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Laparoscopy is the most valuable tool for diagnosis of infertility and the investigation of an infertile woman is not complete if laparoscopy has not been performed. It is a simple outpatient procedure that allows direct visualization of the pelvic organs. Ablation of stage I or II endometriosis adds less than 15 minutes to the procedure; ovulation is not inhibited and operative complications are rare.1 When pregnancy occurs, it is a natural one with its low complication rate. In women who harbor stage I or II endometriosis, type I evidence has shown that this technique improves fertility, which cannot be said for medical treatment of endometriosis or for assisted reproductive technology (ART) such as in vitro fertilization (IVF).2
Between 1992 and 1996, Sylvie Marcoux, MD, an epidemiologist, and I studied 241 infertile women aged 20 to 39 years who had minimal or mild endometriosis. This study, known under the acronym ENDOCAN (EndometriosisCanada), was conducted in 24 centers across Canada. During diagnostic laparoscopy, the women were randomly assigned to undergo resection or ablation of visible endometriosis or diagnostic laparoscopy alone. They were followed for 36 weeks after the laparoscopy or, for those who became pregnant during that interval, for up to 20 weeks of pregnancy.
Among the 172 women who had resection or ablation of endometriosis, 50 became pregnant and had pregnancies that continued for 20 weeks or longer, compared with 29 of the 169 women in the diagnostic-laparoscopy group (cumulative probabilities 30.7% and 17.7%, respectively; P=0.006 by the log-rank test). The corresponding rates of fecundity were 4.7 and 2.4 per 100 person-months (rate ratio = 1.9; 95% confidence interval, 1.2 to 3.1). Figure 1 illustrates the cumulative incidence of 20-week pregnancy observed in those two groups and among 263 comparable infertile women in whom no endometriosis was observed at laparoscopy (stage 0).3 In infertile women, laparoscopic resection or ablation of minimal and mild endometriosis practically doubles fecundity when compared with diagnostic laparoscopy alone.
A recent Italian study on the same topic has been unable to show statistical improvement in birth rates after laparoscopic resection or ablation of endometriosis.4 Not showing a difference, however, is quite different from proving that there is no difference. The number of patients enrolled in the Italian study (n=96 vs. n=341 for ENDOCAN) and the power of this study are so low, 95% of the time, that they would have been unable to detect significant improvement in fecundity of less than 250%. Moreover, half of the Italian patients received postoperative GnRH-a for 3 months "according to the physician's judgment," which is introducing an important cofactor. This study, therefore, cannot infirm the solid evidences of the ENDOCAN trial.
We may observe even better results in some subgroups of women. To be enrolled in the ENDOCAN trial, patients had to present at least one typical bluish-black lesion and, when randomized to therapy, all types of lesions were destroyed. Those who did not have any red lesions at laparoscopy, however, did much better after therapy than those in whom these early lesions of endometriosis were still present (Figure 2). Although these results should be interpreted cautiously because they were not the primary endpoint of the study, they open the possibility of identifying subgroups of infertile women with endometriosis in whom laparoscopic treatment will be even more effective. In this subgroup, nearly half of the patients (48%) became pregnant in the first 36 weeks after the laparoscopic ablation of endometriosis; (incidences density ratio) IDR=4.45 (2.149.23). Moreover, laparoscopy may detect not only endometriosis but also other correctible factors of infertility.5
The bottom line in the United States is that laparoscopy is expensive and to save money, many physicians involved in managed care try to avoid performing the procedure and promote, instead, medical treatment for endometriosis or ART.
But medical treatment for endometriosis does not improve fertility. Indeed, there is only one certainty with medical treatment, and it is that the patient will not become pregnant for the next 6 months because GnRH-a and danazol inhibit ovulation and therefore preclude pregnancy during their administration. The worst aspect is that after medical treatment, the probability of pregnancy is not improved (Table 1). Therefore, a treatment for infertility that inhibits ovulation and does not ultimately improve fecundity does not make a lot of sense.
|Pregnancy rate (mean/range)|
|Study||Therapy||Treatment group||Control arm|
|Bayer 1988||Danazol||35% (20%50%)||47% (31%64%)|
|Thomas 1987||Gestrinone||25% (6%44%)||24% (3%44%)|
|Telimaa 1988||Danazol||33% (12%55%)||43% (17%69%)|
|Telimaa 1988||MPA||41% (18%65%)||43% (17%69%)|
IVF, for its part, completely bypasses natural conception and is still associated with significant complications. A recent survey conducted by the Centers for Disease Control and Prevention of 35,554 IVF transfer procedures in the US reports that, if three embryos are transferred (which is still the most common number in the US), the multiple-birth rate increases to as much as 45.7% among women aged 20 to 29 years and to 39.8% for women aged 30 to 34 years.6 The end result for the patient is a major increase in hospitalizations due to complications of pregnancy, in deliveries by cesarean section, in low-birthweights, and in high perinatal mortality.
We need to base medical decisions on the evidence. Unfortunately, although we are inundated with unmanageable amounts of information, good-quality evidence is still rare because randomized, controlled trials (RCTs) are difficult to perform, especially if they include a no-treatment arm. When no such evidence is available, I am one of those who believe that we should resist the temptation to fabricate it, as neither consensus conferences, expert opinions, nor meta-analyses of poor-quality papers can replace the clinical judgment of the treating physician at the bedside of the patient. RCTs with a no-treatment arm provide the most reliable information, and in rare instances, such as the current debate, when they are available, it would be a shame not to use them.
1. Marcoux S, Maheux R, Berube S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. N Engl J Med. 1997;337:217-222.
2. Corabian P, Hailey D. The efficacy and adverse effects of in vitro fertilization and embryo transfer. Int J Technol Assess Health Care. 1999;15:66-85.
3. Berube S, Marcoux S, Langevin M, et al. Fecundity of infertile women with minimal or mild endometriosis and women with unexplained infertility. The Canadian Collaborative Group on Endometriosis. Fertil Steril. 1998;69:1034-1041.
4. Parazzini F. 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.
5. Maheux R, Berube S, Marcoux S, and the Canadian Collaborative Group on Endometriosis. Red lesions in endometriosis: impact on fecundity and effect of ablation. Abstract presented at the SOGC Annual Meeting; June 1721, 2000; Montreal, Canada.
6. Schieve LA, Peterson HB, Meikle SF, et al. Live-birth rate and multiple-birth risk using in vitro fertilization. JAMA. 1999;282:1832-1838.
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David B. Seifer, MD, Series Editor
Department of Obstetrics, Gynecology, and Reproductive Sciences
UMDNJ-Robert Wood Johnson Medical School
New Brunswick, N.J.
Rodolphe Maheux. Does surgery have a role in treatment of endometriosis? Yes..