoing pregnancy rate in
good prognosis patients. Further large prospective studies are needed to elucidate the role of ERA testing in both good prognosis
patients and in patients with recurrent implantation failure.
Keywords ERA . Endometrial receptivity
Introduction
With the recent trend toward single embryo transfer (ET)
adopted in an attempt to reduce the risk of multiple pregnancy
[1], the remaining extra embryos are cryopreserved, allowing
further possibilities for conception following subsequent
frozen-thawed embryo transfer (FET) cycles. Moreover, stud-
ies comparing fresh and frozen-thawed embryo transfer (FET)
cycles in normal responders have recently demonstrated a
significantly higher clinical pregnancy rate per transfer in the
FET versus the fresh cycles [2–5], a difference that may be
attributed to the high estrogen levels in the fresh stimulated
cycles, negatively affecting the endometrium, with the conse-
* Jigal Haas
jigalh@hotmail.com
1
TRIO Fertility partners, 655 Bay St 11th floor, Toronto, Ontario M5G
2K4, Canada
2
Division of Reproductive Sciences, Lunenfeld-Tanenbaum Research
Institute, Mount Sinai Hospital, University of Toronto,
Toronto, Canada
3
Infertility and IVF Unit, Department of Obstetrics and Gynecology,
Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Tel Aviv
University, Israel
4
Tarnesby-Tarnowski Chair for Family Planning and Fertility
Regulation, Sackler Faculty of Medicine, Tel-Aviv University,
Journal of Assisted Reproduction and Genetics (2018) 35:1301–1305
https://doi.org/10.1007/s10815-018-1190-9

9. • After 10 years of its introduction ERA is still
not the game changer it was expected to be.