Prevalence of endometriosis in diagnostic and therapeutic laparoscopy among women with chronic pelvic pain

In: Research Square · 2024 · doi:10.21203/rs.3.rs-4177916/v1 · W4396219979
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Macroscopic endometriosis was detected in 52.4% of women undergoing laparoscopy for chronic pelvic pain, with peritoneal endometriosis being the most common type, and dyschezia and earlier onset of pain differentiating affected patients.

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This registry-based historical cohort study examined 296 women aged 15–49 who underwent diagnostic or therapeutic laparoscopy for chronic pelvic pain suggestive of endometriosis at Turku University Hospital between 2009 and 2020, excluding those with preoperative ultrasound evidence of endometriosis or prior endometriosis history. Intraoperative documentation in medical records was used to classify endometriosis prevalence, with macroscopic endometriosis found in 52.4% of laparoscopies (most commonly peritoneal disease), and deep endometriosis present in 4.7% and a small endometrioma in 2%; women without and with endometriosis reported similar acyclic abdominal pain and dyspareunia, but dyschezia was more common in those with endometriosis. The authors limited diagnostic confirmation to macroscopic findings from operative notes and did not report long-term benefit of laparoscopy. This paper is centrally about endometriosis — it quantifies how often endometriosis is verified at laparoscopy in ultrasound-negative women with chronic pelvic pain.

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Abstract

Abstract Background: When peritoneal endometriosis is clinically suspected, empirical medical therapy should be the first-line treatment. Diagnostic and therapeutic laparoscopy may be offered after failed or unsuitable medical therapy in women with severe pelvic pain and no imaging findings. Our objective was to determine how often endometriosis is verified among these women via laparoscopy. Methods: In our registry-based historical cohort we identified 296 women aged 15–49 undergoing laparoscopy due to chronic pelvic pain, between 2009 and 2020 at Turku University Hospital. Women without preoperative ultrasound findings and no history of endometriosis were included in the study. We collected preoperative characteristics and intraoperative findings from the hospital patient records. The prevalence of endometriosis in laparoscopy was the primary outcome. Results: Macroscopic endometriosis was detected in 52.4% of laparoscopies, and the rate was similar throughout the study period. Peritoneal endometriosis was found in 52% of participants, deep endometriosis in 4.7% and a small endometrioma in 2%. Women with and without endometriosis reported similar preoperative rates of acyclic abdominal pain (91.8% vs 93.9%, P=0.64) and dyspareunia (84.6% vs 78.9%, P =0.32), while dyschezia was significantly more common among women with endometriosis (44.4% vs 26.9%, P =0.006). The prevalence of dysmenorrhea is not reported, as 62.5% of patients used hormonal therapy commonly aiming to amenorrhea. The median age at the onset of symptoms was significantly lower in women with endometriosis (14 vs 19, P =0.048). Conclusions: Endometriosis was confirmed in 52.4% of the women undergoing laparoscopy due to chronic pelvic pain, and in most women, peritoneal endometriosis was the only finding. However, the other half of the women did not have endometriosis despite having similar pain symptoms. Two preoperative characteristics differed significantly between the groups; women with endometriosis had earlier onset of pain symptoms and they reported dyschezia more commonly. It remains unknown whether patients benefit long-term from undergoing diagnostic and therapeutic laparoscopy.
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Prevalence of endometriosis in diagnostic and therapeutic laparoscopy among women with chronic pelvic pain | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prevalence of endometriosis in diagnostic and therapeutic laparoscopy among women with chronic pelvic pain Saima Siivonen, Pia Suvitie This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4177916/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: When peritoneal endometriosis is clinically suspected, empirical medical therapy should be the first-line treatment. Diagnostic and therapeutic laparoscopy may be offered after failed or unsuitable medical therapy in women with severe pelvic pain and no imaging findings. Our objective was to determine how often endometriosis is verified among these women via laparoscopy. Methods : In our registry-based historical cohort we identified 296 women aged 15–49 undergoing laparoscopy due to chronic pelvic pain, between 2009 and 2020 at Turku University Hospital. Women without preoperative ultrasound findings and no history of endometriosis were included in the study. We collected preoperative characteristics and intraoperative findings from the hospital patient records. The prevalence of endometriosis in laparoscopy was the primary outcome. Results : Macroscopic endometriosis was detected in 52.4% of laparoscopies, and the rate was similar throughout the study period. Peritoneal endometriosis was found in 52% of participants, deep endometriosis in 4.7% and a small endometrioma in 2%. Women with and without endometriosis reported similar preoperative rates of acyclic abdominal pain (91.8% vs 93.9%, P =0.64) and dyspareunia (84.6% vs 78.9%, P =0.32), while dyschezia was significantly more common among women with endometriosis (44.4% vs 26.9%, P =0.006). The prevalence of dysmenorrhea is not reported, as 62.5% of patients used hormonal therapy commonly aiming to amenorrhea. The median age at the onset of symptoms was significantly lower in women with endometriosis (14 vs 19, P =0.048). Conclusions : Endometriosis was confirmed in 52.4% of the women undergoing laparoscopy due to chronic pelvic pain, and in most women, peritoneal endometriosis was the only finding. However, the other half of the women did not have endometriosis despite having similar pain symptoms. Two preoperative characteristics differed significantly between the groups; women with endometriosis had earlier onset of pain symptoms and they reported dyschezia more commonly. It remains unknown whether patients benefit long-term from undergoing diagnostic and therapeutic laparoscopy. endometriosis peritoneal diagnosis prevalence laparoscopy pain symptoms chronic pelvic pain Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Diagnostic laparoscopy with positive histology has previously been the gold standard diagnostic method for endometriosis. The latest European Society of Human Reproduction and Embryology (ESHRE) guidelines challenge this idea and suggest that laparoscopy should be offered only to women who have no signs of endometriosis in ultrasound (ultrasound negative) or MRI imaging and when empirical treatment has failed or is not suitable [1]. Limited data exist on the prevalence of endometriosis among ultrasound negative women with chronic pelvic pain (CPP). According to the latest systematic review, visible endometriosis is detected via laparoscopy in 64% of adolescents with pelvic pain [2]. In 42 % of adult women with CPP, endometriosis occurs [3]. The prevalence of endometriosis is reported to be 21% in adult women undergoing laparoscopic hysterectomy due to CPP [4]. Turku University Hospital, Department of Obstetrics and Gynecology, is a tertiary referral center, and during our study period (2009–2020) diagnostic laparoscopies were performed following current recommendations by the ESHRE. Laparoscopy was performed if a woman had pain symptoms that decreased her quality of life despite hormonal treatment or if hormonal treatment was inappropriate because of pregnancy seeking, side effects or contraindications. When performing a laparoscopy there was an intention to treat endometriosis if it was found. Considering this background, the primary aim of our study was to determine how often endometriosis is detected in our diagnostic laparoscopies. In addition, our objective was to determine the annual number of these procedures and to explore the characteristics of these women. Methods This retrospective registry study was conducted at the Department of Obstetrics and Gynecology, at Turku University Hospital. Our intention was to identify women who had undergone diagnostic laparoscopy due to suspicion of endometriosis between years 2009 and 2020. The formation of the study cohort is illustrated in detail in Figure 1. We searched for eligible women under the age of 50 from the electronic hospital database by using the Finnish Classification of Surgical Procedures [5], which is based on the Nordic Classification of Surgical Procedures (NCPS). The following procedures were searched: 1) diagnostic laparoscopy (JAH01) as the main or subsidiary procedure, 2) laparoscopic excision or destruction of peritoneal lesions (JAL21), 3) laparoscopic adhesiolysis in the peritoneal cavity (JAP01) or 4) laparoscopic appendectomy (JEA01) as the main procedure. Laparoscopies performed due to gynecological cancer were excluded from the search by ruling out postoperative International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes C50-58. There were 879 women found in the primary data search. All these women had undergone gynecological examination and transvaginal ultrasound prior to laparoscopic surgery. These investigations were performed at the Gynecological Outpatient Clinic by a specialist or a trainee in Obstetrics and Gynecology, who are consistently trained to perform ultrasound imaging. The women’s medical history was systemically screened by using a general questionnaire that included binary classifications (yes/no) of dysmenorrhea and dyspareunia. Patients were also asked about other endometriosis-related pain symptoms if relevant. A visual analog scale was not systemically used. The women’s medical history as well as clinical examination and ultrasound findings were documented in the electronic patient files by the gynecologist. We retrospectively examined the preoperative and surgical notes from the patient files and excluded women with 1) a previous visual or histological diagnosis of endometriosis via laparoscopy or laparotomy 2) deep or ovarian endometriosis detected via preoperative ultrasound 3) other obvious preoperative findings than endometriosis explaining pain symptoms 4) emergency laparoscopy due to acute pain, and 5) the indication for surgery solely other than pain or suspicion of endometriosis. After these exclusions, our final cohort consisted of 296 women. These women were referred to the Gynecology Outpatient Clinic for the most part by private gynecologists (37.9%), public health care general practitioners (34.4%) or other discipline units within the hospital (15.1%). After careful medical history taking and clinical evaluation, laparoscopy was considered indicated if a woman had pain symptoms decreasing her quality of life despite hormonal treatment or if hormonal treatment was inappropriate because of pregnancy seeking, side effects or contraindications. The waiting time for laparoscopy was less than six months. In every procedure, the primary or assisting surgeon was an experienced gynecological laparoscopist with knowledge of diagnosing endometriosis. The preoperative characteristics and intraoperative findings were collected from the patient files to a uniform Excel spreadsheet. Positive cases for endometriosis were identified based on documentation of the presence of macroscopic endometriosis lesions (superficial, deep or ovarian) in the electronic operation notes. The surgical prevalence of endometriosis was the primary outcome. Second, we wanted to explore preoperative pain symptoms. Statistical analyses Statistical analyses were performed using JMP pro16.2.0. The data were pseudoanonymized prior to analysis. The basic characteristics are presented as the mean and standard deviation (SD) for normally distributed continuous variables, median and interquartile range (IQR) for nonnormally distributed continuous variables and number and percentage for categorical variables. Basic characteristics were compared using two sample t-test for normally distributed variables, Wilcoxon rank sum test for nonnormally distributed variables and Fisher’s exact test for nominal variables. Fisher’s exact test was also used when comparing different age groups. Ethical approval According to Finnish Medical Research Act (488/1999) patient’s informed consent or ethical approval is not required in a registry-based study. This study was approved by Southwest Finland Hospital District in April 2021 (approval number: T07/009/21). Participant confidentiality was protected, and the data was pseudoanonymized prior to analysis. Results Between 2009 and 2020, laparoscopy was performed on 296 women with pain symptoms suggestive of endometriosis. The annual number of these procedures (Figure 2) varied between 13 and 39 (mean 24.6 and SD 7.1). The mean age of the women was 27.3 years (SD 6.8). The baseline characteristics of the study population are presented in Table 1 and Table 2. Women with and without endometriosis were comparable by age, BMI, and age at menarche. Macroscopic endometriosis was found in 155 (52.4%) laparoscopies (Table 3), and the most common finding was peritoneal endometriosis. Table 1 Baseline characteristics of women undergoing diagnostic laparoscopy for chronic pelvic pain suggestive of endometriosis Total n=296 Subgroups: Endometriosis n=155 No endometriosis n=141 P -value a Mean age at surgery, years (SD) 27.3 (6.8) 26.9 (6.5) 27.7 (7.2) 0.32 Mean age at menarche (SD) 12.6 (1.4) 12.5 (1.4) 12.7 (1.4) 0.36 Median BMI (IQR) 23.1 (20.9­­­–26.5) 23.0 (21.0–26.0) 23.7(20.8–27.0) 0.51 Median age at onset of pain symptoms b (IQR) 16 (12.8–26) 14 (12–24) 19 (13–27) 0.048 Smoking 83/289 (28.0) 46/152 (30.0) 37/137 (27.0) 0.60 Migraine 82/296 (27.7) 43/155 (27.7) 39/141 (27.7) 1.00 Depression 55/296 (18.6) 30/155 (19.4) 25/141 (17.7) 0.77 Dyspareunia 201/245 (82.0) 115/136 (84.6) 86/109 (78.9) 0.32 Dyschezia 85/234 (36.3) 56/126 (44.4) 29/108 (26.9) 0.006 Dysuria 39/199 (19.6) 24/102 (23.5) 15/97 (15.5) 0.16 Acyclic abdominal pain 245/264 (92.8) 123/134 (91.8) 122/130 (93.9) 0.64 Infertility 57/296 (19.3) 34/155 (21.9) 23/141 (16.3) 0.24 Note: Data are presented as n (%) unless indicated otherwise Abbreviations: SD=standard deviation, BMI=body mass index, IQR=interquartile range a Between subgroups b Age at onset of dysmenorrhea (primary or secondary), dyspareunia, dyschezia, dysuria or acyclic abdominal pain. Table 2 Parity and medication of women undergoing diagnostic laparoscopy for chronic pelvic pain suggestive of endometriosis Total n=296 Subgroups: Endometriosis n=155 No endometriosis n=141 P -value a Nulligravida 184/296 (62.2) 113/155 (72.9) 71/141 (50.4) <0.001 Nullipara 199/296 (67.2) 126/155 (81.3) 73/144 (51.8) <0.001 Current hormonal contraception use 185/296 (62.5) 98/155 (63.2) 87/144 (61.7) 0.81 Have used hormonal contraception b 273/282 (96.8) 148/152 (97.4) 125/130 (96.2) 0.74 Current use of NSAID/ paracetamol 196/230 (85.2) 107/125 (85.6) 89/105 (84.8) 0.85 Current use of weak opioids 53/230 (23.0) 35/125 (28.0) 18/105 (17.1) 0.060 Current use of strong opioids 9/230 (3.9) 6/125 (4.8) 3/105 (2.9) 0.51 Current use of Adjuvant analgesics 18/230 (7.8) 9/125 (7.2) 9/105 (8.6) 0.81 Note: Data are presented as n (%). a Between subgroups b Current or previous hormonal contraception use Table 3 Surgical findings in women undergoing diagnostic laparoscopy for chronic pelvic pain suggestive of endometriosis Total n=296 % Endometriosis 155 52.4 Peritoneal endometriosis 154 52.0 Deep endometriosis 14 4.7 Endometrioma 6 2.0 Peritoneal adhesions 104 35.1 Note: Data are presented as n (%). The most common preoperative symptoms other than dysmenorrhea were acyclic abdominal pain (92.8%) and dyspareunia (82.0%) (Table 1). There was no statistically significant difference in the prevalence of these symptoms between women with and without endometriosis. In total 85/234 (36.3%) women reported dyschezia. Women with endometriosis reported dyschezia more often than women with no endometriosis, 44.4% and 26.9%, respectively ( P =0.006). The prevalence of current dysmenorrhea is not reported, as many patients used continuous hormonal therapy aimed to induce amenorrhea. Preoperative hormonal and analgetic medical therapy are described in Table 2. At the end of laparoscopy an intrauterine device was inserted for 68 (23.0%) women. In this study, no laparoscopies were performed solely because of infertility, but 57 (19.3%) women had infertility with coexisting pelvic pain (Table 1). There was no statistically significant difference in the prevalence of infertility between women with (21.9%) and without (16.3%) endometriosis ( P =0.24). Interestingly, compared with women without visual endometriosis in laparoscopy, women with endometriosis were more often nulligravida (72.6% vs 50.4%, P <0.001) and nulliparous (81.3% vs 51.8%, P <0.001). The age distribution of our cohort is presented in Figure 3. To evaluate whether there were any age-related differences in the prevalence of endometriosis, we divided women into five subgroups: under 20, 20–24, 25–29, 30–34 and over 34 (34–49) years old (Figure 4). The prevalence was highest in the age groups of 20–24 (56.8%) and 25–29 (56.2%), and lowest among women older than 34 years old (38.6%). There was no statistically significant difference in the prevalence of endometriosis between the age groups ( P =0.34). Table 4 shows data on preoperative imaging, laboratory testing and endoscopies performed due to pain symptoms. Investigations were mostly performed by primary health care doctors or specialists in other disciplines prior to referral to the Gynecological Outpatient Clinic. Table 4 Frequency of preoperative investigations among the study population Total n=296 % Lower abdomen MRI 24 8.1 Abdominal ultrasound 30 10.1 Abdominal CT 25 8.4 Colonoscopy 65 22.0 Gastroscopy 30 10.1 Capsule endoscopy 5 1.7 Cystoscopy 7 2.4 Celiac disease screening a 62 20.9 Fecal calprotectin 38 12.8 Note: Data are presented as n (%). Abbreviations: MRI, magnetic resonance imaging. CT, computed tomography. a Tissue transglutaminase immunoglobulin A test Discussion In our historical cohort study, more than half of the women (52.4 %) had endometriosis in diagnostic laparoscopy performed due to CPP. Our study included only women of reproductive age (15–49), and surgery was performed with the intention to treat endometriosis if detected. According to previous meta-analyses, visible endometriosis is found via laparoscopy in 64% of adolescents and in 42% of adult women with CPP [2,3]. Thus, our results are in line with previous findings. To our knowledge, our study exploring the prevalence of endometriosis among fertile aged women with CPP is the largest performed in recent years. During last decades, ultrasound imaging of endometriosis and knowledge about the appearance of peritoneal endometriosis in laparoscopy as well as surgical equipment have notably developed, making it difficult to compare our results with those of previous studies. Many previous studies have included postmenopausal women, for example Moradi et al. (2021) in their meta-analysis of adult women with CPP [3]. In addition, a cohort consisting of 3068 diagnostic laparoscopies, performed on women aged 15–66 years due to CPP between 1994 and 2005 reported a prevalence of 60.2% of endometriosis [6]. The most recent study consisting of 150 women aged 16–30 years, with a similar study design to ours, reported surgically verified endometriosis in only 20% of laparoscopies [7]. These women suffered from CPP and were reported to be ultrasound negative and to have a normal pelvis in clinical examination preoperatively. Laparoscopy should no longer be considered as the gold standard diagnostic tool for endometriosis, but rather an option when endometriosis cannot be detected by noninvasive imaging and empirical treatment is unsuccessful [1]. Recently this transition in the diagnostic process has been widely discussed [8,9]. Furthermore, it is suggested that the definition of endometriosis should not be based on histology but rather on clinical symptoms and findings. This modification to the definition could help change the diagnostic approach globally away from laparoscopy.[10] There is no clear evidence if laparoscopic treatment of peritoneal endometriosis reduces pain symptoms in the long term. A recent systematic review on laparoscopic surgery for endometriosis concluded, that it remains uncertain whether surgery is effective for pain symptoms compared to diagnostic laparoscopy alone [11]. Presently, two ongoing blinded randomized controlled trials intend to provide information on whether laparoscopic excision of peritoneal endometriosis is helpful or harmful [12,13]. Importantly, it has been suggested that laparoscopy may enhance pelvic pain through several different mechanisms, such as increased sensory hypersensitivity or the development of neuropathic pain [13]. The ESHRE guidelines state that there is no comprehensive evidence that endometriosis can be predicted by women’s symptoms, nevertheless having multiple symptoms increases the likelihood of endometriosis [1]. In our study, it would have been impossible to discriminate women with and without endometriosis based on preoperative symptoms only, and almost half of the women (47.6%) undergoing laparoscopy did not have visible endometriosis. Nongynecological pelvic and nonpelvic conditions such as interstitial cystitis, irritable bowel syndrome, fibromyalgia and migraine often contribute to pain symptoms in women with CPP pain [14]. It is estimated that even in 80 % of CPP the origin of the pain is not gynecological [15]. In our study, dyschezia was the only preoperative symptom that differed significantly in prevalence between women with and without endometriosis (44.4% vs 26.9%, P =0.006). Similar to our findings, in previous studies the prevalence of dyschezia among women with laparoscopic endometriosis diagnosis has been reported to be 32.2–44.2% [16,17]. In addition, dyschezia during menstruation has been shown to have a strong correlation with the risk of endometriosis [18]. The mean age at the time of diagnostic laparoscopy was similar in women with and without endometriosis, 26.9 and 27.7 years, respectively ( P =0.32). However, women with endometriosis had significantly earlier onset of pain than women without endometriosis (14 vs 19 years, respectively, P =0.048). This is a major difference clinically and for the individual suffering from pain symptoms. According to the literature, in two-thirds of patients with endometriosis, symptoms start before the age of 20 [19,20]. In one recent study of women with surgically confirmed endometriosis, the median age at the onset of endometriosis symptoms was 14 years old [21]. The strengths of our study include the fact, that all laparoscopies were performed or assisted by an experienced surgeon. Therefore, the visual diagnosis of endometriosis is considered reliable. Another strength is that the indications for laparoscopy remained predominantly the same during our study period, and laparoscopy was not the first-line treatment option nor solely a diagnostic method. In addition, the study cohort was moderately sized. The most important limitation of our study is the retrospective study design. All preoperative symptoms were not collected via a uniform questionnaire; thus, the data may be incomplete. In addition, several gynecologists performed preoperative visits. This increases the heterogeneity of the medical record notes eventually collected for this study. We consider the sensitivity of preoperative ultrasound imaging acceptable as deep endometriosis was found in 4.7% and endometrioma in 2.0% of participants considered ultrasound negative. Conclusions Endometriosis was confirmed in approximately in one half of the women undergoing laparoscopy due to CPP. In most women peritoneal endometriosis was the only finding suggesting that endometrioma and deep endometriosis are detected preoperatively in most cases. Importantly, the other half of the women did not have endometriosis despite having similar pain symptoms prior to surgery. Irrespective of laparoscopy findings, women with CPP should be offered comprehensive and multimodal treatment of chronic pain to improve their quality of life. To date, it remains unknown whether patients benefit long-term from undergoing diagnostic and therapeutic laparoscopy or surgical treatment for peritoneal endometriosis. Hopefully, ongoing randomized clinical trials will provide us with answers to this well-recognized question. Abbreviations CPP, chronic pelvic pain Declarations Ethics approval and consent to participate According to Finnish Medical Research Act (488/1999) patient’s informed consent or ethical approval is not required in a registry-based study. This study was approved by Southwest Finland Hospital District in April 2021 (approval number: T07/009/21). Participant confidentiality was protected, and the data was pseudoanonymized prior to analysis. Consent for publication Not applicable. Availability of data and materials The datasets generated and analyzed during the current study are not publicly available due to privacy restrictions, but anonymized data are available from the corresponding author upon reasonable request. Competing interests Saima Siivonen has stated that there are no conflicts of interest. Pia A. Suvitie has received consultancy and speaker’s fees from Gedeon Richter Nordics. Funding This study was conducted without external funding. Author contributions PS and SS planned and designed the study. SS collected the data with input from PS. SS performed the statistical analysis. SS drafted the first manuscript, which was further thoroughly edited by PS. Both authors contributed to all faces of this study and approved the final version. Acknowledgements Not applicable. References Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022 Mar 4;2022(2). Hirsch M, Dhillon-Smith R, Cutner AS, Yap M, Creighton SM. The Prevalence of Endometriosis in Adolescents with Pelvic Pain: A Systematic Review. J Pediatr Adolesc Gynecol. 2020 Dec 1;33(6):623–30. Moradi Y, Shams-Beyranvand M, Khateri S, Gharahjeh S, Tehrani S, Varse F, et al. A systematic review on the prevalence of endometriosis in women. Vol. 154, Indian Journal of Medical Research. 2021. Mowers EL, Lim CS, Skinner B, Mahnert N, Kamdar N, Morgan DM, et al. 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Approach to Diagnosis and Management of Chronic Pelvic Pain in Women: Incorporating Chronic Overlapping Pain Conditions in Assessment and Management. Obstet Gynecol Clin North Am. 2022 Jun 1;49(2):219–39. Lamvu G, Carrillo J, Ouyang C, Rapkin A. Chronic Pelvic Pain in Women: A Review. JAMA - J Am Med Assoc. 2021;325(23):2381–91. Abrao MS, Andres MP, Miller CE, Gingold JA, Rius M, Neto JS, et al. AAGL 2021 Endometriosis Classification: An Anatomy-based Surgical Complexity Score. J Minim Invasive Gynecol. 2021 Nov 1;28(11):1941-1950.e1. Schliep KC, Mumford SL, Peterson CM, Chen Z, Johnstone EB, Sharp HT, et al. Pain typology and incident endometriosis. Hum Reprod. 2015 Oct 1;30(10):2427–38. Nnoaham KE, Hummelshoj L, Kennedy SH, Jenkinson C, Zondervan KT. Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study. Fertil Steril. 2012;98(3). Ballweg M Lou. Impact of endometriosis on women’s health: Comparative historical data show that the earlier the onset, the more severe the disease. Best Pract Res Clin Obstet Gynaecol. 2004;18(2):201–18. Greene R, Stratton P, Cleary SD, Ballweg M Lou, Sinaii N. Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis. Fertil Steril. 2009 Jan;91(1):32–9. Sasamoto N, Shafrir AL, Wallace BM, Vitonis AF, Fraer CJ, Sadler Gallagher J, et al. Trends in pelvic pain symptoms over 2 years of follow-up among adolescents and young adults with and without endometriosis. Pain. 2023 Mar;164(3):613–24. Additional Declarations Competing interest reported. PS has received consultancy and speaker’s fees from Gedeon Richter Nordics. SS has stated that there are no competing interests. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4177916","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":292964065,"identity":"fa11ec58-267a-4bde-879c-3db03009f9d8","order_by":0,"name":"Saima Siivonen","email":"","orcid":"","institution":"Turku University Hospital and University of Turku","correspondingAuthor":false,"prefix":"","firstName":"Saima","middleName":"","lastName":"Siivonen","suffix":""},{"id":292964066,"identity":"bf6ed401-7546-4a78-a644-3cc40ddec3a2","order_by":1,"name":"Pia Suvitie","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYDACZiTGAYYKIEMCiCsMiNLCDNRyBqrlDD4tKJoZ22Ba8KgzZ2d+wPCDoS5xw3H+gwc+zjssbz67+QHDgQLcWiyb2QwYexgOJ244zMxwcOa2w4Zz7hwzYDiAx2EGhxkMGHgYDiTObGZmOMy7LY1xhkSCAfMHvFrYPzD+AToMrOXvnDT7GRLpHwjYwmPAzMPAnNgPDLHDjA02iTMkcvA7zLKZp+CwjMFhY6AWg4M9x2ySgVoKDuDTYs5/fOPDNxV1sm38Bx9/+FEjYQt02MYHB/7gcRgDKNLRzTyAWwMDhuJRMApGwSgYBZgAANK4T0rQ+UlxAAAAAElFTkSuQmCC","orcid":"","institution":"Turku University Hospital and University of Turku","correspondingAuthor":true,"prefix":"","firstName":"Pia","middleName":"","lastName":"Suvitie","suffix":""}],"badges":[],"createdAt":"2024-03-27 18:36:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4177916/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4177916/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55512356,"identity":"a42827a3-a861-433d-afe4-f784bf606f2d","added_by":"auto","created_at":"2024-04-29 12:45:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":81474,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow chart of the study population\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"SiivonenDGLAPFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4177916/v1/2d47d3c1a7f089274a5c2041.png"},{"id":55513302,"identity":"d5fa0e4a-a7c2-4d64-a176-6d91933e897e","added_by":"auto","created_at":"2024-04-29 12:53:06","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":108034,"visible":true,"origin":"","legend":"\u003cp\u003eThe annual number of diagnostic laparoscopies performed for chronic pelvic pain suggestive of endometriosis\u003c/p\u003e","description":"","filename":"SiivonenDGLAPFigure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4177916/v1/2a8319226d2a1a1538d92cc5.png"},{"id":55511530,"identity":"f2e65886-3c23-4e6d-822a-e708ce9b4bfc","added_by":"auto","created_at":"2024-04-29 12:37:06","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":95584,"visible":true,"origin":"","legend":"\u003cp\u003eAge distribution of women undergoing diagnostic laparoscopy for chronic pelvic pain suggestive of endometriosis\u003c/p\u003e","description":"","filename":"SiivonenDGLAPFigure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4177916/v1/02f1570a22f5d1283adc4449.png"},{"id":55511529,"identity":"736bfb46-642a-4f56-8657-b01c148487dc","added_by":"auto","created_at":"2024-04-29 12:37:06","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":184144,"visible":true,"origin":"","legend":"\u003cp\u003ePrevalence of macroscopic endometriosis in laparoscopy in different age groups\u003c/p\u003e","description":"","filename":"SiivonenDGLAPFigure4.png","url":"https://assets-eu.researchsquare.com/files/rs-4177916/v1/881bd19e271633fcaaec5e62.png"},{"id":58105057,"identity":"1a74e046-3359-4cb7-b263-a4d805bf575c","added_by":"auto","created_at":"2024-06-11 07:34:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":843918,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4177916/v1/d9d5f796-8e1d-4be9-a18f-ee1f6601eec4.pdf"}],"financialInterests":"Competing interest reported. PS has received consultancy and speaker’s fees from Gedeon Richter Nordics. SS has stated that there are no competing interests.","formattedTitle":"Prevalence of endometriosis in diagnostic and therapeutic laparoscopy among women with chronic pelvic pain","fulltext":[{"header":"Background","content":"\u003cp\u003eDiagnostic laparoscopy with positive histology has previously been the gold standard diagnostic method for endometriosis. The latest European Society of Human Reproduction and Embryology (ESHRE) guidelines challenge this idea and suggest that laparoscopy should be offered only to women who have no signs of endometriosis in ultrasound (ultrasound negative) or MRI imaging and when empirical treatment has failed or is not suitable\u0026nbsp;[1].\u003c/p\u003e\n\u003cp\u003eLimited data exist on the prevalence of endometriosis among ultrasound negative women with chronic pelvic pain (CPP). According to the latest systematic review, visible endometriosis is detected via laparoscopy in 64% of adolescents with pelvic pain\u0026nbsp;[2]. In 42 % of adult women with CPP, endometriosis occurs\u0026nbsp;[3]. The prevalence of endometriosis is reported to be 21% in adult women undergoing laparoscopic hysterectomy due to CPP\u0026nbsp;[4].\u003c/p\u003e\n\u003cp\u003eTurku University Hospital, Department of Obstetrics and Gynecology, is a tertiary referral center, and during our study period (2009\u0026ndash;2020) diagnostic laparoscopies were performed following current recommendations by the ESHRE. Laparoscopy was performed if a woman had pain symptoms that decreased her quality of life despite hormonal treatment or if hormonal treatment was inappropriate because of pregnancy seeking, side effects or contraindications. When performing a laparoscopy there was an intention to treat endometriosis if it was found.\u003c/p\u003e\n\u003cp\u003eConsidering this background, the primary aim of our study was to determine how often endometriosis is detected in our diagnostic laparoscopies. In addition, our objective was to determine the annual number of these procedures and to explore the characteristics of these women.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis retrospective registry study was conducted at the Department of Obstetrics and Gynecology, at Turku University Hospital. Our intention was to identify women who had undergone diagnostic laparoscopy due to suspicion of endometriosis between years 2009 and 2020. The formation of the study cohort is illustrated in detail in Figure 1.\u003c/p\u003e\n\u003cp\u003eWe searched for eligible women under the age of 50 from the electronic hospital database by using \u0026nbsp;the Finnish Classification of Surgical Procedures\u0026nbsp;[5], which is based on the Nordic Classification of Surgical Procedures (NCPS). The following procedures were searched: 1) diagnostic laparoscopy (JAH01) as the main or subsidiary procedure, 2) laparoscopic excision or destruction of peritoneal lesions (JAL21), 3) laparoscopic adhesiolysis in the peritoneal cavity (JAP01) or 4) laparoscopic appendectomy (JEA01) as the \u0026nbsp;main procedure. Laparoscopies performed due to gynecological cancer were excluded from the search by ruling out postoperative International Classification of Diseases, Tenth Revision (ICD-10) diagnosis codes C50-58.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere were 879 women found in the primary data search. All these women had undergone gynecological examination and transvaginal ultrasound prior to laparoscopic surgery. These investigations were performed at the Gynecological Outpatient Clinic by a specialist or a trainee in Obstetrics and Gynecology, who are consistently trained to perform ultrasound imaging.\u003c/p\u003e\n\u003cp\u003eThe women\u0026rsquo;s medical history was systemically screened by using a general questionnaire that included binary classifications (yes/no) of dysmenorrhea and dyspareunia. Patients were also asked about other endometriosis-related pain symptoms if relevant. A visual analog scale was not systemically used. The women\u0026rsquo;s medical history as well as clinical examination and ultrasound findings were documented in the electronic patient files by the gynecologist. We retrospectively examined the preoperative and surgical notes from the patient files and excluded women with 1) a previous visual or histological diagnosis of endometriosis via laparoscopy or laparotomy 2) deep or ovarian endometriosis detected via preoperative ultrasound 3) other obvious preoperative findings than endometriosis explaining pain symptoms 4) emergency laparoscopy due to acute pain, and 5) the indication for surgery solely other than pain or suspicion of endometriosis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter these exclusions, our final cohort consisted of 296 women. These women were referred to the Gynecology Outpatient Clinic for the most part by private gynecologists (37.9%), public health care general practitioners (34.4%) or other discipline units within the hospital (15.1%). After careful medical history taking and clinical evaluation, laparoscopy was considered indicated if a woman had pain symptoms decreasing her quality of life despite hormonal treatment or if hormonal treatment was inappropriate because of pregnancy seeking, side effects or contraindications. The waiting time for laparoscopy was less than six months.\u0026nbsp;In every procedure, the primary or assisting surgeon was an experienced gynecological laparoscopist with knowledge of diagnosing endometriosis.\u003c/p\u003e\n\u003cp\u003eThe preoperative characteristics and intraoperative findings were collected from the patient files to a uniform Excel spreadsheet. Positive cases for endometriosis were identified based on documentation of the presence of macroscopic endometriosis lesions (superficial, deep or ovarian) in the electronic operation notes. The surgical prevalence of endometriosis was the primary outcome. Second, we wanted to explore preoperative pain symptoms.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analyses\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using JMP pro16.2.0. The data were pseudoanonymized prior to analysis. The basic characteristics are presented as the mean and standard deviation (SD) for normally distributed continuous variables, median and interquartile range (IQR) for nonnormally distributed continuous variables and number and percentage for categorical variables.\u003c/p\u003e\n\u003cp\u003eBasic characteristics were compared using two sample t-test for normally distributed variables, Wilcoxon rank sum test for nonnormally distributed variables and Fisher\u0026rsquo;s exact test for nominal variables. Fisher\u0026rsquo;s exact test was also used when comparing different age groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to Finnish Medical Research Act (488/1999) patient\u0026rsquo;s informed consent or ethical approval is not required in a registry-based study. This study was approved by Southwest Finland Hospital District in April 2021 (approval number: T07/009/21). Participant confidentiality was protected, and the data was pseudoanonymized prior to analysis.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBetween 2009 and 2020, laparoscopy was performed on 296 women with pain symptoms suggestive of endometriosis. The annual number of these procedures (Figure 2) varied between 13 and 39 (mean 24.6 and SD 7.1). The mean age of the women was 27.3 years (SD 6.8). The baseline characteristics of the study population are presented in Table 1 and Table 2. Women with and without endometriosis were comparable by age, BMI, and age at menarche. Macroscopic endometriosis was found in 155 (52.4%) laparoscopies (Table 3), and the most common finding was peritoneal endometriosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003eBaseline characteristics of women undergoing diagnostic laparoscopy for chronic pelvic pain suggestive of endometriosis\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"699\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003eTotal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en=296\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003eSubgroups:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003eEndometriosis\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en=155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003eNo endometriosis\u003c/p\u003e\n \u003cp\u003en=141\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003eMean age at surgery, years (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e27.3 (6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003e26.9 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e27.7 (7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003eMean age at menarche (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e12.6 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003e12.5 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e12.7 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003eMedian BMI (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e23.1 (20.9\u0026shy;\u0026shy;\u0026shy;\u0026ndash;26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003e23.0 (21.0\u0026ndash;26.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e23.7(20.8\u0026ndash;27.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003eMedian age at onset of pain symptoms\u003csup\u003eb\u0026nbsp;\u003c/sup\u003e(IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e16 (12.8\u0026ndash;26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003e14 (12\u0026ndash;24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e19 (13\u0026ndash;27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e83/289 (28.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003e46/152 (30.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e37/137 (27.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003eMigraine\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e82/296 (27.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003e43/155 (27.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e39/141 (27.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003eDepression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e55/296 (18.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003e30/155 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e25/141 (17.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e0.77\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003eDyspareunia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e201/245 (82.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003e115/136 (84.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e86/109 (78.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e0.32\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003eDyschezia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e85/234 (36.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003e56/126 (44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e29/108 (26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003eDysuria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e39/199 (19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003e24/102 (23.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e15/97 (15.5)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003eAcyclic abdominal pain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e245/264 (92.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003e123/134 (91.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e122/130 (93.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.03862660944206%\" valign=\"top\"\u003e\n \u003cp\u003eInfertility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e57/296 (19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.032904148783977%\" valign=\"top\"\u003e\n \u003cp\u003e34/155 (21.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.88412017167382%\" valign=\"top\"\u003e\n \u003cp\u003e23/141 (16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.160228898426324%\" valign=\"top\"\u003e\n \u003cp\u003e0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Data are presented as n (%) unless indicated otherwise\u003c/p\u003e\n\u003cp\u003eAbbreviations: SD=standard deviation, BMI=body mass index, IQR=interquartile range\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eBetween subgroups\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u003c/sup\u003eAge at onset of dysmenorrhea (primary or secondary), dyspareunia, dyschezia, dysuria or acyclic abdominal pain.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e Parity and medication of women undergoing diagnostic laparoscopy for chronic pelvic pain suggestive of endometriosis\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"699\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.714285714285715%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.285714285714285%\" valign=\"top\"\u003e\n \u003cp\u003eTotal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en=296\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23%\" valign=\"top\"\u003e\n \u003cp\u003eSubgroups:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.142857142857142%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.714285714285715%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.285714285714285%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23%\" valign=\"top\"\u003e\n \u003cp\u003eEndometriosis\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en=155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003eNo endometriosis\u003c/p\u003e\n \u003cp\u003en=141\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.142857142857142%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.714285714285715%\" valign=\"top\"\u003e\n \u003cp\u003eNulligravida\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.285714285714285%\" valign=\"top\"\u003e\n \u003cp\u003e184/296 (62.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23%\" valign=\"top\"\u003e\n \u003cp\u003e113/155 (72.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e71/141 (50.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.142857142857142%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.714285714285715%\" valign=\"top\"\u003e\n \u003cp\u003eNullipara\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.285714285714285%\" valign=\"top\"\u003e\n \u003cp\u003e199/296 (67.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23%\" valign=\"top\"\u003e\n \u003cp\u003e126/155 (81.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e73/144 (51.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.142857142857142%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.714285714285715%\" valign=\"top\"\u003e\n \u003cp\u003eCurrent hormonal contraception use\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.285714285714285%\" valign=\"top\"\u003e\n \u003cp\u003e185/296 (62.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23%\" valign=\"top\"\u003e\n \u003cp\u003e98/155 (63.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e87/144 (61.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.142857142857142%\" valign=\"top\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.714285714285715%\" valign=\"top\"\u003e\n \u003cp\u003eHave used hormonal contraception\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.285714285714285%\" valign=\"top\"\u003e\n \u003cp\u003e273/282 (96.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23%\" valign=\"top\"\u003e\n \u003cp\u003e148/152 (97.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e125/130 (96.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.142857142857142%\" valign=\"top\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.714285714285715%\" valign=\"top\"\u003e\n \u003cp\u003eCurrent use of NSAID/ paracetamol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.285714285714285%\" valign=\"top\"\u003e\n \u003cp\u003e196/230 (85.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23%\" valign=\"top\"\u003e\n \u003cp\u003e107/125 (85.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e89/105 (84.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.142857142857142%\" valign=\"top\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.714285714285715%\" valign=\"top\"\u003e\n \u003cp\u003eCurrent use of weak opioids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.285714285714285%\" valign=\"top\"\u003e\n \u003cp\u003e53/230 (23.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23%\" valign=\"top\"\u003e\n \u003cp\u003e35/125 (28.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e18/105 (17.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.142857142857142%\" valign=\"top\"\u003e\n \u003cp\u003e0.060\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.714285714285715%\" valign=\"top\"\u003e\n \u003cp\u003eCurrent use of strong opioids\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.285714285714285%\" valign=\"top\"\u003e\n \u003cp\u003e9/230 (3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23%\" valign=\"top\"\u003e\n \u003cp\u003e6/125 (4.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e3/105 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.142857142857142%\" valign=\"top\"\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.714285714285715%\" valign=\"top\"\u003e\n \u003cp\u003eCurrent use of Adjuvant analgesics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.285714285714285%\" valign=\"top\"\u003e\n \u003cp\u003e18/230 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23%\" valign=\"top\"\u003e\n \u003cp\u003e9/125 (7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.857142857142858%\" valign=\"top\"\u003e\n \u003cp\u003e9/105 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.142857142857142%\" valign=\"top\"\u003e\n \u003cp\u003e0.81 \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Data are presented as n (%).\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eBetween subgroups\u003c/p\u003e\n\u003cp\u003e\u003csup\u003eb\u003c/sup\u003eCurrent or previous hormonal contraception use\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003eSurgical findings in women undergoing diagnostic laparoscopy for chronic pelvic pain suggestive of endometriosis\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"699\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.63519313304721%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.894134477825464%\" valign=\"top\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003en=296\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.470672389127326%\" valign=\"top\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.63519313304721%\" valign=\"top\"\u003e\n \u003cp\u003eEndometriosis\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.894134477825464%\" valign=\"top\"\u003e\n \u003cp\u003e155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.470672389127326%\" valign=\"top\"\u003e\n \u003cp\u003e52.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.63519313304721%\" valign=\"top\"\u003e\n \u003cp\u003ePeritoneal endometriosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.894134477825464%\" valign=\"top\"\u003e\n \u003cp\u003e154\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.470672389127326%\" valign=\"top\"\u003e\n \u003cp\u003e52.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.63519313304721%\" valign=\"top\"\u003e\n \u003cp\u003eDeep endometriosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.894134477825464%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.470672389127326%\" valign=\"top\"\u003e\n \u003cp\u003e4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.63519313304721%\" valign=\"top\"\u003e\n \u003cp\u003eEndometrioma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.894134477825464%\" valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.470672389127326%\" valign=\"top\"\u003e\n \u003cp\u003e2.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"44.63519313304721%\" valign=\"top\"\u003e\n \u003cp\u003ePeritoneal adhesions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.894134477825464%\" valign=\"top\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"29.470672389127326%\" valign=\"top\"\u003e\n \u003cp\u003e35.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Data are presented as n (%).\u003c/p\u003e\n\u003cp\u003eThe most common preoperative symptoms other than dysmenorrhea were acyclic abdominal pain (92.8%) and dyspareunia (82.0%) (Table 1). There was no statistically significant difference in the prevalence of these symptoms between women with and without endometriosis.\u003c/p\u003e\n\u003cp\u003eIn total 85/234 (36.3%) women reported dyschezia. Women with endometriosis reported dyschezia more often than women with no endometriosis, 44.4% and 26.9%, respectively (\u003cem\u003eP\u003c/em\u003e=0.006). The prevalence of current dysmenorrhea is not reported, as many patients used continuous hormonal therapy aimed to induce amenorrhea. Preoperative hormonal and analgetic medical therapy are described in Table 2. At the end of laparoscopy an intrauterine device was inserted for 68 (23.0%) women.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this study, no laparoscopies were performed solely because of infertility, but 57 (19.3%) women had infertility with coexisting pelvic pain (Table 1). There was no statistically significant difference in the prevalence of infertility between women with (21.9%) and without (16.3%) endometriosis (\u003cem\u003eP\u003c/em\u003e=0.24). Interestingly, compared with women without visual endometriosis in laparoscopy, women with endometriosis were more often nulligravida (72.6% vs 50.4%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt;0.001) and nulliparous (81.3% vs 51.8%,\u0026nbsp;\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003eThe age distribution of our cohort is presented in Figure 3. To evaluate whether there were any age-related differences in the prevalence of endometriosis, we divided women into five subgroups: under 20, 20\u0026ndash;24, 25\u0026ndash;29, 30\u0026ndash;34 and over 34 (34\u0026ndash;49) years old (Figure 4). The prevalence was highest in the age groups of 20\u0026ndash;24 (56.8%) and 25\u0026ndash;29 (56.2%), and lowest among women older than 34 years old (38.6%). There was no statistically significant difference in the prevalence of endometriosis between the age groups (\u003cem\u003eP\u003c/em\u003e=0.34).\u003c/p\u003e\n\u003cp\u003eTable 4 shows data on preoperative imaging, laboratory testing and endoscopies performed due to pain symptoms. Investigations were mostly performed by primary health care doctors or specialists in other disciplines prior to referral to the Gynecological Outpatient Clinic.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u0026nbsp;\u003c/strong\u003eFrequency of preoperative investigations among the study population\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.659949622166245%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.410579345088163%\" valign=\"top\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003cp\u003en=296\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.929471032745592%\" valign=\"top\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.659949622166245%\" valign=\"top\"\u003e\n \u003cp\u003eLower abdomen MRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.410579345088163%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.929471032745592%\" valign=\"top\"\u003e\n \u003cp\u003e8.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.659949622166245%\" valign=\"top\"\u003e\n \u003cp\u003eAbdominal ultrasound\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.410579345088163%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.929471032745592%\" valign=\"top\"\u003e\n \u003cp\u003e10.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.659949622166245%\" valign=\"top\"\u003e\n \u003cp\u003eAbdominal CT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.410579345088163%\" valign=\"top\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.929471032745592%\" valign=\"top\"\u003e\n \u003cp\u003e8.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.659949622166245%\" valign=\"top\"\u003e\n \u003cp\u003eColonoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.410579345088163%\" valign=\"top\"\u003e\n \u003cp\u003e65\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.929471032745592%\" valign=\"top\"\u003e\n \u003cp\u003e22.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.659949622166245%\" valign=\"top\"\u003e\n \u003cp\u003eGastroscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.410579345088163%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.929471032745592%\" valign=\"top\"\u003e\n \u003cp\u003e10.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.659949622166245%\" valign=\"top\"\u003e\n \u003cp\u003eCapsule endoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.410579345088163%\" valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.929471032745592%\" valign=\"top\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.659949622166245%\" valign=\"top\"\u003e\n \u003cp\u003eCystoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.410579345088163%\" valign=\"top\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.929471032745592%\" valign=\"top\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.659949622166245%\" valign=\"top\"\u003e\n \u003cp\u003eCeliac disease screening\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.410579345088163%\" valign=\"top\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.929471032745592%\" valign=\"top\"\u003e\n \u003cp\u003e20.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"54.659949622166245%\" valign=\"top\"\u003e\n \u003cp\u003eFecal calprotectin \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.410579345088163%\" valign=\"top\"\u003e\n \u003cp\u003e38\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.929471032745592%\" valign=\"top\"\u003e\n \u003cp\u003e12.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eNote: Data are presented as n (%).\u003c/p\u003e\n\u003cp\u003eAbbreviations: MRI, magnetic resonance imaging. CT, computed tomography.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003ea\u003c/sup\u003eTissue transglutaminase immunoglobulin A test\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our historical cohort study, more than half of the women (52.4 %) had endometriosis in diagnostic laparoscopy performed due to CPP. Our study included only women of reproductive age (15\u0026ndash;49), and surgery was performed with the intention to treat endometriosis if detected. According to previous meta-analyses, visible endometriosis is found via laparoscopy in 64% of adolescents and in 42% of adult women with CPP\u0026nbsp;[2,3]. Thus, our results are in line with previous findings.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo our knowledge, our study exploring the prevalence of endometriosis among fertile aged women with CPP is the largest performed in recent years. During last decades, ultrasound imaging of endometriosis and knowledge about the appearance of peritoneal endometriosis in laparoscopy as well as surgical equipment have notably developed, making it difficult to compare our results with those of previous studies.\u003c/p\u003e\n\u003cp\u003eMany previous studies have included postmenopausal women, for example Moradi et al. (2021) in their meta-analysis of adult women with CPP\u0026nbsp;[3]. In addition, a cohort consisting of 3068 diagnostic laparoscopies, performed on women aged 15\u0026ndash;66 years due to CPP between 1994 and 2005 reported a prevalence of 60.2% of endometriosis\u0026nbsp;[6]. The most recent study consisting of 150 women aged 16\u0026ndash;30 years, with a similar study design to ours, reported surgically verified endometriosis in only 20% of laparoscopies\u0026nbsp;[7]. These women suffered from CPP and were reported to be ultrasound negative and to have a normal pelvis in clinical examination preoperatively.\u003c/p\u003e\n\u003cp\u003eLaparoscopy should no longer be considered as the gold standard diagnostic tool for endometriosis, but rather an option when endometriosis cannot be detected by noninvasive imaging and empirical treatment is unsuccessful\u0026nbsp;[1]. Recently this transition in the diagnostic process has been widely discussed\u0026nbsp;[8,9]. Furthermore, it is suggested that the definition of endometriosis should not be based on histology but rather on clinical symptoms and findings. This modification to the definition could help change the diagnostic approach globally away from laparoscopy.[10]\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThere is no clear evidence if laparoscopic treatment of peritoneal endometriosis reduces pain symptoms in the long term. A recent systematic review on laparoscopic surgery for endometriosis concluded, that it remains uncertain whether surgery is effective for pain symptoms compared to \u0026nbsp; diagnostic laparoscopy alone\u0026nbsp;[11]. Presently, two ongoing blinded randomized controlled trials intend to provide information on whether laparoscopic excision of peritoneal endometriosis is helpful or harmful\u0026nbsp;[12,13]. Importantly, it has been suggested that laparoscopy may enhance pelvic pain through several different mechanisms, such as increased sensory hypersensitivity or the development of neuropathic pain\u0026nbsp;[13].\u003c/p\u003e\n\u003cp\u003eThe ESHRE guidelines state that there is no comprehensive evidence that endometriosis can be predicted by women\u0026rsquo;s symptoms, nevertheless having multiple symptoms increases the likelihood of endometriosis\u0026nbsp;[1]. In our study, it would have been impossible to discriminate women with and without endometriosis based on preoperative symptoms only, and almost half of the women (47.6%) undergoing laparoscopy did not have visible endometriosis. Nongynecological pelvic and nonpelvic conditions such as interstitial cystitis, irritable bowel syndrome, fibromyalgia and migraine often contribute to pain symptoms in women with CPP pain\u0026nbsp;[14]. It is estimated that even in 80 % of CPP the origin of the pain is not gynecological\u0026nbsp;[15].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn our study, dyschezia was the only preoperative symptom that differed significantly in prevalence between women with and without endometriosis (44.4% vs 26.9%, \u003cem\u003eP\u003c/em\u003e=0.006). Similar to our findings, in previous studies the prevalence of dyschezia among women with laparoscopic endometriosis diagnosis has been reported to be 32.2\u0026ndash;44.2%\u0026nbsp;[16,17]. In addition, dyschezia during menstruation has been shown to have a strong correlation with the risk of endometriosis\u0026nbsp;[18].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe mean age at the time of diagnostic laparoscopy was similar in women with and without endometriosis, 26.9 and 27.7 years, respectively (\u003cem\u003eP\u003c/em\u003e =0.32). However, women with endometriosis had significantly earlier onset of pain than women without endometriosis (14 vs 19 years, respectively,\u0026nbsp;\u003cem\u003eP\u003c/em\u003e =0.048). This is a major difference clinically and for the individual suffering from pain symptoms. According to the literature, in two-thirds of patients with endometriosis, symptoms start before the age of 20\u0026nbsp;[19,20]. In one recent study of women with surgically confirmed endometriosis, the median age at the onset of endometriosis symptoms was 14 years old\u0026nbsp;[21].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe strengths of our study include the fact, that all laparoscopies were performed or assisted by an experienced surgeon. Therefore, the visual diagnosis of endometriosis is considered reliable. Another strength is that the indications for laparoscopy remained predominantly the same during our study period, and laparoscopy was not the first-line treatment option nor solely a diagnostic method. In addition, the study cohort was moderately sized.\u003c/p\u003e\n\u003cp\u003eThe most important limitation of our study is the retrospective study design. All preoperative symptoms were not collected via a uniform questionnaire; thus, the data may be incomplete. In addition, several gynecologists performed preoperative visits. This increases the heterogeneity of the medical record notes eventually collected for this study. We consider the sensitivity of preoperative ultrasound imaging acceptable as deep endometriosis was found in 4.7% and endometrioma in 2.0% of participants considered ultrasound negative.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eEndometriosis was confirmed in approximately in one half of the women undergoing laparoscopy due to CPP. In most women peritoneal endometriosis was the only finding suggesting that endometrioma and deep endometriosis are detected preoperatively in most cases. Importantly, the other half of the women did not have endometriosis despite having similar pain symptoms prior to surgery. Irrespective of laparoscopy findings, women with CPP should be offered comprehensive and multimodal treatment of chronic pain to improve their quality of life.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo date, it remains unknown whether patients benefit long-term from undergoing diagnostic and therapeutic laparoscopy or surgical treatment for peritoneal endometriosis. Hopefully, ongoing randomized clinical trials will provide us with answers to this well-recognized question.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCPP, chronic pelvic pain\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAccording to Finnish Medical Research Act (488/1999) patient\u0026rsquo;s informed consent or ethical approval is not required in a registry-based study. This study was approved by Southwest Finland Hospital District in April 2021 (approval number: T07/009/21). Participant confidentiality was protected, and the data was pseudoanonymized prior to analysis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are not publicly available due to privacy restrictions, but anonymized data are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSaima Siivonen has stated that there are no conflicts of interest. Pia A. Suvitie has received consultancy and speaker\u0026rsquo;s fees from Gedeon Richter Nordics.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted without external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePS and SS planned and designed the study. SS collected the data with input from PS. SS performed the statistical analysis. SS drafted the first manuscript, which was further thoroughly edited by PS. Both authors contributed to all faces of this study and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBecker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, et al. ESHRE guideline: endometriosis. Hum Reprod Open. 2022 Mar 4;2022(2). \u003c/li\u003e\n\u003cli\u003eHirsch M, Dhillon-Smith R, Cutner AS, Yap M, Creighton SM. The Prevalence of Endometriosis in Adolescents with Pelvic Pain: A Systematic Review. J Pediatr Adolesc Gynecol. 2020 Dec 1;33(6):623\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eMoradi Y, Shams-Beyranvand M, Khateri S, Gharahjeh S, Tehrani S, Varse F, et al. A systematic review on the prevalence of endometriosis in women. Vol. 154, Indian Journal of Medical Research. 2021. \u003c/li\u003e\n\u003cli\u003eMowers EL, Lim CS, Skinner B, Mahnert N, Kamdar N, Morgan DM, et al. Prevalence of Endometriosis During Abdominal or Laparoscopic Hysterectomy for Chronic Pelvic Pain. Obstet Gynecol. 2016 Jun 1;127(6):1045\u0026ndash;53. \u003c/li\u003e\n\u003cli\u003e| 2013 OHJAUS THL-Toimenpideluokitus THL-\u0026Aring;tg\u0026auml;rdskalssifikation. \u003c/li\u003e\n\u003cli\u003eKang SB, Chung HH, Lee HP, Lee JY, Chang YS. Impact of diagnostic laparoscopy on the management of chronic pelvic pain. Surg Endosc Other Interv Tech. 2007;21(6):916\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eTempest N, Efstathiou E, Petros Z, Hapangama DK. Laparoscopic outcomes after normal clinical and ultrasound findings in young women with chronic pelvic pain: A cross-sectional study. J Clin Med. 2020;9(8):1\u0026ndash;10. \u003c/li\u003e\n\u003cli\u003eChapron C, Marcellin L, Borghese B, Santulli P. Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol. 2019;15(11):666\u0026ndash;82. \u003c/li\u003e\n\u003cli\u003eTaylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet. 2021;397(10276):839\u0026ndash;52. \u003c/li\u003e\n\u003cli\u003eAgarwal SK, Chapron C, Giudice LC, Laufer MR, Leyland N, Missmer SA, et al. Clinical diagnosis of endometriosis: a call to action. Am J Obstet Gynecol. 2019 Apr 1;220(4):354.e1-354.e12. \u003c/li\u003e\n\u003cli\u003eBafort C, Beebeejaun Y, Tomassetti C, Bosteels J, Duffy JMN. Laparoscopic surgery for endometriosis. Cochrane database Syst Rev. 2020 Oct 23;10(10). \u003c/li\u003e\n\u003cli\u003eMackenzie SC, Stephen J, Williams L, Daniels J, Norrie J, Becker CM, et al. Effectiveness of laparoscopic removal of isolated superficial peritoneal endometriosis for the management of chronic pelvic pain in women (ESPriT2): protocol for a multi-centre randomised controlled trial. Trials. 2023;24(1):1\u0026ndash;15. \u003c/li\u003e\n\u003cli\u003eMarschall H, Forman A, Lunde SJ, Kesmodel US, Hansen KE, Vase L. Is laparoscopic excision for superficial peritoneal endometriosis helpful or harmful? Protocol for a double-blinded, randomised, placebo-controlled, three-armed surgical trial. BMJ Open. 2022;12(11):1\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eTill SR, Nakamura R, Schrepf A, As-Sanie S. Approach to Diagnosis and Management of Chronic Pelvic Pain in Women: Incorporating Chronic Overlapping Pain Conditions in Assessment and Management. Obstet Gynecol Clin North Am. 2022 Jun 1;49(2):219\u0026ndash;39. \u003c/li\u003e\n\u003cli\u003eLamvu G, Carrillo J, Ouyang C, Rapkin A. Chronic Pelvic Pain in Women: A Review. JAMA - J Am Med Assoc. 2021;325(23):2381\u0026ndash;91. \u003c/li\u003e\n\u003cli\u003eAbrao MS, Andres MP, Miller CE, Gingold JA, Rius M, Neto JS, et al. AAGL 2021 Endometriosis Classification: An Anatomy-based Surgical Complexity Score. J Minim Invasive Gynecol. 2021 Nov 1;28(11):1941-1950.e1. \u003c/li\u003e\n\u003cli\u003eSchliep KC, Mumford SL, Peterson CM, Chen Z, Johnstone EB, Sharp HT, et al. Pain typology and incident endometriosis. Hum Reprod. 2015 Oct 1;30(10):2427\u0026ndash;38. \u003c/li\u003e\n\u003cli\u003eNnoaham KE, Hummelshoj L, Kennedy SH, Jenkinson C, Zondervan KT. Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study. Fertil Steril. 2012;98(3). \u003c/li\u003e\n\u003cli\u003eBallweg M Lou. Impact of endometriosis on women\u0026rsquo;s health: Comparative historical data show that the earlier the onset, the more severe the disease. Best Pract Res Clin Obstet Gynaecol. 2004;18(2):201\u0026ndash;18. \u003c/li\u003e\n\u003cli\u003eGreene R, Stratton P, Cleary SD, Ballweg M Lou, Sinaii N. Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis. Fertil Steril. 2009 Jan;91(1):32\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eSasamoto N, Shafrir AL, Wallace BM, Vitonis AF, Fraer CJ, Sadler Gallagher J, et al. Trends in pelvic pain symptoms over 2 years of follow-up among adolescents and young adults with and without endometriosis. Pain. 2023 Mar;164(3):613\u0026ndash;24. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"endometriosis, peritoneal, diagnosis, prevalence, laparoscopy, pain symptoms, chronic pelvic pain","lastPublishedDoi":"10.21203/rs.3.rs-4177916/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4177916/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e When peritoneal endometriosis is clinically suspected, empirical medical therapy should be the first-line treatment. Diagnostic and therapeutic laparoscopy may be offered after failed or unsuitable medical therapy in women with severe pelvic pain and no imaging findings. Our objective was to determine how often endometriosis is verified among these women via laparoscopy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: In our registry-based historical cohort we identified 296 women aged 15–49 undergoing laparoscopy due to chronic pelvic pain, between 2009 and 2020 at Turku University Hospital. Women without preoperative ultrasound findings and no history of endometriosis were included in the study. We collected preoperative characteristics and intraoperative findings from the hospital patient records. The prevalence of endometriosis in laparoscopy was the primary outcome.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Macroscopic endometriosis was detected in 52.4% of laparoscopies, and the rate was similar throughout the study period. Peritoneal endometriosis was found in 52% of participants, deep endometriosis in 4.7% and a small endometrioma in 2%. Women with and without endometriosis reported similar preoperative rates of acyclic abdominal pain (91.8% vs 93.9%, \u003cem\u003eP\u003c/em\u003e=0.64) and dyspareunia (84.6% vs 78.9%, \u003cem\u003eP\u003c/em\u003e =0.32), while dyschezia was significantly more common among women with endometriosis (44.4% vs 26.9%, \u003cem\u003eP\u003c/em\u003e =0.006). The prevalence of dysmenorrhea is not reported, as 62.5% of patients used hormonal therapy commonly aiming to amenorrhea. The median age at the onset of symptoms was significantly lower in women with endometriosis (14 vs 19, \u003cem\u003eP\u003c/em\u003e =0.048).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Endometriosis was confirmed in 52.4% of the women undergoing laparoscopy due to chronic pelvic pain, and in most women, peritoneal endometriosis was the only finding. However, the other half of the women did not have endometriosis despite having similar pain symptoms. Two preoperative characteristics differed significantly between the groups; women with endometriosis had earlier onset of pain symptoms and they reported dyschezia more commonly. It remains unknown whether patients benefit long-term from undergoing diagnostic and therapeutic laparoscopy.\u003c/p\u003e","manuscriptTitle":"Prevalence of endometriosis in diagnostic and therapeutic laparoscopy among women with chronic pelvic pain","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-29 12:37:01","doi":"10.21203/rs.3.rs-4177916/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"47decd22-8051-449c-a9db-11890ca1d81c","owner":[],"postedDate":"April 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-11T07:26:41+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-29 12:37:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4177916","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4177916","identity":"rs-4177916","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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