Effect of laparoscopic excision of endometriomas on ovarian reserve: serial changes in the serum antim ullerian hormone levels

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1 Effect of laparoscopic excision of endometriomas on ovarian reserve: serial changes in the serum antim ullerian hormone levels Hale Goksever Celik, M.D., a Erbil Dogan, M.D., b Emre Okyay, M.D., b Cagnur Ulukus, M.D., c Bahadir Saatli, M.D., b Sezer Uysal, M.D., d and Meral Koyuncuoglu, M.D. c a Department of Obstetrics and Gynecology, Kayseri Develi General Hospital; b Department of Obstetrics and Gynecology, c Department of Pathology, and d Department of Biochemistry, Dokuz Eylul University, Inciralti, Izmir, Turkey Objective: To investigate the effect of laparoscopic endometrioma stripping on serum antim ullerian hormone (AMH) and the correlation between the clinicopathologic factors. Design: Prospective study. Setting: University hospital. Patient(s): Sixty-five women with endometriomas. Intervention(s): All patients underwent laparoscopic cystectomy. Serum AMH, FSH, LH, E 2, and antral follicle count (AFC) were measured preoperatively, at 6 weeks, and at 6 months postoperatively. Specimens were analyzed histopathologically. Main Outcome Measure(s): The primary end point was to assess the ovarian reserve damage based on alterations of AMH and the secondary end point was to detect the changes in FSH, LH, E 2, and AFC. Result(s): Serum AMH decreased significantly at the sixth month (61%) postoperatively. The FSH level increased significantly at the sixth week, but returned to normal at the sixth month. The AFC increased significantly at the sixth week and at the sixth month. The AMH level decrease was more evident in patients with the cyst <5 cm (65.7% vs. 41.3%). The AMH decrease was more in bilateral compared with unilateral endometriomas (67% versus 57%, respectively). No correlation was detected between the histopathologic analyses and tamh level. Initially the AMH level was the only independent factor affecting the AMH decrease (odds ratio, 3.68; 95% confidence interval ). Conclusion(s): Laparoscopic cystectomy of ovarian endometriomas causes a significant and progressive decline in serum AMH levels. (Fertil Steril Ò 2012;97: Ó2012 by American Society for Reproductive Medicine.) Key Words: Endometrioma, laparoscopy, ovarian reserve, antim ullerian hormone, antral follicle count Endometriosis is the presence of endometrial glands and stroma outside the uterine cavity affecting mostly women of reproductive age. The disease is usually manifested with pelvic pain, dysmenorrhea, and infertility. The prevalence is found to be 7% 10%, but among infertile women it increases up to 50% (1). Endometrioma is the formation of a cyst within the ovary with ectopic endometrium tissue lining and is found to be in 17% 44% of patients with endometriosis (2). It is hypothesized that endometriomas arise as a consequence of coelomic metaplasia of the ovarian epithelium or the invagination of the inverted ovarian cortex after implantation of the endometriotic foci on the ovarian surface (3). In either case the cyst has a pseudocapsule adjacent to the normal ovarian tissue. The treatment of endometriosis must aim at the destruction of all lesions, adhesiolysis to ensure the normal anatomical structure, prevent Received September 22, 2011; revised and accepted March 15, 2012; published online April 21, H.G.C. has nothing to disclose. E.D. has nothing to disclose. E.O. has nothing to disclose. C.U. has nothing to disclose. B.S. has nothing to disclose. S.U. has nothing to disclose. M.K. has nothing to disclose. Supported by grant (2009 KB SAG43) from Dokuz Eylul University Research Fund. Reprint requests: Erbil Dogan, M.D., Department of Obsterics and Gynecology, Dokuz Eylul University Faculty of Medicine, 35320, Inciralti, Izmir, Turkey ( erbil.dogan@deu.edu.tr). Fertility and Sterility Vol. 97, No. 6, June /$36.00 Copyright 2012 American Society for Reproductive Medicine, Published by Elsevier Inc. doi: /j.fertnstert recurrences, and increase conception rates in patients with subfertility. Although the most effective treatment modality of endometrioma is controversial, laparoscopic excision by the stripping technique is accepted to be the gold standard surgical approach. A recent meta-analysis showed that in comparison to drainage and ablative surgery, excision of endometriomas are better in terms of reduced pain, increased pregnancy, and decreased recurrence and reoperation rates (4). One of the major concerns about excision of endometriomas is their negative effect on ovarian reserve because of follicle loss (5). Removal of endometriomas has been associated with poorer performances in IVF procedures, and decreased ovarian volumes have also been reported after surgery (6) VOL. 97 NO. 6 / JUNE 2012

2 Fertility and Sterility Ovarian reserve describes the number and quality of the follicles in the ovaries at any given time. At present, there is no ideal test to measure ovarian reserve, but age, basal levels of FSH, LH, E 2, inhibin B, and recently antim ullerian hormone (AMH) have emerged as clinically useful markers (7). Sonographic measurements, like basal antral follicle count (AFC), ovarian volume, and stromal blood flow, are also being used for ovarian reserve testing (8). Among these markers AMH and AFC are accepted to be the most reliable markers. Antim ullerian hormone belongs to the transforming growth factor-b (TGF-b) family and is secreted by the granulosa cells (GC) of the recruited follicles until they become sensitive to FSH (9). Major advantages of AMH are that it is menstrual cycle independent and is also unaffected by the use of oral contraceptive (OC) pills and GnRH agonists (10). In the present study, our purpose was to assess the effect of laparoscopic endometrioma excision on the ovarian reserve tests. We measured basal serum levels of FSH, LH, E 2, and AMH serially before and after laparoscopic surgery. Antral follicle count was also measured preoperatively and postoperatively. In addition we investigated the correlation between the changes in these ovarian reserve markers with the histopathologic analysis of follicle loss after the operation. MATERIALS AND METHODS This prospective cohort study was conducted on 65 patients, who underwent laparoscopic ovarian endometrioma excision in the Department of Obstetrics and Gynecology at Dokuz Eylul University between January 2009 and March Inclusion criteria were: 1) presence of endometrioma with a diameter of at least 3 cm, 2) absence of previous ovarian surgery, 3) years of age with regular menstrual cycles, and 4) absence of any endocrine disease. Exclusion criteria were as follows: 1) evidence of postmenopausal FSH levels, and 2) any suspicion of malignant ovarian disease and OC use or any other hormone therapy (HT) during past 3 months. This study was approved by the Institutional Review Board of Dokuz Eylul University Medical School and informed consent was obtained from all patients. Endometrioma was diagnosed mainly by transvaginal ultrasonography or any other imaging techniques like computed tomography (CT) or magnetic resonance imaging (MRI). Age, gravidity and parity, tobacco use, menstrual regularity, drug use, and operation history of patients were recorded. Ultrasonographic examination for AFC was performed by Medison SonoAceX6 with a transvaginal 7-MHz probe. Antral follicle was considered as cysts measuring 2 10 mm in diameter within the ovary. Mean endometrioma diameter was measured in two dimensions. Definitive diagnosis of endometrioma was done by observation of endometriotic foci during laparoscopy and histopathologic examination of these samples. All blueblack powder burn lesions or atypical white and opaque, red or vesicular lesions, and all ovarian cysts containing dense brown chocolate-like fluid were excised and examined histopathologically. During laparoscopy, patients were scored according to the revised American Fertility Society (AFS) for Reproductive Medicine Classification of Endometriosis and staged as minimal, mild, moderate, or severe endometriosis (11). Hormonal Measurements Preoperatively on the third day of the menstrual cycle FSH, LH, E 2, and AMH were measured and the FSH:LH ratio was calculated. The AFC in both ovaries and dimensions of endometrioma were assessed by transvaginal ultrasonography. On the day of ultrasonography, blood samples were obtained by venipuncture. The patient's sera were obtained from blood samples by centrifuge at 3,000 g for 10 minutes to separate cellular contents and debris. The serum was stored at 80 C until assayed. Serum FSH, LH, and E 2 levels were measured by the chemiluminescence method with original Abbott assays. The intra-assay and interassay coefficient of variations (CV) were 5.4% and 4.2% for FSH, 3.8% and 4.6% for LH, and 7.5% and 3.7% for E 2, respectively. Serum AMH levels were measured by ELISA (Diagnostic Systems Laboratories). For AMH, intra-assay CV was 4.57% with a detection limit of ng/ml. Operation Technique All the laparoscopic cystectomies were performed under general anesthesia by one of the experienced surgeons. The surgery was done as follows. After establishment of pneumoperitoneum with the Verres needle through a 10-mm subumbilical vertical incision, a 10-mm laparoscope was introduced. Then, two to three additional 5-mm trocars were placed suprapubically for the introduction of ancillary instruments. At entrance to the abdomen pelvis, abdomen, and the surface of the cyst was assessed for possible evidence of malignancy. If no sign of malignancy was present, the ovary was mobilized from its adhesions, if there were any. The cyst was ruptured almost in all cases inevitably, and the contents were aspirated and the chocolate fluid content was rinsed and the inner wall of the cyst was checked for possible vegetations. If there were no vegetations present, the cleavage plane was identified and the cyst wall was stripped off the ovary by traction and countertraction exerted by using two atraumatic grasping forceps. In addition, sharp dissection with scissors was necessary when the cyst capsule was adherent to the surrounding ovarian tissue. Bipolar electrocoagulation was applied occasionally for hemostasis on the ovarian parenchyma with caution not to damage ovarian hilus and vascularity. The cyst wall was removed from the abdomen by means of an endobag. No major intraoperative or postoperative complication occurred in any patient and all were discharged 24 hours after the surgery. Histopathologic Analysis The pathologist evaluated the presence or absence of the ovarian tissue adjacent to the cyst wall and graded the morphological characteristics of this tissue on a semiquantitative scale of 0 4(0¼complete absence of follicles; 1 ¼ primordial follicles only; 2 ¼ primordial and primary follicles; 3 ¼ secondary follicles; and 4 ¼ pattern of primary and secondary VOL. 97 NO. 6 / JUNE

3 follicles as seen in the normal ovary) (12). These follicle numbers were correlated with ovarian reserve tests. Follow-up Postoperatively on the sixth week and sixth month, patients were called in for follow-up consultation on the third day of their menstrual cycle. Hormone profiles including FSH, LH, E 2, and AMH were measured, the FSH:LH ratio was calculated, and AFC were counted by transvaginal ultrasonography. Sixty-five patients came to follow-up visit on the sixth week and 39 patients came to the sixth month visit. Ten patients became pregnant within 6 months after operation and were excluded in the final analysis. Statistical Analysis Statistical analyses were performed with SPSS software (Statistics Package for Social Sciences) version 15 for Windows. Concentrations of serum FSH, LH, E 2, and AMH were compared between each sampling point (preoperatively, postoperatively at week 6 and month 6) using paired samples t-test and Wilcoxon signed-rank test. Means were presented with SD. P<.05 was considered statistically significant. RESULTS The mean age of the patients was years. Most of the patients had regular menses (89.2%), and were mainly nulligravid (76.9%). The endometriomas were R5 cm in diameter in 40 patients (61.5%) and bilateral in 19 cases (29.2%). The preoperative mean endometrioma diameter, which was measured with transvaginal ultrasonography, was cm, and the mean endometrioma diameter in the pathologic specimens was cm. All patients were in the moderate or severe stage (stage 3 and 4) according to the revised AFS classification. Distributions of the semiquantitative histopathologic scoring were as follows: 10 patients in score 0 (15.4%), 4 patients in score 1 (6.2%), 15 patients in score 2 (23.1%), and 36 patients in score 4 (55.4%). None of the patients were included in score 3. Because of the small number of patients were in scores 0, 1, and 2, these patients were taken into consideration in only two groups. The serial changes in the ovarian reserve tests after the surgery are presented in Table 1. There was a significant decrease in serum AMH levels both at week 6 and month 6 after surgery compared to preoperative levels (P<.001). The serial changes in the AMH level are shown in Figure 1A and the change in AMH for each case is demonstrated in Figure 2. The mean decrease in the serum AMH level at week 6 was 26% and 61% at month 6. In addition, basal FSH level was significantly increased at the sixth week postoperatively, yet at month 6 the levels were not different compared with preoperative levels. The FSH:LH ratio increased at week 6; however, it was not different from the preoperative levels at the sixth month. A similar change was observed for the basal E 2 levels. Comparing to preoperative measurements AFC was increased both at week 6 and month 6 postoperatively (P¼.008). The results are presented in Table 1. The serial changes in ovarian reserve tests both in patients with bilateral or unilateral endometrioma and in patients with mean cyst diameter <5 cm or R5 cm were compared separately. The preoperative AMH level was statistically significantly higher in patients with mean endometrioma size R5 cm compared with cyst size <5 cm(p¼.014), whereas this difference was not detected according to bilaterality (P>.05; Fig. 1B and C). The mean decrease in serum AMH level at 6 months postoperatively was 41.3% (mean, ng/ml) for endometriomas <5 cm and it was 65.7% for endometriomas R5 cm (mean, ng/ml). The difference was statistically significant (P¼.003) (Fig. 1B). Similarly, at 6 months postoperatively the decrease in the AMH level in patients with bilateral endometriomas was 67% (mean, ng/ml). This decrease was 57% in patients with unilateral endometriomas (mean, ng/ml). The difference between the two groups was also statistically significant (P¼.039; Fig. 1C). There was a weak negative correlation between the age of the patient and the preoperative AMH levels (P¼.024, r ¼ 0.280). There was no correlations between the preoperative serum AMH level and the preoperative AFC (P>.05). There was also no correlation between the preoperative AMH level and the histopathologic analysis of follicle loss after surgery (P>.05). We analyzed the AMH decrease according to the preoperative values. Multivariate statistical analysis was performed to detect which factor independently influences AMH decrease after surgery. Initial AMH value was found to be the only independent factor affecting AMH decrease (P<.001; odds ratio, 3.68, 95% confidence interval TABLE 1 The mean levels of ovarian reserve markers before and after laparoscopic ovarian cystectomy. Postoperative 6th week Preoperative (n [ 65) (mean ± SD; n [ 64) Postoperative 6th month (mean ± SD; n [ 39) P value a FSH (miu/ml) <.001 LH (miu/ml) NS FSH:LH ratio NS E 2 (pg/ml) NS AFC AMH (ng/ml) <.001 Note: AFC ¼ antral follicle count; AMH ¼ antim ullerian hormone; NS ¼ not significant. a Analysis of variance (ANOVA) with repeated measures. Celik. Endometrioma excision and AMH. Fertil Steril VOL. 97 NO. 6 / JUNE 2012

4 Fertility and Sterility FIGURE 1 Box-and-whisker plots showing the serum antim ullerian hormone (AMH) levels before and after laparoscopic ovarian cystectomy. Lines inside boxes indicate median, and the upper and lower limits of the boxes and whiskers indicate interquartile and total ranges. (A) The whole group; (B) AMH levels according to cyst diameter; and (C) AMH levels according to bilaterality of the endometrioma. Preoperative and sixth week postoperative values are for 65 patients and the sixth month value is for 39 patients. Celik. Endometrioma excision and AMH. Fertil Steril ). However, endometrioma size, age, and bilaterality did not have any independent effects on the AMH decrease after surgery. endometrioma >5 cm, which was not detected in bilateral cases. We hypothesize that larger endometriomas may inhibit follicular transition from the preantral to the antral stage. DISCUSSION Treatment of endometriomas is a controversial issue. Medical treatment alone is very limited because, despite the regression of the lesion, it leads only to a little reduction in size. Danazol, progestins, OCs, GnRH agonists, and gestrinone are alternatives for medical therapy. Other treatment options are follow-up, aspiration, cystectomy, and fenestration and ablation of cyst wall (13). Despite all the controversy, operative laparoscopy is the first line treatment option available to the general consensus in the treatment of endometriomas. However, debate still continues on the type of laparoscopic procedure. The main point of debate is excision or ablation of the cyst capsule. Our study is one of the largest series on this topic which included 65 patients and continued with 6 months of follow-up. It demonstrated that laparoscopic removal of endometriomas with the stripping technique causes a decrease in the ovarian reserve at sixth months after surgery as measured by the serum AMH levels. In addition, the decrease in the AMH level was more severe when endometriomas were bilateral or R5 cm. An interesting finding was that the initial serum AMH levels were significantly higher in patients with FIGURE 2 Serum AMH level (ng/ml) Preop 6 weeks 6 months The serial changes in serum antim ullerian hormone (AMH) levels in each case before and after laparoscopic ovarian cystectomy for 39 patients. Celik. Endometrioma excision and AMH. Fertil Steril VOL. 97 NO. 6 / JUNE

5 Because AMH is secreted from the preantral follicles, initial AMH levels may be higher in patients with larger endometriomas. There is growing amount of evidence that excision of endometriomas with the stripping technique removes adjacent healthy ovarian tissue. In a retrospective analysis we recently demonstrated that the stripping technique removes normal ovarian tissue in up to 90% of the cases both in endometriotic and nonendometriotic ovarian cysts. However, tissue loss was more in endometriotic cysts (14). Similarly, Roman et al. (15) performed a retrospective study in 35 patients with endometriomas and concluded that there was normal ovarian tissue found in 97% the specimens. Furthermore, the amount of tissue removed increased with the increase in the cyst diameter, which is in parallel with our results. When the cyst diameter is R5 cm there is a greater decrease in the serum AMH level. Therefore, when the amount of tissue removed during cystectomy is increased, there is a greater decrease in the AMH level. However, we did not find any correlation between the histopathologic analysis of the removed ovarian tissue and the reduction in the AMH levels. This suggests that other mechanisms are also involved other than healthy ovarian tissue removal. The damage to the ovarian reserve is mainly due to the inadvertent removal of healthy ovarian tissue, but vascular compromise due to electrosurgical coagulation or postsurgical inflammation may also cause damage (16, 17). These latter two types of damage may only be measured by the postoperative changes in the ovarian reserve markers. There are few studies measuring postoperative changes in the serum AMH levels after laparoscopic cystectomy for endometriomas and these have inconsistent results. In addition, the study groups were limited in number and the follow-up periods were 1 week to 6 months. Lee et al. (18) investigated serum AMH levels at baseline, 1 week, 1 month, and 3 months after surgery in 27 women with endometriomas who had either unilateral cystectomy (n ¼ 13) or oopherectomy (n ¼ 14). They reported that AMH levels decreased significantly immediately after surgery and for up to 3 months. In addition, the decrease in the AMH level was similar between the unilateral cystectomy and oopherectomy groups. Tsolakidis et al. (19) compared the change in serum AMH levels, AFC, and basal ovarian reserve tests at 6 months after laparoscopic cystectomy with a three-stage management protocol (aspiration, 3 months on GnRH analogue, laser vaporization) in a total of 20 patients (10 patients in each group). The decrease in AMH level was only significant in the one-step stripping group. Interestingly, the AFC levels increased in both groups, but it was only significant in the three-stage treatment group. The changes in the other ovarian reserve tests (basal FSH, LH, E 2, and inhibin B) were not remarkable. Our study and the other studies did not demonstrate a significant change in other ovarian reserve tests after endometrioma excision. This is mainly because basal FSH, E 2, and inhibin B have low sensitivity in detecting the early decrease in the ovarian reserve. Unexpectedly, AFC was found to be increased after endometrioma excision. This contradictory to the findings also reported by Tsolakidis et al. (19), where they found that AFC was significantly increased in the three-step laser vaporization group. We can speculate that this increase in the AFC may be either due to a reactive response of ovarian parenchyma after surgery or due to the endometrioma's presence preventing the correct measurement of AFC preoperatively and underestimating AFC. These findings show that AFC measurement may not be a reliable ovarian reserve marker after endometrioma excision. Chang et al. (20) prospectively evaluated serum AMH levels preoperatively and postoperatively at 1 week, 1 month, and 3 months in 20 patients who were treated for benign ovarian cysts (13 endometrioma and 7 nonendometrioma). They reported that mean serum AMH level was 2.23 ng/ml preoperatively, but reduced to 0.67 ng/ml at the first postoperative week. Then it increased to 1.14 ng/ml in the first month and 1.5 ng/ml in the third month. At the first postoperative week serum AMH decreased more in the endometrioma compared with nonendometrioma (69.2% vs. 33.9%). It was the same in the bilateral group compared with the unilateral group (62.9% vs. 16.9%). These results are similar to our results; bilateral cyst excision decreases AMH levels more when it is compared with unilateral cyst excision. Contrary to our finding, Chang et al. (20) reported that the serum AMH level gradually increased after 1 month and that there was a 65% recovery of the preoperative level after 3 months. This recovery was not observed in our patients, rather the gradual decline continued in our patients. This may be because there were only patients with endometrioma and no nonendometriomatic cysts were included in our study. It has been shown that because of the absence of real tissue planes, significantly more healthy ovarian tissue is removed in endometriomas when compared to nonendometriomas. This may be one of the explanations for this gradual decline in our patients. Improvement of serum AMH level has been postulated as a result of the following: reperfusion of ovarian tissue and release of AMH from the remaining follicles; compensatory hyperactivation of GCs after surgery related to ovarian damage; inflammation after surgery may stimulate regeneration of ovarian follicles from ovarian surface epithelium (20). These are controversial theories that need to be proved. Similar to our findings, other investigators did not find any recovery of serum AMH levels after endometrioma excision. Because the follicular life span is around 120 days, measuring serum AMH level at 6 months after surgery may be more informative for the assessment of ovarian reserve. The technique of the surgery may also affect the change in the ovarian reserve. Li et al. (16) treated 191 patients with benign ovarian cysts using three different methods: bipolar electrocoagulation, harmonic scalpel at laparoscopy, or simple suturing at laparotomy. Basal FSH and AMH levels were measured serially postoperatively. They reported that in patients with bilateral cysts at month 12 postoperatively, basal FSH levels were increased and AMH levels were decreased significantly more in the bipolar and harmonic scalpel group when compared with the suturing group. This study also supports the idea that damage to the ovarian vascular system by the energy modalities is an additional factor for the decreased ovarian reserve. Hirokawa et al. (21) measured serum AMH levels preoperatively and postoperatively at 1 month 1476 VOL. 97 NO. 6 / JUNE 2012

6 Fertility and Sterility after laparoscopic or laparotomic cystectomy in 38 patients with endometrioma (20 unilateral and 38 bilateral). Serum AMH levels significantly decreased from ng/ml after surgery (P<.001). The decrease in the AMH level was found to be correlated with the bilaterality and the severity of the disease, but not with cyst diameter, age, or blood loss during operation. Not all studies found decreased serum AMH level after laparoscopic endometrioma excision. For example, Ercan et al. (22) measured serum AMH levels in 47 patients with endometrioma (33 unilateral and 14 bilateral) 1 month after surgery. In this short-term follow-up they did not observe a significant reduction in the mean serum AMH level postoperatively ( ng/ml; P>.05). However, the decrease was more in patients with unilateral cysts compared with bilateral ones, which makes the interpretation difficult. A recent study (23) showed that combination of excisional and ablative surgery of endometriomas was not deleterious to the ovary. Donnez et al. (23) evaluated the ovarian reserve with AFC and ovarian volume by comparing operated ovaries to nonoperated ovaries in 52 patients 6 months after laparoscopic surgery. They removed 80% 90% of the endometrioma by the stripping technique and the remaining 10% 20% of the cyst close to the hilus was vaporized by CO 2 laser. They claimed that with this combined method ovarian volume and AFC are unaffected with high pregnancy rate (PR; 40% at 8 months) and low recurrence (<2%). Vaporization with CO 2 laser may be more tissue protective than bipolar coagulation, as the depth of vaporization is shallow. Pados et al. (24) compared one-stage laparoscopic cystectomy with three-stage management (laparoscopic drainage, followed by 3 months of GnRH agonist treatment, and then laser vaporization of the cyst wall during a second laparoscopic surgery) in 20 patients with ovarian endometriomas. The AFC on the operated ovary was significantly increased after 6 months of surgery in the three-stage management group compared with the one-stage laparoscopy group. However, two patients (20%) had recurrence of endometrioma in the three-stage management group, whereas no recurrences were detected in the other group. As we mentioned, we believe that AFC may not be a suitable ovarian reserve marker in patients undergoing endometiroma surgery because AFC may be measured as erroneously increased after surgery whereas AMH is decreased. Therefore, the AMH level may be used for the preoperative evaluation of these patients instead of AFC. In addition, we found that initial preoperative serum AMH level is the only independent factor affecting the AMH decrease, which makes it a valuable marker for preoperative counseling of patients with endometrioma. In conclusion, laparoscopic excision of ovarian endometriomas gradually decreases serum AMH levels at 6 months after surgery. The decrease is associated with the bilaterality and the size (R5 cm) of the endometrioma but not with the amount of the follicular loss measured histopathologically. The initial AMH level was an independent factor in the decrease of AMH level. Therefore, gynecologic surgeons should inform their patients about the possible decrease in the ovarian reserve after surgery and counsel them on the implication for future fertility potentials. Additionally more studies with longer follow-up periods are needed to better understand the impact of laparoscopic endometrioma excision on ovarian reserve. REFERENCES 1. ACOG practice bulletin. Medical management of endometriosis. Int J Gynaecol Obstet 2000;71: Busacca M, Vignali M. Ovarian endometriosis: from pathogenesis to surgical treatment. Curr Opin Obstet Gynecol 2003;15: Speroff L, Fritz MA. Endometriosis. In: Clinical gynecologic endocrinology and infertility. 8th ed. Philadelphia: Lippincott Williams & Wilkins, 2011: Vercellini P, Fedele L, Aimi G, De Giorgi O, Consonni D, Crosignani 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: Exacoustos C, Zupi E, Amadio A, Szabolcs B, De Vivo B, Marconi D, et al. Laparoscopic removal of endometriomas: sonographic evaluation of residual functioning ovarian tissue. Am J Obstet Gynecol 2004;191: Garcia-Velasco JA, Mahutte NG, Corona J, Zuniqa V, Giles J, Arici A, et al. Removal of endometriomas before in vitro fertilization does not improve fertility outcomes: a matched, case-control study. Fertil Steril 2004;81: Broekmans FJ, Kwee J, Hendriks DJ, Mol BW, Lambalk CB. A systematic review of tests predicting ovarian reserve and IVF outcome. Hum Reprod Update 2006;12: de Carvalho BR, Rosa e Silva AC, Rosa e Silva JC, dos Reis RM, Ferriani RA, Silva de Sa MF. Ovarian reserve evaluation: state of the art. J Assist Reprod Genet 2008;25: Fanchin R, Schonauer LM, Righini C, Guirbourdenche J, Frydman R, Taieb J. Serum AMH is more strongly related to ovarian follicular status than serum inhibin B, oestradiol, FSH and LH on day 3. Hum Reprod 2003;18: La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, et al. Anti-Mullerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update 2010;16: American Society for Reproductive Medicine. Revised American Society for Reproductive Medicine classification of endometriosis: Fertil Steril 1997;67: Maneschi F, Marasa L, Incandela S, Mazzarese M, Zupi E. Ovarian cortex surrounding benign neoplasms: a histologic study. Am J Obstet Gynecol 1993;169: Chapron C, Vercellini P, Barakat H, Vieira M, Dubuisson JB. Management of ovarian endometriomas. Hum Reprod Update 2002;8: Dogan E, Ulukus EC, Okyay E, Ertugrul C, Saygili U, Koyuncuoglu M. Retrospective analysis of follicle loss after laparoscopic excision of endometrioma compared with benign nonendometriotic ovarian cysts. Int J Gynaecol Obstet 2011;114: Roman H, Tarta O, Pura I, Opris I, Bourdel N, Marpeau L, et al. Direct proportional relationship between endometrioma size and ovarian parenchyma inadvertently removed during cystectomy, and its implication on the management of enlarged endometriomas. Hum Reprod 2010;25: Li CZ, Liu B, Wen ZQ, Sun Q. The impact of electrocoagulation on ovarian reserve after laparoscopic excision of ovarian cysts: a prospective clinical study of 191 patients. Fertil Steril 2009;92: Hachisuga T, Kawarabayashi T. Histopathological analysis of laparoscopically treated ovarian endometriotic cysts with special reference to loss of follicles. Hum Reprod 2002;17: Lee DY, Young Kim N, Jae Kim M, Yoon BK, Choi D. Effects of laparoscopic surgery on serum anti-m ullerian hormone levels in reproductive-aged women with endometrioma. Gynecol Endocrinol 2011;27: VOL. 97 NO. 6 / JUNE

7 19. Tsolakidis D, Pados G, Vavilis D, Athanatos D, Tsalikis T, Giannakou A, et al. The impact on ovarian reserve after laparoscopic ovarian cystectomy versus three-stage management in patients with endometriomas: a prospective randomized study. Fertil Steril 2010;94: Chang HJ, Han SH, Lee JR, Jee BC, Lee BI, Suh CS, et al. Impact of laparoscopic cystectomy on ovarian reserve: serial changes of serum anti-m ullerian hormone levels. Fertil Steril 2010;94: Hirokawa W, Iwase A, Goto M, Takikawa S, Nagatomo Y, Nakahara T, et al. The post-operative decline in serum anti-mullerian hormone correlates with the bilaterality and severity of endometriosis. Hum Reprod 2011;26: Ercan CM, Sakinci M, Duru NK, Alanbay I, Karasahin KE, Baser I. Antimullerian hormone levels after laparoscopic endometrioma stripping surgery. Gynecol Endocrinol 2010;26: Donnez J, Lousse JC, Jadoul P, Donnez O, Squifflet J. Laparoscopic management of endometriomas using a combined technique of excisional (cystectomy) and ablative surgery. Fertil Steril 2010;94: Pados G, Tsolakidis D, Assimakopoulos E, Athanatos D, Tarlatzis B. Sonographic changes after laparoscopic cystectomy compared with three-stage management in patients with ovarian endometriomas: a prospective randomized study. Hum Reprod 2010;25: VOL. 97 NO. 6 / JUNE 2012