IN VITRO FERTILIZATION
Effect of coasting on the implantation potential
of embryos transferred after cryopreservation
and thawing
Murat Arslan, M.D.,a,b Silvina Bocca, M.D., Ph.D.,a Estella Jones, M.S.,a Jacob Mayer, Ph.D.,a
Laurel Stadtmauer, M.D., Ph.D.,a and Sergio Oehninger, M.D., Ph.D.a
a
Department of Obstetrics and Gynecology, The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School,
Norfolk, Virginia; and b Department of Obstetrics and Gynecology, Mersin University, Mersin, Turkey
Objective: To examine the effect of withholding gonadotropins on the outcome of embryos after cryopreservation
and thawing.
Design: Retrospective clinical evaluation of patients having cryopreserved–thawed ET trials with coasting during
the corresponding ovarian stimulation cycle.
Setting: Academic tertiary clinical care unit.
Patient(s): Patients with cryopreserved embryos having coasting in their fresh IVF cycle and age-matched
controls without coasting, both groups receiving the same stimulation protocol (long GnRH agonist plus
recombinant FSH).
Intervention(s): All patients had a cycle in which embryos were transferred fresh and a cycle of thawing of
cryopreserved embryos with the aim of transferring in a steroid-supplemented cycle.
Main Outcome Measure(s): Embryo survival, implantation, and clinical pregnancy rates.
Result(s): Post-thawing embryo survival (66.4% vs. 73%), implantation (12.3% vs. 13.0%), and clinical pregnancy
rates (31.5% vs. 38.0%) were similar in study and control groups, respectively. Patients with coasting for ⱖ3 days had
significantly lower post-thawing embryo survival rates compared with patients having shorter duration of coasting (⬍3
days) and controls. Implantation and pregnancy rates, however, were similar in the three groups.
Conclusion(s): Coasting did not seem to have a detrimental effect on oocyte and embryo quality because the
implantation competence of transferred concepti after cryopreservation and thawing was similar to that of
controls. However, prolonged coasting (ⱖ3 days) had a subtle negative impact on the post-thaw survival rate.
(Fertil Steril威 2005;84:867–74. ©2005 by American Society for Reproductive Medicine.)
Key Words: Cryopreservation–thawing, coasting, embryo quality, estradiol, survival rate
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic
and potentially dramatic clinical condition initially characterized by increased capillary permeability and shift of intravascular fluid to extravascular spaces. Elevated E2 and
cytokine levels have been implicated in its pathogenesis (1).
Women prone to developing OHSS are commonly younger
(⬍35 years) with lean body mass and/or with polycystic
ovary syndrome (2). Despite the well-established predictive
value of such markers, some OHSS cases cannot be anticipated before the initiation of ovarian stimulation (1). Serum
E2 levels at the time of hCG administration have been found
to be closely correlated with OHSS (1). Critical values of E2
that trigger the syndrome are under debate and differ for
assisted reproductive techniques (⬎4,000 pg/mL) and con-
Received January 14, 2005; revised and accepted March 31, 2005.
Reprint requests: Sergio Oehninger, M.D., Ph.D., The Jones Institute for
Reproductive Medicine, 601 Colley Avenue, Norfolk, Virginia 23507
(FAX: 757-446-8998; E-mail: OehninSC@EVMS.edu).
0015-0282/05/$30.00
doi:10.1016/j.fertnstert.2005.03.069
ventional ovulation induction methods (⬎1,700 pg/mL),
possibly as a reflection of the patient’s physiological background and pretreatment ovarian suppression (2).
Because hCG is the only known triggering factor for the
development of OHSS, withdrawing gonadotropins and
postponing hCG administration (“coasting”) has been a commonly proposed method for reducing the risk of OHSS in
those patients with E2 above certain critical values (3, 4).
The concept of gonadotropin withdrawal during the late
follicular phase was originally introduced by Jones et al. (5)
as a means of allowing for follicle and oocyte maturation
before ovulation triggering according to the interval between
FSH/LH and hCG administration. Substitution of hCG by
shorter-acting compounds like GnRH agonists (6), use of the
recently introduced recombinant LH (7), and cryopreservation of all embryos, thus avoiding transfer in the fresh cycle
(8, 9), have also been proposed as alternatives to decrease or
prevent the occurrence of the syndrome.
Fertility and Sterility姞 Vol. 84, No. 4, October 2005
Copyright ©2005 American Society for Reproductive Medicine, Published by Elsevier Inc.
867
The introduction of embryo cryopreservation has been
instrumental in the advancement of assisted reproductive
technology. Embryo cryopreservation offers multiple advantages, including [1] allowing the possibility of inseminating
all retrieved mature oocytes without the need to discard any
embryos, [2] limiting the number of embryos transferred to
reduce the incidence of multiple pregnancy, [3] enhancing
couples’ chances of pregnancy by allowing multiple transfers originating from a single stimulated cycle (thereby optimizing their total reproductive potential), [4] aiding in the
clinical management of OHSS, and [5] providing a valid
ethical means for evaluation of research alternative protocols
(10). Although there are many factors affecting embryo
survival and clinical outcome after cryopreservation (10,
11), embryo quality seems to be the most significant determinant of viability after cryopreservation and thawing (12).
The potential impact of coasting on cycle outcome in
patients at imminent risk of ovarian hyperstimulation has
been analyzed in several studies. There are conflicting reports regarding a potential detrimental effect of gonadotropin withdrawal on pregnancy outcome in the fresh cycle (4,
13–17). Ulug et al. (18) investigated the effect of the duration of the coasting period on conception and reported that
although embryo quality was not affected, reduced implantation and pregnancy rates were observed in patients who
required coasting for ⬎3 days. It was speculated that the
poor implantation rates observed in such patients were due to
disruption of synchronization between endometrial and embryonic development. A similar outcome was demonstrated
in oocyte donation cycles, with lower implantation and pregnancy rates in the recipients after fresh transfers with ⬎4
days of coasting (19). The investigators speculated that this
result was due to detrimental effects of prolonged coasting
on oocyte and embryo quality not detected by current oocyte
and embryo grading systems.
We hypothesized that if coasting has a negative impact on
oocyte and embryo quality, then further evidence of this effect
could be sought by evaluating the outcome of cryopreserved–
thawed embryos originating from such stimulation cycles.
Moreover, the effects of variable coasting periods could be
examined. Cryopreserved–thawed embryos are typically transferred in hormonally (estrogen/progesterone)-supplemented cycles in which the endometrium is not exposed to the hyperestrogenic milieu that characterizes the stimulated cycles.
Hence, the primary objective of the present study was to determine the effect of coasting on the outcome of embryos after
cryopreservation and thawing. The primary endpoint was the
examination of post-thawing embryo survival and implantation
competence.
MATERIALS AND METHODS
Subjects: Study and Control Groups
We retrospectively evaluated all IVF cycles performed during a 5-year period in our program between September 1999
and September 2004. The institutional review board of East868
Arslan et al.
Effect of coasting on embryo quality
ern Virginia Medical School approved this study. From the
computerized database we identified patients who were prepared to undergo a transfer cycle with cryopreserved–thawed
embryos and who had coasting in their corresponding ovarian stimulation (“fresh”) cycle. Coasting was defined as
withholding gonadotropin administration for at least 24
hours before triggering ovulation with hCG. The decision to
coast was based on the presence of E2 levels ⱖ4,000 pg/mL
associated with ⱖ20 follicles, each ⬎12 mm in diameter and
some of them in the range of 15–18 mm.
Cryopreservation–thawing cycles resulting from the use
of a different ovarian stimulation protocol other than the one
described below, or in which intracytoplasmic sperm injection (ICSI) or assisted hatching had been performed, were
excluded from the analysis.
Thirty-nine cryopreserved–thawed ET cycles performed
in 33 patients who had undergone coasting during ovarian
stimulation fulfilled the inclusion criteria and constituted the
study group. Thirty-three IVF patients with 42 cryopreserved–thawed ET cycles were used as the controls. These
patients were identified from the database as the consecutive
IVF patient to each study subject who received the same
stimulation protocol, achieved a peak serum E2 level of
3,000 – 4,000 pg/mL at the time of hCG administration, did
not undergo coasting, and had excess embryos that were
cryopreserved. In addition, groups were matched by woman’s age at the time of their fresh IVF cycle and basal cycle
serum day-3 FSH levels.
IVF Protocol
In the fresh IVF cycle, all patients were down-regulated
according to a long protocol with a GnRH agonist and
stimulated with recombinant FSH. The GnRH agonist leuprolide acetate was initiated on day 21 of the preceding luteal
phase (0.5 mg/d SC) until menses and dropped to 0.25 mg/d
until triggering ovulation. Ovarian stimulation was started
with a fixed regimen for the first 4 days of recombinant FSH
(225 IU/d SC), and thereafter the gonadotropin dose was
continued according to the individual’s ovarian response
with a step-down regimen. Human chorionic gonadotropin
(10,000 IU) was administered IM to trigger ovulation when
at least two follicles were ⱖ17 mm in diameter.
Transvaginal follicular aspiration was performed under
ultrasound guidance, 34 –36 hours after hCG injection. Gamete processing and embryo culture procedures and transfer
techniques were previously described (20). Embryo quality
(cleavage and morphology) was assessed according to the
criteria of Veeck (21). Transfer of embryos was performed
on day 3. All stimulation cycles underwent a fresh cycle. The
luteal phase was supported with micronized P vaginally (600
mg/d). Clinical pregnancy was defined as visualization of a
gestational sac with a heart beat by transvaginal ultrasound
in patients with normally rising serum -hCG levels. Implantation rate was defined as the number of gestational sacs
visualized divided by the number of embryos transferred.
Vol. 84, No. 4, October 2005
Cryopreservation–Thawing Protocol
Cryopreservation of embryos was performed at the pronuclear or cleaving (day-3) stage according to a slow-freeze,
slow-thaw protocol (10, 22) with a programmed cell freezer
(Planer Kryo 10-1.7; T.S. Scientific, Perkasie, PA) and 1.5
mol/L 1,2 propanediol as the cryoprotectant. Briefly, the
zygote freezing protocol started at room temperature and
continued at ⫺1°C/min to ⫺6°C; this was followed by 5
minutes holding, manual seeding with forceps (to avoid ice
crystal formation), holding again for 5 minutes, and freezing
to ⫺80°C at a rate of ⫺0.5°C/min (slow cooling).
Specimens were kept in cryovials containing 0.3 mL of
cryoprotective medium and maintained at ⫺196°C under
liquid nitrogen in storage tanks (35 VHC liquid nitrogen
storage tank; Taylor-Warton Cryogenic Equipment, Indianapolis, IN). Slow thawing of the embryos to room temperature was followed by dilution of the cryoprotectant and
transfer of the specimen to equilibrated culture medium and
incubation at 37°C under 5% CO2 in air until cleavage was
established.
The freezing protocol for cleavage-stage embryos was
very similar to that described above except for the addition
of sucrose (0.2 mol/L) to the freezing medium and with a
post-seeding cooling rate of ⫺0.3°C/min. Cleavage-stage
embryos were plunged into liquid nitrogen at ⫺30°C. Thawing of day-3 embryos was performed with a 37°C water bath
for 1 minute, followed by 5 minutes at room temperature.
Assessment of Embryo Survival
Post-thaw survival of pronuclear-stage embryos was defined
as the ability of the zygotes to enter syngamy and proceed to
at least the first cleavage division; one-cell specimens that
appeared viable but failed to meet these criteria were not
considered survivors. Thawed day-3 embryos were defined
as surviving “morphologically” after identification of zona
pellucida intactness and ⬎50% intact blastomeres (22).
Transfer of Cryopreserved–Thawed Embryos
Patients were prepared for ET in all cycles as follows.
Transdermal 17-E2 patches were used (Vivelle Dot; Novogyne Pharmaceuticals, Miami, FL; each patch delivering
0.1 mg/day of E2) and replaced every other day. On day 1,
two patches were applied, and then E2 administration was
gradually increased on cycle days 7 (to three patches every
other day) and on cycle day 11 (to four patches every other
day). In addition, from cycle day 12 and every other day, 1
mg 17-E2 (Estrace; Warner Chilcot, Rockaway, NJ) was
started vaginally and continued with the same dose every
other alternate day to the estrogen patch.
From cycle day 15, the transdermal E2 dose was decreased
(to two patches every other day) alternating with the vaginal
Estrace pills (at the same dose). From cycle day 15 on,
vaginal micronized P (Prometrium; Solvay Pharmaceutical,
Baudette, MN) was added to the regimen (600 mg/d). ProFertility and Sterility姞
nuclear stage concepti were thawed on day 16 and transferred on day 17, whereas day-3 embryos were thawed on
day 17 and transferred on day 18.
Statistical Analysis
Data are presented as mean ⫾ SE. Comparisons between
groups of continuous outcomes were performed by Student’s
t-test, Mann-Whitney U test, analysis of variance with least
significant difference post hoc test, or the Kruskal-Wallis
rank sum test, as appropriate, after testing for normal distribution by the Kolmogorov-Smirnov test. Nominal data were
analyzed by 2 test. These analyses were performed with
commercial software (SPSS for Windows, version 9.05;
SPSS, Chicago, IL).
RESULTS
The mean age and serum FSH levels on basal cycle day 3 for
patients in the study and controls were 31.0 ⫾ 0.5 years vs.
31.0 ⫾ 0.5 years and 6.01 ⫾ 0.17 mIU/mL vs. 6.01 ⫾ 0.17
mIU/mL, respectively. There was no difference between
study (6.05 ⫾ 0.33 mIU/mL) and control (5.67 ⫾ 0.53
mIU/mL) groups in mean serum LH levels on basal cycle
day 3. The etiology of infertility was similar: tubal factor,
35% and 31%; unexplained, 25% and 27%; male infertility,
21% and 24%; endometriosis, 14% and 16%; and other
causes, 5% and 2%, respectively, for study and control
groups.
The results of the fresh cycles for the study and control
groups are presented in Table 1. By study design, all patients
reached the transfer stage. The groups were similar in serum
E2 levels at the time of hCG administration, number of
metaphase II oocytes harvested per retrieval, fertilization
rate, and mean number of embryos transferred per cycle. As
expected, the day of hCG administration was significantly
delayed in the study group (P⬍.01). There were no significant differences between groups regarding the quality of the
embryos transferred: proportion of embryos grade 1 (best
quality), 25.1% and 26.1%; grade 2, 39.7% and 35.2%;
grade 3, 35.2% and 38.6%, respectively, for study and control groups. No grade 4 to 5 embryos were transferred in
fresh cycles in any group. Patients with coasting (study
group) had significantly lower implantation and pregnancy
rates compared with controls: 7.7% vs. 26.9% and 18.1% vs.
48.4%, respectively (P⬍.01 for all comparisons).
Table 2 presents the characteristics of the transfer cycles
after embryo cryopreservation and thawing. The mean duration of freezing was comparable in both groups (8.1 and
8.7 months in study and control groups, respectively,
P⬎.05). There was no significant difference between groups
regarding the stage at cryopreservation: 36% pronuclear and
64% cleaving, and 45% pronuclear and 55% cleaving, for
study and control groups, respectively. In the study group
(with coasting) there were 39 thawing cycles, and 38 of them
reached the transfer stage. There were 42 thawing cycles in
869
TABLE 1
Results of the fresh IVF cycles in the study (with coasting) and control (without coasting) groups.
Variable
Study group
(coasting)
Control group
(no coasting)
No. of patients/transfers
Total dose of rFSH (IU)
Day of hCG
E2 at the beginning of coasting (pg/mL)
E2 at hCG administration (pg/mL)
Duration of coasting (d)
No. of metaphase II oocytes retrieved
Fertilization rate (%)
Mean no. of embryos transferred
Implantation rate, n (%)
Clinical pregnancy rate, n (%)
33
1,725 ⫾ 95
13.24 ⫾ 1.30a
5,804 ⫾ 221
3,572 ⫾ 205
2.06 ⫾ 0.15
16.64 ⫾ 1.22
82.1 ⫾ 2.5
2.75 ⫾ 0.13
7/91 (7.7)a
6/33 (18.1)a
33
2,010 ⫾ 115
12.09 ⫾ 1.18
—
3,498 ⫾ 179
—
14.82 ⫾ 0.80
79.8 ⫾ 1.7
2.67 ⫾ 0.12
24/89 (26.9)
16/33 (48.4)
Note: Data are presented as mean ⫾ SE, unless otherwise noted.
a
P⬍.01.
Arslan. Effect of coasting on embryo quality. Fertil Steril 2005.
the control group. Embryo viability (survival rate) was
66.4% and 73.0% in study and control groups, respectively,
and the difference was not statistically significant. In the
study group, one cycle was canceled because there was no
viable embryo available after thaw. The mean number of
embryos transferred, implantation rates, and pregnancy rates
were not significantly different between groups. There were
no significant differences between groups regarding the
quality of the embryos at the time of cryopreservation (not
shown).
Cycles in the study group (with coasting) were further
divided into two subgroups according to the duration of
coasting (ⱖ3 days or ⬍3 days). Results of the fresh IVF
cycles are presented in Table 3. As expected, serum E2 levels
at the time of coasting were significantly higher in patients
with ⱖ3 days of coasting (P⬍.05). Also, the day of hCG
administration was significantly delayed in patients with ⱖ3
days of coasting compared with patients with ⬍3 days of
coasting or controls (P⬍.01). Although the fertilization rates
and the number of embryos transferred were similar in the
groups, both subgroups of patients receiving coasting had
significantly lower implantation and pregnancy rates than the
control group (P⬍.05 for all comparisons).
Table 4 presents results of the same three subgroups of
patients after embryo cryopreservation and thawing. There
were no differences between groups in the quality of the
cryopreserved embryos (not shown). The survival rate of
embryos in patients with ⱖ3 days of coasting was significantly lower compared with controls and compared with the
subgroup of patients having coasting ⬍3 days (P⬍.05). The
numbers of embryos transferred, the implantation rates, and
pregnancy rates were similar in all groups.
TABLE 2
Results of cycles of cryopreserved–thawed embryos in patients with and without coasting in their
fresh IVF cycle.
Variable
Study group
(coasting)
Control group
(no coasting)
No. of cycles with thaw
No. of transfers
Mean (⫾SE) duration of freezing (mo)
Embryo survival (%)
Mean (⫾SE) no. of embryos transferred
Implantation rate, n (%)
Clinical pregnancy rate, n (%)
39
38
8.1 ⫾ 2.4
66.4
2.92 ⫾ 0.15
14/113 (12.3)
12/38 (31.5)
42
42
8.7 ⫾ 3.1
73.0
2.75 ⫾ 0.19
15/115 (13.0)
16/42 (38.0)
Arslan. Effect of coasting on embryo quality. Fertil Steril 2005.
870
Arslan et al.
Effect of coasting on embryo quality
Vol. 84, No. 4, October 2005
TABLE 3
Evaluation of fresh IVF cycles subgrouped according to duration of coasting.
Variable
Age (y)
Basal FSH (mIU/mL)
E2 at the beginning of coasting (pg/mL)
E2 at hCG administration (pg/mL)
Day of hCG administration
Total dose of FSH (IU)
No. of metaphase II oocytes retrieved
Fertilization rate (%)
Mean no. of embryos transferred
Implantation rate, n (%)
Clinical pregnancy rate, n (%)
Coasting <3 days
(n ⴝ 22)
Coasting ≥ 3 days
(n ⴝ 11)
Controls
(no coasting)
(n ⴝ 33)
31.4 ⫾ 0.5
5.96 ⫾ 0.28
5,342 ⫾ 164a
3,525 ⫾ 132
12.59 ⫾ 0.14b
1,697 ⫾ 113
18.18 ⫾ 1.60
84.84 ⫾ 2.66
2.78 ⫾ 0.13
5/62 (8.0)d
4/22 (18.1)d
30.2 ⫾ 0.4
6.11 ⫾ 0.31
6,729 ⫾ 478
3,666 ⫾ 280
14.55 ⫾ 0.39c
1,779 ⫾ 183
14.64 ⫾ 1.66
76.68 ⫾ 4.93
2.68 ⫾ 0.13
2/29 (6.9)d
2/11 (18.1)d
31.0 ⫾ 0.5
6.01 ⫾ 0.17
—
3,498 ⫾ 179
12.09 ⫾ 1.18
2,010 ⫾ 115
14.82 ⫾ 0.80
79.83 ⫾ 1.76
2.67 ⫾ 0.12
24/89 (26.9)
16/33 (48)
Note: Data are presented as mean ⫾ SE, unless otherwise noted.
a
P⬍.05 vs. the “coasting ⱖ3 days” group.
b
P⬍.01 vs. the “coasting ⱖ3 days” group.
c
P⬍.01 vs. controls.
d
P⬍.05 vs. controls.
Arslan. Effect of coasting on embryo quality. Fertil Steril 2005.
DISCUSSION
To test the hypothesis that coasting during ovarian stimulation has a detrimental effect on oocyte/embryo quality, we
examined the effect of withholding gonadotropins on the
outcome of embryos after cryopreservation and thawing.
To the best of our knowledge, this is the first study to
evaluate the effect of coasting on the performance of
cryopreserved–thawed embryos. We compared patients
with coasting having excess cryopreserved embryos with
a well-matched control group of patients without coasting.
Although our own previous results have demonstrated that
ICSI does not have an impact on embryo quality after
cryopreservation and thawing (23), others have reported a
negative impact of oocyte and zona pellucida micromanipulation techniques on implantation potential after
thawing (11). Therefore, we excluded from the analysis
all cases in which ICSI or assisted hatching had been
performed.
Results of this study showed that coasting did not seem to
have a detrimental effect on oocyte and embryo quality
because the implantation competence of transferred concepti
after cryopreservation–thawing was similar to that of con-
TABLE 4
Performance of cryopreserved–thawed embryos subgrouped according to duration of coasting.
Variable
No. of cycles with thaw
No. of transfers
Embryo survival (%)
Mean (⫾SE) no. of embryos transferred
Implantation rate, n (%)
Clinical pregnancy rate, n (%)
a
b
Coasting <3 days
(n ⴝ 22)
Coasting ≥ 3 days
(n ⴝ 11)
Controls
(no coasting)
(n ⴝ 33)
24
23
72.26a
2.91 ⫾ 0.13
8/67 (11.9)
7/23 (30.4)
15
15
54.70b
2.98 ⫾ 0.15
6/46 (13.0)
5/15 (33.3)
42
42
73.00
2.75 ⫾ 0.19
15/115 (13.0)
16/42 (38)
P⬍.05 vs. “coasting ⱖ3 days” group.
P⬍.05 vs. controls.
Arslan. Effect of coasting on embryo quality. Fertil Steril 2005.
Fertility and Sterility姞
871
trols. However, prolonged coasting (ⱖ3 days) had a negative
impact on the post-thaw survival rate.
There are many studies in the literature evaluating the
effects of coasting on fresh IVF cycle outcomes (3, 13–17,
24 –27). As detailed in a review by Delvigne and Rozenberg
(28), fertilization rate (36.7%–71%), implantation rate
(9.5%–31%), and pregnancy rate (20%– 63%) have varied,
mainly because of differences in patient selection criteria
and design of the studies. Of all such studies, only a few
focused directly on the effects of coasting on oocyte and
embryo quality. Aboulgar et al. (27) found a lower percentage of high-quality oocytes and a decreased fertilization rate
in a group of patients who developed OHSS and had coasting in their stimulation protocol. However, because the number of oocytes was large enough, this impaired percentage of
high-quality oocytes affected neither the quality nor the
number of embryos transferred nor the pregnancy rate.
Delvigne et al. (16) investigated oocyte quality and IVF
outcomes of fresh cycles after different periods of coasting.
These investigators could not demonstrate any difference in
oocyte quality and mean embryo quality scores compared
with controls. Isaza et al. (19) also evaluated oocyte and
embryo quality after coasting and their effects on implantation and pregnancy rates after fresh transfer in oocyte donation cycles. Because of the study design, they were able to
eliminate the possible detrimental effect of high serum E2
levels on endometrium and implantation. Similar to our
experiment, the study and control donor cycles had comparable serum E2 levels on the day of hCG administration, but
there were higher serum peak E2 levels in coasted patients.
There were no differences between groups in terms of embryo quality or implantation rates after transfer in the recipients. However, when donors were further subdivided into
two groups according to the length of coasting (ⱕ4 days and
⬎4 days), both implantation and pregnancy rates in recipients were lower with longer duration of coasting. This finding was coincident with no difference between groups in the
quality of the embryos transferred. The investigators concluded that prolonged coasting had possible deleterious effects on oocyte and embryo quality that were unable to be
determined by currently used oocyte and embryo grading
systems.
Our results demonstrated, overall, that embryos transferred after cryopreservation and thawing in hormonally
supplemented cycles had similar implantation competence
when compared with controls without coasting (Table 2).
Because our study was designed as a model to exclude an
endometrial effect due to the hyperestrogenism of ovarian
hyperstimulation cycles, we might therefore conclude that
coasting seems not to have a detrimental effect on oocyte and
embryo quality. Our results only point out a subtle effect of
prolonged coasting, manifested by a lower survival rate in
cryopreserved–thawed embryos with ⱖ3 days of coasting in
their stimulation cycle (Table 4). Nevertheless, although the
embryo survival rate was diminished in the group with
872
Arslan et al.
Effect of coasting on embryo quality
prolonged coasting, implantation and pregnancy rates were
not. This can be explained by the fact that the number of
embryos surviving thawing was large enough to still select
good-quality embryos for transfer.
We cannot, therefore, entirely rule out that high serum E2
levels or an extended exposure in the group with prolonged
coasting might have affected the quality of oocytes, resulting
in decreased resistance to freezing and thawing. If present,
this effect could be due to either the absolute increase in
serum concentration of the steroid or to increased time of
exposure to a high estrogenic milieu. Owing to the high risk
of development of OHSS and ethical concerns, it was not
acceptable to examine a group of patients having peak serum
E2 levels similar to those of the coasted patients but in whom
coasting was not performed.
Ng et al. (29) examined oocyte and embryo quality in
patients having an excessive ovarian response and reported
no difference in the number of blastomeres per embryo
comparing groups of patients with different levels of E2
levels on the day of hCG administration. It has also been
shown that high serum E2 concentrations in fresh IVF cycles
do not impair implantation and pregnancy rates in subsequent cryopreserved–thawed ET cycles (30). However, in an
in vitro study, Valbuena et al. (31) found direct evidence of
a detrimental effect of E2 on embryo developmental competence that might lead to lower embryo adhesion capability. It
is obvious that the effect of high levels of serum E2 during
ovarian stimulation on embryo quality is still under debate
and is open to new studies.
Although our main objective was to determine the effect
of coasting on the outcome of embryos transferred after
cryopreservation and thawing, results of the study and control groups in their fresh cycles were quite different and
worth analyzing. We observed lower implantation and pregnancy rates in the group of patients with coasting, irrespective of its duration (short or prolonged) (Tables 1 and 3).
This could be due to the associated hyperestrogenism leading to either an oocyte or an endometrial effect. The fact that
the results of cryopreserved–thawed embryos showed no
impact on implantation suggests an endometrial effect.
The relationship between decreased endometrial receptivity and ovarian hyperstimulation in fresh IVF cycles has
been studied for more than a decade (32). It has been
hypothesized that ovarian hyperstimulation, by leading to
supraphysiologic E2 levels, prematurely induces P receptors
in the endometrium in the follicular phase (33, 34). This
might result in extremely advanced endometrium that negatively affects implantation (35). Simon et al. (36) reported
lower implantation rates when serum levels of E2 were
⬎2,500 pg/mL on the day of hCG administration. These
investigators presented further and strong evidence in favor
of a detrimental effect of high E2 levels on uterine receptivity
(37, 38).
Conversely, other studies have shown no detrimental effects (39 – 41). The study of Toner et al. (39) did not reveal
Vol. 84, No. 4, October 2005
impaired implantation rates in high responders, except for
the infrequent group of patients with peak serum E2 levels
⬎5,000 pg/mL in whom there was a remarkable absence
(down-regulation) of P4 receptors. We are presently conducting studies that might shed some light on this issue
through the comparative analysis of gene expression profiles
in stimulated and natural cycles (42).
In conclusion, our studies showed that, overall, coasting
does not seem to have a detrimental effect on oocyte/embryo
quality, because the implantation competence of transferred
concepti after cryopreservation and thawing was similar to
that of controls. Prolonged coasting (ⱖ3 days), on the other
hand, had a subtle and negative impact on post-thaw survival
rates, but because of the adequate number of embryos available to transfer demonstrating implantation competence,
pregnancy rates were not affected. Our data also indirectly
support the concept of a negative effect of hyperestrogenism
on the endometrium, evidenced by the lower pregnancy rate
observed in the fresh cycles with coasting.
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