{"paper_id":"482d3666-fc51-47b1-9e28-8273fb279327","body_text":"Endometriosis is a benign gynaecologic disorder mainly observed in reproductive age women that has a global\nprevalence of 5-15% ( 1 ). The most common symptoms\nof endometriosis include chronic pelvic pain, dysmenorrhea, menorrhagia, dyspareunia, gastrointestinal (GI)\ncomplaints, and urinary symptoms ( 2 ); some cases may\nremain asymptomatic or may have mild symptoms,\nwhereas others may only present with disease complications such as chronic pelvic pain and infertility ( 3 ).\nThe disease severity of endometriosis varies based on\nthe lesion site and penetration of the endometriotic lesions into the peritoneum; deep infiltrating endometriosis (DIE) has the worst prognosis and most severe symptoms ( 4 ).\nSeveral hypotheses have been proposed for the pathogenesis of endometriosis; however, the majority of patients’ symptoms appear to be associated with inflammation and proliferation of endometriotic lesions ( 5 ) that\nresult from the secretion of cytokines and growth factors\nsuch as tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), and cancer antigen 125 (CA-125,\nused for diagnosis of endometriosis) ( 6 ). Anti-Müllerian\nhormone (AMH) is a member of the TGF-β superfamily and considered a valuable serum marker for a general measurement of ovarian reserve and also in women with\nendometriosis ( 7 ).\nThe clinical symptoms of endometriosis are not specific\nand serum/peripheral biomarkers can only predict endometriosis ( 8 ); therefore, direct observation of lesions during surgery and histologic confirmation of the specimens\nare considered the gold standard for diagnosis and treatment ( 9 ). A six-year follow-up of 1315 patients confirmed\nthat laparoscopic treatment of endometriosis resulted in\nsignificant reductions in pain and resolution of infertility,\nwhich resulted in pregnancy after surgery (spontaneous or\nassisted) ( 10 ). Due to the need for ongoing reporting and\nmore detailed follow-up after surgery for endometriosisassociated pain, in this study we aimed to describe the\nclinical characteristics of women who underwent laparoscopic surgery for treatment of endometriosis as well as\nthe effect of surgery on patients’ pain and serum levels of\nAMH and CA-125.\n\nIn this cohort study, all women who referred to Farmaniyeh Hospital in Tehran, from August 2015 to December 2017 for surgical treatment of endometriosis\nenrolled in this study. Diagnosis of endometriosis was\nbased on the clinical symptoms of endometriosis and the\nresults of imaging tests (ultrasound and magnetic resonance imaging [MRI]) in patients with severe pain or\nboth pain and infertility who were indicated for surgical treatment. Those with surgically confirmed endometriosis stages III or IV were included in this study\nby the census method, after they received explanations\nabout the study objectives and read and sign the written\ninformed consent form. The Ethics Committee of Farmaniyeh Hospital approved the study protocol (FH-02-\n005). This study was conducted in accordance with the\nprinciples of the Declaration of Helsinki and its subsequent amendments.\nThe surgeries for all enrolled patients were performed\nby one surgical team of two gynaecologic laparoscopic\nsurgeon.\nFor this purpose, after induction of general anaesthesia by the anaesthesiologist, the trocars were inserted in\ntheir place and the abdomen and pelvic cavity were explored. After visualization of the endometrioma, the cyst\nwall was excised and the ovarian adhesions were released\nto mobilize the ovaries, and the DIE lesions were totally\nresected.\nThe researcher used a study checklist to record the\nparticipants’ demographic characteristics (age, height,\nweight, body mass index [BMI], marital status, educational level, and occupational status), gynaecological characteristics (age at menarche and menopause,\nmenorrhagia, metrorrhagia, dysmenorrhea, dyspareunia, regular or irregular menstruation, history of endometriosis surgery, history of infertility before surgery, and indication for surgery), and endometriotic-related\ncharacteristics (type of endometriotic lesion, presence\nof endometrioma, its type and side, and the anatomical\nsite of the DIE). The information was collected from\nthe hospital medical records and completed by conferring with the patients (history taking). Cases of recurrence, reoperation, and pregnancy after surgery with or\nwithout assisted reproductive technique (ART) were\nrecorded. Follow-up information was collected during\npost-surgical follow-up visits or by phone contact with\npatients who did not return for their follow-up visits.\nRecurrence was defined as recurrence of endometrioma\nor pain. Cases with recurrence were treated by medical\ntherapy and surgery, if required.\nThe participants were asked to record their pain severity\nbefore and three months after surgery on a numeric rating\nscale (NRS), which was scored from 0 to 10 where 0 indicated no pain and 10 indicated the worst pain. Two blood\nsamples were taken from the patients, one before surgery\nand three months after surgery. The samples were sent to\nthe laboratory for measurement of serum levels of AMH\nand CA-125 antigen. The tumour markers were measured\nusing an Enzyme linked Fluorescent Assay (ELFA) technique (TOSOH Co.) and CA-125 levels <35 were considered normal. AMH was measured using ELISA kits\n(Beckman Coulter Co., USA). AMH levels of 4.0-6.8\nindicated optimal fertility, 2.2-4.0 indicated satisfactory\nfertility, 0.3-2.2 indicated low fertility, and <0.3 indicated\nvery low fertility.\nCases who were not confirmed as having endometriosis\nby surgical inspection were excluded from the study and\nnot included in the statistical analysis.\nThe results were described by frequency (%) for categorical variables and by mean ± standard deviation (SD)\nfor quantitative variables. The results of the Kolmogorov-Smirnov test showed normal distribution of the data;\ntherefore, we used the paired t test to compare numeric\nvariables before and after surgery. The chi square test\nwas used to compare frequencies between the groups. For\nstatistical analysis, we used the IBM SPSS Statistics for\nWindows version 21.0 (IBM Corp., Armonk, NY, USA.)\nstatistical software. P<0.05 were considered statistically\nsignificant.\n\nThe 174 women who completed the study had a\nmean age of 34.86 ± 6.47 (18-49) years. Most (60.9%)\nwere married, about half (49.4%) were unemployed/\nhousewives, and 64.3% had an academic education. Table\n1 lists the demographic and gynaecologic characteristics\nof the participants. The indication for surgery was pain\nin the majority (68.4%) of patients and both pain and\ninfertility in the rest.\nTypes of endometriotic lesions included:\nendometrioma (19%, n=33), DIE (3.4%, n=6), and both endometrioma and DIE (77.6%, n=135); 77.4%\nof cases with endometrioma were bilateral (n=130)\nand 22.6% (n=38%) were unilateral. The frequency\nof endometrioma located on the left side (57.9%) was\nsignificantly higher than the right side (42.1%, P=0.003),\nbut the frequency of DIE on the left or right sides did\nnot have any significant difference (47.6 vs. 52.4%,\nrespectively, P=0.371). As shown, the most common site\nof DIE was the ovarian fossa and the least common site\nwas the vaginal vault (1.19%).\nDemographic and gynaecologic characteristics of the study\npopulation\nSD; Standard deviation and BMI; Body mass index.\nParticipants reported a reduction in pain from 6.79 ± 2.19\nbefore surgery to 1.48 ± 1.68 after surgery; in addition,\nserum levels of AMH reduced from 2.80 ± 1.86 ng/mL\nbefore surgery to 1.76 ± 1.40 ng/mL after surgery and that\nof CA-125 from 220.25 ± 257.06 U/mL before surgery to\n23.27 ± 23.25 U/mL after surgery (all P<0.001,  Table 2 ).\nFigure 1 shows the trend of changes in pain, AMH, and\nCA-125. Postoperative follow-up showed recurrence in\n21.2% of patients and 13.5% of these patients underwent\nadditional surgery. The total reoperation rate was 2.8%.\nOf 55 patients who had a positive history of infertility, 43\n(78.1%) became pregnant after surgery, 54.5% of these\nwere spontaneous and without ART, and 23.6% with the\nuse of ART.\nThe post-surgical outcome of the study participants\nSD; Standard deviation, AMH; Anti-Müllerian hormone, CA-125; Cancer antigen 125, and\nART; Assisted reproductive technique.\nThe changes in mean scores of pain, and serum levels of anti-Müllerian hormone (AMH) and cancer antigen 125 (CA-125) post-surgery\ncompared to pre-surgery. CI; Confidence interval.\n\nIn this study, we described the characteristics of\n174 women with endometriosis, indicated for surgical\ntreatment, and reported the follow-up results of these\npatients. The age range of 18 to 49 years (mean age:\n34.86 years) and menopause in only seven of our patients\nconfirmed the main occurrence of endometriosis in\nwomen of reproductive age and its rare occurrence after\nmenopause ( 1 ). The mean age of menarche in the present\nstudy (12.15 years) also confirmed the results of a meta-analysis of 47 Iranian studies ( 11 ).\nEndometrioma and DIE were present in 96.6% and 81%\nof patients, respectively, alone or in combination. The\nhigh frequency of coexistence of endometrioma and DIE\nrefers to their association, as reported previously ( 12 ).\nFurthermore, as our patients were surgical candidates,\nthe high frequency of endometrioma and DIE confirmed\nthe association of these two with increased disease\nseverity, as suggested previously ( 13 ). Most cases of\nendometrioma were bilateral (77.4%) and the frequency of\nleft-sided endometrioma was higher. A higher frequency\nof endometriosis on the left side is anticipated to result\nfrom the anatomical differences of abdomen (presence\nof diaphragm on the right side) and hemipelvis (presence\nof sigmoid colon on the left side) ( 14 ). Right and left\novarian fossa were also the most common sites of DIE in\nour study, which was in line with evidence that suggested\nan association of ovarian involvement with more severe\nDIE ( 15 ).\nThe primary endometriosis symptoms in our patients\nincluded dysmenorrhea (95.9%) and dyspareunia (58%),\nwhile menstruation-related problems such as menorrhagia,\nmetrorrhagia, and irregular menstruation had a frequency\nof 20-25%. Different frequencies have been reported in\nwomen with endometriosis ( 16 ,  17 ). However, of note is\nthe significance of different forms of pain (dysmenorrhea\nand dyspareunia) in women with endometriosis in our\nstudy that referred to the importance of endometriosisassociated pain, which was in line with the results of\nprevious studies that referred to the important role of pain\nand the impact of endometriosis on a woman’s life ( 18 ).\nPain was the indication of surgery in all patients (with or\nwithout infertility) and assessing the pain severity in our\npatients showed a high severity of pain in women before\nsurgery (mean: 6.79), which confirmed the significance of\npain in these patients. After surgery, a significant decrease\nwas observed in patients’ pain. In the study by Alborzi et\nal. ( 10 ), a six-year follow-up of patients showed reduced\npain scores from 8.23 to 4.46 in 93.07% of patients. The\ndifferences in the scores could be due to the different\nevaluations of the patients from pain, as the assessment\ntool is a self-report tool and due to the different surgical\ndetails used because of the different sites and penetrations\nof endometriotic lesions. A meta-analysis of 1847 patients\n(23 studies) also showed significant reductions in pain after\nendometriosis surgery with a decrease of approximately\n4.5-5.2 units in the pain scores, which differed based on the duration of the follow-up period ( 19 ). These results\nalso confirmed the present study findings and suggested\nthat the endometriotic lesions caused inflammation and\nactivated the central nervous system (CNS). Therefore,\nexcision of these lesions resolved these problems and the\nresulting pain ( 20 ). However, it has been reported that\nsome cases may recur over time ( 21 ). In our study, we\nobserved recurrence in 21.2% cases and a total of 2.8%\nrequired additional surgery. These results were in line with\nthat reported by Asadzadeh and colleagues on an Iranian\npopulation where 28.6% of cases recurred after surgery\n( 22 ). The different surgical details and the difference in\nthe frequency of lesions’ sites might affect the recurrence\nrate.\nAnother important aspect of endometriosis is infertility.\nIn the present study, the majority of our patients were\nmarried and infertility was observed in more than half\nof the married cases (51.8%) and about one-third of\nall cases (31.6%), which referred to the significance of\ninfertility in women with endometriosis. The follow-up in our study showed that 78.1% of infertile women\nbecame pregnant after surgery, 54.5% were spontaneous\nand 23.6% after ART. In a study by Alborzi et al. ( 10 ),\n58.1% of infertile women became pregnant during the\nfollow-up period, which was lower than the present\nstudy results. Furthermore, the frequency of infertility\nwas also lower in their study (about 15%) compared\nto the current study. Infertility is one of the indications\nof surgical treatment for endometriosis and one of the\nmain goals of the surgical treatment ( 23 ). Therefore, it is\nnecessary to pay more attention to this issue. Depletion\nof ovarian reserve is reported to be one of the causes\nof endometriosis-related infertility ( 24 ). Hence, AMH,\nlevels are commonly measured for assessment of ovarian\nreserve and it is also suggested to be measured in women\nwith endometriosis ( 25 ). In the present study, although a\nstatistically significant reduction was observed in serum\nlevels of AMH, both pre- and post-surgical values were\nwithin the normal range. These results were in line with\na report by Streuli and colleagues, which suggested that\nendometriosis did not result in decreased serum AMH\nlevels and low AMH levels were only observed in patients\nwith surgical histories of endometriosis ( 26 ). Others have\nalso reported a decline in serum AMH levels after surgery\n( 27 ) that was associated with bilaterality and disease\nseverity ( 28 ), which confirmed the results of the present\nstudy.\nAs a reliable marker for diagnosis of endometriosis, CA-125 was also measured in the present study and the results\nshowed that the significantly high mean pre-surgical level\nof CA-125 reduced after surgery. These results confirmed\nthe previous study results, considering the high level\nof CA-125 in peritoneal fluid and sera of patients with\nendometriosis ( 8 ) and significant reduction (25.8%) in\nCA-125 levels after surgery ( 29 ). This high molecular\nweight glycoprotein, produced in the epithelium, can be a\ngood marker for diagnosis and follow-up of endometriosis.\nOne of the limitations of the present study was the small sample size and nonrandomized patient enrolment.\nFurthermore, the pain assessment tool is a self-report\ntool and is exposed to subjective bias. Because of the\nmultifactorial nature of endometriosis, the effect of\nconfounders on the study results cannot be rejected;\nhowever, we evaluated a wide range of variables to\novercome this issue.\n\nThe results of the present study showed that surgical\ntreatment of endometriosis could have a favourable effect\non patients’ pain and infertility with a minimal rate of\nreoperation and acceptable recurrence rate. However, the\nrole of AMH in endometriosis and the serum level of CA-125 after surgery should be studied in future research.","source_license":"CC0","license_restricted":false}