TREATMENT OF INFERTILITY
ASSOCIATED WITH ENDOMETRIOSIS
Drug Treatment
Most of the medical therapies used to treat the pain associated with endometriosis have also been used to treat infertility in women with endometriosis. Four randomized trials with a total of five treatment groups that received drugs compared medical treatment directed at endometriosis with either placebo or no treatment; these trials were designed with fertility as the outcome measure. In another eight trials danazol was compared with a second drug. All were summarized recently in a meta-analysis (Fig.2).The results clearly indicate that none of these drugs are any better than any of the others and, more important, that none of them result in greater fertility than placebo. Not only do these drugs not increase fertility, but they may also delay fertility, since women are unable to conceive while receiving treatment. Thus, there appears to be no role for drug therapy in the treatment of the infertility associated with endometriosis.
Surgical Treatment
Endometriosis of sufficient severity to cause distortion of the pelvis (stage III or IV) probably impairs fertility by interfering with the oocyte’s reaching and being transported through the fallopian tubes. This anatomical distortion is commonly treated by surgery. No randomized trials exist to determine the efficacy of this approach to treating advanced endometriosis. However, the facts that the background rate of pregnancy approaches zero in women with late-stage endometriosis and that numerous uncontrolled trials have proved that pregnancies do occur after reparative surgery suggest that this approach is of value.
More controversial is the situation in women with early-stage (stage I or II) endometriosis. Although an association clearly exists between even early-stage endometriosis and reproductive dysfunction, it has been unclear whether there is a causal relation. A metaanalysis of nonrandomized trials suggested that surgical treatment of infertility associated with early-stage endometriosis might be of value; however, there was sufficient heterogeneity among the studies to diminish confidence in such a conclusion.
Subsequently, two trials comparing operative and diagnostic laparoscopy have been completed. One was a Canadian trial in which 341 infertile women with stage I or II endometriosis were randomly assigned either to diagnostic laparoscopy with no treatment or to operative laparoscopy with ablation or excision of the endometriotic tissue. The women were followed for 36 weeks postoperatively and for up to an additional 20 weeks if they conceived. The rate of pregnancy of at least 20 weeks’ duration was significantly higher among the surgically treated women
(31 percent vs. 18 percent).
In a similar Italian trial involving 101 women, however, the live-birth rate was 20 percent in the operative laparoscopy group and 22 percent in the diagnostic-laparoscopy group after one year of followup. This trial differed from the Canadian trial in that the women had a longer median duration of infertility and slightly more extensive disease. Despite these disparate results, when the studies are combined, analysis reveals a significant benefit of surgical treatment (odds ratio for pregnancy, 1.7; 95 percent confidence interval, 1.1 to 2.5). Thus, although the efficacy of surgery in increasing fertility among women with early-stage endometriosis remains unsettled, the current evidence points to an increase in fertility with this treatment. However, it is likely that the effect is small. Even if the results of the Canadian study are representative, the number of women who need to be treated in order to achieve one additional pregnancy is 7.7. This figure may prove unacceptable to many women, physicians, and health plans.
Assisted Reproduction
Three randomized trials have evaluated the induction of ovulation for increasing fertility in women with endometriosis (Table 1); two of these trials included intrauterine insemination. The results indicate that these approaches do increase fertility in women with endometriosis.
The role of assisted reproductive techniques such as in vitro fertilization has also been studied, albeit inadequately. In a retrospective cohort study of 118 women with infertility and endometriosis, the cumulative three-year pregnancy rate in women who underwent in vitro fertilization was similar to that in untreated women. Whereas it is probably self-evident that in vitro fertilization is of value in women with advanced endometriosis, the value of this approach in those with early-stage disease is as yet unproven. In other words, although pregnancies certainly occur rapidly with in vitro fertilization in women with endometriosis or any other diagnosis related to infertility, it is unclear whether one cycle of in vitro fertilization is comparable to one month, six months, two years, or a reproductive lifetime of attempting conception naturally.
The effect of endometriosis on the