The Prognostic Value of Individual Adhesion Scores from the Revised American Fertility Society Classification System for Recurrent Endometriosis

Endometriosis is a common benign gynecologic disease defined by the presence of Original Article http://dx.doi.org/10.3349/ymj.2015.56.4.1079 pISSN: 0513-5796, eISSN: 1976-2437 Yonsei Med J 56(4):1079-1086, 2015 Bo Hyon Yun, et al. Yonsei Med J http://www.eymj.org Volume 56 Number 4 July 20151080 the uterus and at least one ovary intact. Exclusion criteria in- cluded previous medical or surgical treatment of endometri- osis, previous pelvic surgery for uterine or ovarian masses, extrapelvic endometriosis, such as vaginal, abdominal wall, or pulmonary endometriosis, and malignancy. Conservative laparoscopy was performed by three gynecologic laparosco- py specialists. All surgical procedures aimed for complete removal of all gross lesions and anatomical restoration to preserve or restore reproductive function; additionally, the procedure included electrofulguration or excision of endo- metriotic implants on the peritoneum, excision of endome- triomas, and lysis of adhesions. The type of surgery was chosen and tailored for each individual case, with consider- ation for the severity of the disease. Postoperative medica- tions included gonadotropin-releasing hormone agonists (GnRHa) and/or hormone therapy such as oral contracep- tives, oral progestins, and a levonorgestrel-intrauterine sys- tem. After surgery, pelvic ultrasonography was performed every 6‒12 months. The recurrence of endometriosis was defined as the recurrence of dysmenorrhea as pain recurring after surgery with a severity score equal to or higher than that before surgery or the recurrence of endometriomas with the presence of ovarian cysts 2 cm in diameter for more than two consecutive menstrual cycles.4,5,9,11 Clinical characteristics and operative findings were record- ed for all study subjects including age at the time of surgery, body mass index, age at menarche, parity, menstrual history, coexisting adenomyosis, type of surgery, postoperative med- ications, pregnancy after surgery, the preoperative serum CA-125 level, the size of the largest cyst, anatomical loca- tion, rAFS stage, and rAFS score. The severity of endometri- osis was determined by scores derived from the rAFS classi- fication system10 according to operative findings including the location, size, extent, depth, and density of the endometri- oma and adhesions. These rAFS component scores included a spot score, an ovarian cyst score, an ovarian and tubal ad- hesion score, the bilaterality of ovarian cysts and ovarian and tubal adhesions, and cul-de-sac (CDS) obliteration. The scores were assigned by the gynecologist who performed the surgery. Serum CA-125 was checked after the initial di- agnosis, up to 2 weeks prior to surgery. The level of serum CA-125 was measured with a CA-125 II electrochemilumi- nescence immunoassay using the Roche/Hitachi Modular Analytics E170 (Roche Diagnostics, Tokyo, Japan). Continuous data are presented as means±standard devia- tions or medians and interquartile ranges. Categorical data are presented as numbers and percentages. To compare vari- endometrial glands and stroma outside of the uterus.1,2 The disease typically affects women of reproductive age and re- mains a major cause of disability stemming from dysmenor- rhea, chronic pelvic pain, and subfertility.1 Surgery is a con- firmed option for relieving pain and also may improve fertility; since recent years, it has been performed by lapa- roscopy with results equivalent to or better than surgery by laparotomy.3 However, the postoperative recurrence rates af- ter 3 years range from 15‒30%,3 with half of these patients requiring reoperation.4 Recurrence of endometriosis leads to several concerns in women of reproductive age in terms of lowered quality of life caused by recurrent pain and a compromised ovarian re- serve due to recurrent endometriomas; such issues may cause the clinician to hesitate when deciding the treatment modality. As is well known, a longer postoperative treat- ment of endometriosis results in less recurrence. However, there are no definite prognostic factors for recurrence that can be used in the clinical field during the follow-up period, although many studies have been conducted to identify the risk factors for recurrence of endometriosis.5-9 The revised American Fertility Society (rAFS) classifica- tion system is the most widely-used method of determining the severity of endometriosis by point scoring followed by staging. Almost all studies that have utilized the rAFS clas- sification system have addressed the use of rAFS stage and score as risk factors; however, few studies have evaluated the predictive value of each separate component of the sys- tem.10 In the present study, we aimed to investigate the risk factors of recurrent endometriosis by evaluating components of rAFS system from previous surgeries.

We retrospectively reviewed the medical records of women ages 18 to 49 years who underwent conservative laparosco- py with histologic confirmation of endometriosis at Gang- nam Severance Hospital from March 2003 to May 2010. The participants provided written informed consent to par- ticipate in this study, and we received the data in an anony- mized form. This study was carried out in accordance with the ethical standards of the Helsinki Declaration and was ap- proved by the Institutional Review Board of Gangnam Sev- erance Hospital (3-2011-0282). Conservative laparoscopy was defined as laparoscopic surgical removal of all endometriotic lesions while leaving Prognostic Factors for Recurrent Endometriosis Yonsei Med J http://www.eymj.org Volume 56 Number 4 July 2015 1081 whom 80 (21.2%) had recurrent endometriosis after laparo- scopic surgery. The median duration of follow-up was 19.0 months. The clinical characteristics of patients with and without recurrence of endometriosis are presented in Table 1. Significant differences were found between the two groups with respect to age at the time of surgery, parity, the type of surgery performed, and preoperative CA-125 level. Table 2 shows operative findings including data for the rAFS classification system components for both groups. In addition to the rAFS total score and stage, the size of the largest cyst, the rAFS cyst score, the rAFS adnexal adhesion score, the rAFS ovarian adhesion score, and the rAFS tubal adhesion score were significantly higher in the recurrent en- dometriosis group than in the non-recurrent group. There were also significant differences between the two groups in terms of the anatomical location of the cysts, the bilaterality of the cysts, and the bilaterality of the adnexal adhesions. Of the adnexal adhesions, only the frequency of bilateral ovari- an adhesions showed a significant difference between gro- ups, while bilateral tubal adhesions did not. The frequencies of no, partial, and complete CDS obliteration were 36.3%, 27.4%, and 36.3% in the recurrent endometriosis group and 45.2%, 36.4%, and 18.4% in the non-recurrent group, re- ables between the recurrent and non-recurrent groups, two- sample t-tests were used for continuous variables, and chi- square or Fisher’s exact tests were used for categorical var- iables where appropriate. A Kaplan-Meier survival analysis was used to determine the univariate relationship of the rAFS ovarian adhesion scores to disease-free survival times. Log-rank tests were used to examine significant differences in hazard distributions between groups according to rAFS ovarian adhesion scores. A Cox multivariate analysis was performed to eliminate confounding factors and to identify significant variables that could independently contribute to the recurrence of endometriosis. A multivariate model was built using factors that had p-values<0.05 on univariate anal- ysis and excluding factors that potentially had either multi- collinearity or clinical correlation. For all analyses, a p-val- ue<0.05 was considered to be statistically significant. All statistical analyses were conducted using SPSS software version 18.0 (SPSS Inc., Chicago, IL, USA).

The medical records of 379 patients were reviewed, of Table 1. Clinical Characteristics of Participants Variables Descriptive statistics Univariate analysis Recurrent (n=80) Non-recurrent (n=299) p value Hazard ratio (95% CI) p value Duration of follow-up (months) 27.21±16.87 25.02±21.88 0.041 Age at time of surgery (yrs) 28.78±5.51 32.51±6.99 <0.0001 0.926 (0.893‒0.959) <0.0001 Parity (%) 0.006 0 (ref) 66 (82.5) 194 (64.9) 1 1 9 (11.3) 46 (15.4) 0.518 (0.258‒1.040) 0.064 ≥2 5 (6.3) 59 (19.7) 0.256 (0.103‒0.636) 0.003 Type of surgery (%) 0.011 Laparoscopic electrocauterization only (ref) 7 (8.8) 6 (2.0) 1 Laparoscopic cystectomy 64 (80.0) 242 (80.9) 0.576 (0.263‒1.262) 0.168 Laparoscopic oophorectomy 9 (11.3) 51 (17.1) 0.318 (0.118‒0.855) 0.023 Postoperative medication (%) 0.071 None 13 (16.3) 58 (19.4) 0.721 (0.387‒1.345) 0.304 GnRHa only (ref) 43 (53.8) 114 (38.1) 1 GnRHa with subsequent hormone therapy 22 (27.5) 106 (35.5) 0.398 (0.238‒0.666) 35 62 (83.8) 184 (64.8) 2.375 (1.279‒4.407) 0.006 GnRHa, gonadotropin-releasing hormone agonist; CI, confidence interval. Data are expressed as mean±SD, or number of cases (%). Two sample t-test, chi-square test. Bo Hyon Yun, et al. Yonsei Med J http://www.eymj.org Volume 56 Number 4 July 20151082 endometriosis group (48.8%) experienced recurrent pelvic pain. Patients with recurrent bilateral lesions had a higher in- cidence of bilateral cysts prior to surgery than those with unilateral or spot lesions (p=0.002) (Table 3). Univariate analyses using Cox regression for the recur- rence of endometriosis were performed on factors that showed significant differences between the two groups. The hazard ratios (HRs) for the factors used in the univariate spectively, showing an increased frequency of complete obliteration in patients with recurrence. The rAFS spot score and the frequency of bilateral tubal adhesions were not dif- ferent between the two groups. Of the 80 patients who experienced recurrence, 3 (3.8%) were diagnosed due to recurrent pain symptoms, 47 (58.7%) by ultrasonography, and the remaining 30 (37.5%) by surgi- cal confirmation. About half of the patients in the recurrent Table 2. Operative Findings in Patients with and without Recurrence of Endometriosis Variables Descriptive statistics Univariate analysis Recurrent (n=80) Non-recurrent (n=299) p value Hazard ratio (95% CI) p value Size of the largest cyst (cm) 5.53±2.58 4.88±2.42 0.038 1.102 (1.021‒1.188) 0.012 Anatomical location of cyst (%) 0.001 Spot only 2 (2.5) 4 (1.3) 1 Left-sided unilateral 20 (25.0) 121 (40.5) 0.382 (0.144‒1.013) 0.053 Right-sided unilateral 20 (25.0) 99 (33.1) 0.597 (0.227‒1.573) 0.297 Bilateral 38 (47.5) 75 (25.1) 0.507 (0.186‒1.380) 0.184 rAFS stage (%) <0.0001 I 0 (0) 2 (0.7) 1 II 1 (1.3) 5 (1.7) III 26 (32.5) 175 (58.5) 0.631 0.649 IV 59 (66.3) 117 (39.1) rAFS total score 58.89±30.07 43.91±26.35 <0.0001 1.014 (1.007‒1.022) <0.0001 rAFS spot score 0.68±1.27 0.84±1.47 0.362 rAFS ovarian cyst score 25.95±10.05 22.54±8.29 0.006 1.027 (1.004‒1.051) 0.023 Ovarian cyst bilaterality (%) <0.0001 Unilateral 38 (48.7) 196 (70.8) 1 Bilateral 40 (51.3) 81 (29.2) 1.955 (1.253‒3.053) 0.003 rAFS adnexal adhesion score 17.06±16.05 11.97±12.97 0.003 1.017 (1.003‒1.031) 0.014 Adnexal adhesion bilaterality (%) 0.004 No adhesion 10 (12.5) 70 (23.4) 1 Unilateral 26 (32.5) 123 (41.1) 1.472 (0.705‒3.071) 0.303 Bilateral 44 (55.0) 106 (35.5) 2.225 (1.116‒4.436) 0.023 rAFS ovarian adhesion score 9.94±8.76 6.90±7.26 0.002 1.038 (1.012‒1.065) 0.004 Ovarian adhesion bilaterality (%) 0.002 No adhesion 11 (13.8) 78 (26.1) 1 Unilateral 26 (32.5) 122 (40.8) 1.466 (0.721‒2.978) 0.291 Bilateral 43 (53.8) 99 (33.1) 2.341 (1.204‒4.549) 0.012 rAFS tubal adhesion score 7.23±8.95 5.08±6.89 0.049 1.024 (0.998‒1.050) 0.072 Tubal adhesion bilaterality (%) 0.288 No adhesion 33 (41.3) 132 (44.1) Unilateral 19 (23.8) 88 (29.4) Bilateral 28 (35.0) 79 (26.4) CDS obliteration (%) 0.003 None 29 (36.3) 135 (45.2) 1 Partial 22 (27.4) 109 (36.4) Complete 29 (36.3) 55 (18.4) 2.182 (1.383‒3.443) 0.001 rAFS, revised American Fertility Society; CDS, cul-de-sac; CI, confidence interval. Data are expressed as mean±SD, or number of cases (%). Two sample t-test, chi-square test. Prognostic Factors for Recurrent Endometriosis Yonsei Med J http://www.eymj.org Volume 56 Number 4 July 2015 1083 bilateral ovarian adhesions (p=0.012), and complete CDS obliteration (p=0.001) were all shown to be factors that may influence the risk for recurrent endometriosis. Fig. 1 show the Kaplan-Meier survival curves for progres- sion-free survival for different rAFS ovarian adhesion score groups. Given that the rAFS ovarian adhesion score classi- fies each subject into a specific category, subjects were placed into four groups that were determined by scores of 0‒8, 9‒16, 17‒24, and >24, and those with higher scores were associated with an increased hazard of recurrence (p= 0.004). Patients with a rAFS ovarian adhesion score of >24 had a significantly higher cumulative hazard of recurrence compared with those having a score of ≤24 (p=0.004). A multivariate Cox regression analysis revealed that a rAFS ovarian adhesion score of >24 was associated with a significantly increased risk of recurrence of endometriosis (Table 4). The variables that we identified as independent risk factors for the recurrence of endometriosis were young- er age at the time of surgery, ovarian cyst bilaterality, rAFS ovarian adhesion score >24, and complete CDS obliteration. A rAFS ovarian score of >24 was the risk factor with the highest (HR: 2.996; 95% CI: 1.133‒7.923; p=0.027), and the HR for complete CDS obliteration was the second high- est (HR: 2.274; 95% CI: 1.227‒4.215; p=0.009). Although not as high, the HR for bilateral ovarian cysts indicated a significantly increased risk of recurrence (HR: 1.835; 95% CI: 1.137‒2.960; p=0.013). In addition, a postoperative med- ication regimen of GnRHa with subsequent hormone therapy indicated a decreased risk of recurrence compared with Gn- RHa alone. analyses are presented in Table 1 and 2, beside the descrip- tive statistics. Age at the time of surgery (p<0.0001), parity (nulliparous versus≥2; p=0.003), type of surgery (electro- cauterization only versus oophorectomy; p=0.023), postop- erative medications (GnRHa only versus GnRHa with sub- sequent hormone therapy; p35 U/mL (p=0.006), size of the largest cyst (p=0.012), rAFS total score (p<0.0001), rAFS ovarian cyst score (p= 0.023), ovarian cyst bilaterality (unilateral versus bilateral; p=0.003), rAFS ovarian adhesion score (p=0.004), Table 3. Characteristics of Patients with Recurrence of En- dometriosis Variables Number (proportion) Recurrent pain (%) 39 (48.8) Diagnostic tool for recurrence (%) Symptoms only 3 (3.8) Ultrasonography only 47 (58.7) Surgical confirmation 30 (37.5) Recurrent cyst bilaterality (%) Only spot 5 (6.3) Unilateral Left side 30 (37.5) Right side 26 (32.5) Bilateral 19 (23.8) Ratio of initial bilateral cyst to recurrent lesion (%), p=0.002* Recurrent spot 0 /4 (0) Recurrent unilateral 25/57 (43.9) Recurrent bilateral 15/19 (78.9) *Chi-square test. Fig. 1. Cumulative incidence of recurrent endometriosis for different ovarian adhesion score groups. (A) Patients divided into four groups. (B) Groups with a cut off level of 24. 2.5 2.0 1.5 1.0 0.5 0.0 2.0 1.5 1.0 0.5 0.0 Cumulative incidence (%) Cumulative incidence (%) 20 2040 4060 60 Months Months 80 800 100 0 100 0‒24 Ovarian adhesion score Ovarian adhesion score Log rank p=0.004 Log rank p=0.004 A B 0‒8 17‒24 25‒40 9‒16 25‒40 Bo Hyon Yun, et al. Yonsei Med J http://www.eymj.org Volume 56 Number 4 July 20151084 trating endometriosis (DIE). This is further complicated by the anatomical location of the lesions, given that they are found just above the ureter. In patients with endometriosis, the more complete the removal of the lesions, the lower the rate of recurrence.12 As a result, dense ovarian adhesions and pelvic-side-wall DIE are associated with a poor prognosis of the recurrence of endometriosis. Our results show that the ovarian adhesion score, rather than the tubal adhesion score, correlated with the recurrence of endometriosis. Several pre- vious studies have examined the relationship between ad- nexal adhesions and clinical outcomes of endometriosis in terms of infertility.13 However, these studies were focused on tubal rather than ovarian adhesions. The difference ob- served in our study offers evidence that tubal involvement may affect infertility due to its distortion of the anatomy and micromovement of fimbriae, while endometriomas involv- ing the ovaries may be more related to recurrence. In our study, the preoperative serum CA-125 level was a predictive factor for the recurrence of endometriosis with borderline significance (p=0.084), although it was signifi- cantly correlated with the rAFS total score, ovarian cyst score, and complete CDS obliteration excluding adhesion. Serum CA-125 is currently the most useful marker of endo- metriosis and is typically checked preoperatively to evaluate the usefulness of postoperative monitoring. Preoperative CA-125 may have limited diagnostic accuracy, however, with low sensitivity and thus limited adequacy for predicting recurrence of endometriosis. We calculated the area under the receiver operating curve for preoperative CA-125 lev- els; however, our results did not provide an adequate level of discrimination or sensitivity (data not shown). As several studies have shown that preoperative CA-125 in conjunc- tion with other markers may have considerable overall sen- sitivity and specificity,14,15 further studies that involve a larg- er number of participants and combine preoperative serum CA-125 levels with rAFS scores from surgery may provide meaningful findings. Previously, several studies have suggested that neither the rAFS classification system nor the stage correlates with post- operative outcomes such as pregnancy, recurrence of dys- menorrhea, and recurrence of the disease.8,9 Although these previous studies compared the rAFS stage itself, we ana- lyzed not only the stage but also the detailed components of the classification. Meanwhile, our results indirectly share the finding of a higher recurrence risk in an advanced stage,11,16 as the combination of ovarian adhesion, bilateral ovarian cysts, and complete CDS obliteration reflect an advanced

In this study, we evaluated each component of the rAFS classification system and demonstrated that the ovarian ad- hesion score of the previous surgery was the best prognostic factor for the recurrence of endometriosis. In addition, we found that complete CDS obliteration and bilateral ovarian cysts were also significant predictors of disease recurrence. Along with the previous studies, our study adds to findings of increased recurrence in advanced-stage endometriosis, re- flected by complete CDS obliteration and bilateral ovarian cysts in our study.11 Our data suggest that a threshold rAFS ovarian adhesion score of >24 correlates with significant disease recurrence. According to the rAFS classification system,10 an ovarian adhesion score of >24 implies the existence of dense adhe- sions invading at least two thirds of the ovary, with subovar- ian adhesions invading the lateral pelvic wall. In cases of dense subovarian adhesions, which consist of reactive fi- brotic tissue involving the lateral pelvic peritoneum, the le- sions are potentially deeply infiltrating, similar to deep infil- Table 4. Hazard Ratios and p Values from Multivariate Analy- sis of Clinical Factors Variables Multivariate analysis p value Hazard ratio (95% CI) Age at time of surgery (yrs) <0.0001 0.920 (0.885‒0.957) Postoperative medication None 0.559 1.236 (0.607‒2.513) GnRHa only (ref) - 1 GnRHa with subsequent hormone therapy 0.001 0.385 (0.224‒0.663) Hormone therapy only 0.799 0.827 (0.193‒3.552) Preoperative serum CA-125 level (U/mL) ≤35 (ref) - 1 >35 0.084 1.773 (0.926‒3.393) Size of the largest cyst (cm) 0.979 1.001 (0.911‒1.100) Ovarian cyst bilaterality Unilateral (ref) - 1 Bilateral 0.013 1.835 (1.137‒2.960) rAFS ovarian adhesion score ≤24 (ref) - 1 >24 0.027 2.996 (1.133‒7.923) CDS obliteration Non-complete (ref) - 1 Complete 0.009 2.274 (1.227‒4.215) GnRHa, gonadotropin-releasing hormone agonist; rAFS, revised American Fertility Society; CDS, cul-de-sac; CI, confidence interval. Prognostic Factors for Recurrent Endometriosis Yonsei Med J http://www.eymj.org Volume 56 Number 4 July 2015 1085 Also, increased preoperative serum CA-125 levels seemed to be associated with the risk of recurrence yet showed bor- derline significance. However, the CA-125 level still re- mains the most commonly-used biomarker of endometrio- sis. Thus, identification of new combinations of markers in addition to serum CA-125 would be more useful in predict- ing recurrence risk.

This research was supported by Basic Science Research Pro- gram through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (NRF-2012R1A1A1013167).

1. Giudice LC. Clinical practice. Endometriosis. N Engl J Med 2010;362:2389-98. 2. Farquhar CM. Extracts from the “clinical evidence”. Endometrio- sis. BMJ 2000;320:1449-52. 3. Fritz MA, Speroff L. Clinical gynecologic endocrinology and in- fertility. 8th ed. PA, USA: Lippincott Williams & Wilkins; 2011. 4. Cheong Y , Tay P, Luk F, Gan HC, Li TC, Cooke I. Laparoscopic surgery for endometriosis: how often do we need to re-operate? J Obstet Gynaecol 2008;28:82-5. 5. Liu X, Yuan L, Shen F, Zhu Z, Jiang H, Guo SW. Patterns of and risk factors for recurrence in women with ovarian endometriomas. Obstet Gynecol 2007;109:1411-20. 6. Fedele L, Bianchi S, Zanconato G, Bettoni G, Gotsch F. Long-term follow-up after conservative surgery for rectovaginal endometrio- sis. Am J Obstet Gynecol 2004;190:1020-4. 7. Kikuchi I, Takeuchi H, Kitade M, Shimanuki H, Kumakiri J, Kinoshita K. Recurrence rate of endometriomas following a lapa- roscopic cystectomy. Acta Obstet Gynecol Scand 2006;85:1120-4. 8. Vercellini P, Fedele L, Aimi G, De Giorgi O, Consonni D, Crosig- nani PG. Reproductive performance, pain recurrence and disease relapse after conservative surgical treatment for endometriosis: the predictive value of the current classification system. Hum Reprod 2006;21:2679-85. 9. Vignali M, Bianchi S, Candiani M, Spadaccini G, Oggioni G, Busacca M. Surgical treatment of deep endometriosis and risk of recurrence. J Minim Invasive Gynecol 2005;12:508-13. 10. Revised American Society for Reproductive Medicine classifica- tion of endometriosis: 1996. Fertil Steril 1997;67:817-21. 11. Koga K, Osuga Y , Takemura Y , Takamura M, Taketani Y . Recur- rence of endometrioma after laparoscopic excision and its preven- tion by medical management. Front Biosci (Elite Ed) 2013;5:676-83. 12. Hart RJ, Hickey M, Maouris P, Buckett W. Excisional surgery ver- sus ablative surgery for ovarian endometriomata. Cochrane Data- base Syst Rev 2008:CD004992. 13. Fujishita A, Khan KN, Masuzaki H, Ishimaru T. Influence of pelvic endometriosis and ovarian endometrioma on fertility. Gynecol Ob- stage of endometriosis of at least stage III. Additionally, dis- crepant results relating stage and recurrence may have also occurred from applying different editions of rAFS. For ex- ample, Vercellini, et al.8 used a previous version of rAFS (1985), whereas we applied a more recent version (1997) that did not include the type of lesion in the scoring system. Our results also confirmed previous reports that younger age5-9 and complete CDS obliteration9 were poor prognostic factors of recurrence of endometriosis. In addition, we found that the use of postoperative medications including hormone therapy following GnRHa compared with GnRHa alone was a favorable prognostic factor, corroborating data from another recent report.17 Therefore, in patients at high risk for recurrence of endometriosis, continuous hormone therapy should be recommended after GnRHa treatment. Differing from others, we evaluated the risk value of each individual component of the rAFS classification system for the recurrence of endometriosis. As a result, we discovered that the rAFS ovarian adhesion score was a risk factor for recurrent endometriosis. Moreover, almost all of the previ- ously reported potential variables were measured in this study as well to eliminate all possible confounding factors. Finally, we excluded all patients who had previously under- gone pelvic surgeries, as they were more likely to have ex- isting surgical adhesions and artificially-increased rAFS scores. However, as a retrospective study, our findings were limited by several factors. First, a second-look laparoscopy was not performed on all patients. As a result, a number of patients were diagnosed with recurrent endometriosis with- out pathological confirmation. Additionally, serum levels of CA-125 are known to change throughout the menstrual cy- cle;18 however, we did not address the relationship of blood sampling with the timing of the menstrual period. Given these limitations, further prospective studies are warranted to corroborate our results. In conclusion, we have documented that the ovarian adhe- sion score, a component of the rAFS classification system, was a significant risk factor for recurrent endometriosis after conservative laparoscopy. A rAFS ovarian adhesion score of >24 was associated with significantly worse progression- free survival rates. This scoring component may provide a new mechanism for identifying and managing patients with poorer prognoses. Therefore, in patients with high rAFS ovarian adhesion scores and suspected dense extended sub- ovarian adhesions or pelvic-side-wall DIE, careful explora- tion and complete resection of the lesions may be superior to adhesiolysis alone for preventing recurrent endometriosis. Bo Hyon Yun, et al. Yonsei Med J http://www.eymj.org Volume 56 Number 4 July 20151086 laterality of recurrent endometriomas after conservative surgery. Gynecol Endocrinol 2013;29:978-81. 17. Lee DY , Bae DS, Yoon BK, Choi D. Post-operative cyclic oral contraceptive use after gonadotrophin-releasing hormone agonist treatment effectively prevents endometrioma recurrence. Hum Re- prod 2010;25:3050-4. 18. Spaczynski RZ, Duleba AJ. Diagnosis of endometriosis. Semin Reprod Med 2003;21:193-208. stet Invest 2002;53 Suppl 1:40-5. 14. Cho S, Cho H, Nam A, Kim HY , Choi YS, Park KH, et al. Neutro- phil-to-lymphocyte ratio as an adjunct to CA-125 for the diagnosis of endometriosis. Fertil Steril 2008;90:2073-9. 15. Medl M, Ogris E, Peters-Engl C, Mierau M, Buxbaum P, Leodolter S. Serum levels of the tumour-associated trypsin inhibitor in pa- tients with endometriosis. Br J Obstet Gynaecol 1997;104:78-81. 16. Lee DY , Kim HJ, Yoon BK, Choi D. Factors associated with the