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Department of Gynaecology and Obstetrics, Research Institute ‘Amsterdam Reproduction and Development’, Amsterdam UMC, location AMC and VU Medical Center, Postbus 22660, 1100 ZD Amsterdam, The Netherlands
Department of Gynaecology and Obstetrics, Research Institute ‘Amsterdam Reproduction and Development’, Amsterdam UMC, location AMC and VU Medical Center, Postbus 22660, 1100 ZD Amsterdam, The Netherlands
Department of Gynaecology and Obstetrics, Catharina Hospital, Postbus 1350, 5602 ZA Eindhoven, The NetherlandsDepartment of Gynaecology and Obstetrics, University Hospital, C Heymanslaan 10, 9000 Ghent, Belgium
Department of Gynaecology and Obstetrics, Research Institute ‘Amsterdam Reproduction and Development’, Amsterdam UMC, location AMC and VU Medical Center, Postbus 22660, 1100 ZD Amsterdam, The Netherlands
Contraction amplitude is significantly elevated in women with a caesarean scar defect
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There is a strong positive correlation between niche sizes and contraction amplitude
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Changes in uterine peristalsis may play an important role in niche-related problems
Abstract
Research question
What is the effect of a caesarean scar defect on subendometrial contractions?
Design
Prospective cohort study in a Dutch medical centre including women with a niche in the uterine caesarean section scar. Data were compared with controls without a caesarean section scar. All women underwent a 5-min recording by transvaginal ultrasound at four phases in the menstrual cycle: during menses; late follicular; early luteal; or late luteal phase. Uterine motion analysis was evaluated by dedicated speckle tracking using two-dimensional optical flow. Main outcome: amplitude of the subendometrial contractions.
Results
Thirty-one women with a niche in the uterine scar and 11 controls, matched for menstrual cycle phase, were included. The amplitude of the subendometrial contractions was significantly higher in women with a niche compared with controls during all phases of the menstrual cycle (menses P < 0.001; late follicular P < 0.001; early luteal P = 0.028; late luteal P = 0.003). Velocity was lower in women with a niche during late follicular phase only (P = 0.012). A positive correlation between niche sizes (depth, length) and amplitude of subendometrial contractions was found.
Conclusion
Subendometrial contractions were affected in women with a niche in the caesarean section scar compared with women who had not undergone a previous caesarean section. Contraction amplitude was higher and independent of the menstrual phase. These findings may cause postmenstrual spotting, dysmenorrhoea and lower implantation rates in women with a niche. Future studies should investigate this association and the underlying pathways.
) and have stimulated interest in the potential long-term morbidity of a caesarean section scar. A niche is an indentation in the uterine wall at the site of the caesarean scar, with a depth of at least 2 mm, and is associated with postmenstrual spotting and dysmenorrhoea (
). Spotting can be explained by the accumulation of blood in the niche after the menstrual period caused by mechanical outflow problems (Vervoort et al., 2015). An alternative explanation for postmenstrual spotting could be disturbed functional outflow caused by a (large) niche, with discontinuity in the myometrium leading to dysfunctional contractility of the uterine muscle (
). A niche might be the underlying cause; apart from the observed coexistence of potentially embryo toxic intrauterine fluid, dysfunctional myometrial contractions may also compromise embryo implantation (
Long-term complications of caesarean section. The niche in the scar: a prospective cohort study on niche prevalence and its relation to abnormal uterine bleeding.
The non-pregnant uterus shows different patterns of contractile activity throughout the menstrual cycle known as uterine peristalsis, originating in the subendometrial myometrium (
). Uterine peristalsis undergoes cyclic changes and occurs in the menstrual phase directed outward to expel endometrium and blood from the uterine cavity. The frequency of contractions increases as ovulation approaches. In the late follicular phase, the direction of subendometrial contractions switches inward, and is now directed from cervix to fundus. The contraction frequency further increases until ovulation to enhance transport of spermatozoa towards the ipsilateral tube of the dominant follicle. Subsequently, after ovulation and during the late luteal phase, the combination of lower frequency and lower amplitude in the uterine activity may contribute to embryo implantation in the midsection of the uterine cavity (
). The underlying physiology of uterine contractions has been studied in human uterine muscle cells, in animal models and in mathematical models to simulate the electrical, mechanical and ionic activity, but has not yet been elucidated (Garrett, 2022).
Transvaginal ultrasound (TVUS) has been proven to offer reliable information on uterine peristalsis (
Uterine contractions, however, have never been evaluated in women with a caesarean section scar defect or niche. The aim of the present study was to evaluate the amplitude of subendometrial contractions in women with a niche in the uterine caesarean section scar compared with women without a caesarean section scar.
Materials and methods
This explorative prospective cohort study (the ‘WAVE study’) was conducted at the Obstetrics and Gynaecology Department of Amsterdam UMC, Amsterdam, The Netherlands. Inclusion period was between 2018 and March 2020.
Participants
All women with a niche in the uterine caesarean section scar participated in the Niche Cohort study (CCMO – NL37922.029.11; date of approval: 12 April 2018). The aim of the Niche cohort study was to evaluate the effect of all applied types of interventions, including expectant management on niche-related symptoms and reproductive outcomes in a prospective fashion with a long-term follow-up. In this study, all women were asked to participate if they were referred to our outpatient clinic because of a niche or niche-related symptoms, such as abnormal uterine bleeding or fertility problems. Exclusion criteria included the following: age younger than 18 years; a (suspected) malignancy; uterine of cervical polyps; submucosal fibroids; atypical endometrial cells; cervical dysplasia; cervical or pelvic infection; and hydrosalphinx. For the WAVE study, women from the Niche Cohort study were included on a random base, when the researcher of this project was available and after informed consent was obtained. Women were scanned only once, if the trained researcher and the specific ultrasound machine with options to record the wave ultrasound were available. The Niche Cohort study was approved by the local Research and Ethics Committee, including the performance of transvaginal ultrasound and wave evaluation for the present study.
Data relating to controls (women without previous caesarean section and with no infertility problems) were collected at the Gynaecology Department, Catherina Hospital, Eindhoven (CCMO – NL52466.100.15; date of approval: 19 January 2018), and the results of the uterine contractions in the different phases of the menstrual cycle were reported earlier (
). Eleven controls participated. Each woman was scanned four times during each of the four selected phases of the menstrual cycle, including menses, defined as cycle day 1–7; late follicular phase (cycle day 8–14); early luteal phase (cycle day 14–17); or late luteal phase (cycle day 18 to menses).
Ultrasound evaluation
All women underwent a standardized protocol of two- and three-dimensional TVUS; general myometrium assessment was evaluated according to the MUSA guidelines (
Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group.
), including examination of the uterine corpus, myometrial walls and existence of myometrial lesions. In the case of a previous caesarean section, the niche was evaluated according to the international recommended guideline for the standard evaluation and reporting system (
) (see Figure 1 for niche evaluation) using two-dimensional ultrasound. Additionally, a 5-min TVUS recording was carried out from the uterus in the midsagittal plane, with the operator holding the probe steady (WAVE ultrasound). Each woman with a previous caesarean section was scanned by one of the trained researchers (IJ or JV). The phase of the menstrual cycle during the ultrasound was registered. Women using oral contraceptives continuously (without a stop period) were also included and registered separately as the oral contraceptive group. Women in the control group underwent four ultrasound evaluations by one experienced gynaecologist, one in each of the four selected phases of the menstrual cycle. All ultrasound scans, in both hospitals, were carried out using a Samsung WS80A ultrasound machine (Samsung Medison, Seoul, South Korea) equipped with a transvaginal V5-9 probe.
Figure 1Example of uterine niche and its measurements in an anteverted uterus, according to
using transvaginal ultrasound. (A) Niche in sagittal plane; (B) Magnification of (A). Measurements in the sagittal plane: length and depth of the niche, and residual myometrial thickness (RMT).
At inclusion, baseline characteristics and medical, obstetrical and fertility history were registered in both groups. Ultrasound features of the uterus (position, length, width) and niche characteristics were registered during their first ultrasound. Niche volume was calculated based on niche measurements (length x depth x width x 0.52) (
). All data were registered in a case report form and a digital database by the researchers. Reporting in accordance with the guideline for reporting a prospective study (STROBE) (
Finally, only the recordings in which the uterine cavity was sufficiently visible, and on which speckle tracking could be performed, were included.
Speckle tracking by using two-dimensional optical flow
For each selected TVUS recording, two grids of tracking markers with an isotropic interval in the transversal and longitudinal direction were positioned along the anterior and posterior endometrial contour of the uterine corpus and fundus to apply speckle tracking by two-dimensional optical flow (Figure 2). A single operator placed the tracking markers for all the ultrasound recordings following a standard protocol. The repeatability and reproducibility of the method were also validated (
). In women with a niche, it was not possible to measure subendometrial contractions at the site of the niche because of the (virtually) absence of the myometrium.
Figure 2Example of the two grids of tracking markers defined on the lining of the subendometrium of the anterior uterine wall (yellow tracking markers) and posterior uterine wall (red tracking markers), recorded during early luteal phase in one of the patients with a niche in a retroflected uterus.
The principle of two-dimensional optical flow is based on the assumption that the intensity (I) of a certain pixel does not change between the reference and the target frames, so that the velocity in the longitudinal ( and transversal ( directions can be represented by the intensity gradients in spatial and temporal dimensions according to the following equation:
To solve this ill-conditioned equation, Lukas et al. (1981) proposed the inclusion of the neighbouring pixels around the tracked one under the assumption of locally constant flow. The velocities in both directions are then obtained by least square estimation. This process was applied to each tracking marker in the grid frame to frame.
Transversal strain
Strain imaging is one of the most widely used approaches for measuring regional or global deformation of a muscle. Therefore, to characterize uterine contraction, transversal strain was derived from both the anterior and posterior sides of the endometrium. Transversal strain was calculated from the ratio between the variation in the distance between each pair of tracking markers in transversal direction (Figure 2) and their original distance as:
where represents the absolute distance between each pair of TMs in the transversal direction at the frame;is the original distance; and N is the total number of frames of the recording.
Uterine contractions were not the only source of motion influencing the movement of the endometrium. Other motions, either originating from different organs, such as, bowels and bladder, or caused by heartbeat, respiration and probe movement during the acquisition, affect the ultrasound recordings. Therefore, a band pass filter was applied to the transvaginal strain signals to remove the interference from these undesired motion sources. The resulting transvaginal strain signals were then analysed to extract a number of relevant features characterizing the subendometrial contraction, namely, amplitude, frequency, velocity, direction and coordination features. Below is a short description of the feature extraction. More details can be found in
Amplitude is derived from the SD of the transversal strain signals between each pair of tracking markers reflecting the degree of strain (contraction strength) of the uterine muscle during the acquisition time; this is presented in Supplementary Figure 1. As strain is unit-less and usually represented as %, its SD is also defined as %. The average of the SD results of the entire endometrium is presented.
Frequency
The frequency is estimated as the mean of the frequency spectrum (given in Hertz) of the transversal strain signals measured over the full recording (Figure 2) in the anterior and posterior uterine wall. The mean frequency is then multiplied by 60 s to derive the corresponding number of contractions per minute.
Velocity
On the basis of the transversal strain signals, a time-space representation of the uterine peristalsis waves propagating along the endometrium was created. Two-dimensional fast Fourier transform was further applied to the time-space representation within a moving time window of 20 s to derive a two-dimensional power spectrum. The temporal and spatial frequencies of the dominant peristaltic motion were then identified at the peak of the power spectrum, and the corresponding uterine peristalsis velocity was calculated as the ratio between the temporal and spatial frequency averaged over the full recording.
Direction
An energy ratio metric was derived to represent the direction of uterine peristalsis as
where and are the integral of the power spectrum over the first and second quadrant, representing the strength of cervix-to-fundus and fundus-to-cervix propagation, respectively. Here E1 and E1 were derived from the two-dimensional power spectrum calculated over the full recording. Being derived as a ratio, energy ratio is clearly unitless. For energy ratio closer to 1, then the cervix-to-fundus propagation is dominant, and vice versa.
Coordination
Similar time evolution of energy ratio, measured over a running window of 20 s, from the anterior and posterior walls was expected to reflect a coordinated and symmetric propagation. Similarity measures, such as cross correlation and mean squared error, were used to assess the similarity (coordination) between the propagation patterns (in terms of energy ratio time evolution) measured from both walls. A low mean squared error indicates similar propagation patterns and, therefore, coordination of the two walls; in fact, zero error reflects identical propagation. Similarly, also a high correlation coefficient, close to one, indicates coordination propagation, whereas lower or even negative values indicate dyscoordination.
Outcomes
The primary outcome was the amplitude of subendometrial contractions in women with a (large) niche compared with women who have not had a previous caesarean section.
Secondary outcomes included frequency and velocity of subendometrial contractions compared between the two study groups. Also, all contraction features (amplitude, frequency, velocity) were evaluated separately during the different phases of the menstrual cycle to gain insight into their cycle dependency. The direction of the subendometrial contractions was also subdivided depending on their propagation direction, cervix-to-fundus or fundus-to-cervix, and all features were also estimated for the different directions, separately. Furthermore, coordinated and symmetric propagation of the contractions were evaluated.
The influence of contraceptive use on uterine contractions is unknown. Therefore, data of women using contraceptives were analysed separately.
Statistical analysis
IBM SPSS Statistics version 26 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis. Demographic data were presented as n (%) for categorical variables and mean SD or median (interquartile range [IQR]) for continuous variables. Differences in baseline characteristics were compared using the independent sample t-test, chi-squared test or Mann–Whitney U test, depending on the type and distribution of the variables. The features of subendometrial contractions (amplitude, contraction frequency, velocity and direction) between the patients with a niche and controls were analysed with linear mixed models by which the use of multiple measurements of the same patient in the control group will be corrected. Mann–Whitney U test was used to analyse contraction features within the niche group because of non-normal distribution. Two-tailed P < 0.05 was considered statistically significant. To examine any correlation between primary outcome and niche features, the Pearson correlation coefficient (P-value) and the squared correlation coefficient (R2) were calculated, the latter ranged between 0 (no correlation) and 1 (strong correlation).
Sample size calculation
At the time of the study design, no comparable studies were available for sample size calculation. Our aim was to include (at least) 25 women with a niche to evaluate our primary outcome and preferably with an equal distribution per menstrual cycle phase.
Results
Inclusion and baseline characteristics
In total, 114 WAVE ultrasounds were carried out, 70 in women with a niche and 44 (n = 11 women) in the controls (Figure 3). In the niche group, 39 ultrasounds were excluded because they could not be analysed by using speckle tracking owing to poor image quality (n = 25), technical problems, i.e. faltering recording (n = 9) or unknown phase in the menstrual cycle (n = 5). In the control group, 41 out of 44 WAVE ultrasounds were of sufficient image quality to be analysed. Finally, 31 WAVE ultrasounds of women with a niche and 41 of the controls were analysed; 17 women during menses, 14 during late follicular, 16 during early luteal, 19 during late luteal phase and six women with continuous use of oral contraceptives. Baseline characteristics are presented in Table 1. Most women with a niche (64%) underwent one previous caesarean section. Subfertility was seen in 58% of these patients. Among the controls, 91% (10/11) had never been pregnant; one had three vaginal deliveries. One woman with a niche used thyroid hormones at time of the WAVE ultrasound; all other participants did not use any medication. Furthermore, one woman with a niche had undergone a diagnostic laparoscopy because of pain without major abnormalities 5 years before participating in this study. The controls had no relevant medical history. All underwent hormonal profile screening to exclude the presence of infertility-related problems (anovulation). Uterine size and position were not significantly different between the study groups. A large niche, defined as a niche with a residual myometrial thickness (RMT) less than 2 mm, was visible in 77% of the patients with a niche.
Available from 29 women. AVF, anteverted anteflexed uterus; BMI, body mass index (weight in kg/m2); CS, caesarean section; ICSI, intracytoplasmic sperm injection; IQR, interquartile range; IUI, intrauterine insemination; IVF, in vitro fertilisation; NA, not applicable; RMT, residual myometrial thickness; RVF, retroverted retroflexed uterus.
NA
Data are reported as mean ± SD, median (interquartile range), n (valid %) or n/total.
a Thickness of myometrium was measured at the same location where the residual myometrial thickness was measured in women with a niche.
b Available from 29 women.AVF, anteverted anteflexed uterus; BMI, body mass index (weight in kg/m2); CS, caesarean section; ICSI, intracytoplasmic sperm injection; IQR, interquartile range; IUI, intrauterine insemination; IVF, in vitro fertilisation; NA, not applicable; RMT, residual myometrial thickness; RVF, retroverted retroflexed uterus.
Subendometrial contraction features in patients with a niche compared with controls
Outcome measures of subendometrial contractions of the study groups are presented in Table 2. The mean amplitude of contractions in patients with a niche (without using oral contraceptives) was significantly higher compared with the controls (8.5%; SD ± 4.2) versus 2.9% (SD ± 1.3, P < 0.001) (Figure 4). No significant differences in frequency and velocity of subendometrial contractions were observed between the groups.
TABLE 2OUTCOME MEASURES OF SUBENDOMETRIAL CONTRACTIONS OF PATIENTS WITH A NICHE AND CONTROLS
Figure 4Mean amplitude (%) of subendometrial contractions in women with a niche (n = 25) and in controls (n = 11). **, Statistically significant difference, P < 0.001.
Subendometrial contraction features during different phases of the menstrual cycle in patients with a niche versus controls
The outcome of subendometrial contractions during the different phases of the menstrual cycle of both study groups is presented in Table 3. Mixed model analysis showed a significantly higher mean contraction amplitude of contractions in patients with a niche during all four phases of the menstrual cycle in patients with a niche compared with controls (Figure 5A). No difference was found in mean frequency of subendometrial contractions between the study groups during each phase of the menstrual cycle (Figure 5B). Mean velocity of subendometrial contractions was significantly lower only during late follicular phase in patients with a niche compared with the controls (P = 0.012).
TABLE 3OUTCOME MEASURES OF SUBENDOMETRIAL CONTRACTIONS DURING DIFFERENT PHASES OF THE MENSTRUAL CYCLE
Figure 5Features of subendometrial contractions during the four phases (menses [ME], late follicular [LF], early luteal [EL] and late luteal [LL]) of the menstrual cycle, in women with a niche (n = 25) and in controls (n = 11). (A) Mean amplitude, SD (%); (B) mean frequency, SD (contractions/min). Subendometrial contractions were evaluated in the same controls during each phase (blue line); in women with a niche, subendometrial contractions were evaluated once during one of the four phases (red dots).
Comparison of contraction features in the anterior versus posterior uterine wall and contraction direction
No significant difference was found between the number of contractions measured in cervix -to-fundus direction compared with the fundus-to-cervix direction in this group (Supplementary Figure 2).
Coordination feature by cross correlation and mean squared error in the menses and late follicular, which is a parameter to evaluate the coordination between the anterior and the posterior wall, were different between women with a niche and controls (Supplementary Figure 2). During both the menses and during the late follicular was the mean squared error of the coordination higher in women with a niche compared with controls (P = 0.200 and P = 0.454, respectively). This means that contractions between the anterior and posterior wall are less coordinated (Figure 6A and Figure 6B).
Figure 6Coordination of endometrial contractions in a health control and in a woman with a niche. (A) Strong coordinated contractions measured in a healthy control during the late follicular phase are shown. The uterine peristalsis, represented by the magnitude of transversal strain, from the anterior and posterior sides of the endometrium propagates in the same direction (from cervix to fundus) simultaneously; (B) weak coordinated contractions measured in a woman with niche are shown. No clear direction of the uterine peristalsis can be visualized.
The direction of the contractions itself was not different between women with a niche and controls.
Niche features in correlation with primary outcome
Median niche depth was 6.5 mm (5.1–9.0) and median niche length was 8.6 mm (IQR 6.5–10.6). The median RMT in patients with a niche was 1.3 mm (IQR 0–1.9). The median myometrial thickness of the controls, measured at the same location as where the RMT was measured in women with a niche, was 10.8 mm (IQR 9.2–11.6). Uterine size was comparable between the patients with a niche and controls (Table 1). There was a strong positive correlation between depth of the uterine niche and amplitude of subendometrial contractions, (Figure 7). An amplitude with a cut-off value of 5% was observed in 16 out of 20 women with a niche depth over 5 mm (80%). Furthermore, amplitude with a cut-off value of 5% was seen in 18 out of 21 women with a niche length of over 5 mm (86%) and in 17 out of 21 women with an RMT less than 3 mm (81%). An amplitude of 5% or above was not observed in any of the controls.
Figure 7Scatterplots of mean amplitude by niche depth, in women with a niche (n = 25) versus controls (n = 11).
Subendometrial contraction features in patients with a niche using oral contraceptives versus controls
The mean contraction amplitude in the women with a niche using continuous oral contraceptives use (n = 6) was significantly higher compared with the controls without a niche and without using oral contraceptives (P < 0.001); frequency and velocity were lower (P = 0.012 and P = 0.010, respectively) (Supplementary Table 1).
Discussion
Main findings
The present study is, to the best of our knowledge, the first to show that features of uterine peristalsis, measured in the subendometrial layer of the uterine corpus and fundus, differ in women with a niche in the uterine caesarean scar compared with women who have not undergone a previous caesarean section, over all phases of the menstrual cycle. The contraction amplitude was higher in women with a niche than in controls. Contractions were less coordinated during the late luteal phase and during menses. The amplitude was correlated to niche depth and length and inversely correlated to the thickness of the residual myometrium. These findings support the hypothesis that, in women with a niche, subendometrial wave patterns are disturbed during all phases of the menstrual cycle, which could lead to spotting due to suboptimal menstrual outflow and lower implantation rates.
The underlying mechanism of uterine contractions is not yet elucidated. Uterine smooth muscle cells are specialized myocytes. Coordinated contractions in a muscular organ are typically initiated and maintained by a region of pacemaker cells that modulate bioelectrical signals. Calcium (Ca2+) influx ultimately leads to an increase in extracellular Ca2+, which then leads to activation of myosin light-chain kinase and initiates the cross-bridging cycle leading to contractions of the uterine smooth muscle cells (
). Increased amplitude may originate from an increased sensitivity to Ca2+ influx. The exact relation between a niche and its effect on these contractions is unknown. We have postulated three theories for the distortion of uterine contractions and higher amplitude found in women with a niche. The first theory is that the presence of intrauterine blood in association with a niche induces stronger subendometrial contractions to expel the blood. This is supported by reports that thrombin and its receptor (protease-activated receptor, PAR1) are able to stimulate myometrial contractions, in pregnant and non-pregnant myometrial tissues (
). A second theory is that inflammation in association with the presence of a niche induces a higher amplitude. It has also been postulated that pro-inflammatory factors (like Interleukin(IL)-1β, IL-8 and cyclo-oxygenase-2) may induce uterine contractions (
). Studies, however, have also shown that pro-inflammatory cytokines (like IL-1β and tumour necrosis factor-α) reduce myoepithelial cells contraction, but these are of other origin (
). Third, we hypothesized that subendometrial contractions, starting in the direction from fundus-to-cervix, are interrupted by the defect in the anterior wall; the disturbance in electro-mechanical signal may in theory affect Ca2+ sensitivity or activation of uterine pacemaker cells. Although this mechanism is uncertain in the uterus, it has been described in case of myocardial infarction in which damaged tissue leads to arrhythmogenic waves (Francis
). Future studies are needed to elucidate the exact underlying pathways.
Clinical implication and comparison to other studies
Uterine contractions may play an important role in the success of embryo implantation. It has been previously reported that, throughout the menstrual cycle, adequate endometrial wave patterns of the uterus seem to be related to successful reproduction in natural cycles and assisted reproduction (
A niche involves a discontinuity in the uterine scar and may play a role in the aetiology of the reported lower implantation and pregnancy rates after a caesarean section compared with a women with a history of a previous vaginal delivery (
To the best of our knowledge, no other studies have reported on uterine contractions by using speckle tracking in women with a niche. Previously, an association between uterine contractions and IVF outcomes was reported by using visual inspection of uterine contractions in which no distinction was made between the different uterine layers (
conducted a 5-min digital recording of the uterus before IVF and embryo transfer in 209 infertile women and concluded that high contraction frequency hinders IVF and embryo transfer outcome, using a computer-assisted image analysis system to count the number of myometrial contractions. These results may be explained by mechanical expulsion of embryos from the uterine cavity. This is in line with the study by
who examined 37 subfertile women and found higher endometrial wavelike activity (contraction frequency) in women who did not conceive compared with women who did conceive.
used speckle tracking to evaluate uterine contractions during IVF cycles. They reported a significantly higher contraction amplitude in women without an ongoing pregnancy compared with women with an ongoing pregnancy. In the present study, we found a higher amplitude in association with a niche; both high amplitude and niche existence were identified previously as associated with lower ongoing pregnancy rates in IVF. The fact that these amplitudes were associated with the size of the niche underlines the causality of a niche and the identified subendometrial contraction features. It also fits our hypothesis that a niche may be the intermediate factor for the reported lower implantations rates in women who have undergone a previous caesarean section (
). Under physiological conditions, under the influence of progesterone, the luteal phase is characterized by a state of relative uteroquiescence, with low amplitude contractions. These may facilitate proper positioning of embryos for implantation and pregnancy (
) (Figure 8A). High amplitude combined with frequency of the uterine contraction contractions with a direction towards the cervix may induce displacement of the embryo towards the cervix in particular if combined with the presence of intra-uterine fluid. This displacement may in theory hamper normal implantation of the embryo (Figure 8B).
Figure 8Hypothesized theories of the influence of subendometrial contractions on implantation of an embryo. (A) a uterus without caesarean section scar with low amplitude contractions, which may facilitate proper positioning of the embryo for implantation; (B) a uterus with a niche illustrating distortion of contraction features (higher amplitude and lower frequency), which may increase the force on the embryo in the direction of the cervix, particularly if the niche is associated with intra-uterine fluid accumulation.
In addition, coordinated contractions with a fundus-to-cervix direction are needed to facilitate outflow of menstrual blood. Postmenstrual spotting and dysmenorrhoea are most prevalent symptoms in women with a niche (
Prevalence, potential risk factors for development and symptoms related to the presence of uterine niches following Cesarean section: systematic review.
Long-term complications of caesarean section. The niche in the scar: a prospective cohort study on niche prevalence and its relation to abnormal uterine bleeding.
). During the menstrual phase, we identified a negative correlation concerning the fundus-to-cervix contractions in the niche group, whereas a positive correlation was observed in the control group. This suggests that contractions in the direction of the cervix were less coordinated, and it may, therefore, disturb functional outflow of menstrual blood. In theory, this may be one of the causal factors for niche-related postmenstrual spotting.
Strengths and limitations
Objectively assessing the uterine contractions with speckle tracking is useful in determining the effect of uterine contractions in women with a niche. In both the included groups, ultrasound recordings were carried out according to a strict protocol using one ultrasound machine with fixed settings. Another strength is that we matched for cycle phase as it is known that uterine contractions are influenced by the menstrual cycle phase.
The present study also has some limitations. The first limitation is the small data set. At the time of the study design, no relevant data of comparable studies were available to calculate a sample size. Furthermore, a high number of recordings were not suitable for speckle tracking analysis, even though the researchers were trained. The quality of the videos could only be assessed in retrospect during speckle tracking analysis. Therefore, inclusion took longer than expected. Main reasons to exclude recordings were movement artefacts and suboptimal region of interest, but also some technical problems occurred, i.e. faltering recording. Another limitation is that, owing to the non-randomized design of our study, there may be differences between the two groups. For example, by definition, all women had undergone a previous caesarean section in the niche group, whereas most women had never been pregnant in the control group. Furthermore, in case of parity, there was no significant difference in uterine size between the study groups, which might have explained the significant higher amplitude in multipara (women with a niche). In the present study, we did not include women with a caesarean section scar but without visible niche, because we had no ethical approval to include this patient group. Our goal was to assess the two extremes first: women with a niche versus women without previous uterotomy.
Future perspectives
Our study results indicate that the presence of a niche influences the amplitude and coordination of subendometrial contractions. The associated change in these contraction features may play an important role in niche-related problems, such as postmenstrual spotting and subfertility. The exact relation needs further exploration.
Furthermore, we found a strong positive correlation between niche sizes (depth, length) and RMT, and amplitude of subendometrial contractions raising the question if uterine peristalsis can be corrected by surgical removal of the uterine niche and restoration of the residual myometrial thickness. After the results of this study showing difference in contraction features, we plan to first evaluate the influence of a caesarean section scar alone on subendometrial contractions in a future study to determine whether a scar itself also affects the amplitude or other characteristics of uterine subendometrial contractions. Future larger studies are needed to confirm our findings and to study the effect of current applied treatments on contraction features, gynaecological symptoms and reproductive outcomes.
In conclusion, the amplitude of subendometrial contractions is higher in women with a niche compared with women who have not undergone a previous caesarean section. The contraction amplitude is correlated to the niche size and inversely correlated to the thickness of the residual myometrium or uterine wall. Furthermore, contractions in women with a niche are less coordinated. In theory, these findings may play a role in the cause of postmenstrual spotting, dysmenorrhoea and lower implantation rates in women with a niche. Future studies are needed to explore the clinical implication of our findings and to see if they can be corrected by pharmacological or surgical strategies and to elucidate the underlying mechanisms for the lower implantation rates in relation to a higher amplitude and the underlying electro-biological signalling pathways that cause these higher amplitudes in association with a niche.
Data Availability
Data will be made available on request.
Acknowledgements
We thank Emiel Post Uiterweer (Amsterdam UMC, location AMC, Amsterdam, The Netherlands) for his critical revision of the article. Acquisition of data, analysis and interpretation of data, drafting the article, final approval of the version to be submitted (IPM J and JV); analysis and interpretation of data, drafting the article, final approval of the version to be submitted (YH); conception and design of the study, interpretation of data, revising the article critically for important intellectual content, final approval of the version to be submitted (MM, BCS and JAFH).
Prevalence, potential risk factors for development and symptoms related to the presence of uterine niches following Cesarean section: systematic review.
Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group.
Long-term complications of caesarean section. The niche in the scar: a prospective cohort study on niche prevalence and its relation to abnormal uterine bleeding.
Professor Dr JAF Huirne is Professor and Head of Gynaecology Department at the Amsterdam University Medical Centre location VUmc and AMC. Her clinical work and research focus on benign gynaecology, in particular on innovative surgical techniques to treat uterine disorders, including caesarean scar defects.
Key message
Characteristics of subendometrial contractions are different in women with a caesarean scar defect compared with women who have not undergone a previous caesarean section; this may play a role in niche-related symptoms and may affect embryo implantation.
Article info
Publication history
Published online: December 05, 2022
Accepted:
December 2,
2022
Received in revised form:
November 16,
2022
Received:
August 17,
2022
Declaration: The authors report no financial or commercial conflicts of interest.
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