Vaporization of ovarian endometrioma using plasma energy: histologic findings of a pilot study

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1 Vaporization of ovarian endometrioma using plasma energy: histologic findings of a pilot study In ten ovarian endometriomas of diameter exceeding 30 mm, managed by complete vaporization of the inner surface using plasma energy followed by cystectomy, we performed histologic evaluation of the depth of necrosis and the effectiveness of endometrial tissue ablation. We observed that plasma energy allows the ablation of endometrial tissue with minimal damage to the ovarian parenchyma, which suggests that this technique might be of particular interest for women with risk factors of postoperative ovarian reserve impairment, such as recurrent and bilateral endometriomas. (Fertil Steril Ò 2011;95: Ó2011 by American Society for Reproductive Medicine.) Key Words: Ovarian endometrioma, vaporization, cystectomy, plasma energy Although surgical management of ovarian endometriosis by cystectomy is routinely performed worldwide, several recent articles have emphasized the potentially harmful consequences of endometrioma cystectomy on the ovarian reserve (1 5), because of the inadvertent excision of adjacent ovarian parenchyma (6 10). The deleterious effect of endometrioma cystectomy has been shown in series focusing on women being managed for bilateral localization of the disease, the compensatory effect of the contralateral, healthy ovary being absent (11). In addition, the postoperative recurrence rate of ovarian endometrioma may be as high as 29% in 2 years (12), and 78% of recurrences may involve the contralateral ovary (13). This finding means that a quarter Horace Roman, M.D., Ph.D. a,b Ioana Pura, M.D. c Oana Tarta, M.D. c Cecile Mokdad, M.D. a Mathieu Auber, M.D. a Nicolas Bourdel, M.D. d Lo ıc Marpeau, M.D. a Jean Christophe Sabourin, M.D., Ph.D. c a Department of Gynecology and Obstetrics, Rouen University Hospital, Rouen, France b Research Group Spermatogenesis and Male Gamete Quality, Rouen University Hospital, Rouen, France c Department of Pathology, Rouen University Hospital, Rouen, France d Department of Gynecology, Obstetrics, and Reproductive Medicine, University Hospital Estaing, Clermont Ferrand, France Received July 23, 2010; revised October 13, 2010; accepted November 11, 2010; published online December 17, H.R. has nothing to disclose. I.P. has nothing to disclose. O.T. has nothing to disclose. C.M. has nothing to disclose. M.A. has nothing to disclose. N.B. has nothing to disclose. L.M. has nothing to disclose. J.C.S. has nothing to disclose. Reprint requests: Horace Roman, M.D., Ph.D., Clinique Gynecologique et Obstetricale, CHU Charles Nicolle, 1 rue de Germont, Rouen, France ( horace.roman@gmail.com). of young patients managed by cystectomy for an ovarian endometrioma might be at risk of undergoing a secondary cystectomy on the contralateral ovary in the first few years following the original procedure. A new energy system, PlasmaJet (Plasma Surgical Limited, Abingdon, U.K.), provided a low depth of tissue penetration and has become available in surgery over the last 2 years (14 16). The aim of our pilot study was to evaluate the feasibility of ovarian endometrioma vaporization using plasma energy, the completeness of endometrial tissue ablation, and the risk of deep necrosis in underlying ovarian parenchyma. The pilot study was performed over a 3-month period in the Department of Gynecology and Obstetrics at Rouen University Hospital (Rouen, France). All procedures were performed by one surgeon (H.R.), who is skilled in the surgical management of endometriosis and has experience using plasma energy. Women included in the study were managed for pelvic endometriosis responsible for either pain or infertility, and they had at least one ovarian localization of diameter exceeding 30 mm. Women were informed of the aim of the study, which was approved by the institutional review board (CPP ) and the French Agency for the Security of Health Products (AFSSAPS 2009-A ). The surgical procedure accounted for physiopathologic theories of the development of ovarian endometrioma (17 20). The point of cyst invagination was usually revealed by lyses of adhesions between the ovary and the adjacent broad ligament, leading to the characteristic chocolate fluid evacuating from the cyst (18), and the surgeon attempted to turn the cyst completely inside out. Vaporization of the inner surface of the cyst was then performed using plasma energy in coagulation mode set at 40, at a distance averaging 5 mm from the tip of the handpiece, and with an exposure time limited to 1 second on each site. Care was taken not to leave any untreated sites and to vaporize around the edges of the invagination site and the corresponding peritoneal implants on the adjacent broad ligament. Where cyst inversion was not feasible, the surgeon progressively exposed the cyst interior to guide the plasma beam at an angle perpendicular to the inner surface of the cyst. The surgical procedure was recorded in each patient, and the operative time was noted. (Supplemental Video 1) /$36.00 Fertility and Sterility â Vol. 95, No. 5, April doi: /j.fertnstert Copyright ª2011 American Society for Reproductive Medicine, Published by Elsevier Inc.

2 A standard endometrioma cystectomy was then performed using an ovarian tissue sparing technique described previously (6). The cyst was retrieved, avoiding any fragmentation, and underwent histologic examination. Serial sections were performed, ten measures of necrosis depth and of the width of the cyst wall were randomly performed on each specimen, and the mean value and ranges were estimated for the whole sample (Supplemental Fig. 1). The necrosis area was defined as dense and homogenous acellular tissue or containing rare ghost cells. On hematoxylin and eosin staining sections, the necrosis areas were clearly separated from normal surrounding tissue. The presence of persistent foci of endometrial epithelium and stroma that had not been destroyed by vaporization was checked, and the percentage estimated was based on the area of the inner surface of the cyst. Cases in which necrosis involved underlying sound ovarian parenchyma were noted. Eight women were included in the study, and two of them had bilateral ovarian endometriomas (Table 1). The cyst was completely reversed without fragmentation in 5 of 10 cases. No difficulties in exposing the inner surface of the cyst were encountered, and no unexpected incidents such as bleeding or inadvertent injuries were recorded. The depth of necrosis induced by vaporization was mean SD, mm, and the width of the endometrioma cyst wall (endometrial epithelium, stroma, and underlying fibrosis) was mean SD, mm (Supplemental Fig. 1). Endometrial epithelium left in place was recorded in four cases and represented less than 10% of the total area of the cyst inner layer (Supplemental Fig. 2). Small foci independent of and at a distance from the inner endometrial epithelium of the cyst were recorded in two cases. Small areas of necrosis were observed in the ovarian parenchyma in seven cases, but in only three cases were they adjacent to the inner surface of the cyst and attributable to the vaporization. In the other four cases, these areas were adjacent to the cleavage plane and probably resulted from the cystectomy. In all cases concerned less than 10% of the ovarian parenchyma inadvertently excised during cystectomy (Supplemental Fig. 3). The number of follicles removed in each case is presented in Table 1 and Supplemental Figure 4. Our pilot study showed that vaporization of ovarian endometrioma is feasible in all patients, as with a CO 2 laser. Although small areas of the underlying, sound ovarian parenchyma were affected by necrosis, the vaporization using plasma energy might spare more than 90% of the ovarian parenchyma usually removed by cystectomy. Further study is required to evaluate whether decreasing the plasma energy setting could diminish the depth of thermal diffusion even further. However, it must be emphasized that our findings concern histologic effects occurring immediately after vaporization and do not provide information about the final depth of the destruction of ovarian parenchyma. The PlasmaJet system has been used in surgery since 2004, and it provides a high-energy jet of argon plasma possessing thermal and kinetic energy that can be used to vaporize, coagulate, and cut various tissues surfaces (14 16). The device behaves in a similar way to a CO 2 laser as it desiccates and effectively vaporizes tissue by forming a series of layers of eschar without sparking, and thus without disrupting the coagulum (14, 16). Compared with the CO 2 laser, plasma energy is less expensive and there is no risk of intraoperative incidents owing to beam overshoot or deviation by metallic instruments. The variability in the range of values of necrosis might be explained by several factors. First, because the exposure time is limited to 1 second on each site, continuous movement of the handpiece leads to slight variations of the distance between the tip of the handpiece and the tissues, and this is directly related to the depth of the induced necrosis (16). Second, necrotic tissues are friable, and the manipulation during the cystectomy, the extraction through the 10-mm parietal incision, and the fixation could partially remove superficial stratums of the inner surface of the cyst. However, we believe that the major finding is the evidence that the depth of necrosis is consistently inferior to the width of the fibrous cyst wall, and therefore that acute necrosis spares ovarian parenchyma. A large majority of surgeons have abandoned ablative techniques following two randomized controlled trials, which reported better outcomes after cyst excision compared with cyst ablation using bipolar current (21 23). Although both trials were well conducted and their conclusions were consistent, it is probable that the negative results observed with the ablation technique were related to the use of bipolar current, most likely responsible for a deeper thermal effect than that of plasma energy or a CO 2 laser. On the other hand, it has been demonstrated that laser vaporization in the hands of an experienced surgeon is associated with good results in regard to recurrence risk and pregnancy rate (24). In addition, and founded on extensive experience and the fact that cystectomy leads to the removal of follicles close to the ovarian hilus (10), Donnez et al. (25) recently advocated performing vaporization of the cyst wall using a CO 2 laser when approaching the ovarian hilus (25). One objection that could be raised is that small, intact foci were found on the endometrial lining in 4 of 10 cases; although they did not represent more than 10% of the whole endometrial epithelium area, it is reasonable to suppose that any residual foci may be at the origin of further cyst recurrence. In 2 of 10 cases, endometrial glands were located far from the endometrioma cyst wall, representing microscopic secondary localizations of the disease that could equally be overlooked and left in place after the cystectomy procedure. It is unlikely that complete removal of endometrial tissue is possible in all cases when endometrioma cystectomy is performed, because all previously published series have observed rates of recurrences varying from 6% 29% at 2 years after cystectomy (12, 13, 21, 22). In our opinion, the major question does not concern what we should do for women without surgical antecedents who have an ovarian endometrioma, but how we should manage them when they require surgical management of bilateral or contralateral recurrences and are still nulliparous. To avoid any heterogeneity of samples, a large majority of the clinical trials available in the literature concern patients free of previous surgical procedures (12, 13, 21, 22); therefore, their results are not intended to be extrapolated to women who have undergone repeated cystectomy resulting in a significant cumulative loss of ovarian parenchyma. It is for this reason we believe that endometrioma vaporization with plasma energy might serve as a valuable alternative to cystectomy, specifically for women with a high risk of irreversible ovarian reserve impairment. However, it remains clear that prospective 1854 Roman et al. Vaporization using plasma energy Vol. 95, No. 5, April 2011

3 Fertility and Sterility â 1855 TABLE 1 Vaporization procedure and findings of the histologic examination of specimens. Endometriomas no. Endometrioma diameter (mm) Vaporization duration (min) Reversion of the cyst Surgeon analysis of vaporization completeness Necrosis depth (mm), mean ± SD Necrosis depth, range (mm) Cyst wall width, (mm), mean ± SD Cyst wall width, range (mm) Area of residual endometrial epithelium, cyst area Ovarian parenchyma concerned by the necrosis attributable to the vaporization, rate Follicles found on specimen, n AFSr score Associated localizations of the endometriosis Yes Complete , Ureteral Yes Complete <0.10 < Peritoneal Yes Complete ,111 < Rectal No Complete < Peritoneal 5 a Yes Maybe < Rectal incomplete 6 a 50 9 No Complete Rectal 7 b No Complete ,035 <0.10 c Rectovaginal 8 b No Complete , Rectovaginal No Complete , ,169 < Sigmoid colon Yes Complete ,207 <0.10 c < Rectal Note: AFSr ¼ American Fertility Society score revised. a Cyst numbers 5 and 6 provided from the right and the left ovaries, respectively, of the same patient. b Cysts numbers 7 and 8 provided from the right and the left ovaries, respectively, of the same patient. c Small endometriotic foci independent and at a distance from the cyst wall.

4 studies comparing cystectomy and vaporization using plasma energy, focusing on recurrences and pregnancy rate, are required before any definitive conclusions can be drawn. Acknowledgment: The authors thank Plasma Surgical Limited (Abingdon, UK) for loaning the PlasmaJet system with console and for donating 11 disposable handpieces. REFERENCES 1. Busacca M, Vignali M. Endometrioma excision and ovarian reserve: a dangerous relation. J Minim Invasive Gynecol 2009;16: Benaglia L, Somigliana E, Vighi V, Ragni G, Vercellini P, Fedele L. Rate of severe ovarian damage following surgery for endometriomas. Hum Reprod 2010;25: Somigliana E, Ragni G, Benedetti F, Borroni R, Vegetti W, Crosignani PG. Does laparoscopic excision of endometriotic ovarian cysts significantly affect ovarian reserve? Insights from IVF cycles. Hum Reprod 2003;18: Somigliana E, Arnoldi M, Benaglia L, Iemmello R, Nicolosi AE, Ragni G. IVF-ICSI outcome in women operated on for bilateral endometriomas. Hum Reprod 2008;23: Almog B, Sheizaf B, Shalom-Paz E, Shehata F, Al-Talib A, Tulandi T. Effects of excision of ovarian endometrioma on the antral follicle count and collected oocytes for in vitro fertilization. Fertil Steril 2010;94: Roman H, Tarta O, Pura I, Opris I, Bourdel N, Marpeau L, Sabourin JC. 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: Matsuzaki S, Houlle C, Darcha S, Pouly JL, Mage G, Canis M. Analysis of risk factors for the removal of normal ovarian tissue during laparoscopic cystectomy for ovarian endometriosis. Hum Reprod 2009;24: Exacoustos C, Zupi E, Amadio A, Szabolcs B, De Vivo B, Marconi D, Romanini ME, Arduini D. Laparoscopic removal of endometriomas: sonographic evaluation of residual functioning ovarian tissue. Am J Obstet Gynecol 2004;191: Hachisuga T, Kawarabayashi T. Histopathological analysis of laparoscopically treated ovarian endometriotic cysts with special reference to loss of follicles. Hum Reprod 2002;17: Muzii L, Bellati F, Bianchi A, Palaia I, Manci N, Zullo MA, et al. Laparoscopic stripping of endometriomas: a randomized trial on different surgical techniques. Part I: pathological results. Hum Reprod 2005;20: Busacca M, Riparini J, Somigliana E, Oggioni G, Izzo S, Vignali M, et al. Postsurgical ovarian failure after laparoscopic excision of bilateral endometriomas. Am J Obstet Gynecol 2006;195: Seracchioli R, Mabrouk M, Frasca C, Manuzzi L, Montanari G, Keramyda A, et al. Long-term cyclic and continuous oral contraceptive therapy and endometrioma recurrence: a randomized controlled trial. Fertil Steril 2010;93: Sesti F, Capozzolo T, Pietropolli A, Marziali M, Bollea MR, Piccione E. Recurrence rate of endometrioma after laparoscopic cyctectomy: a comparative randomized trial between postoperative hormonal suppression treatment or dietary therapy vs. placebo. Eur J Obstet Gynecol Reprod Biol 2009;147: Nezhat C, Kho KA, Morozov V. Use of neutral argon plasma in the laparoscopic treatment of endometriosis. JSLS 2009;13: Deb S, Deen S, Ashford KS, Harwood A, Newman C, Powell MC. Histological quantification of the tissue damage caused by PlasmaJet Coagulator. Gynecol Surg 2010;7: Somoda Y, Olvera N, Chi DS, Brown CL, Abu- Rustum NR, Levine DA. Pathologic analysis of ex vivo plasma energy tumor destruction in patients with ovarian or peritoneal cancer. Int J Gynecol Cancer 2010;20: Donnez J, Nisolle M, Gillet N, Smets M, Bassil S, Casanas-Roux F. Large ovarian endometriomas. Hum Reprod 1996;11: Hughesdon PE. The structure of endometrial cysts of the ovary. J Obstet Gynaecol Br Emp 1957;64: Brosens IA, Puttemans PJ, Deprest J. The endoscopic localization of endometrial implants in the ovarian chocolate cyst. Fertil Steril 1994;61: Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril 1997;68: Alborzi S, Momtahan M, Parsanezhad ME, Dehbashi S, Zolghadri J. A prospective, randomised study comparing laparoscopic ovarian cystectomy versus fenestration and coagulation in patients with endometriomas. Fertil Steril 2004;82: Beretta P, Franchi M, Ghezzi F, Busacca M, Zupi E, Bolis P. Randomized clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation. Fertil Steril 1998;70: Hart RJ, Hickey M, Maouris P, Buckett W. Excisional surgery versus ablative surgery for ovarian endometriomata. Cochrane Database Syst Rev 2008;2:CD Donnez J, Wyns C, Nisolle M. Does ovarian surgery for endometriomas impair the ovarian response to gonadotropin? Fertil Steril 2001;76: 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: Roman et al. Vaporization using plasma energy Vol. 95, No. 5, April 2011

5 SUPPLEMENTAL FIGURE 1 Endometrioma cyst wall: acute necrosis (*, circled in green) is mainly limited to the endometrial epithelium, stroma, and superficial underlying fibrosis (**, circled in black), and it does not involve adjacent ovarian parenchyma (***). Fertility and Sterility â 1856.e1

6 SUPPLEMENTAL FIGURE 2 Endometrial epithelium and stroma left in place (*) along with endometrial epithelium and stroma destroyed by the vaporization (**) e2 Roman et al. Vaporization using plasma energy Vol. 95, No. 5, April 2011

7 SUPPLEMENTAL FIGURE 3 Areas of necrosis in ovarian parenchyma (*) and normal ovarian parenchyma inadvertently excised during cystectomy (**). Fertility and Sterility â 1856.e3

8 SUPPLEMENTAL FIGURE 4 Ovarian follicles (*) removed during cystectomy (the area of necrosis induced by vaporization circled in green, cyst fibrous wall circled in black) e4 Roman et al. Vaporization using plasma energy Vol. 95, No. 5, April 2011

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