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"  \n\nCONTROVERSIES IN OB/GYN \n\nDoes surgery have a role in the treatment of endometriosis-related infertility? \n\n\n\n\n\nBy Eric S. Surrey, MD \n\n\n\nNo. Less invasive methods offer greater likelihood of success.\n\n The primary therapeutic approach for the asymptomatic patient with   endometriosis-related infertility traditionally has been a surgical one. There   is little argument that visualization represents the primary means for diagnosis   of this disease. There has been much debate regarding surgical technique, including   the merits of laparotomy versus laparoscopy and excision versus ablation. The   central issue may be whether any surgical approach is indeed superior   at all in these infertile patients for whom pelvic pain is not a presenting   symptom. A careful review of the literature would suggest that the benefits   of surgical resection in this group are limited, particularly in contrast to   less invasive approaches such as controlled ovarian hyperstimulation and assisted   reproductive technology (ART). \n\n Examining results with surgery by disease stage \n\nIt is certainly logical to think that patients with more advanced stages of endometriosis who have distorted anatomy and pelvic adhesions would benefit most from surgical reconstruction. In this group of patients, however, there is a lack of prospective, randomized trials. In a meta-analysis of conservative laparoscopic surgery for severe endometriosis (revised AFS stage III and IV), Candiani and colleagues reported an impressive overall cumulative pregnancy rate of 47.6%.1 When the data are appropriately analyzed, however, monthly fecundity rates (MFR) were noted to range from 2.1% to 3.3%, a much less impressive but more accurate statistic. Luciano and colleagues reported outcomes in 60 patients with stage III and IV endometriosis and noted a 70% cumulative pregnancy rate.2 The mean MFR, however, was only 6.7% in this trial.\n\n There is less logic in considering the value of surgical therapy in asymptomatic   infertile patients with revised AFS endometriosis score stage I and II disease   who do not have anatomic distortion. A host of investigators have demonstrated   that endometriosis is associated with alterations in the peritoneal immune environment   with identification of inflammatory cytokines and embryotoxic elements within   both peritoneal fluid and maternal serum.3-6 We are unaware of any   evidence that demonstrates that mechanical surgical ablation or excision of   endometriosis would result in a significant change in this altered peritoneal   immunologic state. \n\nOnly two prospective, randomized trials have addressed the effect of laparoscopic ablation of stage I and II endometriosis on fertility. Marcoux and colleagues reported the results of an elegant multicenter trial designed to address this issue.7 In this investigation, ongoing pregnancy rates were significantly higher and pregnancies were achieved more rapidly in patients undergoing surgical ablation of the disease as opposed to those undergoing diagnostic laparoscopy alone. \n\n A closer evaluation of the data, however, reveals a mean MFR of 4.7% in the   ablated group as opposed to 2.4% in those who underwent no therapy at all. Employing   those data, Taylor and Olive calculated that one would need to perform 6.7 laparoscopies   with ablation on patients with stage I and II endometriosis to achieve a single   conception.8 Indeed, a similarly designed prospective, randomized   trial of ablation versus no treatment in 101 infertile women with minimal to   mild endometriosis revealed no significant differences in pregnancy rates after   1 year.9 \n\nTwo well-designed meta-analyses have looked at the overall value of surgical treatment of endometriosis-associated infertility.10,11 Both Adamson and colleagues and Hughes and colleagues demonstrated consistently higher pregnancy rates with surgical treatment in comparison to no treatment or medical suppression. Unfortunately, there have been no studies published comparing surgical therapy alone to other well-established therapeutic options for infertile couples such as gonadotropin therapy with or without intrauterine insemination (IUI) and ART.\n\n Benefits and risks of other forms of therapy \n\nIn a well-designed prospective, randomized trial of infertile women with stage I and II endometriosis without anatomic distortion, Fedele and colleagues have shown that gonadotropin therapy yielded significantly higher monthly fecundity rates (15.5%) versus untreated controls (4.5%).12 When gonadotropin therapy was combined with IUI in a 4-month prospective, randomized trial, Tummon and colleagues reported a cumulative live birth rate of 30%, compared with 10% for expectantly managed controls.13 These outcome rates all are higher than those previously reported with surgical approaches employed in patients with similar stages of endometriosis.\n\n If one accepts the concept that endometriosis might induce an altered or \"toxic\"   peritoneal environment for gamete interaction and zygote development, then the   removal of gametes and zygotes from this environment for early development,   through in vitro fertilization (IVF), should dramatically improve outcomes.   Indeed, this hypothesis has been borne out by the literature. Geber and colleagues   have reported 35% and 55.5% pregnancy rates, respectively, in patients with   stage I and II versus stage III and IV endometriosis in the absence of prior   surgical resection.14 Olivennes and colleagues reported statistically   similar delivery rates per embryo transferranging from 31.1% to 40.9%in   infertile endometriosis patients, regardless of disease stage.15   The results achieved with surgical approaches do not compare. \n\nThe primary drawback of both gonadotropin therapy and IVF is that of higher-order multiple pregnancy. Recent advances in embryo culture technique, however, resulting in both high implantation rates and ongoing pregnancy rates with transfer of only two blastocyst-stage embryos may result in a virtual elimination of this complication.16\n\n Conclusion \n\n A careful review of the literature suggests that surgical resection of endometriosis   may achieve modest improvements over no therapy or medical suppression. Significantly   higher pregnancy rates, however, can be achieved in a less invasive manner with   short-term, judicious use of gonadotropins alone, or more effectively, in combination   with ART. As Mark Twain perhaps most elegantly wrote, \"It's not what you don't   know that hurts you. It's what you know for sure that just ain't so.\"\n\nREFERENCES\n\n 1.\tCandiani GB, Vercellini P, Fedele L, et al. Conservative   surgical treatment for severe endometriosis in infertile women: are we making   progress? Obstet Gynecol Surv. 1991;46:490-498. \n\n 2.\tLuciano AA, Lowney J, Jacobs SL. Endoscopic treatment   of endometriosis-associated infertility. Therapeutic, economic, and social benefits.   J Reprod Med. 1992; 37:573-576. \n\n 3.\tSurrey ES, Halme J. Effect of peritoneal fluid from   endometriosis patients on endometrial stromal cell proliferation in vitro. Obstet   Gynecol. 1990;76:792-797. \n\n 4.\tMorcos RN, Gibbons WE, Findley WE. Effect of peritoneal   fluid on in vitro cleavage of 2-cell mouse embryos: possible role of infertility   associated with endometriosis. Fertil Steril. 1985;44:678-483. \n\n 5.\tMiller KA, Pittaway DE, Deaton JL. The effect of serum   from infertile women with endometriosis on fertilization and early embryonic   development in a murine in vitro fertilization model. Fertil Steril. 1995;64:623-626.   \n\n 6.\tDamewood MD, Hesla JS, Schlaff WD, et al. Effect of   serum from patients with minimal to mild endometriosis on mouse embryo development   in vitro. Fertil Steril. 1990;54:917-920. \n\n 7.\tMarcoux S, Maheux R, Berube S. Laparoscopic surgery   in infertile women with minimal or mild endometriosis. Canadian Collaborative   Group in Endometriosis. N Engl J Med. 1997;337:217-222. \n\n 8.\tTaylor HS, Olive DL. Unexplained infertility: the   role of laparoscopy. Infertil Reprod Med Clin North Am. 1997;8:603-609.   \n\n 9.\tAblation of lesions or no treatment in minimal-mild   endometriosis in infertile women: a randomized trial. Gruppo Italiano per lo   Studio dell Endometriosi. Hum Reprod. 1999;14:1332-1334. \n\n 10.\tAdamson GD, Pasta DJ. Surgical treatment of endometriosis-associated   infertility: meta-analysis compared with survival analysis. [published erratum   appears in Am J Obstet Gynecol. 1995(Jun);72(6):1937] Am J Obstet   Gynecol. 1994;171:1488-1504. \n\n 11.\tHughes EG, Fedorkow DM, Collins JA. A quantitative   overview of controlled trials in endometriosis-associated infertility. Fertil   Steril. 1993;59:963-970. \n\n 12.\tFedele L, Bianchi S, Marchini M, et al. Superovulation   with human menopausal gonadotropins in the treatment of infertility associated   with minimal or mild endometriosis: a controlled randomized study. Fertil   Steril. 1992;58:28-31. \n\n 13.\tTummon IS, Asher LJ, Martin SJ, et al. Randomized   controlled trial of superovulation and insemination for infertility associated   with minimal or mild endometriosis. Fertil Steril. 1997;68:8-12. \n\n 14.\tGeber S, Paraschos T, Atkinson G, et al. Results   of IVF in patients with endometriosis: the severity of the disease does not   affect outcome, or the incidence of miscarriage. Hum Reprod. 1995;10:1507-1511.   \n\n 15.\tOlivennes F, Feldberg D, Liu HC, et al. Endometriosis:   a stage by stage analysisthe role of in vitro fertilization. Fertil Steril.   1995;64:392-398. \n\n 16.\tGardner DK, Schoolcraft WB, Wagley L, et al. A prospective   randomized trial of blastocyst culture and transfer in in vitro fertilization.   Hum Reprod. 1998;13:3434-3440. \n\nDr. Surrey is Medical Director, Colorado Center for Reproductive Medicine,   Englewood, Colo. \n\n \n\n\n\n  \n\nEric Surrey. Does surgery have a role in treatment of endometriosis? No.. Contemporary Ob/Gyn 2000;10:39-52.\n\n"
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