Correspondence: Dr Fabio Parazzini, Istituto di Ricerche Farmacologiche `Mario Negri', via Eritrea, 6220157 Milano, Italy
![]() |
Abstract |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key words: clinical trial/endometriosis/infertility/laparoscopy
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
More convincing evidence emerged from a recent randomized clinical trial comparing diagnostic laparoscopy alone or resection or ablation of visible lesions that included 341 infertile patients with minimal or mild endometriosis (Marcoux et al., 1997), in whom surgery enhanced fertility. However, the 36 weeks cumulative probability of pregnancy in untreated women was about 20%, and only fecundity rates and not delivery rates were considered.
In this paper, we present the results of a randomized clinical trial comparing diagnostic laparoscopy or resection or ablation of visible endometriosis in order to improve the reproductive prognosis in infertile women with minimalmild endometriosis (Struzziero et al., 1998).
![]() |
Materials and methods |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The investigators obtained approval of the protocol from their institutional review board which established the procedures for obtaining informed consent.
A total of 101 women observed between 1994 and 1995 at seven participating centres entered the study. The average number at each centre was 14. The diagnosis of endometriosis before randomization was made under the supervision of a senior physician in each centre.
Eligible women were assigned by computer-generated randomization to either resection or ablation of visible endometriosis (54 patients), or diagnostic laparoscopy only (47 patients). Adhesiolysis was allowed in women allocated to resection or ablation of visible endometriosis, but not in those allocated to diagnostic laparoscopy only. Histological confirmation of diagnosis of endometriosis was not requested.
Treatment was allocated during laparoscopy by telephone calls to the randomization centre (1st Obstetrics and Gynaecology Clinic, University of Milan). Separate randomization lists were used for each centre. Treatment allocation was respected in all cases.
After laparoscopy women tried to conceive spontaneously for 1 year (follow-up period). The protocol allowed after surgery the use of a medical treatment (tryptorelin 3.75 mg slow release every 28 days for 3 months) according to the physician's judgement. Treatment for ovulation induction was allowed only after the end of the follow-up period, i.e. when women were out of the study.
With our sample size, the probability (1ß) of detecting, at = 0.05 (two-tailed test), an increase of ~2.5 times in pregnancies in the treated group, with a baseline pregnancy rate of ~25% in the untreated one, is ~80%. The potential benefit of ablation/resection of lesion in comparison with no surgical treatment was estimated from the results of a meta-analysis published before this study began, which showed an odds ratio (OR) of 2.7 of becoming pregnant in treated versus untreated women (Hughes et al., 1993
).
The usual 2 test was used to established the statistical significance of differences in baseline characteristics of the patients and in the frequency of pregnancy, spontaneous abortions, and delivery on the total of observed pregnancies, in relation to treatment. To allow for potential confounding effect of stage and medical treatment on the fertility rate, the MantelHaenszel procedure was used (Mantel and Haenszel, 1959
).
![]() |
Results |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Table I shows the main characteristics of women randomized to resection/ablation or no treatment. The two groups were similar in terms of baseline characteristics: for example mean age and mean duration of infertility in years were respectively 30.6 and 3.9 and 30.3 and 3.8 in the resection/ablation or no-treatment group. In the resection/ablation group, 20 women (39%) were stage I and 31 (61%) stage II; the corresponding figures were 20 (44%) and 25 (56%) women in the no-treatment group. No subject underwent ovulation induction treatment during the follow-up period.
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The physicians in the various centres were specifically trained to pay the same care to the diagnosis of endometriosis and to the ablation/resection of endometriotic lesions. They were instructed to perform complete resection or ablation of the lesions of visible endometriosis. However, no data are available on depth of ablation or on treatments of margins around areas of resection. The diagnosis of endometriosis was not histologically confirmed. However, though some misdiagnosis cannot be excluded, this potential bias should be similar in both groups.
The results do not confirm previous indications that resection or ablation of minimal and mild endometriosis increases the short-term likelihood of pregnancy in infertile women as compared with diagnostic laparoscopy alone (Nowroozi et al., 1987; Fayez et al., 1988
; Paulson et al., 1991
; Hughes et al., 1993
). Part of this discrepancy may be explained by different criteria for selecting patients. For example, a meta-analysis (Hughes et al., 1993
) suggested that laparoscopic surgery increases the probability of becoming pregnant ~2.7 times compared to no surgery or medical treatment in infertile women with endometriosis. Re-analysis and updating of this review, however, suggested a significant, but less strong beneficial effect of laparoscopic surgery (OR 1.5) (Adamson and Pasta, 1994
). The meta-analysis included some non-randomized studies, some including both minimal/mild and severe conditions, and some comparing no surgery or medical treatment with laparoscopic surgery.
A recent study (Marcoux et al., 1997; Berube et al. 1998
), not considered in the previous meta-analysis, comprising ~350 infertile women with stage III endometriosis, showed that the 36-week cumulative proportion of pregnant women was 31% in the laparoscopic surgery group and 18% in the diagnostic laparoscopy one. The study, however included women with a median duration of infertility of ~2 years, much less than the median infertility period reported in women included in the present study. Another difference between the populations in the Canadian study and in the present one, is the different stage III ratio. In the Canadian study ~30% of women had stage II endometriosis, compared with ~60% in the present study. The distribution of stages of endometriosis we observed is consistent with the findings of a large epidemiological survey conducted in Italy (Gruppo Italiano per lo Studio dell'Endometriosi, 1994
). Other published studies (Pouly et al., 1987
; Levinson 1989
; Chong et al., 1990
; Arumugam and Urquhart, 1991
; Adamson et al., 1993
; Seiler et al., 1996) did not show any effect of ablation/resection of endometriotic lesions in enhancing fertility prognosis.
A secondary finding of this study is that seven out of the 18 patients treated with resection/ablation who received postoperative medical treatment achieved pregnancy versus the pregnancy rate of 18% (five out of 28) for patients who did not receive a medical therapy postoperatively; this finding was, however, not statistically significant.
In conclusion, the results of this study do not confirm that ablation of endometriotic lesions in an early stage markedly improves fertility rates compared with no treatment.
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Adamson, F.D., Hurd, S.J., Pasta, D.J. et al. (1993) Laparoscopic endometriosis treatment is it better? Fertil. Steril., 59, 3544.[ISI][Medline]
American Fertility Society (1985) Revised American Fertility Society classification of endometriosis: 1985. Fertil. Steril., 43, 351352.[Medline]
Arumugam, K. and Urquhart, R. (1991) Efficacy of laparoscopic electrocoagulation in infertile patients with minimal or mild endometriosis. Acta Obstet. Gynecol. Scand., 70, 125127.[Medline]
Berube, S., Marcoux, S., Langevin, M. and Maheux, R. (1998) Fecundity of infertile women with minimal or mild endometriosis and women with unexplained infertility. The Canadian Collaborative Group on Endometriosis. Fertil. Steril., 69, 10341041.[ISI][Medline]
Chong, A.P., Keene, M.E. and Thornton, N.L. (1990) Comparison of three modes of treatment for infertility patients with minimal pelvic endometriosis. Fertil. Steril., 53, 407410.[ISI][Medline]
Fayez, J.A., Collazo, L.M. and Vernon, C. (1988) Comparison of different modalities of treatment for minimal and mild endometriosis. Am. J. Obstet. Gynecol., 159, 927932.[ISI][Medline]
Gruppo Italiano per lo Studio dell'Endometriosi (1994) Prevalence and anatomical distribution of endometriosis in women with selected gynaecological conditions: results from a multicentric Italian study. Hum. Rep., 9, 11581162.[ISI]
Hughes, E.G., Fedorkow, D.M. and Collins, J.A. (1993) A quantitative overview of controlled trials in endometriosis-associated infertility. Fertil. Steril., 59, 963970.[ISI][Medline]
Levinson, C.J. (1989) Endometriosis therapy: rationale for expectant or minimal therapy in minimal/mild cases (AFSI) (Abstract). In: Proceedings of the Second World Congress on Gynecologic Endoscopy. Clermont-Ferrand, France.
Mantel, N. and Haenszel, W. (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J. Natl. Cancer Inst., 22, 719748.[ISI][Medline]
Marcoux, S., Maheux, R., Berube, S. et al. (1997) Laparoscopic surgery in infertile women with minimal or mild endometriosis. N. Engl. J. Med., 337, 217222.
Nowroozi, K., Chase, J.S., Check, J.H. et al. (1987) The importance of laparoscopic coagulation of mild endometriosis in infertile women. Int. J. Fertil., 32, 442444.[ISI][Medline]
Paulson, J.D., Asmar, P. and Saffan, D.S. (1991) Mild and moderate endometriosis: comparison of treatment modalities for infertile couples. J. Reprod. Med., 36, 151155.[ISI][Medline]
Pouly, J.L., Manhes, H., Mage, G. et al. (1987) Laparoscopic treatment of endometriosis (laser excluded). Contrib. Gynecol. Obstet., 16, 280285.[Medline]
Seiler, J.C., Gidwani, G. and Ballard, L. (1986) Laparoscopic cauterization of endometriosis for fertility: a controlled study. Fertil. Steril., 46, 10981100.[ISI][Medline]
Struzziero, E., Gruft, L., Pellegrini, A. et al. (1998) Ablation of lesions vs no treatment in infertile women with endometriosis: a randomized trial. In: VI World Congress on Endometriosis. June 30July 4, Quebec City, Canada, 295, 167.
Submitted on July 20, 1998; accepted on December 4, 1998.