{"paper_id":"fcc58263-4f45-4800-981b-5044dca728b7","body_text":"Yonsei Med J   http://www.eymj.org   Volume 56   Number 4   July 2015 1079\nThe Prognostic Value of  Individual Adhesion Scores  \nfrom the Revised American Fertility Society Classification  \nSystem for Recurrent Endometriosis \nBo Hyon Yun,\n1,2\n Young Eun Jeon,\n2,3\n Seung Joo Chon,\n4\n Joo Hyun Park,\n2,3\n Seok Kyo Seo,\n1,2\n  \nSiHyun Cho,\n2,3\n Young Sik Choi,\n1,2\n Ji Sung Lee,\n4\n and Byung Seok Lee\n1,2\n1Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul;\n2Institute of Women’s Life Medical Science, Yonsei University College of Medicine, Seoul; \n3Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul;\n4Department of Obstetrics and Gynecology, Gil Hospital, Graduate School of Medicine, Gachon University of Medicine and Science, Incheon, Korea.\nReceived: July 25, 2014\nRevised: October 14, 2014\nAccepted: October 14, 2014\nCo-corresponding authors: Dr. Byung Seok Lee, \nDepartment of Obstetrics and Gynecology, \nSeverance Hospital, Yonsei University College \nof Medicine, 50-1 Yonsei-ro, Seodaemun-gu, \nSeoul 120-752, Korea.\nTel: 82-2-2228-2230, Fax: 82-2-313-8357\nE-mail: dr222@yuhs.ac and\nDr. Ji Sung Lee, \nDepartment of Obstetrics and Gynecology, \nGil Hospital, Graduate School of Medicine, \nGachon University of Medicine and Science, \n21 Namdong-daero 774beon-gil, Namdong-gu, \nIncheon 405-760, Korea.\nTel: 82-32-2019-3435, Fax: 82-32-3462-8209\nE-mail: dongwook@gilhospital.com\n∙ The authors have no financial conflicts of \ninterest.\n© Copyright:\nYonsei University College of Medicine 2015\nThis is an Open Access article distributed under the \nterms of the Creative Commons Attribution Non-\nCommercial License (http://creativecommons.org/ \nlicenses/by-nc/3.0) which permits unrestricted non-\ncommercial use, distribution, and reproduction in any \nmedium, provided the original work is properly cited.\nPurpose: This study aimed to evaluate the prognostic value of each component of \nthe revised American Fertility Society (rAFS) classification system for the first re-\ncurrence of endometriosis after conservative laparoscopy. Materials and Meth-\nods: As this was a retrospective cohort study, data were collected by reviewing \nmedical records. A total of 379 women ages 18 to 49 years were included. Women \nwho underwent conservative laparoscopy with histologic confirmation of endome-\ntriosis at Gangnam Severance Hospital between March 2003 and May 2010 were \nincluded. Individual components of the rAFS classification system as well as preop-\nerative serum CA-125 levels were retrospectively analyzed to assess their prognos-\ntic values for recurrence of endometriosis. Results: Of 379 patients, 80 (21.2%) \nwere found to have recurrence of endometriosis. The median duration of follow-up \nwas 19.0 months, and the mean age at the time of surgery was 31.8±6.7 years. In \nendometriosis of advanced stage, younger age at the time of surgery, bilateral ovari-\nan cysts at the time of diagnosis, a rAFS ovarian adhesion score >24, and complete \ncul-de-sac obliteration were independent risk factors of poor outcomes, and a rAFS \novarian adhesion score >24 had the highest risk of recurrence [hazard ratio=2.948 \n(95% CI: 1.116‒7.789), p=0.029]. Conclusion: Our results suggest that of the \nrAFS adnexal adhesion scores, the ovarian adhesion score rather than the tubal ad-\nhesion score was associated with a significantly increased risk of recurrent endome-\ntriosis. The preoperative serum CA-125 level may be also a significant prognostic \nfactor for recurrence, as known. However, it seemed to only have borderline signifi-\ncance in affecting recurrence in the current study.\nKey Words:\n   Endometriosis, recurrence, prognostic factor, rAFS classification, \novarian adhesion\nINTRODUCTION\nEndometriosis is a common benign gynecologic disease defined by the presence of \nOriginal Article\nhttp://dx.doi.org/10.3349/ymj.2015.56.4.1079\npISSN: 0513-5796, eISSN: 1976-2437          Yonsei Med J 56(4):1079-1086, 2015\n\n\nBo Hyon Yun, et al.\nYonsei Med J   http://www.eymj.org   Volume 56   Number 4   July 20151080\nthe uterus and at least one ovary intact. Exclusion criteria in-\ncluded previous medical or surgical treatment of endometri-\nosis, previous pelvic surgery for uterine or ovarian masses, \nextrapelvic endometriosis, such as vaginal, abdominal wall, \nor pulmonary endometriosis, and malignancy. Conservative \nlaparoscopy was performed by three gynecologic laparosco-\npy specialists. All surgical procedures aimed for complete \nremoval of all gross lesions and anatomical restoration to \npreserve or restore reproductive function; additionally, the \nprocedure included electrofulguration or excision of endo-\nmetriotic implants on the peritoneum, excision of endome-\ntriomas, and lysis of adhesions. The type of surgery was \nchosen and tailored for each individual case, with consider-\nation for the severity of the disease. Postoperative medica-\ntions included gonadotropin-releasing hormone agonists \n(GnRHa) and/or hormone therapy such as oral contracep-\ntives, oral progestins, and a levonorgestrel-intrauterine sys-\ntem. After surgery, pelvic ultrasonography was performed \nevery 6‒12 months. The recurrence of endometriosis was \ndefined as the recurrence of dysmenorrhea as pain recurring \nafter surgery with a severity score equal to or higher than \nthat before surgery or the recurrence of endometriomas with \nthe presence of ovarian cysts 2 cm in diameter for more than \ntwo consecutive menstrual cycles.4,5,9,11\nClinical characteristics and operative findings were record-\ned for all study subjects including age at the time of surgery, \nbody mass index, age at menarche, parity, menstrual history, \ncoexisting adenomyosis, type of surgery, postoperative med-\nications, pregnancy after surgery, the preoperative serum \nCA-125 level, the size of the largest cyst, anatomical loca-\ntion, rAFS stage, and rAFS score. The severity of endometri-\nosis was determined by scores derived from the rAFS classi-\nfication system10 according to operative findings including \nthe location, size, extent, depth, and density of the endometri-\noma and adhesions. These rAFS component scores included \na spot score, an ovarian cyst score, an ovarian and tubal ad-\nhesion score, the bilaterality of ovarian cysts and ovarian and \ntubal adhesions, and cul-de-sac (CDS) obliteration. The \nscores were assigned by the gynecologist who performed \nthe surgery. Serum CA-125 was checked after the initial di-\nagnosis, up to 2 weeks prior to surgery. The level of serum \nCA-125 was measured with a CA-125 II electrochemilumi-\nnescence immunoassay using the Roche/Hitachi Modular \nAnalytics E170 (Roche Diagnostics, Tokyo, Japan). \nContinuous data are presented as means±standard devia-\ntions or medians and interquartile ranges. Categorical data \nare presented as numbers and percentages. To compare vari-\nendometrial glands and stroma outside of the uterus.1,2 The \ndisease typically affects women of reproductive age and re-\nmains a major cause of disability stemming from dysmenor-\nrhea, chronic pelvic pain, and subfertility.1 Surgery is a con-\nfirmed option for relieving pain and also may improve \nfertility; since recent years, it has been performed by lapa-\nroscopy with results equivalent to or better than surgery by \nlaparotomy.3 However, the postoperative recurrence rates af-\nter 3 years range from 15‒30%,3 with half of these patients \nrequiring reoperation.4\nRecurrence of endometriosis leads to several concerns in \nwomen of reproductive age in terms of lowered quality of \nlife caused by recurrent pain and a compromised ovarian re-\nserve due to recurrent endometriomas; such issues may \ncause the clinician to hesitate when deciding the treatment \nmodality. As is well known, a longer postoperative treat-\nment of endometriosis results in less recurrence. However, \nthere are no definite prognostic factors for recurrence that \ncan be used in the clinical field during the follow-up period, \nalthough many studies have been conducted to identify the \nrisk factors for recurrence of endometriosis.5-9\nThe revised American Fertility Society (rAFS) classifica-\ntion system is the most widely-used method of determining \nthe severity of endometriosis by point scoring followed by \nstaging. Almost all studies that have utilized the rAFS clas-\nsification system have addressed the use of rAFS stage and \nscore as risk factors; however, few studies have evaluated \nthe predictive value of each separate component of the sys-\ntem.10 In the present study, we aimed to investigate the risk \nfactors of recurrent endometriosis by evaluating components \nof rAFS system from previous surgeries. \nMATERIALS AND METHODS\nWe retrospectively reviewed the medical records of women \nages 18 to 49 years who underwent conservative laparosco-\npy with histologic confirmation of endometriosis at Gang-\nnam Severance Hospital from March 2003 to May 2010. \nThe participants provided written informed consent to par-\nticipate in this study, and we received the data in an anony-\nmized form. This study was carried out in accordance with \nthe ethical standards of the Helsinki Declaration and was ap-\nproved by the Institutional Review Board of Gangnam Sev-\nerance Hospital (3-2011-0282).\nConservative laparoscopy was defined as laparoscopic \nsurgical removal of all endometriotic lesions while leaving \n\nPrognostic Factors for Recurrent Endometriosis\nYonsei Med J   http://www.eymj.org   Volume 56   Number 4   July 2015 1081\nwhom 80 (21.2%) had recurrent endometriosis after laparo-\nscopic surgery. The median duration of follow-up was 19.0 \nmonths. The clinical characteristics of patients with and \nwithout recurrence of endometriosis are presented in Table \n1. Significant differences were found between the two \ngroups with respect to age at the time of surgery, parity, the \ntype of surgery performed, and preoperative CA-125 level. \nTable 2 shows operative findings including data for the \nrAFS classification system components for both groups. In \naddition to the rAFS total score and stage, the size of the \nlargest cyst, the rAFS cyst score, the rAFS adnexal adhesion \nscore, the rAFS ovarian adhesion score, and the rAFS tubal \nadhesion score were significantly higher in the recurrent en-\ndometriosis group than in the non-recurrent group. There \nwere also significant differences between the two groups in \nterms of the anatomical location of the cysts, the bilaterality \nof the cysts, and the bilaterality of the adnexal adhesions. Of \nthe adnexal adhesions, only the frequency of bilateral ovari-\nan adhesions showed a significant difference between gro-\nups, while bilateral tubal adhesions did not. The frequencies \nof no, partial, and complete CDS obliteration were 36.3%, \n27.4%, and 36.3% in the recurrent endometriosis group and \n45.2%, 36.4%, and 18.4% in the non-recurrent group, re-\nables between the recurrent and non-recurrent groups, two-\nsample t-tests were used for continuous variables, and chi-\nsquare or Fisher’s exact tests were used for categorical var-\niables where appropriate. A Kaplan-Meier survival analysis \nwas used to determine the univariate relationship of the \nrAFS ovarian adhesion scores to disease-free survival times. \nLog-rank tests were used to examine significant differences \nin hazard distributions between groups according to rAFS \novarian adhesion scores. A Cox multivariate analysis was \nperformed to eliminate confounding factors and to identify \nsignificant variables that could independently contribute to \nthe recurrence of endometriosis. A multivariate model was \nbuilt using factors that had p-values<0.05 on univariate anal-\nysis and excluding factors that potentially had either multi-\ncollinearity or clinical correlation. For all analyses, a p-val-\nue<0.05 was considered to be statistically significant. All \nstatistical analyses were conducted using SPSS software \nversion 18.0 (SPSS Inc., Chicago, IL, USA). \nRESULTS\nThe medical records of 379 patients were reviewed, of \nTable 1. Clinical Characteristics of Participants\nVariables\nDescriptive statistics Univariate analysis\nRecurrent \n(n=80)\nNon-recurrent \n(n=299) p value Hazard ratio \n(95% CI) p value\nDuration of follow-up (months)   27.21±16.87   25.02±21.88 0.041\nAge at time of surgery (yrs) 28.78±5.51 32.51±6.99 <0.0001 0.926 (0.893‒0.959) <0.0001\nParity (%) 0.006\n0 (ref) 66 (82.5) 194 (64.9) 1\n1   9 (11.3)   46 (15.4) 0.518 (0.258‒1.040) 0.064\n≥2 5 (6.3)   59 (19.7) 0.256 (0.103‒0.636) 0.003\nType of surgery (%) 0.011\nLaparoscopic electrocauterization  \n  only (ref) 7 (8.8)   6 (2.0) 1\nLaparoscopic cystectomy 64 (80.0) 242 (80.9) 0.576 (0.263‒1.262) 0.168\nLaparoscopic oophorectomy   9 (11.3)   51 (17.1) 0.318 (0.118‒0.855) 0.023\nPostoperative medication (%) 0.071\nNone 13 (16.3)   58 (19.4) 0.721 (0.387‒1.345) 0.304\nGnRHa only (ref) 43 (53.8) 114 (38.1) 1\nGnRHa with subsequent hormone  \n  therapy 22 (27.5) 106 (35.5) 0.398 (0.238‒0.666) <0.0001\nHormone therapy only 2 (2.5) 21 (7.0) 0.397 (0.096‒1.645) 0.203\nPreoperative serum CA-125 (U/mL) (%) 0.002\n≤35 (ref) 12 (16.2) 100 (35.2) 1\n>35 62 (83.8) 184 (64.8) 2.375 (1.279‒4.407) 0.006\nGnRHa, gonadotropin-releasing hormone agonist; CI, confidence interval.\nData are expressed as mean±SD, or number of cases (%). Two sample t-test, chi-square test.\n\nBo Hyon Yun, et al.\nYonsei Med J   http://www.eymj.org   Volume 56   Number 4   July 20151082\nendometriosis group (48.8%) experienced recurrent pelvic \npain. Patients with recurrent bilateral lesions had a higher in-\ncidence of bilateral cysts prior to surgery than those with \nunilateral or spot lesions (p=0.002) (Table 3). \nUnivariate analyses using Cox regression for the recur-\nrence of endometriosis were performed on factors that \nshowed significant differences between the two groups. The \nhazard ratios (HRs) for the factors used in the univariate \nspectively, showing an increased frequency of complete \nobliteration in patients with recurrence. The rAFS spot score \nand the frequency of bilateral tubal adhesions were not dif-\nferent between the two groups. \nOf the 80 patients who experienced recurrence, 3 (3.8%) \nwere diagnosed due to recurrent pain symptoms, 47 (58.7%) \nby ultrasonography, and the remaining 30 (37.5%) by surgi-\ncal confirmation. About half of the patients in the recurrent \nTable 2. Operative Findings in Patients with and without Recurrence of Endometriosis\nVariables\nDescriptive statistics Univariate analysis\nRecurrent \n(n=80)\nNon-recurrent \n(n=299) p value Hazard ratio \n(95% CI) p value\nSize of the largest cyst (cm) 5.53±2.58   4.88±2.42  0.038 1.102 (1.021‒1.188)  0.012\nAnatomical location of cyst (%)  0.001\nSpot only 2 (2.5)   4 (1.3) 1\nLeft-sided unilateral 20 (25.0) 121 (40.5) 0.382 (0.144‒1.013)  0.053\nRight-sided unilateral 20 (25.0)   99 (33.1) 0.597 (0.227‒1.573)  0.297\nBilateral 38 (47.5)   75 (25.1) 0.507 (0.186‒1.380)  0.184\nrAFS stage (%) <0.0001\nI 0 (0)   2 (0.7) 1\nII 1 (1.3)   5 (1.7)\nIII 26 (32.5) 175 (58.5) 0.631  0.649\nIV 59 (66.3) 117 (39.1)\nrAFS total score 58.89±30.07   43.91±26.35 <0.0001 1.014 (1.007‒1.022) <0.0001\nrAFS spot score 0.68±1.27   0.84±1.47  0.362\nrAFS ovarian cyst score 25.95±10.05 22.54±8.29  0.006 1.027 (1.004‒1.051)  0.023\nOvarian cyst bilaterality (%) <0.0001\nUnilateral 38 (48.7) 196 (70.8) 1\nBilateral 40 (51.3)   81 (29.2) 1.955 (1.253‒3.053)  0.003\nrAFS adnexal adhesion score 17.06±16.05   11.97±12.97  0.003 1.017 (1.003‒1.031)  0.014\nAdnexal adhesion bilaterality (%)  0.004\nNo adhesion 10 (12.5)   70 (23.4) 1\nUnilateral 26 (32.5) 123 (41.1) 1.472 (0.705‒3.071)  0.303\nBilateral 44 (55.0) 106 (35.5) 2.225 (1.116‒4.436)  0.023\nrAFS ovarian adhesion score 9.94±8.76   6.90±7.26  0.002 1.038 (1.012‒1.065)  0.004\nOvarian adhesion bilaterality (%)  0.002\nNo adhesion 11 (13.8)   78 (26.1) 1\nUnilateral 26 (32.5) 122 (40.8) 1.466 (0.721‒2.978)  0.291\nBilateral 43 (53.8)   99 (33.1) 2.341 (1.204‒4.549)  0.012\nrAFS tubal adhesion score 7.23±8.95   5.08±6.89  0.049 1.024 (0.998‒1.050)  0.072\nTubal adhesion bilaterality (%)  0.288\nNo adhesion 33 (41.3) 132 (44.1)\nUnilateral 19 (23.8)   88 (29.4)\nBilateral 28 (35.0)   79 (26.4)\nCDS obliteration (%)  0.003\nNone 29 (36.3) 135 (45.2) 1\nPartial 22 (27.4) 109 (36.4)\nComplete 29 (36.3)   55 (18.4) 2.182 (1.383‒3.443)  0.001\nrAFS, revised American Fertility Society; CDS, cul-de-sac; CI, confidence interval.\nData are expressed as mean±SD, or number of cases (%). Two sample t-test, chi-square test.\n\nPrognostic Factors for Recurrent Endometriosis\nYonsei Med J   http://www.eymj.org   Volume 56   Number 4   July 2015 1083\nbilateral ovarian adhesions (p=0.012), and complete CDS \nobliteration (p=0.001) were all shown to be factors that may \ninfluence the risk for recurrent endometriosis. \nFig. 1 show the Kaplan-Meier survival curves for progres-\nsion-free survival for different rAFS ovarian adhesion score \ngroups. Given that the rAFS ovarian adhesion score classi-\nfies each subject into a specific category, subjects were \nplaced into four groups that were determined by scores of \n0‒8, 9‒16, 17‒24, and >24, and those with higher scores \nwere associated with an increased hazard of recurrence (p= \n0.004). Patients with a rAFS ovarian adhesion score of >24 \nhad a significantly higher cumulative hazard of recurrence \ncompared with those having a score of ≤24 (p=0.004).\nA multivariate Cox regression analysis revealed that a \nrAFS ovarian adhesion score of >24 was associated with a \nsignificantly increased risk of recurrence of endometriosis \n(Table 4). The variables that we identified as independent \nrisk factors for the recurrence of endometriosis were young-\ner age at the time of surgery, ovarian cyst bilaterality, rAFS \novarian adhesion score >24, and complete CDS obliteration. \nA rAFS ovarian score of >24 was the risk factor with the \nhighest (HR: 2.996; 95% CI: 1.133‒7.923; p=0.027), and \nthe HR for complete CDS obliteration was the second high-\nest (HR: 2.274; 95% CI: 1.227‒4.215; p=0.009). Although \nnot as high, the HR for bilateral ovarian cysts indicated a \nsignificantly increased risk of recurrence (HR: 1.835; 95% \nCI: 1.137‒2.960; p=0.013). In addition, a postoperative med-\nication regimen of GnRHa with subsequent hormone therapy \nindicated a decreased risk of recurrence compared with Gn-\nRHa alone.\nanalyses are presented in Table 1 and 2, beside the descrip-\ntive statistics. Age at the time of surgery (p<0.0001), parity \n(nulliparous versus≥2; p=0.003), type of surgery (electro-\ncauterization only versus oophorectomy; p=0.023), postop-\nerative medications (GnRHa only versus GnRHa with sub-\nsequent hormone therapy; p<0.0001), preoperative serum \nCA-125 level >35 U/mL (p=0.006), size of the largest cyst \n(p=0.012), rAFS total score (p<0.0001), rAFS ovarian cyst \nscore (p= 0.023), ovarian cyst bilaterality (unilateral versus \nbilateral; p=0.003), rAFS ovarian adhesion score (p=0.004), \nTable 3. Characteristics of Patients with Recurrence of En-\ndometriosis\nVariables Number \n(proportion)\nRecurrent pain (%)        39 (48.8)\nDiagnostic tool for recurrence (%)\nSymptoms only        3 (3.8)\nUltrasonography only        47 (58.7)\nSurgical confirmation        30 (37.5)\nRecurrent cyst bilaterality (%)\nOnly spot        5 (6.3)\nUnilateral\nLeft side        30 (37.5)\nRight side        26 (32.5)\nBilateral        19 (23.8)\nRatio of initial bilateral cyst to recurrent  \n  lesion (%), p=0.002*\nRecurrent spot 0 /4 (0)\nRecurrent unilateral   25/57 (43.9)\nRecurrent bilateral   15/19 (78.9)\n*Chi-square test.\nFig. 1. Cumulative incidence of recurrent endometriosis for different ovarian adhesion score groups. (A) Patients divided into four groups. (B) Groups with a \ncut off level of 24.\n2.5\n2.0\n1.5\n1.0\n0.5\n0.0\n2.0\n1.5\n1.0\n0.5\n0.0\nCumulative incidence (%)\nCumulative incidence (%)\n20 2040 4060 60\nMonths Months\n80 800 100 0 100\n0‒24\nOvarian adhesion score\nOvarian adhesion score\nLog rank p=0.004 Log rank p=0.004\nA B\n0‒8\n17‒24\n25‒40\n9‒16 25‒40\n\nBo Hyon Yun, et al.\nYonsei Med J   http://www.eymj.org   Volume 56   Number 4   July 20151084\ntrating endometriosis (DIE). This is further complicated by \nthe anatomical location of the lesions, given that they are \nfound just above the ureter. In patients with endometriosis, \nthe more complete the removal of the lesions, the lower the \nrate of recurrence.12 As a result, dense ovarian adhesions and \npelvic-side-wall DIE are associated with a poor prognosis of \nthe recurrence of endometriosis. Our results show that the \novarian adhesion score, rather than the tubal adhesion score, \ncorrelated with the recurrence of endometriosis. Several pre-\nvious studies have examined the relationship between ad-\nnexal adhesions and clinical outcomes of endometriosis in \nterms of infertility.13 However, these studies were focused \non tubal rather than ovarian adhesions. The difference ob-\nserved in our study offers evidence that tubal involvement \nmay affect infertility due to its distortion of the anatomy and \nmicromovement of fimbriae, while endometriomas involv-\ning the ovaries may be more related to recurrence. \nIn our study, the preoperative serum CA-125 level was a \npredictive factor for the recurrence of endometriosis with \nborderline significance (p=0.084), although it was signifi-\ncantly correlated with the rAFS total score, ovarian cyst \nscore, and complete CDS obliteration excluding adhesion. \nSerum CA-125 is currently the most useful marker of endo-\nmetriosis and is typically checked preoperatively to evaluate \nthe usefulness of postoperative monitoring. Preoperative \nCA-125 may have limited diagnostic accuracy, however, \nwith low sensitivity and thus limited adequacy for predicting \nrecurrence of endometriosis. We calculated the area under \nthe receiver operating curve for preoperative CA-125 lev-\nels; however, our results did not provide an adequate level \nof discrimination or sensitivity (data not shown). As several \nstudies have shown that preoperative CA-125 in conjunc-\ntion with other markers may have considerable overall sen-\nsitivity and specificity,14,15 further studies that involve a larg-\ner number of participants and combine preoperative serum \nCA-125 levels with rAFS scores from surgery may provide \nmeaningful findings. \nPreviously, several studies have suggested that neither the \nrAFS classification system nor the stage correlates with post-\noperative outcomes such as pregnancy, recurrence of dys-\nmenorrhea, and recurrence of the disease.8,9 Although these \nprevious studies compared the rAFS stage itself, we ana-\nlyzed not only the stage but also the detailed components of \nthe classification. Meanwhile, our results indirectly share the \nfinding of a higher recurrence risk in an advanced stage,11,16 \nas the combination of ovarian adhesion, bilateral ovarian \ncysts, and complete CDS obliteration reflect an advanced \nDISCUSSION\nIn this study, we evaluated each component of the rAFS \nclassification system and demonstrated that the ovarian ad-\nhesion score of the previous surgery was the best prognostic \nfactor for the recurrence of endometriosis. In addition, we \nfound that complete CDS obliteration and bilateral ovarian \ncysts were also significant predictors of disease recurrence. \nAlong with the previous studies, our study adds to findings \nof increased recurrence in advanced-stage endometriosis, re-\nflected by complete CDS obliteration and bilateral ovarian \ncysts in our study.11\nOur data suggest that a threshold rAFS ovarian adhesion \nscore of >24 correlates with significant disease recurrence. \nAccording to the rAFS classification system,10 an ovarian \nadhesion score of >24 implies the existence of dense adhe-\nsions invading at least two thirds of the ovary, with subovar-\nian adhesions invading the lateral pelvic wall. In cases of \ndense subovarian adhesions, which consist of reactive fi-\nbrotic tissue involving the lateral pelvic peritoneum, the le-\nsions are potentially deeply infiltrating, similar to deep infil-\nTable 4. Hazard Ratios and p Values from Multivariate Analy-\nsis of Clinical Factors\nVariables Multivariate analysis\np value Hazard ratio (95% CI)\nAge at time of surgery (yrs) <0.0001 0.920 (0.885‒0.957)\nPostoperative medication\nNone 0.559 1.236 (0.607‒2.513)\nGnRHa only (ref) - 1\nGnRHa with subsequent  \n  hormone therapy 0.001 0.385 (0.224‒0.663)\nHormone therapy only 0.799 0.827 (0.193‒3.552)\nPreoperative serum CA-125  \n  level (U/mL)\n≤35 (ref) - 1\n>35 0.084 1.773 (0.926‒3.393)\nSize of the largest cyst (cm) 0.979 1.001 (0.911‒1.100)\nOvarian cyst bilaterality\nUnilateral (ref) - 1\nBilateral 0.013 1.835 (1.137‒2.960)\nrAFS ovarian adhesion score\n≤24 (ref) - 1\n>24 0.027 2.996 (1.133‒7.923)\nCDS obliteration\nNon-complete (ref) - 1\nComplete 0.009 2.274 (1.227‒4.215)\nGnRHa, gonadotropin-releasing hormone agonist; rAFS, revised American \nFertility Society; CDS, cul-de-sac; CI, confidence interval.\n\nPrognostic Factors for Recurrent Endometriosis\nYonsei Med J   http://www.eymj.org   Volume 56   Number 4   July 2015 1085\nAlso, increased preoperative serum CA-125 levels seemed \nto be associated with the risk of recurrence yet showed bor-\nderline significance. However, the CA-125 level still re-\nmains the most commonly-used biomarker of endometrio-\nsis. Thus, identification of new combinations of markers in \naddition to serum CA-125 would be more useful in predict-\ning recurrence risk. \nACKNOWLEDGEMENTS\nThis research was supported by Basic Science Research Pro-\ngram through the National Research Foundation of Korea \n(NRF) funded by the Ministry of Education, Science, and \nTechnology (NRF-2012R1A1A1013167).\nREFERENCES\n1. Giudice LC. Clinical practice. Endometriosis. N Engl J Med \n2010;362:2389-98.\n2. Farquhar CM. Extracts from the “clinical evidence”. Endometrio-\nsis. BMJ 2000;320:1449-52.\n3. Fritz MA, Speroff L. Clinical gynecologic endocrinology and in-\nfertility. 8th ed. PA, USA: Lippincott Williams & Wilkins; 2011.\n4. Cheong Y , Tay P, Luk F, Gan HC, Li TC, Cooke I. Laparoscopic \nsurgery for endometriosis: how often do we need to re-operate? J \nObstet Gynaecol 2008;28:82-5.\n5. Liu X, Yuan L, Shen F, Zhu Z, Jiang H, Guo SW. Patterns of and \nrisk factors for recurrence in women with ovarian endometriomas. \nObstet Gynecol 2007;109:1411-20.\n6. Fedele L, Bianchi S, Zanconato G, Bettoni G, Gotsch F. Long-term \nfollow-up after conservative surgery for rectovaginal endometrio-\nsis. Am J Obstet Gynecol 2004;190:1020-4.\n7. Kikuchi I, Takeuchi H, Kitade M, Shimanuki H, Kumakiri J, \nKinoshita K. Recurrence rate of endometriomas following a lapa-\nroscopic cystectomy. Acta Obstet Gynecol Scand 2006;85:1120-4.\n8. Vercellini P, Fedele L, Aimi G, De Giorgi O, Consonni D, Crosig-\nnani PG. Reproductive performance, pain recurrence and disease \nrelapse after conservative surgical treatment for endometriosis: the \npredictive value of the current classification system. Hum Reprod \n2006;21:2679-85. \n9. Vignali M, Bianchi S, Candiani M, Spadaccini G, Oggioni G, \nBusacca M. Surgical treatment of deep endometriosis and risk of \nrecurrence. J Minim Invasive Gynecol 2005;12:508-13.\n10. Revised American Society for Reproductive Medicine classifica-\ntion of endometriosis: 1996. Fertil Steril 1997;67:817-21.\n11. Koga K, Osuga Y , Takemura Y , Takamura M, Taketani Y . Recur-\nrence of endometrioma after laparoscopic excision and its preven-\ntion by medical management. Front Biosci (Elite Ed) 2013;5:676-83.\n12. Hart RJ, Hickey M, Maouris P, Buckett W. Excisional surgery ver-\nsus ablative surgery for ovarian endometriomata. Cochrane Data-\nbase Syst Rev 2008:CD004992. \n13. Fujishita A, Khan KN, Masuzaki H, Ishimaru T. Influence of pelvic \nendometriosis and ovarian endometrioma on fertility. Gynecol Ob-\nstage of endometriosis of at least stage III. Additionally, dis-\ncrepant results relating stage and recurrence may have also \noccurred from applying different editions of rAFS. For ex-\nample, Vercellini, et al.8 used a previous version of rAFS \n(1985), whereas we applied a more recent version (1997) \nthat did not include the type of lesion in the scoring system. \nOur results also confirmed previous reports that younger \nage5-9 and complete CDS obliteration9 were poor prognostic \nfactors of recurrence of endometriosis. In addition, we found \nthat the use of postoperative medications including hormone \ntherapy following GnRHa compared with GnRHa alone \nwas a favorable prognostic factor, corroborating data from \nanother recent report.17 Therefore, in patients at high risk for \nrecurrence of endometriosis, continuous hormone therapy \nshould be recommended after GnRHa treatment.\nDiffering from others, we evaluated the risk value of each \nindividual component of the rAFS classification system for \nthe recurrence of endometriosis. As a result, we discovered \nthat the rAFS ovarian adhesion score was a risk factor for \nrecurrent endometriosis. Moreover, almost all of the previ-\nously reported potential variables were measured in this \nstudy as well to eliminate all possible confounding factors. \nFinally, we excluded all patients who had previously under-\ngone pelvic surgeries, as they were more likely to have ex-\nisting surgical adhesions and artificially-increased rAFS \nscores. However, as a retrospective study, our findings were \nlimited by several factors. First, a second-look laparoscopy \nwas not performed on all patients. As a result, a number of \npatients were diagnosed with recurrent endometriosis with-\nout pathological confirmation. Additionally, serum levels of \nCA-125 are known to change throughout the menstrual cy-\ncle;18 however, we did not address the relationship of blood \nsampling with the timing of the menstrual period. Given \nthese limitations, further prospective studies are warranted \nto corroborate our results. \nIn conclusion, we have documented that the ovarian adhe-\nsion score, a component of the rAFS classification system, \nwas a significant risk factor for recurrent endometriosis after \nconservative laparoscopy. A rAFS ovarian adhesion score of \n>24 was associated with significantly worse progression-\nfree survival rates. This scoring component may provide a \nnew mechanism for identifying and managing patients with \npoorer prognoses. Therefore, in patients with high rAFS \novarian adhesion scores and suspected dense extended sub-\novarian adhesions or pelvic-side-wall DIE, careful explora-\ntion and complete resection of the lesions may be superior to \nadhesiolysis alone for preventing recurrent endometriosis. \n\nBo Hyon Yun, et al.\nYonsei Med J   http://www.eymj.org   Volume 56   Number 4   July 20151086\nlaterality of recurrent endometriomas after conservative surgery. \nGynecol Endocrinol 2013;29:978-81. \n17. Lee DY , Bae DS, Yoon BK, Choi D. Post-operative cyclic oral \ncontraceptive use after gonadotrophin-releasing hormone agonist \ntreatment effectively prevents endometrioma recurrence. Hum Re-\nprod 2010;25:3050-4. \n18. Spaczynski RZ, Duleba AJ. Diagnosis of endometriosis. Semin \nReprod Med 2003;21:193-208.\nstet Invest 2002;53 Suppl 1:40-5.\n14. Cho S, Cho H, Nam A, Kim HY , Choi YS, Park KH, et al. Neutro-\nphil-to-lymphocyte ratio as an adjunct to CA-125 for the diagnosis \nof endometriosis. Fertil Steril 2008;90:2073-9. \n15. Medl M, Ogris E, Peters-Engl C, Mierau M, Buxbaum P, Leodolter \nS. Serum levels of the tumour-associated trypsin inhibitor in pa-\ntients with endometriosis. Br J Obstet Gynaecol 1997;104:78-81.\n16. Lee DY , Kim HJ, Yoon BK, Choi D. Factors associated with the","source_license":"CC0","license_restricted":false}