ORIGINAL ARTICLES: ASSISTED REPRODUCTION

Live birth after transfer of a single

euploid vitrified-warmed blastocyst
according to standard timing vs.
timing as recommended by
endometrial receptivity analysis
Nicole Doyle, M.D., Ph.D.,a Joshua C. Combs, M.D.,b Samad Jahandideh, Ph.D.,a Victoria Wilkinson, B.A.,a
Kate Devine, M.D.,a and Jeanne E. O’Brien, M.D., M.S.a
a
Shady Grove Fertility Center, Rockville, Maryland; and b Eunice Kennedy Shriver National Institute of Child Health and
Human Development, Reproductive Endocrinology and Infertility Fellowship Program, National Institutes of Health,
Bethesda, Maryland

Objective: To determine whether endometrial receptivity analysis (ERA) improves live births in patients with and without a history of
unsuccessful frozen embryo transfers (FETs).
Design: Retrospective cohort study.
Setting: Large reproductive center.
Patient(s): Patients with and without ERA before euploid single FET were included in the analysis.
Intervention(s): Subjects in the exposed group underwent ERA and ERA-timed FETs. Subjects in the unexposed group followed a
standard protocol FET without ERA. Outcomes were compared between nonreceptive and receptive subjects undergoing an ERA-
timed FET and between ERA-timed vs. standard protocol FETs.
Main Outcome Measure(s): The primary outcome was a live birth; secondary outcomes were biochemical and clinical pregnancy rates.
Result(s): A total of 307 ERA-timed FETs and 2,284 standard protocol FETs were analyzed. One hundred twenty-five patients (40.7%)
were ERA receptive, and 182 (59.3%) were ERA nonreceptive. After adjusting for the number of the previously failed FETs, there was no
difference in the proportion of receptive and nonreceptive ERA results. There were no statistically significant differences in live births in
patients with ERA-receptive vs. ERA-nonreceptive results (48.8% and 41.7%, respectively; adjusted odds ratio 1.17; 95% CI, 0.97–1.40).
There were no statistically significant differences in live births in patients with or without ERA testing results before FET (44.6% and
51.3%, respectively; adjusted odds ratio 0.87; 95% CI, 0.73–1.04).
Conclusion(s): Patients with an increasing number of previous failed euploid FET cycles are not at an increased risk of a displaced
window of implantation. Patients categorized as receptive vs. nonreceptive and those without ERA testing results have comparable
FET success rates. (Fertil SterilÒ 2022;118:314–21. Ó2022 by American Society for Reproductive Medicine.)
El resumen está disponible en Español al final del artículo.
Key Words: Endometrial receptivity analysis, ERA, window of implantation, PGT-A

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T
he implantation phase of the and immune cells, as well as changes be achieved after euploid embryo trans-
menstrual cycle is a complex bio- in the pattern of gene expression. The fer. Although this represents substantial
logic process characterized by 2 most crucial components for success- improvement during the short history of
significant morphologic and functional ful implantation are a competent em- assisted reproductive technology (ART),
changes in the endometrium, including bryo and a receptive endometrium. At it also reflects the considerable gaps
an increase in capillary permeability best, live birth rates of up to 65% can that remain in our knowledge and con-
Received July 18, 2021; revised May 5, 2022; accepted May 6, 2022; published online June 13, 2022.
trol of sustained implantation of the hu-
N.D. has nothing to disclose. J.C.C. has nothing to disclose. S.J. has nothing to disclose. V.W. has man embryo (1). In natural reproductive
nothing to disclose. K.D. has nothing to disclose. J.E.O has nothing to disclose. physiology, the endometrium is permis-
Reprint requests: Nicole Doyle, M.D., Shady Grove Fertility Center, 9601 Blackwell Road, 4th Floor,
Rockville, Maryland 20850 (E-mail: nicole.pfaeffle.doyle@gmail.com). sive to an embryo during days 6–12 af-
ter ovulation, and ART embryo transfer
Fertility and Sterility® Vol. 118, No. 2, August 2022 0015-0282/$36.00 cycles generally attempt to mimic this
Copyright ©2022 American Society for Reproductive Medicine, Published by Elsevier Inc.
https://doi.org/10.1016/j.fertnstert.2022.05.013 timing (2).

314 VOL. 118 NO. 2 / AUGUST 2022


Much attention has been devoted to selecting the best em-
bryo for transfer. Advances in embryo culture systems have
enabled a push from routine day 3 cleavage stage to day 5
blastocyst embryo transfers. Extended culture has provided
the embryologists with more morphologic features to identify
and select the embryos with a higher implantation potential.
Preimplantation genetic testing for aneuploidy assesses the
overall chromosomal composition, and several studies have
demonstrated improved outcomes after the transfer of a
known euploid embryo (3, 4).
Validated diagnostic tools to determine the receptivity of
the endometrium are lacking. The assessment of adequate endo-
metrial estrogen priming can be performed through serum
estradiol levels and ultrasonic measurement of endometrial
thickness and morphological patterns (5, 6). Endometrial recep-
tivity analysis (ERA) assesses the expression of 238 genes in the
endometrial tissue, focusing predominantly on those associated
with progesterone exposure (7). It employs a computational pre-
dicter model that classifies the endometrium as prereceptive,
receptive, or postreceptive on the basis of its transcriptomic pro-
file. The RNA panel employed by ERA was developed through
an assessment of natural cycles (optimal fertile group);
controlled ovarian hyperstimulation cycles as (subfertile); and
intrauterine device–induced refractory endometrium in other-
wise fertile patients (negative control) (8). The ERA aims to iden-
tify a personalized window of implantation (WOI) and guide the
optimal duration of progesterone exposure before embryo
transfer, for an individual patient. Several, mainly retrospec-
tive, studies have been conducted to assess the use of ERA; how-
ever, whether ERA-timed embryo transfers result in superior
clinical outcomes compared with standard embryo transfers
remain controversial (9–11). As expected, previous studies
have limitations because of design heterogeneity; small
sample size; the use of euploid and untested embryos; single
and double embryo transfers; and fresh and frozen transfer
cycles and very few included a control group with
standardized timing (9–11). The goal of the current study was
to compare live birth after single euploid frozen embryo
transfer (FET) according to ERA timing vs. routine protocol.
MATERIAL AND METHODS
Ethical Statement and Study Setting
The Advarra Institutional Review Board approval under pro-
tocol 00027148 was obtained for the retrospective review of
internal practice data. This retrospective cohort study was
TABLE 1
Baseline and cycle characteristics.
Exposed group (ERA-timed FET)
(n [ 307)
Age, y a
36.7 (4.1)
BMI, kg/m2a 26.1 (5.3)
History of previous total 2.4 (2.2)
failed embryo transfer(s)b
Note: Data are expressed as mean
SD unless indicated otherwise. BMI ¼ body mass index; ERA ¼ endometrial receptivity analysis; FET ¼ frozen embryo transfer.
a
Age and BMI were recorded at the start of the in vitro fertilization cycle.
b
Failed embryo transfers (negative human chorionic gonadotropin) with euploid and untested embryos.
Doyle. Endometrial receptivity analysis. Fertil Steril 2022.
VOL. 118 NO. 2 / AUGUST 2022
Fertility and Sterility®
conducted from 2018 to 2019 at a large reproductive center
in the United States.
Study Population Selection
All FET cycles from January 2018 to April 2019 were re-
viewed. Only the most recent single euploid FET per patient
within this study period was included in the analysis. All pa-
tients received either 50 mg/d intramuscular progesterone
only or 200-mg twice daily progesterone vaginal (Endome-
trin) plus 50-mg intramuscular progesterone every third day
for luteal phase support. Standardized FET timing was defined
as 123
3 hours of progesterone exposure. A normal uterine
cavity was documented for all subjects by a saline sonogram
and/or hysterosalpingogram within 6 months before FET. Pa-
tients with unmitigated uterine cavity defects, donor egg, or
donor embryo cycles were excluded. At our center, a body
mass index of >40 kg/m2 and current breast feeding are
considered contraindications to embryo transfer.
Study Design
All patients underwent a standard controlled ovarian hyper-
stimulation cycle with stimulation protocol at the primary
physician’s discretion. Intracytoplasmic sperm injection was
used to fertilize mature oocytes, and embryos were cultured
to the blastocyst stage. Trophectoderm biopsy and vitrifica-
tion were performed for all embryos meeting the criteria (blas-
tocyst with morphologic grade BB or better) by days 5, 6, or 7
of embryonic development (12). Preimplantation genetic
testing for aneuploidy (PGT-A) was performed using next-
generation sequencing. All embryos biopsied for PGT-A
were vitrified; no fresh embryo transfers were performed.
All patients in the exposed group underwent ERA, followed
by an ERA-timed FET. Patients in the unexposed group did
not undergo ERA before undergoing a standard protocol
FET. All patients returned approximately 14 days after FET
for a quantitative serum human chorionic gonadotropin
(hCG) evaluation to confirm pregnancy with repeat measure-
ment for positive results and transvaginal ultrasound between
6 and 7 weeks of estimated gestational age to confirm clinical
intrauterine pregnancy (Supplemental Fig. 1, available on-
line). The same hormone replacement protocol was continued
until a negative hCG test report was obtained, confirmation of
nonviable pregnancy, or until 10-weeks estimated gestational
age in the case of a viable intrauterine pregnancy.
Unexposed group (Standard FET)
(n [ 2,284) P value
36.7 (4.3) >.99
25.7 (5.0) .12
2.5 (2.1) .46
315
ORIGINAL ARTICLE: ASSISTED REPRODUCTION
Endometrial Receptivity Analysis
Endometrial priming for ERA testing was achieved with the
administration of estradiol for approximately 14 days before
the assessment of endometrial thickness and serum estradiol
and progesterone concentrations. Exogenous progesterone
was initiated once endometrial thickness measured R7 mm,
with serum estradiol concentration of >150 pg/mL and serum
progesterone concentration of <1.0 ng/mL, or at the primary
physician’s discretion. Either daily intramuscular progester-
one or vaginal progesterone with intramuscular progesterone
once every 3 days was used, as these 2 regimens have demon-
strated equivalent outcomes in a recent randomized
controlled trial (13). An endometrial pipelle biopsy was then
performed to obtain endometrial tissue for ERA testing 123

3 hours after the first progesterone injection. Endometrial
tissue sample was sent to Igenomix (Valencia, Spain), where
ERA analysis was conducted using a proprietary protocol,
which involves the assessment of a specific transcriptomic
signature to assess the endometrial receptivity status. Any pa-
tient whose ERA analysis did not provide sufficient informa-
tion to recommend timing for FET underwent repeat ERA
testing.
Embryo Transfer
Endometrial preparation for FET was performed using the
same protocol as followed for ERA. A single vitrified-
warmed euploid blastocyst was transferred using ultrasound
guidance and the afterload technique, after 123
3 hours
of progesterone exposure or according to ERA recommended
progesterone adjustment (14).
Outcome
The primary outcome was a live birth at 23 weeks gestation or
beyond after single euploid FET performed according to ERA
timing vs. standard protocol timing. The secondary objectives
were to compare biochemical and clinical pregnancy rates be-
tween the study groups. The secondary endpoints were
defined as follows: biochemical pregnancy (detection of
b-hCG R 5 IU/L) and clinical pregnancy (presence of an in-
trauterine gestational sac on ultrasound).
Statistical Analysis
Descriptive statistics were used to demonstrate the mean stan-
dard deviation and median (range) for continuous variables,
whereas nominal variables were expressed as case numbers
and percentages. To determine the differences in baseline
characteristics (age, body mass index, and previous history
of failed) between the groups, parametric (independent sam-
ples t test) and nonparametric analyses (Mann-Whitney
U test) were performed as appropriate after normality ana-
lyses. Logistic regression was used to adjust for age, body
mass index, and previous embryo transfers. A P value of
< .05 was considered significant. Proportions were compared
with chi-square test and Fisher’s exact test. Logistic regres-
sion was used to adjust for age, body mass index, and previ-
ous embryo transfers.
316
All data cleaning, analysis, and modeling steps were per-
formed using the R statistical computing system (version
3.6.1) and the R base packages and the add-on R packages
ggplot2, tableone, glm2, and tidyverse (15, 16). A post hoc po-
wer calculation for the current sample size of 307 subjects in
the study group and 2,284 subjects in the control group indi-
cated a 95% power to demonstrate a 10% difference in the live
birth rate between the groups, given an a level of <0.05 and a
55% anticipated live birth rate in the control study (on the ba-
sis of 2018 and 2019 success rates among single euploid FET
at our center).
RESULTS
A total of 307 ERA-timed FETs and 2,284 standard FETs were
included in the analysis (Supplemental Fig. 1). As shown in
Table 1, there were no differences between the exposed and
unexposed groups in terms of demographic variables. The
number of previously unsuccessful FETs (negative hCG)
with euploid and untested embryos was comparable between
the groups.
The results of ERA were considered ‘‘receptive’’ if no
change from the standard 123
3 hours of progesterone
exposure was recommended. Any result recommending an
adjustment in progesterone exposure timing outside the stan-
dard progesterone exposure was considered ‘‘nonreceptive’’;
this included the early and late receptive results for which a
12-hour progesterone adjustment is typically recommended.
As shown in Table 2, a higher proportion of patients in the
exposed group had nonreceptive ERA results compared with
receptive ERA results (59.3% and 40.7%, respectively).
Among the nonreceptive results, most patients were catego-
rized as prereceptive (34.2%). A total of 12 patients underwent
a repeat ERA cycle because of a noninformative result in their
first ERA cycle, mostly because of a poor quality endometrial
biopsy sample insufficient to determine the gene expression
profile.
ERA Results According to the Number of Previous
Unsuccessful FET Cycles
When adjusting for the number of previous failed FETs with
euploid embryos, there was no statistically significant
TABLE 2
ERA results.
ERA result Exposed group (N [ 307)
Receptive 125 (40.7)
Nonreceptive* 182 (59.3)
Prereceptive 105 (34.2)
Early receptive 60 (19.5)
Late receptive 9 (2.9)
Postreceptive 8 (2.6)
Second biopsy required for 12 (3.9)
informative result
Note: Data are expressed as n (%). ERA ¼ endometrial receptivity analysis.
* ERA result recommended change in the timing of FET from standard 123
3 hours of pro-
gesterone exposure.
Doyle. Endometrial receptivity analysis. Fertil Steril 2022.
VOL. 118 NO. 2 / AUGUST 2022

difference in terms of ERA results between the groups.
Patients with no previous history of an unsuccessful FET cycle
were likely to receive a nonreceptive result compared with pa-
tients with previous failed FET cycle(s), regardless of whether
they had 1, 2, or 3 previous unsuccessful FETs. Thirty-two of
48 (66.7%) patients with no previous unsuccessful FET were
classified as nonreceptive. For patients with 1 previous unsuc-
cessful FET, the number of nonreceptive results was 93 of 163
(57.1%). Similarly, for patients with 2 previous FETs, ERA re-
ported 47 of 81 (58.1%) patients as nonreceptive vs. 34 of 81
(41.9%) patients as receptive. The total number of patients
with 3 previous unsuccessful FETs before ERA was small,
but results were comparable, as 10 of 15 (66.7%) patients
were categorized as nonreceptive vs. 5 of 15 (33.3%) patients
categorized as receptive (Fig. 1).
ERA-Timed FET Outcomes
Comparing ERA-timed FET outcomes in the exposed group,
there were no statistically significant differences between
the ERA-receptive and ERA-nonreceptive groups for any of
the assessed outcomes. The rate of positive hCG was compa-
rable in both groups (75.2% vs. 67.0%, respectively, P¼.16;
adjusted odds ratio (aOR) 1.12; 95% confidence interval (CI),
0.92–1.34). The clinical pregnancy rate was 59.2% in the
ERA-receptive group vs. 51.6% in the ERA-nonreceptive
FIGURE 1
Endometrial receptivity analysis results according to the number of previous unsuccessful FETs. FET ¼ frozen embryo transfer; NR ¼ nonreceptive;
R¼ receptive.
Doyle. Endometrial receptivity analysis. Fertil Steril 2022.
VOL. 118 NO. 2 / AUGUST 2022
Fertility and Sterility®
group (P¼.23; aOR 1.15; 95% CI, 0.95–1.38). There was no
statistically significant difference in live birth between the
groups (48.8% and 41.7%, respectively, P¼.27; aOR 1.17;
95% CI, 0.97–1.40) (Table 3).
ERA-Timed FET Outcomes Stratified by the
Number of Previous Failed FET cycles
When stratifying according to the number of previous failed
FETs, there were no differences in any of the assessed out-
comes when comparing the ERA-receptive group to the
ERA-nonreceptive group for patients with 0,1, and 3 previous
unsuccessful euploid FETs, although the total number of pa-
tients with 3 previous unsuccessful FETs was small
(Supplemental Table 1, available online). Patients with a his-
tory of 2 previous unsuccessful euploid FETs and a receptive
ERA had a statistically significantly higher live birth rate
compared with patients in the ERA nonreceptive group
(P¼.01; OR 3.37; 95% CI, 1.33–8.53); however, as reflected
by the wide CI, the sample size was too small to draw a clin-
ically meaningful conclusion (Supplemental Table 2).
ERA-Timed FET Outcomes Categorizing Early and
Late Receptive as Receptive ERA Results
Early and late receptive ERA results recommend a 12-hour
adjustment of progesterone and were, therefore, defined as
317
ORIGINAL ARTICLE: ASSISTED REPRODUCTION
TABLE 3
ERA-timed FET outcomes within the exposed group and ERA-timed FET outcomes for exposed vs. unexposed groups.
ERA receptive n (%)
Total patients 125
Positive hCG 94 (75.2)
Clinical pregnancya 74(59.2)
Live birthb 61 (48.8)
Exposed group
(ERA-timed FET) n (%)
Total patients 307
Positive hCG 215 (70.0%)
Clinical pregnancya 166 (54.1%)
Live birthb 137 (44.6%)
Note: aOR ¼ adjusted odds ratio; CI ¼ confidence interval; ERA ¼ endometrial receptivity analysis; FET ¼ frozen embryo transfer; hCG ¼ human chorionic gonadotropin.
a
Clinical pregnancy ¼ presence of gestational sac at 5 to 7 weeks of estimated gestational age.
b
Live birth ¼ live birth at 23 weeks gestation or beyond.
Doyle. Endometrial receptivity analysis. Fertil Steril 2022.
nonreceptive results for statistical analysis. However,
including early and late receptive results in the receptive
group (early receptive, late receptive, receptive), did not sta-
tistically significantly change live birth rates in the ERA-
receptive compared with the ERA-nonreceptive group
(44.8% and 44.2%, respectively, P¼1.00; RR 1.01; 95% CI,
0.72–1.44).
ERA-Timed Versus Standard Protocol FET
Outcomes
There were no statistically significant differences for any
outcomes assessed between patients in the exposed group,
undergoing an ERA-timed FET vs. those in the unexposed
group, who did not undergo ERA testing before embryo
transfer.
The rate of positive hCG was comparable in the exposed
and unexposed groups (70% vs. 69.4%, respectively, P¼.74;
aOR 1.01; 95% CI, 0.84–1.16). The clinical pregnancy rate
was 54.1% in the ERA-timed FET group vs. 58.9% in the stan-
dard FET group (P¼.25; aOR 0.92; 95% CI, 0.79–1.2). There
was no difference in live birth between the ERA-timed FET
group and the standard FET group (44.6% and 51.3%, respec-
tively, P¼.08; aOR 0.87; 95% CI, 0.73–1.04) (Table 3).
DISCUSSION
The present study demonstrated no statistically significant
differences in live birth for patients opting for ERA testing
and subsequent ERA-guided FET or a standard protocol FET
without previous ERA. The transfer outcomes were compara-
ble between the exposed (ERA-timed FET) and unexposed (no
ERA and standard FET) groups. The transfer outcomes were
also comparable between ERA-receptive patients with subse-
quent standard FET and nonreceptive patients with ERA-
timed FETs and adjusted progesterone exposure. Furthermore,
there were no statistically significant differences between the
groups in any of the secondary outcomes observed (biochem-
ical pregnancy and clinical pregnancy). For the exposed
group, FET outcomes between ERA-receptive and
318
ERA nonreceptive n (%) aOR (95% CI) P value
182
122 (67.0) 1.12 (0.92-1.34) .16
94 (51.6) 1.15 (0.95-1.38) .23
76 (41.7) 1.17 (0.97-1.40) .27
Unexposed group
(Standard FET) n (%) aOR (95% CI) P value
2,284
1,585 (69.4%) 1.01 (0.84-1.16) .74
1,346 (58.9%) 0.92 (0.79-1.2) .25
1,173 (51.3%) 0.87 (0.73-1.04) .08
ERA-nonreceptive patients were comparable regardless of
the number of previous failed embryo transfers.
In this study, ERA results were defined as receptive if no
change from the standard 123
3 hours progesterone expo-
sure before FET was recommended. Any recommended
change in progesterone exposure outside this transfer window
(120–126 hours of progesterone) was classified as nonrecep-
tive. As such, most ERA results were nonreceptive (59.3%;
182/307), compared with receptive results (40.7%; 125/307).
A review of the literature reveals a wide range of nonre-
ceptive ERA results (24%–64%) although many of these
studies had challenges with small sample sizes (17). In 2017,
a retrospective study of 50 patients with recurrent implanta-
tion failure and ERA reported 12 (24%) patients who were
classified as nonreceptive (11). Similarly, 22 of 85 (26%) pa-
tients with recurrent implantation failure were categorized
as nonreceptive in a 2013 multicenter clinical trial (18). A
large data set analyzing >6,000 ERA cycles classified approx-
imately 30% as nonreceptive (19). More recent data suggest a
high proportion of nonreceptive ERA results—41% (23/56),
37.5% (30/80), and 59.2% (87/147) in studies published in
2019, 2020, and 2021, respectively (7, 10, 20).
Previous studies have suggested that patients with recur-
rent implantation failure are at a high risk for a shifted WOI
outside the standard timing for FET cycles and, therefore,
have higher proportions of nonreceptive ERA results (11,
18). Our study included patients with no previous failed FET
and up to a maximum of 3 previous unsuccessful FET cycles
with euploid embryos. Endometrial receptivity analysis out-
comes (receptive vs. nonreceptive) were comparable for pa-
tients with and without a history of previous unsuccessful
FET cycles. It appears that the probability for a displaced
WOI does not increase with an increasing number of previous
failed embryo transfers.
In the present study, there were no statistically significant
differences in the primary or secondary outcomes for patients
with nonreceptive ERA results who underwent a euploid
adjusted FET compared with patients with receptive results
and subsequent euploid standard FET. It has been argued in
the literature that the comparable FET outcomes for patients
VOL. 118 NO. 2 / AUGUST 2022

with nonreceptive ERA results can be attributed to the adjust-
ment in progesterone exposure time before embryo transfer
rescuing these cycles from an otherwise expected poor
outcome. However, outcome data from patients with nonre-
ceptive ERA results and unadjusted progesterone exposures
are lacking and, therefore, an adequate interpretation with
regard to the use of ERA remains challenging.
The question of whether an ERA-timed transfer improves
in vitro fertilization outcomes has been debated in the litera-
ture with studies reporting both superior transfer outcomes, as
well as lack of efficacy for ERA-timed FET cycles. In 2013,
Ruiz-Alonso et al. (18) reported no significant difference in
pregnancy rates for nonreceptive patients undergoing ERA-
guided transfers compared with receptive patients. However,
the study included a small number of nonreceptive patients
for analysis (n ¼ 8), both natural and hormone replacement
therapy ERA cycles, transfer of both cleavage and blastocyst
embryos and an average of 2 transferred embryos. Superior
outcomes for 10 patients with displaced WOI and ERA-
guided transfers were reported in 2017 with a pregnancy
rate of 50% compared with 35% for patients in the receptive
group (11). A moderately larger data set that included a con-
trol group was published in 2018 and compared 41 patients
with ERA (27 nonreceptive, 14 receptive) and subsequent
FET with 503 patients without ERA before embryo transfer
(17). The investigators concluded that their data did not sup-
port ERA as a diagnostic tool to improve ART outcomes as the
ongoing pregnancy rates between groups did not differ
significantly. A study controlling for an embryo factor was
published in 2019 and included patients with either euploid
embryo transfers or transfers with embryos derived from
donor oocytes. The study also included a control group of pa-
tients with euploid embryo transfers according to a standard-
ized protocol. Pregnancy rates did not improve between
groups using the ERA. The first prospective randomized 3-
arm clinical trial comparing FET in ERA-timed cycles to stan-
dardized FET cycles and fresh blastocyst transfers was pub-
lished in 2020. The investigators reported no statistically
significant differences in live births when comparing ERA-
timed FET to standardized FET cycles or ERA-timed FET to
fresh blastocyst transfers in the intention-to-treat analysis
and per-protocol analyses (7). Unfortunately, the study noted
a higher than anticipated drop-out rate (intention-to-treat
analysis ¼ 434 subjects, per-protocol analysis ¼ 266 sub-
jects), which rendered it underpowered for evaluation of the
primary outcome (live birth). They also had challenges with
study heterogeneity, including different protocols for all 3
trial arms, transfer of both PGT-A tested and untested em-
bryos, and varying luteal phase protocols. Recently, in
2021, a prospective cohort study compared live births be-
tween ERA-timed single euploid FET and standardized FET
and included 228 subjects undergoing their first autologous
FET. The study reported no statistically significant differences
in live births in the ERA-timed group vs. the standardized FET
group (56.6% and 56.5%, respectively) and did not
support the routine use of ERA in this particular patient
population (20).
The goal of this study was to control for variables and
confounders that could impact FET outcomes to yield the
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Fertility and Sterility®
most accurate analysis of the intervention effect (i.e., ERA-
timed euploid FET). Therefore, only patients with vitrified
euploid blastocysts, a standardized luteal phase protocol,
and no uterine factor were included. This current data set rep-
resents the largest sample size of patients with ERA and sub-
sequent euploid FET reported in the literature to date (13).
Limitations include the retrospective nature of the study
design and the lack of an unexposed group without ERA,
matched for the number of previous failed FETs. Furthermore,
residual confounding should be acknowledged as a limitation
as only 3 covariates were included. Factors such as endome-
triosis, history of surgery, the day of vitrification of the trans-
ferred embryo or endometrial lining thickness at initiating
progesterone therapy were not accounted for.
CONCLUSION
In conclusion, an increasing number of previous unsuccessful
FETs does not increase the rate of nonreceptive ERA results.
Furthermore, live birth rates do not differ when ERA agrees
with the standard FET protocol (receptive) vs. when it dis-
agrees (nonreceptive) and an adjustment in progesterone
exposure time is suggested. Patients with ERA-guided FET cy-
cles have comparable live birth outcomes to patients under-
going standard protocol transfers without previous ERA. A
randomized controlled trial is required to sufficiently assess
whether ERA serves as a beneficial diagnostic adjunct in
ART cycles.
DIALOG: You can discuss this article with its authors and
other readers at https://www.fertstertdialog.com/posts/
33520
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 Fertility and Sterility®

Nacido vivo despu
es de la transferencia de un
unico blastocisto euploide vitrificado seg

un el momento est

andar de transferencia contra
el momento recomendado por an
alisis de receptividad endometrial.
Objetivo: Determinar si el an
alisis de receptividad endometrial (ERA) mejora los nacidos vivos en pacientes con y sin una historia de
transferencias fallidas de embriones congelados (TECs).
~o: Estudio de cohorte retrospectivo.
Disen
Escenario: Gran centro reproductivo.

nico embri

Paciente(s): Fueron incluidas en el an
alisis pacientes con y sin ERA previo a TEC de un u on euploide.
Intervenci
on(s): Sujetos en el grupo expuesto sometidos a ERA y TEC seg
un recomendaci
on por ERA. Sujetos en el grupo no expuesto
siguiendo un protocolo est
andar de TEC sin ERA. Los resultados fueron comparados entre sujetos no receptivos y receptivos sometidos a
TEC seg
un recomendaci
on por ERA y entre recomendaci
on por ERA contra protocolo est
andar de TEC.
Medici
on(es) del resultado principal: El resultado primario fue el nacido vivo; los resultados secundarios fueron embarazos bio-
químicos y clínicos.
Resultado(s): Se analizaron un total de 307 TEC seg
un recomendaci
on por ERA y 2284 TEC de protocolo est
andar. Ciento veinticinco
pacientes (40,7%) eran receptivos por ERA, y 182 (59,3%) eran no receptivos por ERA. Despu
es de ajustar el n

umero de TEC que fallaron
anteriormente, no hubo diferencia en la proporci
on de resultados ERA receptivos y no receptivos. No hubo diferencias estadísticamente
significativas en los nacidos vivos en pacientes con resultados receptivos por ERA frente a no receptivos por ERA (48,8 % y 41,7 %,
respectivamente; raz
on de probabilidad ajustada 1,17; IC 95 %, 0,97–1,40). No hubo diferencias estadísticamente significativas en
los nacidos vivos en pacientes con o sin resultados de pruebas de ERA antes de TEC (44,6% y 51,3%, respectivamente; raz
on de prob-
abilidad ajustada 0,87; IC del 95 %, 0,73–1,04).
Conclusi
on(es): Los pacientes con un n

umero creciente de ciclos de TEC euploides fallidos previos no tienen un mayor riesgo de des-
plazamiento de la ventana de implantaci

on. Los pacientes categorizados como receptivos frente a no receptivos y aquellos sin resultados
de la prueba ERA tienen resultados comparables de tasas de
exito de TEC.

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