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• W2034001837 abstract "After repetitive surgery for recurrent endometriosis, 20 of 89 (22%) women achieved spontaneous pregnancy, compared with 165 of 411 (40%) after first-line procedure (adjusted incidence rate ratio, 0.51; 95% confidence interval, 0.32 to 0.82), and the 12- and 24-month cumulative pregnancy rates were 14% and 26% in the former group compared with 32% and 38% in the latter. Among infertile patients at baseline, 13 of 67 (19%) conceived after reoperation compared with 98 of 290 (34%) after primary surgery (adjusted incidence rate ratio, 0.55; 95% confidence interval, 0.30 to 0.99), and the 12- and 24-month cumulative pregnancy rates were 13% and 22% in the former group and 25% and 30% in the latter. After repetitive surgery for recurrent endometriosis, 20 of 89 (22%) women achieved spontaneous pregnancy, compared with 165 of 411 (40%) after first-line procedure (adjusted incidence rate ratio, 0.51; 95% confidence interval, 0.32 to 0.82), and the 12- and 24-month cumulative pregnancy rates were 14% and 26% in the former group compared with 32% and 38% in the latter. Among infertile patients at baseline, 13 of 67 (19%) conceived after reoperation compared with 98 of 290 (34%) after primary surgery (adjusted incidence rate ratio, 0.55; 95% confidence interval, 0.30 to 0.99), and the 12- and 24-month cumulative pregnancy rates were 13% and 22% in the former group and 25% and 30% in the latter. A recurrence will develop in a large proportion of women who undergo an operation for endometriosis (1DeCherney A.H. Endometriosis: recurrence and retreatment.Clin Ther. 1992; 14: 766-772PubMed Google Scholar), and those seeking pregnancy will face the dilemma of undergoing repetitive conservative surgery (2Adamson G.D. Laparoscopy, in vitro fertilization, and endometriosis: an enigma.Fertil Steril. 2005; 84: 1582-1584Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar). Because of a paucity of available information, the benefit of reoperation on reproductive performance is unclear (3Kelly R. Diamond M.P. Laparotomy in infertility patients with endometriosis. Use of the CO2 laser.J Reprod Med. 1989; 34: 25-28PubMed Google Scholar, 4Candiani M. Fedele L. Vercellini P. Bianchi S. Di Nola G. Repetitive conservative surgery for recurrence of endometriosis.Obstet Gynecol. 1991; 77: 421-424PubMed Google Scholar, 5Fedele L. Bianchi S. Zanconato G. Berlanda N. Raffaelli R. Fontana E. Laparoscopic excision of recurrent endometriomas: long-term outcome and comparison with primary surgery.Fertil Steril. 2006; 85: 694-699Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar, 6Vercellini P. Somigliana E. Viganò P. Abbiati A. Barbara G. Crosignani P.G. Surgery for endometriosis-associated infertility: a pragmatic approach.Hum Reprod. 2009; 24: 254-269Crossref PubMed Scopus (188) Google Scholar). Moreover, further surgery may worsen damage to ovarian reserve, thus potentially compromising the success of subsequent IVF (7Somigliana E. Vercellini P. Viganó P. Ragni G. Crosignani P.G. Should endometriomas be treated before IVF-ICSI cycles?.Hum Reprod Update. 2006; 12: 57-64Crossref PubMed Scopus (122) Google Scholar, 8Tsoumpou I, Kyrgiou M, Gelbaya TA, Nardo LG. The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta-analysis. Fertil Steril. Published online August 8, 2008 [Epub ahead of print].Google Scholar). We evaluated the effect of second-line surgery on reproductive outcome of women with recurrent endometriosis and compared the observed postoperative pregnancy rate with that achieved after first-line surgery in a large cohort of patients operated on in our department in the same time period. We considered consecutive patients under 40 years of age who underwent repetitive or first-line conservative surgery for stage I to IV endometriosis. Women with persistent anovulation, bilateral tubal occlusion, or severe dyspermia of the partner were excluded, as were those with other diseases that might affect reproduction or who planned to undergo immediate IVF-ET. A total of 438 women seeking spontaneous conception after second- or first-line surgery and for whom complete follow-up information was available were included in the analyses. Women who underwent two operations in our institution were included as separate cases in both study groups. Data were collected with use of patients' records, and further information was obtained during an interview. Selected patients were contacted by phone and invited to refer to our tertiary care center for women with endometriosis to undergo clinical and ultrasonographic evaluation. A standardized questionnaire was completed at that time. Infertility was defined as unsuccessful regular attempts at conception for >12 months. Conservative surgery at laparoscopy was performed with a three- or four-puncture technique with use of mechanical instruments and electrosurgery only, and surgery at laparotomy was performed according to microsurgical principles (4Candiani M. Fedele L. Vercellini P. Bianchi S. Di Nola G. Repetitive conservative surgery for recurrence of endometriosis.Obstet Gynecol. 1991; 77: 421-424PubMed Google Scholar). Endometriosis was staged according to the revised American Fertility Society classification (9The American Fertility Society Revised American Fertility Society classification of endometriosis: 1985.Fertil Steril. 1985; 43: 351-352Abstract Full Text PDF PubMed Google Scholar). Institutional Review Board approval for the study was obtained. The product limit method was used to calculate the cumulative proportion of women who became pregnant. The curves obtained after subgrouping according to first- and second-line surgery were compared by the log-rank test. The event data used in the computation of time to pregnancy were the beginning of postoperative conception search and the date of the last menstrual period or follow-up visit. Subjects with a clinical and/or symptomatic recurrence, or who used postoperative ovulation-inhibiting treatments for short periods (≤3 months), were not excluded from the analysis, whereas long-term ovulation-inhibiting treatments or interruption of active pregnancy seeking were considered censoring events. Pregnancies obtained with controlled ovarian hyperstimulation and/or IUI were considered in vivo conceptions and thus included in the group of women conceiving spontaneously. Conversely, subjects who achieved pregnancy with IVF were censored. Quantitative variables were compared by means of unpaired Student's t-test, whereas qualitative variables were analyzed with Fisher's exact test. To estimate the effect of several covariates on time to pregnancy after repetitive surgery, Cox's proportional hazards models were adopted. Included in the regression equations were terms for pelvic pain, presence of ovarian endometriomas, surgical approach, and revised American Fertility Society classification stage. Results from these analyses are reported as adjusted incidence rate ratio (IRR). When appropriate, 95% confidence intervals (CI) were calculated for the observed differences. All statistical tests were two-sided. Probability values of <5% were considered significant. A total of 717 patients were evaluated, 438 of whom were eligible for the study. We included 27 women in the second-line intervention group and 349 in the first-line intervention group. The 62 patients who were operated on twice in our department were included in both groups. Considering the number of procedures, we analyzed data relative to 89 second- and 411 first-line operations. Mean ± SD age was 32.6 ± 3.8 years in the repeat surgery group and 31.9 ± 3.9 in the primary surgery group. In the former group, endometriosis was at stage I in 9 (10%) women, II in 3 (3%), III in 29 (33%), and IV in 48 (54%). Corresponding figures in the latter group were 96 (23%), 43 (10%), 146 (35%), and 126 (31%), respectively. Laparoscopy was performed in 71 (89%) cases at second-line surgery and in 369 (90%) at first-line surgery. The median (interquartile range) time spent in pregnancy seeking after repetitive and primary surgery was 21 (10–35) and 15 (6–36) months, respectively. After the second operation 20 of 89 (22%) of patients achieved spontaneous conception compared with 165 of 411 (40%) women who underwent first-line surgery (Fisher's exact test, P=.002; Relative risk [RR], 0.56; 95% CI, 0.37 to 0.84). Survival analysis confirmed a significantly reduced chance of pregnancy after second-line compared with first-line surgery (log-rank test, χ21 = 8.16, P=.004, Fig. 1, upper panel). The 12- and 24-month cumulative pregnancy rates were 14% and 26% after repetitive surgery compared with, respectively, 32% and 38% after a first-line procedure. Of the women operated on twice in our department, 24% (15 of 62) achieved conception, and 19% (5 of 27) of patients who underwent primary surgery in another hospital succeeded in conceiving (Fisher's exact test, P=.78). Cox regression models confirmed a statistically significant reduced probability of conception after second-line compared with first-line surgery (P=.006), the adjusted IRR being 0.51 (95% CI, 0.32 to 0.82). The analyses were repeated in the subgroup of patients reporting infertility at the time of surgery (67 and 290 respectively in the second- and first-line surgery group). Thirteen (19%) conceived after repetitive surgery compared with 98 (34%) after primary surgery (Fisher's exact test, P=.027). Survival analysis confirmed a significantly reduced chance of pregnancy after second- compared with first-line surgery (log-rank test, χ21 = 4.11, P=.043, Fig. 1, lower panel). The 12- and 24-month cumulative pregnancy rates after repetitive surgery were 13% and 22% compared with, respectively, 25% and 30% after a primary procedure. Cox regression models confirmed a statistically significant reduced probability of conception after second-line compared with first-line surgery (P=.047), the adjusted IRR being 0.55 (95% CI, 0.30 to 0.99). According to a post-hoc subgroup analysis, the pregnancy rate was 32% (7 of 22) in the women who sought conception only after repetitive surgery, 25% (6 of 24) in those who sought conception only before second-line surgery, and 16% (7 of 43) in those who failed to conceive before both procedures (24-month cumulative pregnancy rate, 30%, 25%, and 17%, respectively; log-rank test, P=.29). In our cohort, only one out of four women who underwent repetitive surgery for recurrent endometriosis conceived at 24 months follow-up (one in five among infertile subjects). The chances of conception were almost half of those observed after a first-line procedure. Although the two study groups were not entirely homogeneous, multivariate analysis confirmed that a second operation is associated with a significantly worse reproductive performance. The adjusted IRR for pregnancy after repetitive surgery was 0.51 in the entire case series and 0.55 in the subgroup of infertile women, respectively. Disease stage was not associated with probability of conception, thus confirming previous observation (10Vercellini P. Fedele L. Aimi G. De Giorgi O. Consonni D. Crosignani P.G. Reproductive performance, pain recurrence and disease relapse after conservative surgical treatment for endometriosis: the predictive value of the current classification system.Hum Reprod. 2006; 21: 2679-2685Crossref PubMed Scopus (166) Google Scholar). The group of women who underwent first-line surgery was an internal reference standard in terms of operator experience and capabilities, surgical techniques and instrumentation, as well as general patient characteristics. In fact, all subjects were operated on consecutively in the same department by a fairly stable surgical staff, and the vast majority of women in the repetitive surgery group (62 of 89, 70%) were operated on both times in our hospital, representing an adequate self-control group. The crude and 24-month cumulative pregnancy rates observed after a primary procedure are consistent with prior experience from our center, with the available published evidence, and with the expected absolute benefit of surgery in women seeking conception (3Kelly R. Diamond M.P. Laparotomy in infertility patients with endometriosis. Use of the CO2 laser.J Reprod Med. 1989; 34: 25-28PubMed Google Scholar, 4Candiani M. Fedele L. Vercellini P. Bianchi S. Di Nola G. Repetitive conservative surgery for recurrence of endometriosis.Obstet Gynecol. 1991; 77: 421-424PubMed Google Scholar, 5Fedele L. Bianchi S. Zanconato G. Berlanda N. Raffaelli R. Fontana E. Laparoscopic excision of recurrent endometriomas: long-term outcome and comparison with primary surgery.Fertil Steril. 2006; 85: 694-699Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar, 6Vercellini P. Somigliana E. Viganò P. Abbiati A. Barbara G. Crosignani P.G. Surgery for endometriosis-associated infertility: a pragmatic approach.Hum Reprod. 2009; 24: 254-269Crossref PubMed Scopus (188) Google Scholar). Our study did not include a control group of subjects who underwent surgical exploration for diagnosis alone. Accordingly, we cannot exclude that the absolute benefit of repetitive surgery was actually smaller than that indicated, as the background pregnancy rate remains unknown. When reoperation is being considered with the specific aim of achieving conception, and not because severe symptoms or large cysts are present, the caring gynecologist should warn the patient that the chances of pregnancy may be substantially lower than after the primary procedure and the role of IVF should be considered adequately as an alternative to repetitive surgery (11Pagidas K. Falcone T. Hemmings R. Miron P. Comparison of reoperation for moderate (stage III) and severe (stage IV) endometriosis-related infertility with in vitro fertilization–embryo transfer.Fertil Steril. 1996; 65: 791-795Abstract Full Text PDF PubMed Scopus (125) Google Scholar, 12Copperman A.B. DeCherney A.H. Turn, turn, turn.Fertil Steril. 2006; 85: 12-13Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 13Feinberg E.C. Levens E.D. DeCherney A.H. Infertility surgery is dead: only the obituary remains?.Fertil Steril. 2008; 90: 242-243Abstract Full Text Full Text PDF PubMed Google Scholar, 14The Practice Committee of the American Society for Reproductive MedicineEndometriosis and infertility.Fertil Steril. 2004; 81: 1441-1446Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar). However, infertile women with recurrent endometriosis may represent a particular subgroup with worse prognosis due to injuries caused by the disease itself and by previous surgery (15Aboulghar M.A. Mansour R.T. Serour G.I. Al-Inany H.G. Aboulghar M.M. The outcome of in vitro fertilization in advanced endometriosis with previous surgery: a case-controlled study.Am J Obstet Gynecol. 2003; 188: 371-375Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar, 16Barnhart K. Dunsmoor-Su R. Coutifaris C. Effect of endometriosis on in vitro fertilization.Fertil Steril. 2002; 77: 1148-1155Abstract Full Text Full Text PDF PubMed Scopus (607) Google Scholar). Moreover, it should be taken into account that adherence to IVF programs may be low in these patients and a high rate of drop-outs should be foreseen (17Somigliana E, Daguati R, Vercellini P, Barbara G, Benaglia L, Crosignani PG. The use and effectiveness of in vitro fertilization in women with endometriosis: the surgeon's perspective. Fertil Steril. Published online April 2, 2008 [Epub ahead of print].Google Scholar). Indeed, randomized controlled trials on IVF versus repetitive surgery are needed urgently to define the best therapeutic option in terms of both pregnancy rate and patient compliance." @default.
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• W2034001837 title "The second time around: reproductive performance after repetitive versus primary surgery for endometriosis" @default.
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