Pelvic floor dysfunction at transperineal ultrasound and chronic constipation in women with endometriosis

To assess the association between sonographic findings at transperineal ultrasound (TPU) and chronic constipation (CC) in women with endometriosis.


| INTRODUC TI ON
Endometriosis is a chronic and recurrent disease defined as the presence and proliferation of endometrial glands and stroma outside the uterine cavity. It can be classified into superficial, ovarian, and deep infiltrating endometriosis (DIE). 1,2 DIE is characterized by the infiltration of ectopic endometrial tissue under the peritoneum, pelvic structure, and organ walls. DIE most frequently involves the posterior pelvic compartment including the uterosacral ligaments, rectosigmoid colon, vagina, and rectovaginal septum. 2,3 The major clinical problems of endometriosis are chronic/recurrent pelvic pain during menstruation, sexual intercourse, and defecation, with significant negative impact on women's health and quality of life. 4,5 Endometriosis can cause digestive complaints, including abdominal pain, bloating, diarrhea, constipation, rectal bleeding, and dyschezia. [6][7][8] In particular, the prevalence of chronic constipation (CC) in women with endometriosis varies from 12% to 85%. 9,10 CC in women with endometriosis is multi-factorial and possible involved pathophysiologic mechanisms include cyclic inflammatory phenomena, reduction of intestinal lumen dimensions, fixation and angulation of intestinal wall, and damage of pelvic autonomic nerves. 4,[6][7][8] It is acknowledged that women with endometriosis are more likely to have pelvic floor muscle dysfunctions. 11,12 Improper pelvic floor muscle relaxation or coordination may contribute to defecation dysfunctions characterized by consistent contraction. 11 In these cases, several authors used the terms obstructed defecation syndrome or dyssynergic defecation. 13 Three-dimensional/four-dimensional (3D/4D) transperineal ultrasound is a feasible and reproducible tool in the assessment of pelvic floor muscle integrity, contraction, and relaxation. 14-16 Women affected by endometriosis were recently shown to have transperineal ultrasound signs of pelvic floor muscle hypertonia. 17,18 These include smaller levator hiatal dimensions at rest and a higher prevalence of levator ani muscle (LAM) contraction at Valsalva in comparison with controls, a phenomenon called also LAM coactivation. 18 These effects are more pronounced in women with DIE. 17,18 To the best of our knowledge, no data exist on the association between transperineal ultrasound findings and CC in women affected by endometriosis.
The aim of our study was to evaluate the correlation between CC and 3D/4D pelvic floor ultrasound findings in women affected by endometriosis.

| Study protocol and selection criteria
The study was performed according to an a priori defined study protocol and was designed as a single-center observational prospective cohort study. The whole study was reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and checklist. 19 We recruited all consecutive nulliparous women with a clinical and sonographic diagnosis of endometriosis scheduled for surgery at our tertiary level referral Academic Center, between September 2019 and October 2020, in order to assess 3D/4D pelvic floor ultrasound findings in women with endometriosis with and without CC.
Women were excluded if they had any of the following criteria: age <18 years or older than 45 years, current or previous pregnancy, postmenopausal status, other confirmed cause of chronic pelvic pain, pelvic organ prolapse, vulvodynia, previous rectal surgery, or rectosigmoid endometriosis with bowel stenosis more than 50% detected by magnetic resonance imaging. bowel symptoms, with a total score ranging from 0 (no symptoms) to 39 (high symptom severity). A cut-off score of 10 or more indicates CC. 8,20 Patients were divided into two groups according to the presence of CC as detected using the validated KESS questionnaire. 20 We performed 3D/4D transperineal ultrasound for each woman. LAM coactivation was defined as an APD at Valsalva smaller than that at rest. 18,[22][23][24] This represents contraction of the pelvic floor muscle during the Valsalva maneuver rather than relaxation. 22,25 All scans were performed by the same experienced operator (DR), using a Voluson E6 system (GE Healthcare, Chicago, IL, USA) with RAB 8-to 4-MHz volumetric transducer. All Measurements were evaluated offline anonymously using a dedicated software (4DView 14.4; GE) by one of the investigators, all blinded to the patient's clinical data.

| Study outcomes
Primary outcome was the difference in prevalence of LAM coactivation between women with endometriosis and CC and those without

CC.
Secondary outcomes were: • The difference in LHA during Valsalva maneuver between women with endometriosis and CC and those without CC; F I G U R E 1 Three-dimensional/four-dimensional transperineal ultrasound showing the antero-posterior diameter and levator hiatus area at rest (a, b) and under maximum Valsalva (c, d) • The difference in APD of the levator hiatus during Valsalva maneuver between women with endometriosis and CC and those without CC; • The difference in absolute and proportional change of LHA from resting state to Valsalva maneuver between women with endometriosis and CC and those without CC; • The difference in absolute and proportional change of APD of the levator hiatus from resting state to Valsalva maneuver between women with endometriosis and CC and those without CC.

| Statistical analysis
Continuous data were expressed as mean ± standard deviation or median (interquartile range). Categorical variables were expressed as numbers and percentages.
Student's t-test or Mann-Whitney U-test and χ 2 or Fisher's exact test were used for continuous and categorical data, as appropriate. A value of P < 0.05 was considered significant for all tests.
Additional analyses were performed as subgroup analysis based on endometriosis localization (ovarian versus DIE) confirmed by surgical visualization and histologic examination.
Statistical analysis was carried out using the SPSS software version 24.0 (IBM Corp., Armonk, NY, USA).

| Ethical statement
The study received approval from the local ethics committee (CE-AVEC 196/2015/O/Sper) and was performed in accordance with the Helsinki declaration. All women gave informed written consent to participate in the study and all data were anonymized.

| Study population
Overall, 87 women were enrolled in the study. These were divided into two groups according to the KESS questionnaire score: 29 (33%) women with CC and 58 (67%) without CC. Diagnosis of endometriosis was subsequently confirmed by histologic examination in all cases.
Baseline characteristics, disease localization, and pain symptoms did not differ significantly between the two groups ( Table 1), except for dyspareunia symptoms, which were of higher severity in the CC group.

| Main analyses
Transperineal ultrasound was successfully performed in all patients, with none excluded because of discomfort or pain. The ultrasound findings are displayed in Table 2

| Additional analyses
Of the 87 patients enrolled in the study, 42 (48%) presented exclusively ovarian endometriosis, while the remaining 45 (52%) were affected also by DIE.
Patient characteristics, disease localization, and pain symptoms in the two subgroups are reported in Table 3, and the ultrasound findings compared between women with and without CC in the two subgroups are shown in Table 4. As shown in Table 3, the clinical characteristics were comparable between women with and without CC in both subgroups, with the exception of dyspareunia, which was more pronounced in women with CC in the DIE subgroup.
In the ovarian endometriosis subgroup, 12 out of 42 (29%) patients complained of CC. In this subgroup of patients, women with CC had smaller LHA at Valsalva maneuver, less enlargement of LHA and APD from rest to maximum Valsalva (both absolute and proportional) and a higher prevalence of LAM coactivation in comparison with non-CC patients ( Table 4).
Among the DIE subgroup, 17 out of 45 (38%) patients presented CC ( Table 4). As shown in Table 4, in the DIE subgroup, no significant difference was demonstrated between the ultrasound findings in women with and without CC.

| DISCUSS ION
This study showed that women with CC and endometriosis had so- found also to correlate with superficial dyspareunia and voiding dysfunction in endometriosis patients. 26 Recently, it has been demonstrated that nulliparous women with LAM coactivation at term of pregnancy were more likely to have a longer second stage of labor and to have a less engaged fetal head. 23,24 Our data not only increase our understanding of the relationship between endometriosis and bowel symptoms, but more importantly they may have significant clinical implications. The management of constipation in endometriosis patients remains challenging. Our data may help in the selection of women who have the potential to benefit from specific interventions targeting the pelvic floor hypertonia, such as physiotherapy. Furthermore, in these patients, ultrasound can help in the improvement of symptoms. In a recent study, the authors found that ultrasound visual feedback improves superficial and deep dyspareunia symptoms, and improved ultrasound signs of hypertonia in women with endometriosis. 27

ACK N OWLED G M ENTS
Open Access Funding provided by Universita degli Studi di Bologna.
[Correction added on 09-May-2022, after first online publication: CRUI-CARE funding statement has been added].

CO N FLI C T S O F I NTE R E S T
The authors report no conflict of interest.

AUTH O R CO NTR I B UTI O N S
DR was responsible for study conception and design, data acquisition, statistical analysis, and manuscript drafting. LC, AR, SDF, and RI contributed to study design, statistical analysis and interpretation, and manuscript drafting. MM, ACA, PS, and MA were responsible for data acquisition and contributed to manuscript drafting. AM was responsible for data analysis and interpretation, and manuscript revision; AY, PC, and RS were reponsible for study conception and design, and manuscript drafting and revision. All authors read and approved the final manuscript and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from the corresponding author upon reasonable request.