The relationship between endometrial thickness
and outcome of medicated frozen embryo
replacement cycles
Tarek El-Toukhy, M.R.C.O.G.,a Arri Coomarasamy, M.R.C.O.G.,a Mohammed Khairy, M.R.C.O.G.,a
Kamal Sunkara, M.R.C.O.G.,a Paul Seed, M.Sc., C.Stat.,b Yacoub Khalaf, M.R.C.O.G.,a
and Peter Braude, F.R.C.O.G.a,b
a
Assisted Conception Unit, Guy’s and St. Thomas’ Hospital NHS Trust, and b Department of Women’s Health, and Division of
Reproduction and Endocrinology, King’s College London, United Kingdom
Objective: To examine the relationship between endometrial thickness and outcome of medicated frozen-thawed
embryo replacement (FER) cycles.
Design: A retrospective observational study.
Setting: Assisted conception unit at a university hospital.
Patient(s): All patients who underwent an FER cycle between 1997 and April 2006 and met the inclusion criteria.
Intervention(s): For endometrial preparation, a daily dose of 6 mg of oral E2 valerate was started on menstrual day
1, and P pessaries (800 mg daily) were administrated when the endometrial thickness had reached 7 mm or more,
with ET taking place 2–3 days later. The FER cycles were categorized according to endometrial thickness measurement on the day of P supplementation.
Main Outcome Measure(s): Implantation, clinical pregnancy, ongoing pregnancy, and live birth rates.
Result(s): In all, 768 consecutive medicated FER cycles were analyzed. The lowest pregnancy rates were associated with endometrial thickness <7 mm (n ¼ 13) and >14 mm (n ¼ 12; 7% in both groups). Significantly higher
implantation (19% vs. 12%), clinical pregnancy (30% vs. 18%), ongoing pregnancy (27% vs. 16%), and live birth
(25% vs. 14%) rates were achieved in cycles where endometrial thickness was 9–14 mm (n ¼ 386), compared with
those in which endometrial thickness was 7–8 mm (n ¼ 357). These differences remained significant after adjusting
for confounding variables (adjusted odds ratio [OR] ¼ 1.83 [confidence interval {CI} ¼ 1.3–2.6] for clinical pregnancy, 1.8 [CI ¼ 1.2–2.6] for ongoing pregnancy and 1.9 [CI ¼ 1.3–2.8] for live birth).
Conclusion(s): In medicated FER cycles, an endometrial thickness of 9–14 mm measured on the day of P supplementation is associated with higher implantation and pregnancy rates compared with an endometrial thickness of
7–8 mm. (Fertil SterilÒ 2008;89:832–9. Ó2008 by American Society for Reproductive Medicine.)
Key Words: Pituitary suppression, embryo cryopreservation, cryothawed cycle outcome, endometrium, endometrial thickness
With the general move to reduce the number of embryos
transferred to address the escalation in multiple pregnancy
rates, the importance of embryo cryopreservation programs
increases. Compared with fresh IVF attempts, frozen-thawed
embryo replacement (FER) cycles are associated with lower
implantation and pregnancy rates (1). This has led to a drive
among clinicians to improve the outcome of FER cycles
through better understanding of the association between various cycle characteristics and treatment outcome (2).
Successful FER cycle outcome depends on a delicate interaction between embryo quality and endometrial receptivity.
So far, most studies conducted on FER cycles have focused
on embryological factors such as blastomere survival and resumption of mitotic activity (3–6), while little attention has
been paid to endometrial factors.
Received October 9, 2006; revised and accepted April 17, 2007.
Reprint requests: Tarek El-Toukhy, M.D., M.R.C.O.G., Assisted Conception Unit, 4th Floor, Thomas Guy House, Guy’s Hospital, St. Thomas
Street, London SE1 9RT, United Kingdom (FAX: 44-0-207-188-0490;
E-mail: tarekeltoukhy@hotmail.com).
832
Replacement of cryopreserved embryos can be timed with
ovulation in natural cycles or after endometrial preparation
with exogenous hormones (7–10). In medicated FER cycles,
estrogen therapy is commenced in the early phase of the menstrual cycle and P supplementation is not started until endometrial thickness has reached a threshold measurement.
However, this ‘‘target’’ thickness is poorly defined in the literature and needs further evaluation (11).
The aim of our study was to examine retrospectively the relationship between endometrial thickness and the outcome of
medicated FER cycles after controlling for the potentially
confounding variables.
MATERIALS AND METHODS
A consecutive series of 1032 FER cycles performed at Guy’s
and St. Thomas’ Hospital Assisted Conception Unit between
April 1997 and April 2006 were studied. These cycles were
carried out for patients who had previously undergone IVF/
intracytoplasmic sperm injection (ICSI) with cleavage-stage
embryo cryopreservation and had regular menstrual cycles.
Fertility and Sterilityâ Vol. 89, No. 4, April 2008
Copyright ª2008 American Society for Reproductive Medicine, Published by Elsevier Inc.
0015-0282/08/$34.00
doi:10.1016/j.fertnstert.2007.04.031
Because the present work did not involve either therapeutic
interventions or change to our routine IVF-ET protocols,
we did not require additional approval from our institutional
ethics committee. However, each couple gave written informed consent for the use of their data for analysis upon entering our IVF program and before starting an FER cycle.
uated. If endometrial thickness was <7 mm, the dose of climaval was increased to 8 mg/day for a further 7–12 days. If
endometrial thickness had failed to reach 7 mm after this period, the cycle was usually canceled and restarted in a natural
cycle. Interventions such as using vaginal estrogen, low-dose
aspirin, or sildenafil were not used during the study period.
Frozen cycles in which cryothawed embryos were created
from donated oocytes (n ¼ 7) or for the purpose of fertility
preservation before cancer therapy (n ¼ 6) and in which
the embryos were biopsied for preimplantation genetic diagnosis (n ¼ 16) or cryopreserved at the pronuclear or blastocyst stage (n ¼ 67) were excluded. In addition, FER cycles
where none of the embryos survived after thawing (n ¼ 58)
or the cryothawed ET took place in a natural cycle without
artificial endometrial preparation (n ¼ 32) were not included.
Only the first FER cycle performed after embryo cryopreservation was included (n ¼ 78 second or subsequent cycles
were excluded).
P supplementation in the form of micronized P pessaries
(Cyclogest, Shire Pharmaceuticals, Hants, UK) 400 mg twice
daily was commenced 48–72 hours before transfer depending
on the day of embryo freezing.
Fresh Embryo Grading and Cryopreservation
Fresh cleavage-stage embryos generated using IVF or ICSI
were assigned grades according to strict criteria (12, 13),
which were not changed during the study period. Embryos
were selected for cryopreservation if they had reached 4–5
cells on day 2 (40–42 hours) or 6–8 cells on day 3 (64–66
hours) of in vitro culture, had symmetrical component blastomeres devoid of multinucleation, and showed no more than
10% cytoplasmic fragmentation. A standard slow freezing
protocol, employing 1,2-propanediol and sucrose as cryoprotectants, was used throughout the study period (14, 15).
Thawing
Embryos were thawed rapidly by removal from liquid nitrogen and exposure to air for 45 seconds followed by immersion in a water bath at 30 C for 30 seconds. Propanediol
was then removed by a three-step process in the presence
of 0.2 m sucrose at room temperature for 5 minutes per
each step until final rehydration in a HEPES-buffered salt solution. Thawed embryos were then assessed for blastomere
survival using an inverted microscope (Nikon UK, Kingston,
Surrey, UK) at a magnification of 200 before being transferred into culture medium at 37 C. Blastomeres were considered damaged when they were lysed, degenerated, or
dark. Embryos that had lost more than 50% of their original
blastomeres were not transferred. A second evaluation was
performed before transfer (usually 20 hours later) to record
the resumption of mitosis as indicated by cleavage of at least
one blastomere.
Endometrial Preparation
E2 valerate 6 mg daily (climaval; Novartis Pharmaceuticals,
Surrey, UK) was commenced orally on day 2 of menstruation
(with or without prior pituitary suppression) and continued
for 13–15 days, after which endometrial thickness was evalFertility and Sterilityâ
Endometrial Evaluation
Endometrial thickness was measured consistently by experienced sonographers in the midsagittal plane on the day of P
supplementation using an ultrasound scanner with a 6.5-MHz
probe (Hitachi EUB 525; Hitachi, Tokyo). Measurements
were made from the outer edge to the outer edge of the endometrial-myometrial interface in the widest part of the endometrium. In cases where any difficulty was encountered,
endometrial thickness measurement was confirmed by a second sonographer. Endometrial morphology was classified as
one of two main types: a triple-line echo pattern characterized by two external hyperechogenic lines representing the
endometrial-myometrial interface at the anterior and posterior uterine walls with two inner hypoechogenic areas separated by a central hyperechogenic line representing the
endometrial surfaces interface and a homogenously echogenic endometrial pattern. Endometrial evaluation protocol
remained unchanged during the study period.
Frozen-Thawed ET and Hormonal Support
Between one and three embryos were transferred to the uterus
2–3 days after P administration using an Edwards-Wallace
ET catheter (Sims Portex, Hythe, Kent, UK). After embryo
replacement, hormonal supplementation was continued for
14 days until a urine pregnancy test was performed using
commercially available kits. Patients with a positive test continued with estrogen and P supplementation until they were
12 weeks pregnant.
Cycle Outcome
Pregnancy was diagnosed by a positive urine test for hCG 14
days after ET. A clinical pregnancy was defined as the observation of a gestational sac with fetal heartbeat on ultrasound
scanning between 4 and 5 weeks after the positive pregnancy
test. An ongoing pregnancy was defined as a viable pregnancy beyond 20 weeks of gestation. Implantation rate was
defined as the number of gestational sacs observed on ultrasound compared with the number of embryos transferred.
Statistical Analysis
Data were collected for patient demographics and fresh and
cryothawed cycle characteristics and outcomes. Treatment
833
outcomes in relation to endometrial thickness were examined
at 2-mm increments to obtain reasonable subgroup sample
sizes adequate for meaningful statistical analysis. Univariate
analysis of the study outcome measures and associated clinical variables was performed using a two-sample t-test, c2
test, or Fisher’s exact test where appropriate.
A step-wise multiple logistical regression analysis was
used to assess the impact of endometrial thickness, patient
age, infertility cause, outcome of the fresh IVF/ICSI cycle,
protocol used for endometrial preparation, endometrial
echo pattern, number of embryos thawed, number of embryos
that survived thawing, proportion of embryos that survived
with all blastomeres intact and showed post-thaw resumption
of mitosis, and number of embryos transferred on the cryothawed cycle outcome. Any potential interaction between endometrial thickness and other factors was also assessed using
logistic regression analysis. In addition, the predictive relationship between endometrial thickness and treatment outcome was examined by a receiver operator characteristic
(ROC) curve to determine its predictive value. Stata software
package (Stata version 8.0, Stata Corp LP, College Station,
TX) was used for statistical analysis. P<.05 was considered
statistically significant.
RESULTS
Out of the 1032 initiated FER cycles, 768 cycles satisfied the
study criteria and were included in the analysis. In these
cycles, 3441 frozen embryos were thawed (a mean SD of
4.5 1.9 embryo per thaw), 2227 (65%) embryos survived
the process of thawing with 50% or more of their original
blastomeres intact, and 1620 (47%) embryos were replaced
(mean of 2.1 0.9 embryo/transfer). The mean endometrial
thickness recorded on the day of P supplementation was 9.3
2.1 mm (range, 5–20 mm). The overall clinical pregnancy,
ongoing pregnancy, and live birth rates per cryothawed transfer were 24%, 20%, and 19%, respectively. The implantation
rate in the study was 15%. The clinical pregnancy rate was
similar in cycles in which IVF (n ¼ 398) or ICSI (n ¼ 370)
was used for oocyte insemination (26% vs. 23%, respectively; P¼.31) and in cycles where the fresh embryos were
cryopreserved on either day 2 (n ¼ 474) or day 3 (n ¼ 294)
of in vitro culture (24% vs. 24.5%, respectively; P¼.86).
Figure 1 shows the clinical pregnancy rates according to
the endometrial thickness recorded on the day of P supplementation. The lowest rates were associated with endometrial
thicknesses of <7 mm and R15 mm (7%). Higher clinical
pregnancy rates were maintained at endometrial thicknesses
ranging from 9 to 14 mm (Fig. 1). There was a significant difference in the clinical pregnancy rate between FER cycles
with an endometrial thickness of 7–8 mm (18%) and those
with an endometrial thickness of 9–10 mm (32%; P<.001)
or 11–14 mm (27%; P<.01). However, the clinical pregnancy
rates in cycles with 9–10 mm thickness and in those with
11–14 mm thickness were not different (32% vs. 27%; P¼.3,
respectively).
834
El-Toukhy et al.
FIGURE 1
Clinical pregnancy rate according to endometrial
thickness on day of P supplementation.
El-Toukhy. Endometrial thickness and frozen cycles. Fertil Steril 2008.
Subgroup Analysis
Based on the above analysis, the study cycles were then
divided into two groups according to their endometrial thickness; group A (n ¼ 357) included FER cycles in which endometrial thickness recorded on the day of P supplementation
was 7–8 mm (mean, 8.1 0.5 mm), and group B (n ¼ 386)
included cycles in which the endometrial thickness was 9–14
mm (mean, 10.5 1.3 mm; P<.001) (11, 16–19). Cycles in
which endometrial thicknesses were <7 mm (n ¼ 13) or R15
mm (n ¼ 12) were not included in this comparison because of
their small number and the low pregnancy rate (7% in both
groups) associated with these extremes of endometrial thickness (17, 20, 21).
The two subgroups were comparable with respect to their
demographic and retrieval cycle characteristics including age
at cryopreservation, cause of infertility, history of previous
pregnancy, basal FSH level before starting the fresh cycle,
daily dose of FSH injections during stimulation, number of
fertilized oocytes and embryos replaced per cycle, and fresh
cycle outcome (Table 1).
No significant difference was observed between the two
groups in relation to mean age at the time of the cryothawed
replacement, mean duration between the original fresh and
subsequent cryothawed cycles, proportion of FER cycles performed in the first (1997–2001) or second (2002–2006) half
of the study period, type of endometrial preparation protocol
used, post-thawing embryo survival rate and the proportion of
cycles in which all embryos transferred had survived thawing
with all their original blastomeres intact, and cycles in which
all embryos replaced had both survived fully intact and resumed cleavage before transfer. The mean number of embryos thawed was higher in group B, but the two groups
had a similar mean number of cryothawed embryos replaced
per cycle (Table 2).
Frozen-thawed cycle outcomes are summarized in Table 2.
Group B (endometrial thickness 9–14 mm) showed
Endometrial thickness and frozen cycles
Vol. 89, No. 4, April 2008
TABLE 1
Patient demographics and fresh cycle characteristics.
Variable
Group A (n [ 357)
Age at stimulation, years
Percentage with secondary infertility
Cause of infertility, %:
Tubal factor
Male factor
Unexplained
Other
Basal serum FSH level, IU/L
Fresh cycle order
Dose of FSH, IU/day
No. of fertilized oocytes
Proportion requiring ICSI
No. of fresh embryos replaced/cycle
Proportion of cycles with day 2 freezing
Clinical pregnancy rate in fresh cycle (%)
Group B (n [ 386)
P
33.4 4
38
33.3 4
36
.87
.71
36
31
19
14
6.3 1.7
1.7 1.1
238 90
10.9 4.6
0.49
2.1 0.3
0.71
26
31
32
22
15
6.4 2
1.6 1
241 89
11.3 4.9
0.48
2.1 0.3
0.74
29
.31
.5
.1
.72
.19
.91
.74
.7
.33
Note: Values are given as mean SD or percentage as shown. Group A had an endometrial thickness of 7–8 mm, and
group B had an endometrial thickness of 9–14 mm.
El-Toukhy. Endometrial thickness and frozen cycles. Fertil Steril 2008.
significantly higher implantation (19% vs. 12%), clinical
pregnancy (OR 1.94; 95% confidence interval [CI], 1.37–
2.74; P<.001), ongoing pregnancy (OR ¼ 1.94; 95% CI,
1.3–2.8; P<.001), and live birth (OR ¼ 2; 95% CI, 1.37–
2.96; P<.001) rates compared with group A (endometrial
thickness, 7–8 mm). The rate of first trimester pregnancy
loss was similar in the two groups (44% vs. 43%, respectively; OR ¼ 1.02; 95% CI, 0.77–1.36; P¼.87).
Single Embryo Transfer (SET)
The two groups underwent a similar number of cycles with
single embryo replacement (42 cycles in group A and 41 cycles in group B). Patient age (33.6 4.4 vs. 33.1 4 years;
P¼.6) and outcome at fresh cycle (33.3% vs. 38% clinical
pregnancy rate; P¼.6) were similar in both groups. Likewise,
intact survival of the cryothawed embryo without blastomere
loss was comparable in both groups (62% vs. 59%, respectively; P¼.8). However, the clinical pregnancy rate in group
B SET cycles was double that in group A SET cycles (19.5%
vs. 9.5%, respectively; P¼.1) but similar to the clinical pregnancy rate achieved in group A cycles where more than one
embryo was replaced (n ¼ 315; 19.4%; P¼.87).
Controlling for Confounding Factors
To control for confounding variables, endometrial thickness
before P supplementation was employed in a logistic regression model with the following variables: age at cryopreservation, cause of infertility, history of previous pregnancy,
outcome of fresh cycle, type of protocol used for endometrial
preparation, number of embryos thawed and survived per
Fertility and Sterilityâ
FER cycle, intact cryothawed embryo survival, post-thawing
resumption of mitosis, and number of cryothawed embryos
replaced per transfer. Endometrial thickness of 9–14 mm remained significantly associated with a positive pregnancy
outcome after adjusting for these variables (Table 3). In addition, the interactions between endometrial thickness and
other variables shown to be significantly associated with
treatment outcome were tested, and there was no evidence
of significant interactions (P¼.73 for age at cryopreservation,
P¼.62 for fresh clinical pregnancy, and P¼.73 for intact
embryo survival).
Subsequently, a ROC curve was produced for endometrial
thickness to predict clinical pregnancy outcome and the area
under the curve (AUC) was 0.7 (Fig. 2), confirming the value
of endometrial thickness in predicting FER cycle outcome.
DISCUSSION
Ultrasound measurement of endometrial thickness is a simple
and reproducible method to evaluate endometrial proliferation (22) and has been studied as a possible indicator of uterine receptivity in fresh IVF cycles (23, 24). Understanding its
significance is even more important in medicated FER cycles
since endometrial thickness is the predominant factor determining the timing of P supplementation and cryothawed
ET (25). Nevertheless, there is still a gap in our knowledge
of the endometrial factors that determine a successful outcome of medicated FER cycles.
The present study investigated the association between endometrial thickness and treatment outcome in medicated
FER cycles. Although our results concur with the consensus
835
TABLE 2
FER cycle characteristics and outcome.
Group A (n [ 357)
Group B (n [ 386)
P
11.7 11.2
34.4 4.3
12.8 13.9
34.4 4.1
.23
.8
38
62
53
19.9 8.2
39
4.3 1.8
69 25
36
64
54
19.1 5.4
22
4.7 2
70 23
.73
51
49
2.1 1.2
43
27
49
51
2.1 0.5
47
33
.7
12
18
16
14
19
30
27
24
< .001
< .001
< .001
.002
Cryopreservation: replacement time, months
Age at replacement, years
Percentage of FER cycles performed between:
1997 and 2001
2002 and 2006
Percentage of down-regulated cycles
Duration of the proliferative phase, days
Percentage requiring E2 valerate dose increase
No. of embryos thawed/cycle
Post-thaw embryo survival rate, %
Percentage of cyclesa showing endometrial:
Triple-line echo pattern
Homogenous echo pattern
No. of embryos replaced/cycle
ETs with all embryos survived fully intact, %
ETs with all embryos fully intact and cleaved
post-thawing, %
Implantation rate, %
Clinical pregnancy rate/cycle, %
Ongoing pregnancy rate/cycle, %
Live birth rate/cycle, %
.88
.4
.01
.05
.72
.54
.31
.1
Note: Values are given as mean SD or percentage as shown. Group A had an endometrial thickness of 7–8 mm, and
group B had an endometrial thickness of 9–14 mm.
a
Data available for only 480 cycles: 236 (66%) of 357 cycles in group A and 244 (63%) of 386 cycles in group B.
El-Toukhy. Endometrial thickness and frozen cycles. Fertil Steril 2008.
that there is no endometrial thickness value that precludes
pregnancy (26), they indicate that an endometrial thickness
of 9–14 mm before P supplementation is associated with
a higher chance of implantation and pregnancy compared
with a thickness of 7–8 mm.
Because the success of any assisted reproductive technology treatment is influenced by multiple factors, we aimed
to control for factors that could impact on the outcome of
a FER cycle. In the present study, only the first FER cycle
was included. We also excluded cryothawed ETs performed
without hormonal supplementation since endometrial characteristics in natural cycles are considerably different from
those in medicated cycles (27). Prefreeze embryo quality
was also controlled for as all the frozen embryos included
in the study were selected according to strict morphological
criteria at the fresh state (12, 13, 28). Additionally, markers
of post-thaw embryo developmental potential, namely, cryothawed embryo survival rate, blastomere loss, and post-thaw
resumption of mitosis, were comparably distributed between
the two studied groups. Likewise, patient demographics as
well as retrieval and FER cycle characteristics were not
TABLE 3
Odds ratio (OR) and 95% confidence interval of successful treatment outcome associated with
endometrial thickness of 9–14 mm after adjusting for confounders.
Clinical pregnancy
Ongoing pregnancy
Live birth
Unadjusted OR
Adjusted OR
P
1.94 (1.37–2.74)
1.94 (1.3–2.8)
2 (1.37–2.96)
1.83 (1.3–2.6)
1.8 (1.2–2.6)
1.9 (1.3–2.8)
< .001
.003
.001
Note: The 95% CIs are in parentheses.
El-Toukhy. Endometrial thickness and frozen cycles. Fertil Steril 2008.
836
El-Toukhy et al.
Endometrial thickness and frozen cycles
Vol. 89, No. 4, April 2008
FIGURE 2
Receiver operator characteristic (ROC) curve for the
predictive value of endometrial thickness for clinical
pregnancy.
El-Toukhy. Endometrial thickness and frozen cycles. Fertil Steril 2008.
different in the two groups (Tables 1 and 2). We also used
a multivariate logistic regression model to adjust for potential
predictors of FER cycle outcome (1, 4–6, 14, 29, 30; Table 3).
Moreover, our SET data, although limited, provide further
evidence for the increased implantation potential in the presence of an endometrial thickness of 9–14 mm and could improve our ability to use cryopreserved embryos more
economically (5, 6).
Only one previous study has evaluated the relationship
between endometrial thickness in medicated frozen ETs and
cycle outcome (11). This study found no difference in the
clinical pregnancy rate per cycle for women with an endometrial thickness %8 mm and those with an endometrial thickness of 9–14 mm. However, it is difficult to compare the two
studies because patient demographics, fresh and FER cycle
characteristics, and embryo quality before freezing and after
thawing were not reported in that study. Unlike the present
study, the study of Check (11) also included oocyte recipients, used a different protocol of estrogen supplementation,
and made no adjustment for confounding variables.
On the other hand, considerable evidence that an endometrial thickness of 9 mm or more is associated with higher
pregnancy rates already exists in assisted reproductive technology treatments including ovulation induction (31), fresh
IVF/ICSI (16, 17, 19, 32–34), and oocyte donation cycles
(26, 35).
For example, Dickey and colleagues (32) found that fecundity after IVF was increased when the endometrium was
9–13 mm thick compared with an endometrial thickness of
<9 mm on the day of hCG administration. Noyes et al.
(16) evaluated 516 fresh IVF cycles and reported higher implantation and ongoing pregnancy rates when endometrial
thickness was at least 9 mm. Rinaldi and colleagues (33)
also demonstrated a higher pregnancy rate during IVF if
Fertility and Sterilityâ
the endometrium had a minimum thickness of 10 mm on
the day of hCG administration. Kupesic and colleagues
(17) reported no pregnancies in a group of 89 good-prognosis
women when the endometrial thickness before ET was
<9 mm, and all pregnancies in their study (28/89) occurred
when endometrial thickness was 9–15 mm. Kovacs and colleagues (34) retrospectively studied 1228 IVF/ICSI cycles
and found improved pregnancy rates when the endometrium
reached at least 10 mm on the day of ET. More recently,
Zhang et al. (19) analyzed 897 fresh IVF/ICSI cycles and
found improved treatment outcome in cycles with endometrial thicknesses of 9–14 mm measured on the day of
hCG administration compared with those with a thickness
of <9 mm.
Evidence that increased endometrial proliferation improves treatment outcome also exists in oocyte donation cycles. Check and colleagues (35) reported a higher pregnancy
rate (39% vs. 9%) among donor oocyte recipients when endometrial thickness was 10 mm or more immediately before
transfer. Among 343 oocyte donation cycles, Noyes et al.
(26) noted a significantly higher pregnancy rate in cycles in
which endometrial thickness before P supplementation was
9 mm or more compared to cycles in which the endometrium
was 8 mm or less in thickness (P<.002) and concluded that the
most reliable predictive factors for pregnancy in oocyte donation cycles were embryo quality and endometrial thickness.
For successful implantation to occur, the endometrium
must undergo key alterations that prepare it to receive the developing embryo during a defined period known as the ‘‘implantation window’’ (36). This intricate process leading to
acquisition of the endometrial receptive state is regulated
by timely interaction of ovarian hormones, adhesions molecules, cytokines, and growth factors (37). Given that endometrial morphology may reflect such changes (38, 39), it is
possible that achieving an endometrial thickness of R9 mm
predicts optimum histological maturation and acquisition of
this receptive state. This theory is supported by the study of
Hofmann et al. (40), which examined endometrial samples
in 46 women undergoing preparatory cycles for oocyte donation and concluded that endometrial thickness is predictive of
the degree of endometrial maturation.
Subendometrial blood flow has also been linked with endometrial thickness (41, 42), and it is conceivable that when the
endometrium reaches a thickness of 9 mm or more after
hormone supplementation, improved vascularity may allow
markers of endometrial receptivity (such as the expression
of fully developed pinopodes) to cover a longer period (43),
thereby prolonging the receptive phase and increasing the
chance of embryo implantation (44). In addition, the ability
of the endometrium to proliferate adequately in response to
a fixed dose of estrogen supplementation could be a marker
of improved receptivity and overall pregnancy potential,
whereas poor endometrial thickness could be a marker of
an intrinsic endometrial deficiency, which may not be rectified by prolonging the treatment duration or increasing the
estrogen dose (19).
837
Finally, the pregnancy loss rate in our study did not appear
to be related to endometrial thickness. This observation concurs with the study of Kovacs and colleagues (34) and implies
that miscarriage is predominantly determined by embryonic
(rather than endometrial) factors (2).
In conclusion, this large study shows that adequate endometrial development can have a significant impact on the outcome of medicated FER cycles. An endometrial thickness of
9–14 mm on the day of P supplementation is associated with
improved outcomes compared with a thickness of 7–8 mm.
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