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Q2 Article
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3 bs_bs_query The changing pattern of uterine contractions before

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5 bs_bs_query and after fresh embryo transfer and its relation to

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7 bs_bs_query clinical outcome

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Q1 Cathy Hoi Sze Chung, Alice Wai Yee Wong, Carol Pui Shan Chan,
10 bs_bs_query Sotirios H Saravelos, Grace Wing Shan Kong, Lai Ping Cheung,
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Q3 Jacqueline Pui Wah Chung, Tin Chiu Li *
12 bs_bs_query Department of Obstetrics and Gynaecology, 1E, Block EF, Prince of Wales Hospital, Shatin, Hong Kong
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15 bs_bs_query Dr Chung is a Clinical Professional Consultant at the Department of Obstetrics and Gynaecology, The Chinese
16 bs_bs_query University of Hong Kong. She is further subspecializing in the field of reproductive medicine and is currently un-
17 bs_bs_query dergoing overseas training in the UK. Her research interests are assisted reproductive technology and implantation
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Q4 failure.

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20 bs_bs_query A B S T R A C T
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22 bs_bs_query In this prospective cohort study of 286 women undergoing fresh embryo transfer after IVF, uterine contraction frequency and direction were measured
23 bs_bs_query before (–5 min), 5 min after (+5 min) and 60 min after (+60 min) embryo transfer. Mean ± SD uterine contraction frequency at −5 min was 1.8 ± 1.1 con-
24 bs_bs_query tractions per min, increasing significantly (P < 0.05) to 2.0 ± 1.1 at +5 min, and returning back to baseline 1.8 ± 1.1 at +60 min. At −5 min, the proportion
25 bs_bs_query of women the with retrograde, antegrade, indeterminate direction and absent contractions were 33%, 44%, 17% and 6%; at +5 min, 40%, 42%, 13%
26 bs_bs_query and 5%, and at +60 min, 42%, 38%, 14% and 6%. No significant change was observed in the proportion of direction at these three time points. Logistic
27 bs_bs_query regression analysis showed live birth rate was significantly reduced in older women (P = 0.035) and in those with higher uterine contraction frequency
28 bs_bs_query at +5 min (P = 0.006). Frequency of uterine contraction immediately after embryo transfer (+5 min) seemed to be a significant predictor of IVF outcome
29 bs_bs_query and may help to identify women who could benefit from the use of muscle relaxant therapy to improve outcome.
30 bs_bs_query © 2016 Published by Elsevier Ltd on behalf of Reproductive Healthcare Ltd.

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33 bs_bs_query * Corresponding author.

34 bs_bs_query E-mail address: tinchiu.li@gmail.com (TC Li).
35 bs_bs_query http://dx.doi.org/10.1016/j.rbmo.2016.12.011
36 bs_bs_query 1472-6483/© 2016 Published by Elsevier Ltd on behalf of Reproductive Healthcare Ltd.

Please cite this article in press as: Cathy Hoi Sze Chung, et al., The changing pattern of uterine contractions before and after fresh embryo transfer and its relation to clinical
outcome, Reproductive BioMedicine Online (2016), doi: 10.1016/j.rbmo.2016.12.011
 ARTICLE IN PRESS
2 REPRODUCTIVE BIOMEDICINE ONLINE ■■ (2016) ■■–■■

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ceding cycle. In the antagonist protocol, Cetrorelix (Cetrotide, Merck 96

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38 bs_bs_query Introduction Serono, Germany) or Ganirelix (Orgalutran, MSD, Ireland) was started 97
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once oestradiol was greater than 800 pmol/l or the leading follicle 98
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40 bs_bs_query Several studies have suggested that excessive uterine contractions was greater than 14 mm. Ovarian stimulation was started using HMG 99
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41 bs_bs_query at the time of embryo transfer are associated with a reduced chance (Pergonal, Serono, Aubonne/Switzerland) or recombinant FSH (Gonal- 100
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42 bs_bs_query of successful implantation in natural (Ijland et al., 1997) and stimu- F, Serono, Aubonne/Switzerland; or Puregon, Organon, Holland) 101
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43 bs_bs_query lated (Fanchin et al., 1998; Zhu et al., 2014a) cycles. In natural cycles, ranging from 150 to 450 IU/day according to patients’ age, ovarian 102
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44 bs_bs_query Ijland et al. (1997) found that endometrial activity in conception cycles reserve test and ovarian response. Ovarian response was moni- 103
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45 bs_bs_query was less than that of non-conception cycles. In stimulated cycles, tored by transvaginal ultrasonography and serum oestradiol 104
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46 bs_bs_query Fanchin et al. (1998) observed that uterine contraction frequency im- measurements from stimulation day 6 onwards. An injection of 5000 IU 105
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47 bs_bs_query mediately before embryo transfer was inversely related to implantation of HCG was given once three or more mature follicles were 18 mm 106
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48 bs_bs_query rate and clinical pregnancy rate. The latter finding was confirmed by or wider in diameter and transvaginal oocyte retrieval was carried 107
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49 bs_bs_query a subsequent study involving both fresh and frozen embryo cycles (Zhu out 36 h later. Embryo transfer was carried out 3 days after oocyte 108
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50 bs_bs_query et al., 2014a), in which uterine contraction frequencies in women who retrieval and surplus embryos were cryopreserved. 109
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51 bs_bs_query conceived were significantly lower than that of women who did not Serum LH and oestradiol were measured on the day of ovulation 110
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52 bs_bs_query conceive. trigger whereas oestradiol and progesterone level were measured 111
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53 bs_bs_query Little, however, is known about how uterine contraction fre- on the day of embryo transfer. Vaginal progesterone (Crinone gel 8% 112
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54 bs_bs_query quency and direction change after embryo transfer and to what extent daily, Merck Serono, or Endometrin 100 mg BD, Ferring) was given 113
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55 bs_bs_query these changes affect clinical outcome. In this prospective cohort study, as luteal phase support after the embryo transfer until the day of the 114
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56 bs_bs_query the effect of an embryo transfer procedure on both the frequency and pregnancy test (16 days after oocyte retrieval). If the pregnancy test 115
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57 bs_bs_query direction of uterine contractions was examined at 5 min and 60 min was positive, transvaginal ultrasonography was carried out 2 weeks 116
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58 bs_bs_query after the procedure and to relate the results to live birth rate (LBR) later to determine the number of gestational sacs as well as fetal vi- 117
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59 bs_bs_query in women undergoing fresh embryo transfer after IVF treatment. ability. Clinical pregnancy was defined as the presence of one or more 118
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intrauterine gestational sacs 4 weeks after oocyte retrieval. Miscar- 119
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riage was defined as a non-viable pregnancy after ultrasonographic 120

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61
visualization of an intrauterine gestational sac before 24 weeks of ges- 121
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62 bs_bs_query Materials and methods tation. Live birth was defined as a viable delivery at or after 24 weeks 122
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of gestation. 123
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64 bs_bs_query Patients 124

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Embryo transfer 125
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66 Women undergoing IVF between July 2011 and August 2013 in the
126
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67 Assisted Reproductive unit of Prince of Wales Hospital, Chinese Uni-

After the first 3-min transabdominal ultrasound scan to measure the 127
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68 versity of Hong Kong, were invited to participate in this study. Women

frequency and direction of any uterine contractions, patients were 128
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69 were recruited during their treatment cycle and the enrolment was
placed in a lithotomy position. A bivalve speculum was inserted into 129
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70 confirmed on the day of embryo transfer. Exclusion criteria for re-

the vagina to expose the cervix, and the cervical mucus was cleared 130
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71 cruitment included women aged 40 years or over; congenital uterine

using a moist cotton wool stick. One or two embryos were loaded into 131
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72 anomaly or acquired uterine pathology such as myoma, adenomyo-

an atraumatic Cook Sydney embryo transfer catheter (Cook Medical, 132
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73 sis or endometrial polyp; presence of a hydrosalpinx; and repeated

Indiana, USA) by the embryologist and then transferred transcervically 133
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74 implantation failure (failed to conceive after three or more embryo

to the middle of the uterine cavity aiming for a distance of 15 mm from 134
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75 transfer cycles with good-quality embryos). Congenital uterine anomaly

the fundus by one of the three experienced reproductive medicine 135
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76 and acquired uterine pathology were excluded by two-dimensional

subspecialists under ultrasound guidance. The total duration of the 136
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77 ultrasound scan in all cases, and one or more additional investiga-

inner and outer catheter insertion, along with the difficulty in trans- 137
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78 tions, including hysterosalpingogram, three-dimensional ultrasound

fer and the subjective feeling about the urge of micturition (mild, 138
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79 scan, two- and three-dimensional saline-infusion-sonography, hys-

moderate and severe) at the time of embryo transfer were recorded. 139
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80 teroscopy and laparoscopy in selected cases. Women with a history

140
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81 of mid-trimester loss or recurrent pregnancy loss were routinely

Uterine contraction measurement 141
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82 offered three-dimensional saline-infusion-sonography. The study was

142
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83 approved by the Joint Chinese University of Hong Kong – New Ter-

On the day of embryo transfer, all recruited women underwent trans- 143
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84 ritories East Cluster Clinical Research Ethics Committee on 23 July

abdominal ultrasonography with the use of a General Electric Voluson 144
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85 2011 (registration number CRE 2011.303) and all patients com-

730 Expert series ultrasound machine and a RAB4-8L, 4.0–8.0 MHz 145
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86 pleted a written informed consent before enrolment. We previously

3D/4D probe (GE Medical Systems Kretztechnik GmbH & Co, Austria), 146
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87 reported on the migration of the embryo flash (air bubble) after embryo
which was connected to a dedicated monitor and DVD player for re- 147
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88 transfer in this cohort (Saravelos et al., 2016).

cording in live time. To reduce bias and variability, all examinations 148
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89 bs_bs_query
were carried out using the same machine and by a single operator 149
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90 bs_bs_query Ovarian stimulation cycle (CPSC). Uterine contraction measurements were assessed at three 150
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91 bs_bs_query different time points: 5 min before (–5 min), 5 min after (+5 min), and 151
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92 bs_bs_query Pituitary suppression was achieved either by long (luteal) GnRHa or 1 h after (+60 min) the embryo transfer procedure. A mid-sagittal plane 152
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93 bs_bs_query antagonist protocol. For long down-regulation protocol, Buserelin nasal of uterine image was taken and a video of the live ultrasound image 153
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94 bs_bs_query spray (Suprecur, Hoechst, Germany) 600 μg daily was administered was recorded for at least 3 min. This was then subsequently analysed 154
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95 bs_bs_query for at least 14 days starting from the mid-luteal phase of the pre- for both uterine contraction frequency and uterine contraction di- 155
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Please cite this article in press as: Cathy Hoi Sze Chung, et al., The changing pattern of uterine contractions before and after fresh embryo transfer and its relation to clinical
outcome, Reproductive BioMedicine Online (2016), doi: 10.1016/j.rbmo.2016.12.011
 ARTICLE IN PRESS
REPRODUCTIVE BIOMEDICINE ONLINE ■■ (2016) ■■–■■ 3

156 bs_bs_query rection. Patients had bed rest after embryo transfer until the last
Table 1 – Demographic characteristics of patients (n = 283). 215 bs_bs_query

157 bs_bs_query ultrasound assessment was completed.

158 bs_bs_query For contraction frequency (number of contractions per minute), Clinical pregnancy 216 bs_bs_query

159 bs_bs_query the recorded video was accelerated fourfold and the number of con- Yes (n = 119) No (n = 164) 217 bs_bs_query

160 bs_bs_query tractions was measured over 3 min by manual method (Nakai et al., Age (year)a,c 34.6 ± 3.0 35.1 ± 3.4 218 bs_bs_query

161 bs_bs_query 2004; Zhu et al., 2014a). All the measurements throughout the study Body mass indexa,c 21.5 ± 3.4 21.1 ± 2.7 219 bs_bs_query

162 bs_bs_query were made by a single experienced observer (CPSC). The intra- Smokerb,d 13 (10.9%) 12 (7.5%) 220 bs_bs_query

163 bs_bs_query observer variability was validated using Cohen kappa statistics based Type of infertilityb,d 221 bs_bs_query

164 bs_bs_query on repeated measurement of 30 video-recorded cases (kappa value Primary 68 (57.1%) 87 (53.0%) 222 bs_bs_query

Secondary 51 (42.9%) 77 (47.0%) 223

165 for uterine contraction frequency was 0.8 whereas, that for contrac-
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Main cause of infertilityb,d 224 bs_bs_query

166 tion direction was 0.9).

225
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Ovulatory problem 6 (5.0%) 7 (4.3%) bs_bs_query

167 bs_bs_query During the observation period, the contraction directions were de- Tubo-peritoneal 62 (52.1%) 81 (49.4%) 226 bs_bs_query

168 bs_bs_query scribed as follows: retrograde (from the cervix to the fundus); Male 35 (29.4%) 47 (28.7%) 227 bs_bs_query

169 bs_bs_query antegrade (from the fundus to the cervix); indeterminate; and nil/ Endometriosis 8 (6.7%) 12 (7.3%) 228 bs_bs_query

170 bs_bs_query absent (no contraction/direction). Unexplained 8 (6.7%) 17 (10.4%) 229 bs_bs_query

Baseline FSH (IU/L)a,c 7.1 ± 1.5 7.5 ± 2.4 230

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2.5 ± 1.6 2.9 ± 1.8

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Baseline LH (IU/L)a,c 231 bs_bs_query

172 bs_bs_query Power calculation Baseline E2 (pmol/L)a,c 82.0 ± 80.2 76.2 ± 45.9 232 bs_bs_query

173 bs_bs_query
Treatment protocolb,d 233 bs_bs_query

174 bs_bs_query Fanchin et al. (1998) reported that high versus low contraction fre- Long 98 (82.4%) 133 (81.1%) 234 bs_bs_query

175 bs_bs_query quencies resulted in a change in clinical pregnancy rate from 14% Antagonist 21 (17.6%) 31 (18.9%) 235 bs_bs_query

176 bs_bs_query to 53%. We have chosen a more conservative estimate of an in- Oestradiol on day of 11877.9 ± 6691.4 10639.2 ± 6304.5 236 bs_bs_query

HCG (pmol/L)a,c 237

177 bs_bs_query crease from 20% to 35%. Using the median contraction frequency to bs_bs_query

Number of mature 8.6 ± 3.2 8.1 ± 3.7 238 bs_bs_query

178 divide participants into two groups with high and low uterine con-
oocytesa,cretrieved per patienta,c 239
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179 bs_bs_query traction frequencies, and accepting an alpha value of 0.05 and a power Number of embryos transferred 1.9 ± 0.3 1.8 ± 0.4 240 bs_bs_query

180 bs_bs_query of 80%, a sample size of 276 participants would be required. per patienta,c 241 bs_bs_query

181 bs_bs_query
Oestradiol on day of embryo 5928.8 ± 3030.8 5629.1 ± 3720.5 242 bs_bs_query

182 bs_bs_query Statistical analysis transfer (pmol/L)a,c 243 bs_bs_query

Progesterone on day of embryo 304.2 ± 140.3 261.2 ± 133.5 244

183
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transfer (nmol/L)a,c,f 245 bs_bs_query

184 Statistical Package for Social Sciences (SPSS) version 20 for Windows
Endometrial thickness on day of 11 ± 0.2 11 ± 0.3 246
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185 bs_bs_query (IBM Corp., USA) was used for data analysis. Normality testing was embryo transfer (mm)a,c 247 bs_bs_query

186 bs_bs_query conducted, and data distribution for uterine contraction frequency, Outer catheter insertion (s)a,c 154.8 ± 28.4 153.8 ± 32.2 248 bs_bs_query

187 bs_bs_query age and body mass index (BMI) were all confirmed to be close to Inner catheter insertion (s)a,c 51.7 ± 14.2 52.0 ± 17.6 249 bs_bs_query

188 bs_bs_query normal distribution, with skewness measurement of 0.16 for uterine Assessment of embryo transfer 250 bs_bs_query

189 bs_bs_query contraction frequency at −5 min, 0.16 for uterine contraction fre- procedureb,d 251 bs_bs_query

Easy 112 (94.1%) 157 (95.7%) 252 bs_bs_query

190 bs_bs_query quency at +5 min and 0.19 for uterine contraction frequency at +60 min;
Difficult 7 (5.9%) 7 (4.3%) 253 bs_bs_query

191 bs_bs_query −0.22 for age and −0.38 for BMI. Continuous data were expressed in Operatorb,e 254 bs_bs_query

192 bs_bs_query mean ± SD and were compared using Student’s t-test, analysis of vari- A (11 years’ experience in 10 (8.4%) 4 (2.4%) 255 bs_bs_query

193 bs_bs_query ance and Pearson’s correlation test. Categorical data were expressed embryo transfer) 256 bs_bs_query

194 bs_bs_query in number (%) and compared using chi-squared and Fisher’s exact B (3 years’ experience in 52 (43.7%) 79 (48.2%) 257 bs_bs_query

195 bs_bs_query test. Logistic regression analysis was used to ascertain which vari- embryo transfer) 258 bs_bs_query

196 bs_bs_query ables were predictive of uterine contraction frequency and live birth. C (2 years’ experience in 57 (47.9%) 81 (49.4%) 259 bs_bs_query

embryo transfer) 260

A two-sided value of P < 0.05 was considered as statistically significant.
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197
Urinary urgencyb,e 261
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Mild 39 (32.8%) 39 (23.8%) 262 bs_bs_query

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Moderate 29 (24.4%) 59 (36.0%) 263 bs_bs_query

Severe 51 (42.9%) 66 (40.2%) 264

Results
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200 bs_bs_query

a
Presented as mean ± SD. 265
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b
Presented as number (percentage). 266 bs_bs_query

202 bs_bs_query Of a total of 311 eligible patients, 15 were subsequently excluded from c
Student’s t-test. 267 bs_bs_query

203 bs_bs_query the study owing to cancellation of embryo transfer (nine with all d
Chi-square test. 268 bs_bs_query

e
204 bs_bs_query embryos being cryopreserved owing to risk of ovarian hyperstimu- Chi-square test in a 2x3 contingency table. 269 bs_bs_query

f
205 bs_bs_query lation syndrome, three with no viable embryo, two with symptoms of The only variable with statistical significant difference (P = 0.009) between 270 bs_bs_query

206 genital tract infection and one patient withdrew from the study for the two groups; all other variables had a P-value > 0.05. 271 bs_bs_query

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207 bs_bs_query personal reasons). As a result, 286 patients were enrolled in the study.
273
208 Among the 286 participants, 119 (42%) had a clinical pregnancy and
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209 bs_bs_query three (1%) had ectopic pregnancy, which were analysed separately. The mean frequency of uterine contractions for all women at −5 min 274 bs_bs_query

210 bs_bs_query Overall, 93 women had live birth achieving a LBR of 32.5%. The de- (baseline) was 1.8 ± 1.1 contractions per min, which increased sig- 275 bs_bs_query

211 bs_bs_query mographic characteristics of women who did or did not have a clinical nificantly (P < 0.05) to 2.0 ± 1.1 at +5 min. The frequency decreased 276 bs_bs_query

212 bs_bs_query pregnancy are presented in Table 1. No significant differences were to 1.8 ± 1.1 at +60 min, which was significantly (P < 0.05) lower than 277 bs_bs_query

213 bs_bs_query found between the two groups except for the serum progesterone level that at +5 min but similar to that at −5 min. In terms of contraction 278 bs_bs_query

214 bs_bs_query on the day of embryo transfer (P = 0.009) (Table 1). direction, the proportion of women with retrograde, antegrade, 279 bs_bs_query

Please cite this article in press as: Cathy Hoi Sze Chung, et al., The changing pattern of uterine contractions before and after fresh embryo transfer and its relation to clinical
outcome, Reproductive BioMedicine Online (2016), doi: 10.1016/j.rbmo.2016.12.011
 ARTICLE IN PRESS
4 REPRODUCTIVE BIOMEDICINE ONLINE ■■ (2016) ■■–■■

280 bs_bs_query Figure 1 – A comparison of uterine contraction frequency (number of uterine contractions per minute) in the pregnant and non-pregnant
281 bs_bs_query groups at 3 selected time points. Presented as mean ± SE. a, Significant difference (P < 0.05) to 5 min before embryo transfer (non-
282 bs_bs_query pregnant group); b, significant difference (P < 0.05) to 5 min after embryo transfer (pregnant group); *, significant difference between
283 bs_bs_query pregnant and non-pregnant groups (P < 0.05); **Significant difference between pregnant and non-pregnant groups (P < 0.01); no other
284 bs_bs_query significant differences within or between the groups were observed.
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286 bs_bs_query indeterminate direction and absent contractions were 33%, 44%, 17% Clinical outcomes according to contraction frequency 320 bs_bs_query

287 bs_bs_query and 6%, respectively, at −5 min; 40%, 42%, 13% and 5%, respec- 321 bs_bs_query

288 bs_bs_query tively, at +5 min; and 42%, 38%, 14% and 6%, respectively, at +60 min. In our study, the median uterine contraction frequency after embryo 322 bs_bs_query

289 bs_bs_query No significant change in the proportion of the four different direc- transer was found to be 2.0; this value was selected as cut-off to divide 323 bs_bs_query

290 bs_bs_query tions was observed between −5 min and +5 min, between −5 min and women into two groups with high and low uterine frequency. The clini- 324 bs_bs_query

291 bs_bs_query +60 min and between +5 min and +60 min when all women were cal outcomes of women with high (two or more) and low (less than 325 bs_bs_query

292 bs_bs_query analysed together. two) contraction frequency at different time points are shown in 326 bs_bs_query

293 bs_bs_query
Table 2. The LBR was significantly higher in women with low uterine 327 bs_bs_query

294 bs_bs_query Uterine contractions in pregnant versus non-pregnant groups contraction frequency at all time points (P = 0.032 at −5 min, P = 0.003 328 bs_bs_query

295 bs_bs_query
at +5 min and P = 0.022 at +60 min). 329 bs_bs_query

296 bs_bs_query The contraction frequency at three time points for women in the preg- 330 bs_bs_query

297 bs_bs_query nant and non-pregnant groups are analysed in Figure 1. The mean Clinical outcomes according to contraction direction 331 bs_bs_query

298 bs_bs_query contraction frequency was consistently higher in the non-pregnant 332 bs_bs_query

299 bs_bs_query group than that in pregnant group at all time points (1.8 ± 1.1, 2.1 ± The clinical outcomes of women with different contraction direction 333 bs_bs_query

300 bs_bs_query 1.1, 2.0 ± 1.1 versus 1.6 ± 1.1, 1.8 ± 1.1, 1.6 ± 1.1, respectively) with at the three time points are shown in Table 3. The direction of uterine 334 bs_bs_query

301 bs_bs_query the differences being statistically significant at +5 min (P < 0.05) and contraction at +60 min, but not −5 min and +5 min, significantly af- 335 bs_bs_query

302 bs_bs_query at +60 min (P < 0.01). fected the clinical pregnancy rate (P = 0.002) and LBR (P = 0.004), with 336 bs_bs_query

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305 bs_bs_query Table 2 – A comparison of the clinical outcomes, progesterone and oestradiol levels on the day of embryo transfer according to high
306 bs_bs_query (≥2/min) and low (<2/min) uterine contraction frequency at three different time points.
307 bs_bs_query Time from Uterine Clinical P- Live birth P- Miscarriage P- Progesterone P- Oestradiol P-
308 bs_bs_query embryo contraction pregnancy value rate, n (%) value rate value (nmol/L) value (pmol/L) value
309 bs_bs_query transfer frequency rate, n (%)
310 bs_bs_query −5 min Low 70/147 (47.6) NSa 57/147 (38.8) 0.032a 13/70 (18.6) NSa 291 ± 149 NSb 5876.1 ± 3770.5 NSb
311 bs_bs_query High 49/136 (36.0) 36/136 (26.5) 13/49 (26.5) 267.4 ± 125.1 5629.1 ± 3051
312 bs_bs_query +5 min Low 62/122 (50.8) 0.011a 52/122 (42.6) 0.003a 10/62 (16.1) NSa 295.4 ± 153.1 NSb 5936.4 ± 4054.5 NSb
313 bs_bs_query High 57/161 (35.4) 41/161 (25.5) 16/57 (28.1) 267.3 ± 124.5 5617.44 ± 2874.4
314 bs_bs_query +60 min Low 75/148 (50.7) 0.003a 58/148 (39.2) 0.022a 17/75 (22.7) NSa 289.4 ± 144.7 NSb 6050.9 ± 4151.5 NSb
315 bs_bs_query High 44/135 (32.6) 35/135 (25.9) 9/44 (20.5) 268.7 ± 130.5 5431.2 ± 2389.1
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a
Fisher’s exact test.
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b
Student’s t-test.
318 bs_bs_query NS, not statistically significant.
319 bs_bs_query

Please cite this article in press as: Cathy Hoi Sze Chung, et al., The changing pattern of uterine contractions before and after fresh embryo transfer and its relation to clinical
outcome, Reproductive BioMedicine Online (2016), doi: 10.1016/j.rbmo.2016.12.011
 ARTICLE IN PRESS
REPRODUCTIVE BIOMEDICINE ONLINE ■■ (2016) ■■–■■ 5

337 bs_bs_query Table 3 – A comparison of clinical outcomes, progesterone level and oestradiol level on the day of embryo transfer according to the
338 bs_bs_query direction of contraction at three different time points.
339 bs_bs_query Time from Contraction Clinical P- Live birth P- Miscarriage P- Progesterone P- Oestradiol P-
340 bs_bs_query embryo direction pregnancy value rate, n (%) value rate, n (%) value (nmol/L) value (pmol/L) value
341 bs_bs_query transfer rate, n (%)
342 bs_bs_query –5 min Retrograde 38/92 (41.3) NSa 33/92 (35.9) NSa 5/38 (13.2) NSa 279.2 ± 125.9 NSb 5960.7 ± 3588.4 NSb
343 bs_bs_query Antegrade 54/124 (43.5) 40/124 (32.3) 14/54 (25.9) 277.0 ± 130.1 5475.4 ± 2960.0
344 bs_bs_query Indeterminate 19/49 (38.8) 14/49 (28.6) 5/19 (26.3) 286.8 ± 169.5 5440.4 ± 3925.8
345 bs_bs_query Nil 8/18 (44.4) 6/18 (33.3) 2/8 (25.0) 312.3 ± 170.8 6439.1 ± 4204.6
346 bs_bs_query +5 min Retrograde 50/114 (43.9) NSa 37/114 (32.5) NSa 13/50 (26.0) NSa 281.7 ± 133.2 NSb 6178.7 ± 4262.2 NSb
347 bs_bs_query Antegrade 47/119 (39.5) 39/119 (32.8) 8/47 (17.0) 269.0 ± 122.1 5509.6 ± 2944.3
348 bs_bs_query Indeterminate 14/37 (37.8) 10/37 (27.0) 4/14 (28.6) 306.2 ± 195.6 5249.5 ± 2639.2
349 bs_bs_query Nil 8/13 (61.5) 7/13 (53.8) 1/8 (12.5) 286.5 ± 146.0 5312.7 ± 2556.6
350 bs_bs_query +60 min Retrograde 49/120 (40.8) .002a 36/120 (30.0) .004a 13/49 (26.5) NSa 296.1 ± 148.2 NSb 6336.7 ± 4432.3 NSb
351 bs_bs_query Antegrade 34/106 (32.1) 27/106 (25.5) 7/34 (20.6) 267.8 ± 123.4 5303.6 ± 2751.9
352 bs_bs_query Indeterminate 24/40 (60.0) 20/40 (50.0) 4/24 (16.7) 276.7 ± 157.7 5005.2 ± 2326.8
353 bs_bs_query Nil 12/17 (70.6) 10/17 (58.8) 2/12 (16.7) 244.2 ± 101.1 5780.4 ± 2178.5
354 bs_bs_query
a
Chi-square test in 4 × 2 contingency table.
355 bs_bs_query
b
Analysis of variance.
356 bs_bs_query NS, not statistically significant.
357 bs_bs_query

358 bs_bs_query

359 bs_bs_query the highest clinical pregnancy rate and LBR found in women with no +60 min (P < 0.001), suggesting that a particular type of contraction 396 bs_bs_query

360 bs_bs_query contractions, followed by indeterminate direction. direction before embryo transfer was likely to persist afterwards. 397 bs_bs_query

361 bs_bs_query 398 bs_bs_query

362 bs_bs_query Association between contraction frequency and direction Logistic regression analysis 399 bs_bs_query

363 bs_bs_query among different time points 400 bs_bs_query

364 bs_bs_query The various possible factors affecting uterine contraction frequency 401 bs_bs_query

365 bs_bs_query The association between contraction frequency and direction at dif- were examined by binary logistic regression analysis using the fol- 402 bs_bs_query

366 bs_bs_query ferent time points are shown in Tables 4 and 5, respectively. A lowing parameters as independent variables: duration of inner and 403 bs_bs_query

367 bs_bs_query significant association was found between the contraction fre- outer catheter insertion, difficulty in transfer, urge of micturition, op- 404 bs_bs_query

368 bs_bs_query quency at −5 min and +5 min (P < 0.001) and between −5 min and erators and serum progesterone level on day of embryo transfer. The 405 bs_bs_query

369 bs_bs_query +60 min (P < 0.001), suggesting that women who had higher contrac- only variable selected as having significant affect on uterine con- 406 bs_bs_query

370 bs_bs_query tion frequency before embryo transfer were more likely to have higher traction frequency for all three time points (P = 0.029 at −5 min, P = 407 bs_bs_query

371 bs_bs_query contraction frequency at +5 min and +60 min after embryo transfer. 0.004 at +5 min and P = 0.010 at +60 min) was the urge of micturition. 408 bs_bs_query

372 bs_bs_query A significant association was also found between the contraction di- In addition, the various possible factors affecting LBR was also 409 bs_bs_query

373 bs_bs_query rection at −5 min and +5 min (P < 0.001) and between −5 min and examined with the use of forward stepwise logistic regression 410 bs_bs_query

374 bs_bs_query

375 bs_bs_query

376 bs_bs_query Table 4 – The association between the frequency of contractions at −5 min before embryo transfer and the frequency at +5 min and
377 bs_bs_query +60 min after the transfer.
378 bs_bs_query +5 min P-value +60 min P-value
379 bs_bs_query Contraction frequency Contraction frequency
380 bs_bs_query <2/min ≥2/min <2/min ≥2/min
381 bs_bs_query –5 mins Contraction frequency <2/min 102 45 <.001 a
110 37 <.001a
382 bs_bs_query ≥2/min 20 116 38 98
383 bs_bs_query
a
Chi-squared test.
384 bs_bs_query

385 bs_bs_query

386 bs_bs_query Table 5 – The association between the direction of contractions at −5 min before embryo transfer and the direction at +5 min and
387 bs_bs_query +60 min after the transfer.
388 bs_bs_query +5 min P-value +60 min P-value
389 bs_bs_query Retrograde Antegrade Indeterminate Nil Retrograde Antegrade Indeterminate Nil
390 bs_bs_query –5 min Retrograde 48 32 8 4 <0.001a 55 23 11 3 <0.001a
391 bs_bs_query Antegrade 38 70 13 3 39 68 14 3
392 bs_bs_query Indeterminate 19 13 16 1 20 12 14 3
393 bs_bs_query Nil 9 4 0 5 6 3 1 8
394 bs_bs_query
a
Chi-squared test in a 4 × 4 contingency table.
395 bs_bs_query

Please cite this article in press as: Cathy Hoi Sze Chung, et al., The changing pattern of uterine contractions before and after fresh embryo transfer and its relation to clinical
outcome, Reproductive BioMedicine Online (2016), doi: 10.1016/j.rbmo.2016.12.011
 ARTICLE IN PRESS
6 REPRODUCTIVE BIOMEDICINE ONLINE ■■ (2016) ■■–■■

411 bs_bs_query analysis using the following parameters as independent variables: age, implantation over the lower part of uterine cavity (Ijland et al., 1996; 470
bs_bs_query

412 bs_bs_query BMI, years of infertility, baseline FSH, serum level of oestradiol and Kunz et al., 2006). 471
bs_bs_query

413 bs_bs_query progesterone and also endometrial thickness on the day of embryo 472
bs_bs_query

414 bs_bs_query transfer, number of embryo being transfer, urge of micturition, total Factors affecting contractions 473
bs_bs_query

415 bs_bs_query duration of inner and outer catheter insertion, operators, whether 474
bs_bs_query

416 bs_bs_query embryo transfer was difficult, and the uterine contraction frequen- The characteristics (frequency and direction) of uterine contraction 475
bs_bs_query

417 bs_bs_query cies and directions at the three time points. The uterine contraction at the time of embryo transfer may be affected by a number of factors. 476
bs_bs_query

418 bs_bs_query at +5 min after embryo transfer was chosen in the first step (P = 0.006), 477
bs_bs_query

419 bs_bs_query and age was chosen at the second step (P = 0.035). Thereafter, no Uterine pathology 478
bs_bs_query

420 bs_bs_query other individual variable was selected which significantly improved Uterine contractions originate from the myometrium which in turn 479
bs_bs_query

421 bs_bs_query the prediction model. is influenced by any intrinsic uterine pathology such as fibroids (Yoshino 480
bs_bs_query

422 bs_bs_query
et al., 2010) or adenomyosis (Guo et al., 2013). In our study, however, 481
bs_bs_query

423 bs_bs_query Ectopic pregnancy we excluded women with known uterine pathology and therefore the 482
bs_bs_query

424 bs_bs_query
observations are based on a selected group of women with appar- 483
bs_bs_query

425 bs_bs_query Three women in our study had ectopic pregnancy and their mean ently normal uterus. 484
bs_bs_query

426 bs_bs_query uterine contraction frequencies before and after embryo transfer were 485
bs_bs_query

427 bs_bs_query not significantly different from those with intrauterine pregnancy (1.8 Embryo transfer procedure 486
bs_bs_query

428 bs_bs_query versus 1.6 at −5 min, 1.2 versus 1.8 at +5 min and 2.0 versus 1.6 at 487
bs_bs_query

429 bs_bs_query +60 min, respectively). For the direction of uterine contraction, one By assessing the frequency of contraction before and after embryo 488
bs_bs_query

430 bs_bs_query out of three (33%) ectopic pregnancies was associated with a per- transfer, we observed that the transfer procedure did cause an in- 489
bs_bs_query

431 bs_bs_query sistent retrograde uterine contraction at +5 and also +60 min, crease in frequency of uterine contractions from 1.8 per min at baseline 490
bs_bs_query

432 bs_bs_query compared with 27% in women with intrauterine pregnancy. The number to 2.0 per min at 5 min after the embryo transfer procedure, which 491
bs_bs_query

433 bs_bs_query of participants in the ectopic group was too small to permit proper represent an increase of 11%. The increment was not as high as 36% 492
bs_bs_query

434 bs_bs_query statistical analysis. as shown in another study during mock embryo transfer (Zhu et al., 493
bs_bs_query

2014b). Furthermore, we observed two important differences in the 494

435
bs_bs_query

bs_bs_query

response between the pregnant and non-pregnant groups (Figure 1). 495
bs_bs_query

436 bs_bs_query

First, the increment observed at 5 min after embryo transfer was sig- 496
bs_bs_query

437 bs_bs_query Discussion nificant only in the non-pregnant group (14.7%) but not in the pregnant 497
bs_bs_query

438 bs_bs_query
group (8.5%). Second, the increase in the uterine contraction fre- 498
bs_bs_query

439 bs_bs_query Our study seems to have confirmed the findings of two earlier studies, quency was transient in the pregnant group as it had returned to the 499
bs_bs_query

440 bs_bs_query which found an association between uterine contraction and clinical pre-transfer level at +60 min after the procedure. On the contrary, 500
bs_bs_query

441 bs_bs_query outcome (Fanchin et al., 1998; Zhu et al., 2014a). Several important in the non-pregnant group, in addition to the contraction frequency 501
bs_bs_query

442 bs_bs_query differences, however, have been found between the earlier studies being higher throughout the period of observation, the contraction fre- 502
bs_bs_query

443 bs_bs_query and the current one. First, both previous studies examined uterine quency at +60 min remained higher than the pre-transfer level. On 503
bs_bs_query

444 bs_bs_query contractions before embryo transfer, whereas our study examined the basis of these findings, we conclude that a transient increase in 504
bs_bs_query

445 bs_bs_query the contractions both before and after embryo transfer. Specifi- uterine contraction frequency is a common phenomenon in women 505
bs_bs_query

446 bs_bs_query cally, we measured uterine contraction at three time points around undergoing embryo transfer, but a persistently high contraction fre- 506
bs_bs_query

447 bs_bs_query the time of embryo transfer (–5 min, +5 min and +60 min). Second, quency long after the procedure is associated with a poorer outcome. 507
bs_bs_query

448 bs_bs_query both previous studies related their observations to pregnancy rate In addition, a difficult embryo transfer procedure has been re- 508
bs_bs_query

449 bs_bs_query whereas we related our observations to LBR, which we think repre- ported to be associated with a poorer outcome by causing excessive 509
bs_bs_query

450 bs_bs_query sents an improvement. We found that LBR was significantly affected or aberrant uterine contractions (Goudas et al., 1998; Spandorfer et al., 510
bs_bs_query

451 bs_bs_query by both the frequency and direction of uterine contraction after embryo 2003). In our study, we experienced difficulty in the embryo transfer 511
bs_bs_query

452 bs_bs_query transfer. Third, in contrast to earlier studies that used transvaginal procedure in 14 cases (4.9%). In all these difficult cases, we had to 512
bs_bs_query

453 bs_bs_query scan to measure uterine contraction and frequency, we used trans- use a pair of tenaculum to hold onto the cervix to enable the intro- 513
bs_bs_query

454 bs_bs_query abdominal scan to obtain the measurements, mainly because we duction of the embryo transfer catheter. The pregnancy rate in this 514
bs_bs_query

455 bs_bs_query wished to reduce any possible cervical stimulation to a minimum which group of women, however, did not seem to be significantly compro- 515
bs_bs_query

456 bs_bs_query could affect uterine contractions especially as multiple measure- mised. Furthermore, logistic regression analysis suggested that 516
bs_bs_query

457 bs_bs_query ments were made within an hour. We also considered that women contraction frequency was significantly affected only by the sensa- 517
bs_bs_query

458 bs_bs_query were less anxious about transabdominal scan and so were more likely tion of urge of micturition experienced by patients, but not whether 518
bs_bs_query

459 bs_bs_query to participate in the study when transabdominal scan was used. the embryo transfer procedure was easy or difficult or the experi- 519
bs_bs_query

460 bs_bs_query In natural cycles, the frequency and direction of uterine contrac- ence of operators carrying out the embryo transfer. It seems from 520
bs_bs_query

461 bs_bs_query tions vary depending on the stage of the cycle. The frequency reaches our study that an over-distended bladder is directly related to ex- 521
bs_bs_query

462 bs_bs_query a peak just before the time of ovulation (Ijland et al., 1996) with a pre- cessive uterine contraction during embryo transfer and should be 522
bs_bs_query

463 bs_bs_query dominantly cervicofundal wave form (Zhu et al., 2012). This is believed avoided. 523
bs_bs_query

464 bs_bs_query to facilitate an effective upward migration of sperm to fallopian tubes 524
bs_bs_query

465 bs_bs_query (Abramowicz and Archer, 1990; Kunz et al., 1996). Afterwards, the con- Progesterone 525
bs_bs_query

466 bs_bs_query tractile activity was shown to decrease, thereby providing an optimal Hormonal factors, especially progesterone, has been found to affect 526
bs_bs_query

467 bs_bs_query environment for implantation (Ijland et al., 1997). During the luteal uterine contractions (Fanchin et al., 1998). In our study, no signifi- 527
bs_bs_query

468 bs_bs_query phase, some cervicofundal waves were observed, and it has been pos- cant difference was found in serum progesterone level between the 528
bs_bs_query

469 bs_bs_query tulated that this might reduce the chance of improper embryo pregnant and non-pregnant groups but, in contrast to earlier studies, 529
bs_bs_query

Please cite this article in press as: Cathy Hoi Sze Chung, et al., The changing pattern of uterine contractions before and after fresh embryo transfer and its relation to clinical
outcome, Reproductive BioMedicine Online (2016), doi: 10.1016/j.rbmo.2016.12.011
 ARTICLE IN PRESS
REPRODUCTIVE BIOMEDICINE ONLINE ■■ (2016) ■■–■■ 7

530 bs_bs_query we were unable to confirm a significant association between pro- and after the transfer procedure (Table 4). It supports the notion that 590
bs_bs_query

531 bs_bs_query gesterone level on the day of embryo transfer and the frequency of high contractile activity seems to be intrinsic in a significant propor- 591
bs_bs_query

532 bs_bs_query uterine contractions. Reference to the results in Tables 1 and 2 sug- tion of participants rather than primarily due to the transfer procedure 592
bs_bs_query

533 bs_bs_query gested that the mean progesterone level on the day of embryo transfer itself. 593
bs_bs_query

534 bs_bs_query was in the supra-physiological range (304.2 nmol/L in pregnant group Among the three time points studied, uterine contraction fre- 594
bs_bs_query

535 bs_bs_query and 261.2 nmol/L in non-pregnant group) compared with natural quency at 5 min after embryo transfer seemed to be most predictive 595
bs_bs_query

536 bs_bs_query cycles; it is possible that at the supra-physiological range, the effect of outcome, although, as shown in Table 2, the measurements at all 596
bs_bs_query

537 bs_bs_query of a modest amount of change will not significantly affect the con- three time points were significantly different between those who did 597
bs_bs_query

538 bs_bs_query tractions. The arbitrary grouping of uterine contractions into high and or did not have a live birth. By contrast, the direction of uterine con- 598
bs_bs_query

539 bs_bs_query low categories may have also introduced a degree of bias. It is also traction (Table 3) before embryo transfer and at 5 min after embryo 599
bs_bs_query

540 bs_bs_query of interest that we did not observe a significant difference in proges- transfer did not significantly affect the LBR, although the direction 600
bs_bs_query

541 bs_bs_query terone level between those who did or did not have a live birth. Taken of uterine contraction at 60 min after embryo transfer did signifi- 601
bs_bs_query

542 bs_bs_query together, the findings suggested that the relationship between pro- cantly affect LBR, with those having no contraction and indeterminate 602
bs_bs_query

543 bs_bs_query gesterone level, uterine contraction, pregnancy rate and LBR is a rather direction achieving the highest LBR (59% and 50%, respectively) com- 603
bs_bs_query

544 bs_bs_query complex one, partly because uterine contraction frequency is only one pared with those having retrograde and antegrade direction (30% and 604
bs_bs_query

545 bs_bs_query of the many effects of progesterone which can influence the clinical 26%, respectively). On further analysis with the use of logistic re- 605
bs_bs_query

546 bs_bs_query outcome; for example, it is well recognised that progesterone affects gression analysis as mentioned above, we found that only uterine 606
bs_bs_query

547 bs_bs_query endometrial receptivity which may in turn affect pregnancy via a dif- contraction frequency at +5 min (and age) significantly affected LBR 607
bs_bs_query

548 bs_bs_query ferent mechanism. but not contraction direction. It suggests that contraction direction 608
bs_bs_query

549 bs_bs_query had a weaker predictive value than contraction frequency and it loses 609
bs_bs_query

550 bs_bs_query Timing of transfer its significance once the contraction frequency has been included in 610
bs_bs_query

551 bs_bs_query The mean ± SD uterine contraction frequency observed in our pa- the regression model. 611
bs_bs_query

552 bs_bs_query tients was 1.8 ± 1.1 per minute at −5 min before embryo transfer. One Wave direction was also observed at different time points in this 612
bs_bs_query

553 bs_bs_query earlier study reported on a higher mean value of 4.3 ± 0.1 (Fanchin study. In contrast to previous findings (Zhu et al., 2012) in which ret- 613
bs_bs_query

554 bs_bs_query et al., 1998); in that study, however, the contraction frequency was rograde (from the cervix to the fundus) waves were the dominant wave 614
bs_bs_query

555 bs_bs_query measured on day 2 after oocyte retrieval, whereas all the embryo direction (80%) before embryo transfer, such dominance was not ob- 615
bs_bs_query

556 bs_bs_query transfer procedures in our study were carried out on day 3 after oocyte served in our study. Instead, there was a roughly equal proportion 616
bs_bs_query

557 bs_bs_query retrieval. It is recognized that wave frequency reduces significantly (40%) of retrograde and antegrade direction observed before and after 617
bs_bs_query

558 bs_bs_query from the day of oocyte retrieval onwards (Ayoubi et al., 2003). the transfer procedure. No significant association was observed 618
bs_bs_query

559 bs_bs_query between wave direction at −5 min and +5 min and (a) pregnancy 619
bs_bs_query

560 bs_bs_query Factors affecting live birth rate outcome and (b) progesterone level. Significant differences were ob- 620
bs_bs_query

561 bs_bs_query served in LBR between various wave directions at +60 min after the 621
bs_bs_query

562 bs_bs_query In considering clinical outcome, the LBR was found to be signifi- transfer procedure (Table 3) with the highest rate among women with 622
bs_bs_query

563 bs_bs_query cantly affected by two independent variables: age of the woman and no contractions/direction followed by those with indeterminate di- 623
bs_bs_query

564 bs_bs_query uterine contraction frequency at 5 min after the embryo transfer pro- rection. From these findings, it seems that a quiescent uterus or one 624
bs_bs_query

565 bs_bs_query cedure. Although women aged 40 years or over were excluded from with contractions of no definite direction seems to provide a more 625
bs_bs_query

566 bs_bs_query our study, younger women in our study population had a higher LBR, stable environment for embryo implantation. 626
bs_bs_query

567 bs_bs_query which is consistent with earlier reports that age is an important vari- We realized that this study, which involved serial ultrasound mea- 627
bs_bs_query

568 bs_bs_query able affecting LBR. On the other hand, the ability of uterine contraction surements over 60 min, required a high degree of commitment and 628
bs_bs_query

569 bs_bs_query to predict LBR has not been previously reported, despite a number compliance from our patients. In routine clinical practice, espe- 629
bs_bs_query

570 bs_bs_query of earlier studies suggesting a possible link between pregnancy rate cially in a busy IVF clinic, it may not be feasible to keep patients in 630
bs_bs_query

571 bs_bs_query and uterine contractions (Fanchin et al., 1998 and Zhu et al., 2014a). bed for an hour after the embryo transfer procedure. Nevertheless, 631
bs_bs_query

572 bs_bs_query Furthermore, the result of logistic regression analysis in our study we considered it important to make original observations on how 632
bs_bs_query

573 bs_bs_query suggested that uterine contraction at 5 min after embryo transfer was uterine contraction frequency and direction changes after embryo 633
bs_bs_query

574 bs_bs_query more predictive of LBR than contraction frequency immediately before transfer and their relationship to clinical outcome, which enabled us 634
bs_bs_query

575 bs_bs_query embryo transfer and other parameters often considered to affect clini- to discover that the most informative measurement was the one at 635
bs_bs_query

576 bs_bs_query cal outcome, such as the duration of infertility, basal FSH level and 5 min after the embryo transfer procedure, which was the only one 636
bs_bs_query

577 bs_bs_query BMI. One possible explanation for why the contraction frequency at significantly correlated to live birth. 637
bs_bs_query

578 bs_bs_query 5 min after embryo transfer was more predictive of outcome than the 638
bs_bs_query

579 bs_bs_query contraction frequency immediately before embryo transfer is that the Clinical implication 639
bs_bs_query

580 bs_bs_query measurement at +5 min represents the baseline myometrial activ- 640
bs_bs_query

581 bs_bs_query ity immediately before transfer and also the response of the uterus Recently, interest in targeting the adverse effect of excessive uterine 641
bs_bs_query

582 bs_bs_query to the embryo transfer procedure. contractions on pregnancy outcome by the use of a uterine muscle 642
bs_bs_query

583 bs_bs_query relaxant around the time of embryo transfer has increased (Chou 643
bs_bs_query

584 bs_bs_query Comparison of results among the three time points et al., 2011; Moraloglu et al., 2010; Ng et al., 2014). Although a 644
bs_bs_query

585 bs_bs_query recent double-blinded randomized controlled trial conducted in an 645

bs_bs_query

586 bs_bs_query A particular strength of our study is that we made serial measure- unselected group of infertility patients (Ng et al., 2014) showed that 646
bs_bs_query

587 bs_bs_query ments of uterine contraction, at three different time points. Our atosiban treatment did not improve treatment outcomes, it remains 647
bs_bs_query

588 bs_bs_query observation showed that most women seem to have either consis- plausible that only women with high uterine contraction frequency 648
bs_bs_query

589 bs_bs_query tently high or consistently low uterine contraction frequencies before immediately after embryo transfer would benefit from Atosiban 649
bs_bs_query

Please cite this article in press as: Cathy Hoi Sze Chung, et al., The changing pattern of uterine contractions before and after fresh embryo transfer and its relation to clinical
outcome, Reproductive BioMedicine Online (2016), doi: 10.1016/j.rbmo.2016.12.011
 ARTICLE IN PRESS
8 REPRODUCTIVE BIOMEDICINE ONLINE ■■ (2016) ■■–■■

650 bs_bs_query treatment, but not those with low contraction frequency. Future Goudas, V., Hammitt, D., Damario, M., Session, D., Singh, A., Dumesic, 699
bs_bs_query

651 bs_bs_query trials designed to examine the possible benefit of Atosiban or other D., 1998. Blood on the embryo transfer catheter is associated with 700
bs_bs_query

652 bs_bs_query muscle relaxants should consider selecting only those with high decreased rates of embryo implantation and clinical pregnancy with 701
bs_bs_query

the use of in vitro fertilization-embryo transfer. Fertil. Steril. 70, 702

653 uterine contraction frequency immediately after embryo transfer
bs_bs_query

bs_bs_query

878–882. 703
bs_bs_query

654 bs_bs_query for inclusion in the study. Guo, S.W., Mao, X., Ma, Q., Liu, X., 2013. Dysmenorrhea and its severity 704
bs_bs_query

655 bs_bs_query In conclusion, we found that low uterine contraction frequency at are associated with increased uterine contractility and 705
bs_bs_query

656 bs_bs_query 5 min after embryo transer was associated with a significantly higher overexpression of oxytocin receptor (OTR) in women with 706
bs_bs_query

657 bs_bs_query LBR. The contraction frequency at 5 min after embryo transfer was symptomatic adenomyosis. Fertil. Steril. 99, 231–240. 707
bs_bs_query

658 bs_bs_query more predictive of clinical outcome than the measurements made im- Ijland, M.M., Evers, J.L., Dunselman, G.A., Hoogland, H.J., 1996. 708
bs_bs_query

659 bs_bs_query mediately before or 60 min after embryo transfer. The findings are Subendometrial contractions in the nonpregnant uterus: an 709
bs_bs_query

ultrasound study. Eur. J. Obstet. Gynecol. Reprod. Biol. 70, 23–24. 710
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660 not only of prognostic value but may also help to identify women who
711
bs_bs_query

Ijland, M.M., Evers, J.L., Dunselman, G.A., Volovics, L., Hoogland, H.J., bs_bs_query

661 bs_bs_query could benefit from the use of muscle relaxant therapy to improve the 1997. Relation between endometrial wavelike activity and 712
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662 bs_bs_query outcome. fecundability in spontaneous cycles. Fertil. Steril. 67, 492–496. 713
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663 bs_bs_query
Kunz, G., Beil, D., Deininger, H., Wildt, L., Leyendecker, G., 1996. The 714
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dynamics of rapid sperm transport through the female genital tract: 715
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664 bs_bs_query A R T I C L E I N F O evidence from vaginal sonography of uterine peristalsis and 716
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665 bs_bs_query

hysterosalpingoscintigraphy. Hum. Reprod. 11, 627–632. 717

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666 bs_bs_query Article history: Kunz, G., Beil, D., Huppert, P., Leyendecker, G., 2006. Control and 718
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667 bs_bs_query Received 31 May 2016 function of uterine peristalsis during the human luteal phase. 719
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668 bs_bs_query Received in revised form 1 December 2016 Reprod. Biomed. Online 13, 528–540. 720
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669 bs_bs_query Accepted 2 December 2016 Moraloglu, O., Tonguc, E., Var, T., Zeyrek, T., Batioglu, S., 2010. 721
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Treatment with oxytocin antagonists before embryo transfer may 722

670
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bs_bs_query Declaration: The authors report no

increase implantation rates after IVF. Reprod. Biomed. Online 21, 723
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671 bs_bs_query financial or commercial conflicts of 338–343. 724

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672 interest. Nakai, A., Togashi, K., Kosaka, K., Kido, A., Hiraqa, A., Fujiwara, T., 725
673
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bs_bs_query
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674 bs_bs_query
Koyama, T., Fujii, S., 2004. Uterine peristalsis: comparison of 726
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675 bs_bs_query Keywords:

transvaginal ultrasound and two different sequences of cine MR 727
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imaging. J. Magn. Reson. Imaging 20, 463–469. 728

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676 contraction direction

729
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Ng, E.H., Li, R.H., Chen, L., Lan, V.T., Tuong, H.M., Quan, S., 2014. A bs_bs_query

677 bs_bs_query contraction frequency randomized double blind comparison of atosiban in patients 730
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678 bs_bs_query embryo transfer undergoing IVF treatment. Hum. Reprod. 29, 2687–2694. 731
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679 bs_bs_query pregnancy rate Saravelos, S.H., Wong, A.W., Chan, C.P., Kong, G.W., Cheung, L.P., 732
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680 bs_bs_query uterine contractions Chung, C.H., Chung, J.P., Li, T.C., 2016. Assessment of the embryo 733
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flash position and migration with 3D ultrasound within 60 min of 734

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681 bs_bs_query
embryo transfer. Hum. Reprod. 31, 591–596. 735
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Spandorfer, S.D., Goldstein, J., Navarro, J., Veeck, L., Davis, O.K., 736
682
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Please cite this article in press as: Cathy Hoi Sze Chung, et al., The changing pattern of uterine contractions before and after fresh embryo transfer and its relation to clinical
outcome, Reproductive BioMedicine Online (2016), doi: 10.1016/j.rbmo.2016.12.011