CONTROVERSIES IN OB/GYN

Does surgery have a role in the treatment of endometriosis-related infertility?

By Eric S. Surrey, MD

No. Less invasive methods offer greater likelihood of success.

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).

Examining results with surgery by disease stage

It 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.

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.

Only 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.

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

Two 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.

Benefits and risks of other forms of therapy

In 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.

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 transfer—ranging from 31.1% to 40.9%—in infertile endometriosis patients, regardless of disease stage.¹⁵ The results achieved with surgical approaches do not compare.

The 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

Conclusion

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."

REFERENCES

1. Candiani 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.

2. Luciano AA, Lowney J, Jacobs SL. Endoscopic treatment of endometriosis-associated infertility. Therapeutic, economic, and social benefits. J Reprod Med. 1992; 37:573-576.

3. Surrey ES, Halme J. Effect of peritoneal fluid from endometriosis patients on endometrial stromal cell proliferation in vitro. Obstet Gynecol. 1990;76:792-797.

4. Morcos 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.

5. Miller 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.

6. Damewood 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.

7. Marcoux 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.

8. Taylor HS, Olive DL. Unexplained infertility: the role of laparoscopy. Infertil Reprod Med Clin North Am. 1997;8:603-609.

9. Ablation 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.

10. Adamson 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.

11. Hughes EG, Fedorkow DM, Collins JA. A quantitative overview of controlled trials in endometriosis-associated infertility. Fertil Steril. 1993;59:963-970.

12. Fedele 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.

13. Tummon 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.

14. Geber 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.

15. Olivennes F, Feldberg D, Liu HC, et al. Endometriosis: a stage by stage analysis—the role of in vitro fertilization. Fertil Steril. 1995;64:392-398.

16. Gardner 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.

Dr. Surrey is Medical Director, Colorado Center for Reproductive Medicine, Englewood, Colo.

 

Eric Surrey. Does surgery have a role in treatment of endometriosis? No.. Contemporary Ob/Gyn 2000;10:39-52.