Human Reproduction, Vol.29, No.6 pp. 1238 –1243, 2014
Advanced Access publication on March 23, 2014 doi:10.1093/humrep/deu058
ORIGINAL ARTICLE Infertility
Uterine peristalsis before embryo
transfer affects the chance of clinical
pregnancy in fresh and frozen-thawed
embryo transfer cycles
L. Zhu, H.S. Che, L. Xiao, and Y.P. Li*
Department of Reproductive Medicine, Xiangya Hospital, Central-south University, Changsha City, Hunan Province, P.R. China
*Correspondence address. Department of Reproductive Medicine, Xiangya Hospital, 87 Xiangya Road, Changsha City, Hunan Province,
P.R. China. E-mail: [email protected]
Submitted on November 30, 2013; resubmitted on February 22, 2014; accepted on February 26, 2014
study question: Does uterine peristalsis influence the chance of clinical pregnancy in an embryo transfer cycle?
summaryanswer: The uterine peristaltic wave frequency before embryo transfer is inversely related to the clinical pregnancy rates in fresh
and frozen-thawed embryo transfer cycles.
what is known already: Uterine peristalsis participates in regulating fluid migration after mock embryo transfer, but whether it could
potentially influence pregnancy outcomes had remained unclear.
study design, size, duration: This prospective cohort study included a total of 292 infertile women and was conducted between
March 2013 and August 2013.
participants/materials, setting, methods: Patients underwent fresh embryo transfer in a fresh stimulation cycle with a
long down-regulation protocol, a natural frozen-thawed embryo transfer cycle or an artificial frozen-thawed embryo transfer cycle. Uterine peristaltic activity was assessed before embryo transfer by transvaginal ultrasonography.
main results and the role of chance: The uterine peristaltic wave frequencies of most patients were between 1.1 and 3.0
waves/min before embryo transfer (ET). The clinical pregnancy rate was the highest when ,2.0 waves/min was observed and it decreased
with an increasing wave frequency thereafter, with an especially dramatic decrease with .3.0 waves/min. Uterine peristaltic wave frequencies
of the non-pregnant patient group were higher than that of the clinically-pregnant patient group in all types of transfer, fresh embryo transfer,
natural FET or artificial FET cycle. Binary logistic regression analysis demonstrated that the association between uterine peristaltic wave frequency
before embryo transfer and clinical pregnancy was independently significant (odds ratio: 0.49; 95% confidence interval: 0.34 –0.70, P , 0.001).
limitations, reasons for caution: Uterine peristalsis after embryo transfer was not observed in case any possible negative effect
of the observation disturbed embryo implantation or caused psychological stress. Uterine peristalsis after embryo transfer may differ from that
before embryo transfer. Another limitation of the present study was the lack of uterine peristaltic wave type analysis which is also an important
parameter to assess uterine activity.
wider implications of the findings: Patients with uterine peristalsis of ,3.0 waves/min before embryo transfer had a higher
chance of pregnancy compared with those with higher frequencies. This could be a promising quantitative marker of uterine receptivity and pregnancy outcome in an embryo transfer cycle. The predictive validity of the cut-off value needs to be tested in further study.
study funding/competing interest(s): The study is supported by Hunan Provincial Innovation Foundation for Postgraduates.
The authors declare that they have no competing interests in this study.
Key words: uterine peristalsis / uterine receptivity / clinical pregnancy / assisted reproductive technology
& The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
For Permissions, please email: [email protected]
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Uterine peristalsis and pregnancy rates
Introduction
Controlled ovarian stimulation improvements and technological
advancements in the laboratory have provided adequate oocytes and
high-quality embryos to infertile couples, leading to steadily increased
success rates for IVF over the years. However comparatively speaking,
considerably fewer efforts have been devoted to improving uterine receptivity, especially in clinical practice.
In contrast with an invasive endometrium biopsy, uterine peristalsis
can be directly visualized by ultrasonography and has therefore broadened the horizon for exploring uterine receptivity in human reproduction. During the luteal phase in a natural cycle, uterine activity reaches an
absolute minimum and the reduced uterine peristalsis is believed to facilitate embryo implantation (Ijland et al., 1997a; Bulletti et al., 2000; Bulletti
and de Ziegler, 2006). Studies of mock embryo transfer (ET) have also
testified to the important role of uterine peristalsis in controlling the migration of embryo analogues. Lesny et al. (1998) observed that the transferred fluid could be expelled out of the uterine cavity by strong uterine
contractions after touching the uterine fundus with the catheter. Our
previously published study also found that uterine peristaltic wave frequency was positively correlated with the distance that fluid moved
after it was deposited in the uterine cavity (Zhu et al., 2014).
Since uterine peristalsis can exert an influence on the drift of an
embryo analogue during the implantation window, we hypothesized
that it may also have an effect on the subsequent clinical pregnancy
outcome in a real embryo transfer cycle. This inspired us to comprehensively analyse the relationship between uterine peristalsis just before
embryo transfer and the clinical pregnancy rates under different conditions, including fresh embryo transfer, natural frozen-thawed embryo
transfer (FET) and artificial FET cycles.
Materials and Methods
Patients
From March 2013 to August 2013, all patients undergoing IVF/ICSI-ET and
FET treatment at the Department of Reproductive Medicine at Xiangya Hospital of Central-south University were offered participation in the study. To
limit the interference of confounding variables affecting embryo quality
and/or uterine receptivity, patients were only selected if they (i) were 20 –
35 years of age; (ii) had a normal uterus; (iii) had two good-quality day-3 cleavage stage embryos available for transfer (good-quality day-3 embryos were
defined by at least seven cells, ,20% fragmentation, and no apparent morphological abnormalities); and (iv) underwent easy embryo transfer (i.e. the
catheter was smoothly inserted without touching the fundus, no cervix tenaculum was used and the catheter was clean of blood). After excluding 13
patients due to cancellation of embryo transfer (because of ovarian hyperstimulation syndrome or hydrohystera), a change to blastocyst transfer, or the
use of another drug intervention, a total of 166 patients underwent fresh
embryo transfer and 126 patients received either natural FET (n ¼ 69) or
artificial FET (n ¼ 57) were analysed. Written informed consent was
obtained from each patient before inclusion. The study was approved
by the institutional review board (Clinical Trial Registration Number:
ChiCTR-OCH-13003105).
Merck Sharp & Dohme). FSH doses were adjusted individually according to
the patient’s ovarian response as assessed by ultrasound and hormonal measurements performed every 1 – 3 days. A dose of 5000 – 10 000 IU of human
chorionic gonadotrophin (HCG, Livzon, China) was administered when at
least three follicles were ≥18 mm in diameter. Oocyte retrieval was conducted transvaginally 34 – 36 h after the HCG trigger. The luteal phase was
supported with progesterone injections at a dose of 60 mg/day and progesterone soft capsules at a dose of 200 mg/night from the day of oocyte
retrieval.
Cryopreservation cycles
In the natural FET cycles, the development of the dominant follicle and endometrium was monitored from Day 10 by regular vaginal ultrasound, urine LH
tests and serum LH, E2 and progesterone measurements until ovulation. If the
diameter of the dominant follicle was ,14 mm, the patient was asked to
return every second day. If the dominant follicle was ≥14 mm, a urine LH
test was performed and the patient was asked to return the next day.
When the diameter of the dominant follicle was ≥18 mm or the urine LH
test was .45 mIU/ml, serum LH, E2 and progesterone concentrations
were measured to help estimate the maturation of the dominant follicle,
predict ovulation and find out whether the follicle was luteinized. If the
serum progesterone concentration was .1.0 ng/ml and the follicle was
still unruptured, which was usually accompanied by heterogeneous echo of
the follicular fluid, luteinized unruptured follicle was identified and that day
was taken as the ovulation day. To preclude luteal phase defect, luteal
phase support was provided from the day of ovulation day progesterone injection 40 mg/day and added progesterone soft capsules at a dose of
200 mg/night from the day of embryo transfer.
In the artificial FET cycles, patients received increasing doses (6 mg for days
3 – 7, 8 mg for 2 days, and 10 mg for 2 days thereafter) of estradiol valerate
(Progynova, Bayer) in order to prepare the endometrium for embryo transfer. Endometrial thickness was monitored by transvaginal ultrasound every
time before adjusting the doses of estradiol valerate, and when the endometrium reached or exceeded 7 mm, increasing doses (20 mg for 1 day, 40 mg
for 1 day and 60 mg for 1 day thereafter) of progesterone were given intramuscularly once per day. Progesterone soft capsules at a dose of 200 mg/
night were administered orally from the day of embryo transfer.
Embryo transfer
Two good-quality embryos were transferred under abdominal ultrasound
guidance 3 days after oocyte retrieval in a fresh cycle, 2 days after ovulation
in a natural FET cycle and 3 days after progesterone administration in an artificial FET cycle, respectively. All of the embryo transfers were performed by
an experienced doctor (Y.P.L.), who was blind to the frequency of uterine
peristalsis, using the same type of catheter (CCD131230301, Ultrasoft
Frydman Set with Guide, Laboratoire C.C.D., France). Blood samples
were collected on the day of embryo transfer to determine the serum E2
and P using electrochemiluminescence immunoassays. Approximately 80%
of all fresh cycles were conducted as IVF and 20% were conducted as
ICSI/half-ICSI. Patients were confirmed to be clinically pregnant by ultrasonographic visualization of a gestational sac 2 – 3 weeks after a positive pregnancy test. Luteal support was continued either until 1 month after
confirmation of intrauterine pregnancy or until pregnancy was ruled out by
a negative serum HCG measurement, in all types of treatment cycles.
Fresh cycles
Observation and assessment of uterine
peristalsis
Patients underwent ovarian stimulation in a long down-regulation protocol
using urinary FSH (Urofollitropin, Livzon, China), recombinant follitropin
alfa (Gonal-F, Merck Serono) or recombinant follitropin beta (Puregon,
Transvaginal ultrasonography scans (Mindray DC-6 Expert, 5 – 8 MHz transducer) of uterine peristalsis were performed by a single examiner (L.Z.)
about 1 h before embryo transfer while the patient was lying relaxed in a
1240
Zhu et al.
lithotomy position. The probe was introduced into the vagina as gently as
possible to avoid stimulating the cervix. After scanning the mid-sagittal
plane of the uterus, the probe was fixed as steady as possible while a 5 min
video of uterine peristalsis was recorded simultaneously. The records
were analysed at 4× regular speed using a VLC media player 1.1.11 (VideoLAN team) by two independent experienced observers (L.Z. and L.X.). The
uterine peristaltic wave frequency was the mean of the results from each observer. Both observers were blind to the treatment condition (fresh cycle,
natural FET cycle or artificial FET cycle) of all patients.
Statistical analysis
Statistical analyses were carried out using SPSS version 19.0. Continuous data
were presented as mean and standard deviation (SD). A two-sample t-test
was used to determine whether the uterine peristaltic wave frequency on
embryo transfer day differs in the pregnancy and non-pregnancy patients.
Student – Newman – Keuls (SNK) test was used in comparison of every combination of group pairs (fresh versus natural FET cycle, fresh versus artificial
FET cycle and natural FET versus artificial FET cycle) for uterine peristaltic
wave frequency as well as serum progesterone. Inter-observer agreement
of uterine peristaltic wave frequency was evaluated with intraclass correlation
coefficient. Categorical variables were compared by the x 2 test. Binary logistic regression analysis (enter) was conducted to test for association between
demographic variables and clinical pregnancy outcome. The cut-off value of
uterine peristalsis in predicting clinical pregnancy outcome was identified by
ROC curve analysis.
Results
The mean age of this population was 29.1 + 3.5 years and the duration of
infertility ranged from 1–15 years (mean + SD: 4.5 + 2.9). A total of
144 patients had primary infertility and 148 had secondary infertility.
The intraclass correlation coefficient was 0.988 for inter-observer
agreement of uterine peristaltic wave frequency, meaning that the agreement between the two readers was very good.
The demographic characteristics of the study subjects according to
clinical pregnancy outcomes are detailed in Table I. No difference was
found between the two groups, except for the serum progesterone concentration on the day of embryo transfer.
All of the patients were subjectively divided into five groups according
to uterine peristaltic wave frequency on embryo transfer day: ≤1.0, 1.1 –
2.0, 2.1–3.0, 3.1– 4.0 and .4.0 waves/min. Most patients were distributed into group 1.1 –2.0 and 2.1– 3.0. The clinical pregnancy rate was the
highest when no more than 2.0 waves/min were observed before
embryo transfer and it decreased with increasing wave frequency thereafter, with a dramatic decrease when .3.0 waves/min were observed
(Table II).
As shown in Table III, uterine peristaltic wave frequencies of nonpregnancy patients were significantly higher than that of clinical pregnancy patients no matter whether they underwent fresh embryo transfer, natural FET or artificial FET cycles, respectively. Additionally, the
uterine peristaltic wave frequency before embryo transfer seemed to
be a little lower in the fresh cycles (1.80 + 0.77 waves/min) than in
FET cycles (natural FET 2.05 + 0.80 waves/min and artificial FET
2.15 + 0.81 waves/min). But the differences in the comparison of
every combination of group pairs were not significantly different. Eight
patients were diagnosed with ectopic pregnancy in our study, and the
uterine peristaltic wave frequency of those patients showed a higher
trend compared with those with intrauterine pregnancy (2.21 + 1.20
versus 1.73 + 0.65 waves/min), although the difference did not reach
statistical significance (P ¼ 0.29).
Binary logistic regression analysis revealed that the uterine peristaltic
wave frequency on the day of embryo transfer was inversely related to
the clinical pregnancy rate. Women with high uterine peristaltic wave frequency were less likely to get pregnant than those with a relatively low
Table I Demographic comparison of pregnancy group versus non-pregnancy group.
Characteristic
Clinical pregnancy (n 5 156)
Non-pregnancy (n 5 136)
P-value
.............................................................................................................................................................................................
Age (year)
29.1 + 3.4
29.0 + 3.7
0.720a
Duration of infertility (year)
4.2 + 2.9
4.8 + 3.0
0.102a
Fresh cycle
95 (60.9)
71 (52.2)
0.084b
Natural FET cycle
38 (24.4)
31 (22.8)
Treatment cycle (%)
Artificial FET cycle
23 (14.7)
34 (25.0)
Basal serum FSH (IU/l)
6.4 + 2.2
6.3 + 2.0
0.790a
Basal serum LH (IU/l)
5.2 + 3.2
5.5 + 4.0
0.473a
Basal serum E2 (pg/ml)
41.2 + 29.7
40.5 + 38.1
0.854a
Serum E2 on embryo transfer day (pg/ml)
1068.3 + 973.0
947.1 + 903.6
0.273a
Serum P on embryo transfer day (ng/ml)
56.3 + 11.5
52.8 + 15.2
0.030a
Fresh cycle
58.3 + 9.3
59.0 + 7.2
0.582a
Natural FET cycle
53.2 + 13.6
48.4 + 16.4
0.188a
Artificial FET cycle
53.0 + 14.5
43.8 + 20.0
0.049a
Endometrium thickness on embryo transfer day (mm)
11.3 + 2.7
11.2 + 3.0
0.761a
Good-quality embryo rate (%)
68.6 + 22.9
72.9 + 21.9
0.104a
a
Two-sample t-test.
Pearson x 2.
b
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Uterine peristalsis and pregnancy rates
Table II Clinical pregnancy outcomes of different uterine peristaltic wave frequency groups.
Uterine peristaltic wave
frequency (waves/min)
n
Clinical pregnancy
Non-pregnancy
Clinical pregnancy rate (%)
x2
P
.............................................................................................................................................................................................
≤1.0
39
23
16
58.97
1.1– 2.0
118
75
43
63.55
2.1– 3.0
117
57
60
48.71
3.1– 4.0
16
1
15
6.25
2
0
2
0.00
.4.0
Table III Comparison of uterine peristaltic wave
frequencies between clinical pregnancy
non-pregnancy women in different cycles.
Cycles
Uterine peristaltic wave frequency
(waves/min)
and
b
1.69 + 0.69
Natural FET
1.82 + 0.66
1.95 + 0.85
2.34 + 0.86
Odds
ratio
95% CI
P
........................................................................................
Age
Non-pregnancy
(n 5 136)
........................................................................................
Fresh embryo
transfer
,0.001
Table IV Binary logistic regression analysis of factors
potentially associated with the occurrence of clinical
pregnancy.
P
.....................................................
Clinical pregnancy
(n 5 156)
23.0
0.033
Duration of infertility
0.033
1.03
0.96– 1.12
0.405
20.072
0.93
0.85– 1.02
0.125
Basal serum FSH
20.005
1.00
0.88– 1.13
0.942
Basal serum LH
20.046
0.96
0.89– 1.03
0.230
0.006
Basal serum E2
0.002
1.00
0.99– 1.01
0.649
Serum E2 on embryo
transfer day
0.000
1.00
1.00– 1.00
0.261
Serum P on embryo
transfer day
0.016
1.02
1.00– 1.04
0.139
Endometrium thickness
on embryo transfer day
0.033
1.03
0.94– 1.14
0.492
Artificial FET
1.82 + 0.59
2.38 + 0.87
0.010
Total
1.74 + 0.67
2.14 + 0.88
,0.001
wave frequency. The other demographic characteristics included in the
analysis were not significantly associated with the chance of clinical pregnancy (Table IV). The cut-off value of uterine peristalsis was 2.45 waves/
min in predicting clinical pregnancy outcome.
The follow-up showed that up to now, of the 156 clinically pregnant
cases, 70 cases ended up with live birth, 52 pregnancies were still in
ongoing, 9 cases were lost of follow-up, 8 cases had surgery to terminate
ectopic pregnancies, 13 cases underwent spontaneous abortion and
4 cases had induced abortion because of fetal malformation or
complication.
Discussion
In this prospective cohort study, we found a significant, independent association between uterine peristaltic wave frequency on the day of
embryo transfer and clinical pregnancy outcomes. To the best of our
knowledge, this is the first comprehensive study which included both
fresh cycles, natural FET cycles and artificial FET cycles to further
explore the possible role of uterine peristalsis in embryo implantation.
The demographic characteristics of the study subjects were comparable (P . 0.05) between the pregnancy and non-pregnancy groups,
except for serum progesterone levels on the day of embryo transfer
(P ¼ 0.030) (Table I). Although the serum progesterone level was significantly different between the groups, they were both .40 ng/ml which is
much higher than the physiological level of mid-luteal phase (5.97–
14.15 ng/ml) in a natural cycle (John et al., 2008). Furthermore, logistic
regression analysis showed that the serum progesterone level on the day
of embryo transfer did not influence the clinical pregnancy rate in our
Good-quality embryo rate
20.006
0.99
0.98– 1.01
0.277
Types of ART cycles
20.251
0.78
0.49– 1.23
0.279
Uterine peristaltic wave
frequency on embryo
transfer day
20.714
0.49
0.34– 0.70
,0.001
Clinical pregnancy outcome was the dependent binary variable with clinical pregnancy
coded as 1 (positive) and non-pregnancy coded as 0 (negative). b , 0 and OR , 1
means clinical pregnancy outcome is inclined to be negative.
study, implying that the luteal support was adequate for pregnancy occurrence (Table IV).
Before embryo transfer, uterine peristalsis of most patients was maintained at a low level of ,3.0 waves/min, similar to the phenomenon
observed in a natural cycle (IJland et al., 1997a,b; Bulletti et al., 2000). In
line with this, the clinical pregnancy rate was much higher in these patients
compared with those with a frequency of .3.0 waves/min, indicating a
beneficial effect of low frequency uterine peristalsis on pregnancy
(Table II). Our result is in accordance with the study of Fanchin et al.
(1998), who also found a stepwise decrease in clinical pregnancy rates
with increasing uterine contractions before embryo transfer (53, 46, 23
and 14% for group ≤3.0, 3.1–4.0, 4.1–5.0 and .5.0, respectively).
The discrepancy in grouping may be attributed to inter-subject, observer
and cycle differences. It is noteworthy that in our previous study (Zhu et al.,
2014), the uterine peristalsis of those who expelled the transferred fluid
was also .3.0 waves/min. Thus, the result obtained in this study, together
with previously published studies, suggested that patients with the uterine
1242
peristalsis of ,3.0 waves/min before embryo transfer have a better
chance of becoming pregnant.
Our current findings also confirmed that embryo transfer cycles which
ended with successful pregnancy showed less uterine peristalsis before
embryo transfer than non-pregnant cycles (Table III), consistent previous
research (IJland et al., 1997a). It may be because the intense uterine peristalsis adversely affects embryo migration after embryo transfer and
extrudes it out of the uterine cavity, resulting in implantation failure or
ectopic pregnancy. Recently, the application of oxytocin antagonists to
selectively decrease the uterine activity was applied with success (Pierzynski et al., 2007; Moraloglu et al., 2010; Pierzynski, 2011). Other research has also tried to improve pregnancy rates by suppressing
uterine peristalsis with various agents (Moon et al., 2004; Nakai et al.,
2008; Kido et al., 2009; Xu et al., 2013). However molecular mechanisms
modulating uterine peristalsis around the implantation window are
awaiting further study which may contribute to an improvement in endometrial receptivity and pregnancy rates. The incidence of ectopic pregnancy in this population was 2.7%, similar to the reported ectopic rate
following assisted reproductive technologies (Schippert et al., 2012). Although the uterine peristaltic wave frequency was a little higher in the
ectopic pregnancy group than those with intrauterine pregnancy, the difference was not significant. This may be due to the uneven distribution of
sample size in the ectopic pregnancy group (8 cases) and intrauterine
pregnancy group (148 cases).
However, it was contrary to our expectation that the uterine peristaltic wave frequency on the day of embryo transfer showed an uptrend in
fresh, natural FET and artificial FET cycles, although the differences for
comparison of each combination of group pairs did not reach statistical
significance. Previous investigators have found that progesterone had
an inhibitory action on mediating uterine peristalsis (Fanchin et al.,
1998; Mueller et al., 2006; Zhu et al., 2012). In the present study,
serum progesterone levels on the day of embryo transfer were 58.6 +
8.5, 51.0 + 15.0 and 47.5 + 18.4 ng/ml for fresh, natural FET and artificial FET cycles. Statistical analysis showed that the serum progesterone
levels in the fresh cycles were significantly different from that in the
natural FET and artificial FET cycles, while the difference between the
natural FET and artificial FET cycles was not significant. The decreasing
supraphysiological serum progesterone may only partly account for
the uptrend of uterine peristalsis, since we found that uterine peristalsis
was not correlated with supraphysiological concentrations of progesterone in our previous study (Zhu et al., 2012). Another reasonable explanation might be the endogenous corpus luteal function in different cycles.
In a fresh cycle, controlled ovarian stimulation was applied to obtain a
cohort of co-dominant follicles, and multiple corpora lutea were
formed after the collection of oocytes. But in a natural FET cycle, only
one corpus luteum produces progesterone after ovulation; an artificial
cycle is totally dependent upon on exogenous luteal support. In our
study, even though high doses of progesterone were given to the patients
of all cycles reaching supraphysiological concentrations of serum progesterone, the function of local progesterone derived from corpus luteum
could not be underestimated. The utero-ovarian counter-current
system (Einer-Jensen, 1988; Kunz et al., 1998) plays an important role
in local endocrine regulation, especially in guiding sperm transport preferentially into the oviduct ipsilateral to the dominant follicle (Kunz et al.,
1996, 1998; Wildt et al., 1998; Kissler et al., 2004). In addition, gestational
sacs inclined to locate within the uterine horn ipsilateral to the corpus
luteum are also closely related to the utero-ovarian counter-current
Zhu et al.
system (Kunz et al., 2006). Therefore, we have reason to believe that
multiple corpora luteum in fresh cycles secreted more progesterone
which was transferred into the uterus via the utero-ovarian countercurrent system, providing more effective function than the FET cycles
which relied on systemic progesterone.
The uterine peristaltic wave frequency before embryo transfer in the
non-pregnant group was 2.14 + 0.88 waves/min, which seemed to be
moderate for embryo implantation. Nevertheless, if the embryo transfer
procedure is taken into consideration, uterine peristalsis might be
enhanced thereafter (Lesny et al., 1998; Zhu et al., 2014). In the
present study, we did not observe uterine peristalsis after embryo transfer in case any possible negative effect disturbed embryo implantation or
caused psychological stress for the patients. In our previous study, an approximate 36% increase in uterine peristalsis was observed after mock
embryo transfer, no matter whether the fluid was kept inside the
uterine cavity or extruded outside (Zhu et al., 2014). When we take a
rough estimate of the uterine peristalsis after embryo transfer in the
present study accordingly, it would be 2.91 waves/min. ROC curve analysis showed that the cut-off value of uterine peristalsis was 2.45 waves/
min in predicting clinical pregnancy outcome, which was a medium
between 2.14 and 2.91 waves/min. This deduction sheds light on the
predictive validity of the cut-off value and places it as a promising quantitative marker of uterine receptivity and pregnancy outcome in an
embryo transfer cycle. Moreover, binary logistic regression analysis
demonstrated that the association between uterine peristaltic wave frequency before embryo transfer and clinical pregnancy was independently
significant (odds ratio: 0.49; 95% confidence interval: 0.34 –0.70,
P , 0.001). We believe that further investigations are necessary to
testify to the effectiveness of uterine peristalsis in predicting clinical pregnancy before definitive conclusions can be drawn.
Subjective and objective methods were both applied in uterine peristaltic wave counting. Although several studies (Fanchin et al., 1998;
Oczeretko et al., 2006; Meirzon et al., 2011) have explored objective
methods to reduce the influence of the subjective factor, the complicated
approach and professional technology requirement prohibits their widespread use and application. It is also noteworthy that computer analysed
results do not deserve complete trust since a subtle movement of the
ultrasound probe may induce a false wave for analysis which could be
avoided by dynamic analysis of uterine peristalsis video. Furthermore,
comparisons of counting uterine peristaltic wave frequencies of accelerated images and other objective methods have shown that they are
equivalent (Ayoubi et al., 2001; Nakai et al., 2004). Thus, with the rich
experience accumulated in our preliminary experiments and previous
studies, we chose the classic and convenient method to assess uterine
peristalsis.
One limitation of the present study was the lack of uterine peristaltic
wave type analysis which is also an important parameter to assess uterine
activity. Previous studies (Kunz et al., 1996; Leyendecker et al., 1996;
IJland et al., 1997a; Fanchin et al., 1998; Bulletti et al., 2000; Nakai
et al., 2008; Zhu et al., 2012) have reached a consensus on the percentage
distribution of uterine peristalsis wave types in menstrual cycle, i.e. cervicofundal and fundocervical waves took a predominant and second position, respectively, with other types showing lower proportions.
Nevertheless, it was too complicated to tell the definite or even possible
function of each type. We speculate that the cervicofundal waves may
counteract the effect of waves of other types and function predominantly. Thus, we focused on the frequency of uterine peristalsis in the present
Uterine peristalsis and pregnancy rates
study and did not analyse the uterine peristalsis wave types. In order to
clarify the function of uterine peristalsis of different wave types, we think
it would be better to design a more rigorous study in the future.
In conclusion, the uterine peristaltic wave frequency before embryo
transfer was inversely related to the clinical pregnancy in fresh and
frozen-thawed embryo transfer cycles. Uterine peristalsis of ,3.0
waves/min before embryo transfer indicates a favourable pregnancy
outcome. This may represent a convenient, although invasive, indicator
of uterine receptivity and pregnancy outcome in an embryo transfer cycle.
Authors’ roles
L.Z. contributed to the study design, transvaginal ultrasonographic scans,
data analysis and drafting of the manuscript. H.S.C. performed the
follow-up studies and statistical analysis of the data. L.X. participated in
the acquisition and analysis of data. Y.P.L. participated in the study conception and design as well as the embryo transfer procedure. All authors
contributed to the production of the manuscript.
Funding
The study is supported by Hunan Provincial Innovation Foundation for
Postgraduates.
Conflict of interest
The authors declare that they have no competing interests in this study.
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