Laparoscopic cautery in the treatment of endometriosis-related infertility

4 4 FERTILITY AND STERILITY Copyright ID 1991 The American Fertility Society Printed on acid-free paper in U.S.A. Laparoscopic cautery in the treatment of endometriosis-related infertility Ana A. Murphy, M.D.* William D. Schlaff, M.D. Dimitrios Hassiakos, M.D.t Fatih Durmusoglu, M.D.:j: Marian D. Damewood, M.D. John A. Rock, M.D. Department of Gynecology and Obstetrics, The Johns Hopkins University, Baltimore, Maryland Life table analysis and the two-parameter exponential method have been applied to pregnancy rates in 72 patients undergoing laparoscopic cautery exclusively. Patients with male factor infertility were excluded. Estimated cure rates for patients with stage I and II disease were 98.2% and 76.6%, respectively (not significantly different). No significant difference was seen when anovulation complicated the endometriosis (68.6 %). When greater than one infertility factor was present, a significant difference was observed (5.6%). Patients with stage I disease had an average fecundity of 1.3% with decreasing values observed in stage II (7.59%), anovulation (6.67%), and more than one infertility factor (3.33%). We conclude that laparoscopic cauterization is an effective mode of therapy for the treatment of stage I and II endometriosis associated with infertility. Fertil Steril55:246, 1991 The therapy for endometriosis-related infertility remains controversial. Treatment approaches include expectant management, medical intervention, major conservative surgery, and operative laparoscopy. Many surgical modalities have been used in the treatment of endometriosis with the goal of eradicating all visible endometriotic implants. 1-3 Conservative resection of endometriosis has been the procedure of choice, although more recently laparoscopic surgery to debulk the endometriotic lesions, lyse tubo-ovarian adhesions, and restore normal anatomy has been a more common procedure. 4-6 Operative endoscopic techniques, including thermocoagulation and laser ablation, have Received November 1, 1989; revised and accepted October 4, 199. * Reprint requests and present address: Ana A. Murphy, M.D., Department of Reproductive Medicine H-813, University Hospital, University of California Medical Center, 225 Dickinson Street, San Diego, California 9213. t Present address: Department of Obstetrics and Gynecology, Areteion Hospital, University of Athens, Athens, Greece. =!: Present address: Anakara Maternity Hospital, Ankara, Turkey. been utilized to treat endometriosis. 7-9 These techniques have been reported to be effective in the treatment of infertile patients with endometriosis, especially in mild or moderate stages ofthe disease. Crude pregnancy rates (PRs) ranging from 4% to 75% have been reported, although most studies are generally limited by failing to exclude from the analysis other factors that might reduce fertility and by failing to provide more useful statistical information such as monthly fecundity, cure rates, and monthly probability of pregnancy among those cured rather than crude PRs. The purpose ofthe present study is to discuss the potential role of laparoscopic electrocautery in the treatment of endometriosis-related infertility. In this analysis we have specifically addressed the relative impact of other factors, including ovulatory status, that could be detrimental to fertility. Male factor infertility associated with endometriosis has been excluded. Additionally, we have utilized statistical methods including life table analysis, estimated cure rate, and monthly fecundity rate in the analysis of our data rather than just crude PRo We hope thereby to more accurately assess the value of 246 Murphy et ai. Laparoscopic cautery for endometriosis Fertility and Sterility

electrocautery in the treatment of infertility associated with endometriosis and to provide meaningful baseline data. MATERIALS AND METHODS The clinical records of 127 women who underwent operative laparoscopy with cautery for endometriosis by gynecological surgeons of the Johns Hopkins Hospital Department of Gynecology and Obstetrics, Division of Reproductive Endocrinology, during the period of January 1984 to March 1989 were reviewed. Laparoscopic cases in which laser or thermocoagulation was used in addition to cautery were excluded. The data obtained from the operative notes allowed the patients to be staged according to the revised American Fertility Society (AFS) classification system of endometriosis,1o as having stage I (44%), II (4%), III (8%), and stage IV (4%) disease. Before surgery, all couples underwent a complete infertility evaluation that included assessment of ovulatory status, semen analysis, postcoital testing, hysterosalpingography, and diagnostic laparoscopy with chromotubation to assess tubal status. The present analysis includes 82 patients with endometriosis-associated infertility. Patients who had an ovulatory factor contributing to infertility were included in the analysis, although couples with a male factor «2 X 1 6 spermml, <5% motility, or <6% normal morphology) were not. None of the patients had received hormonal therapy or conservative surgery within 6 months before operative laparoscopy. All patients with ovulatory problems had been treated adequately by ovulation induction before laparoscopic treatment of endometriosis. The demographic characteristics of the 82 patients in this study revealed a mean age of 31.4 ± 4.4 years (mean ± SD). Forty-two presented with primary infertility and 4 with secondary infertility. The mean duration of infertility was 3.2 ± 2.1 years. The majority of the patients had either stage I (36%) or stage II (36%) disease, although a small number had stage III (7%) or IV (3%) disease. Patients were subdivided into three groups according to the presence or absence of infertility factors aside from endometriosis. In 53 patients, endometriosis was the only cause for infertility, and in 17 patients anovulation was a contributing factor. More than one additional factor (ovulatory, uterine, or tubal) were identified in 12 patients. There were no significant differences between the groups relative to age, parity, duration of infertility, follow-up, or extent of disease. Mean duration of follow-up was 7.3 ± 6.9 months. Operative laparoscopy was performed under general anesthesia according to the conventional multiple puncture technique. Endometriotic lesions were visualized, and monopolar cautery was applied until the lesion and surrounding tissue blanched or the area was completely resected. Biopsies were performed only when the diagnosis was unclear or when lesions were in any way uncharacteristic of endometriosis. Adhesions were lysed sharply or with monopolar needle point cautery. After coagulation, the pelvis was irrigated with saline. Other adjuncts such as Hyskon were not used. No intraoperative or postoperative complications were noted among these patients. The life-table method was used to calculate the cumulative PR, and a two-parameter exponential model was used to estimate the cure rate and the monthly probability of pregnancy among those cured with the use of Marquardt's method for leastsquares estimation of nonlinear parameters. ll When appropriate, groups were compared using the Student's t-test, and pregnancy outcome was analyzed using X 2 analysis. All statistical calculations and modeling were performed using Statistical Analysis Systems release 5.8 on an IBM 4381-3 Main frame computer (IBM Corporation, Boca Raton, FL). RESULTS The crude PR for the 82 patients is shown in Table 1. Rates ranged from 74% in patients with AFS stage I disease to % in the small number of patients with stage IV disease. Of the 44 pregnancies, 78 (16%) resulted in spontaneous abortions and 2 (4 %) in tubal ectopic pregnancies. Three pregnancies occurred in 12 patients who had had a laparotomy for excision of endometriosis before operative laparoscopy. The influence of the severity of endometriosis and the impact of additional contributing infertility factors on pregnancy outcome are also demonstrated in Table 1. Using X2 analysis, there was no significant difference between pregnancy outcome in patients with stage I versus stage II disease, although there was a difference between those patients with milder stages (I and II) when compared with patients with more advanced disease (III or Murphy et al. Laparoscopic cautery for endometriosis 247

Table 1 Crude PRs by Severity of Endometriosis as Classified by the AFS Extent of disease Study group Stage I Stage II Stage III Stage IV Total Endometriosis alone 2317 (74)a 2112 (57) 72 (29) 2 () 5331 (58) Endometriosis + anovulation 86 (75) 94 (44) 171 (59) Endometriosis + > 1 infertility factor 51 (2) 62 (33) IO () 123 (25) a Values in parentheses are percents (no. of patientsno. of pregnancies). IV). There was no significant difference in crude PR between patients with anovulation (after ovulation induction) and those who ovulated normally regardless of the stage of disease. However, patients with AFS stage I disease who had more than one infertility factor had a significantly lower crude PR than those with the same stage of disease with either no other problem or an associated ovulatory problem (P <.5). Although this trend was also apparent in those patients with stage II disease, the difference did not reach statistical significance. Cumulative pregnancy curves for patients with stage I and II disease as calculated by the life-table method are depicted in Figures 1 and 2. The mean length offollow-up was 7.9 months for all patients and 11.1 months for those who did not conceive. Overall, the curves reflect a mean time interval from operation to conception of 5.5 months with a range of 1 to 26 months. Of the total number of patients who conceived, 71 % did so within 6 months and 95% within 1 year. Fifty percent of pregnancies with stage II disease occurred in the 1st month. Meaningful curves could not be generated for patients with stage III or IV disease because of the small number of pregnancies. The two-parameter exponential model was used to estimate the cure rate and the monthly probabil- g 1.s 8 '" ~ C 6 c '" ~ 4 Q.!i :;:; -- Stage I :; 2 -Stage II E " 4 8 12 16 2 24 Months Figure 1 Cumulative PRs in patients with endometriosis by stage of disease (The AFS'O). ity of pregnancy among those cured as shown in Table 2. Estimated cure rates for patients with stage I and stage II disease were 98.2% and 76.6%, respectively, although these figures were not different statistically (P >.5). No significant difference was seen when anovulation complicated the endometriosis. When greater than one infertility factor was present, a significant difference was observed (P <.1). The monthly probability of pregnancy for those cured was significantly higher for those patients with stage II disease as compared with all others, but no other differences were observed. Monthly fecundity rates are also shown in Table 2. Patients with stage I disease had an average fecundity of 1.3% with decreasing values observed in all other groups to a low of 3.33% in patients with more than one infertility factor. Although a trend may be apparent, there is no statistically significant difference between these values. DISCUSSION Optimal treatment of endometriosis-related infertility continues to be the subject of much contro- g 1 2 8 c a:: >. c: 6 C c: '" ~ a. 4 Q) ~ C 2 :; E " ::J " U ~~ 4 " " ' " 8 12 Months " " - Endometriosis Alone - - Anovulation -. - ) 1 Infertility Factors 16 2 24 Figure 2 Cumulative PRs in patients with stage I and II endometriosis (The AFS'O) alone, complicated by anovulation, or complicated by more than one infertility factor. 248 Murphy et al. Laparoscopic cautery for endometriosis Fertility and Sterility

Table 2 Estimated Cure Rate and Monthly Probability of Pregnancy Among Those Cured Study group No. of patientspregnant Cure rate Parameter estimates a Monthly probability of pregnancy Monthly fecundityb Endometriosis only Stage I Stage II Anovulation > 1 Infertility factor 2317 2112 171 113.982 (±.49).766 (±.32).686 (±.47).56 (±.3).134 (±.17).364 (±.46).118 (±.23).114 (±.19) 1.3 (±4.1) 7.59 (±3.59) 6.67 (±3.46) 3.33 (±3.16) a Values in parentheses are estimates of SE. b Numbers in parentheses are 95% confidence limits. versy. As mentioned, conservative resection of disease by laparotomy was initially the standard approach and has been the subject of many reports with crude PRs generally ranging from 29 to 75%. Hormonal therapy, initially with pseudopregnancy and later with progestins, danazol, and gonadotropin-releasing hormone analogs, has also been utilized resulting in crude PR for mild and moderate disease as high as 72% and 52%, respectively.12-15 It has become increasingly clear, however, that no treatment for minimal and mild disease achieves comparable PRs when compared with danazol, medroxyprogesterone acetate, and conservative surgery.16,17 Thus the major limitation of this and other studies is the absence of a control (nontreatment) group. Laparoscopic treatment, if equally effective, has several important advantages relative to conservative surgery or hormonal therapy. In the first case, both operative and recuperative time are drastically reduced, whereas in the second case undesirable side effects, delayed attempt at conception, and possible progression of disease during therapy can be avoided. Endoscopic techniques, specifically laparoscopic cautery, have been reported by several investigators to be effective in the treatment of endometriosis-associated infertility.18-21 Unfortunately, it is frequently difficult to compare data from these studies because of variation in patient population and length of follow-up, presence of other factors contributing to infertility, variability in classification systems, combination of therapy, and inadequate statistical analysis. Seiler et al. 22 reported a prospective trial of laparoscopic cautery in 9 women with moderate endometriosis (Acosta classification21) compared with 6 months of treatment with danazol. In the cautery group, 2 of 45 women conceived (44%), whereas 16 of the 41 women who completed the course of danazol conceived (39%). However, the follow-up period in the study was only 7 months, and almost one quarter of all patients had other contributing infertility factors. Fayez et al.23 reported a large (n = 238) nonrandomized study oflaparoscopic excision of endometriotic lesions with or without postoperative danazol compared with danazol therapy alone in 1988. After 1 year of follow-up, PRs were 26% for danazol alone, 54% for excision plus danazol, and 73% for laparoscopic excision alone. They concluded that danazol therapy was less effective alone or in combination with laparoscopic excision compared with excision alone. No long-term follow-up was provided. Life table analysis was not used in this study or any of the previously cited studies. The laparoscopic use of lasers has been touted as a significant improvement in the treatment of infertility associated with endometriosis. The largest series reporting on the use of the CO2 laser treatment of infertility associated with endometriosis was by Paulson and Asmar.24 It included 431 patients and showed cumulative PRs of 76% for stage I and 68% for stage II disease. Patients with additional infertility factors had a PR of 28%. Expected cure rates and monthly fecundity were not calculated. Two particularly comprehensive evaluations of CO2 laser laparoscopic vaporization deserve mention. Nezhat et al.25 reported on 243 patients (39 with stage I and 86 with stage II disease), none of whom had associated infertility factors. They found crude PRs of 69.1 % and 71.8% with estimated cure rates of 82.2% and 78.6%, respectively. Monthly fecundity rates were 6.5% for stage I and 5.7% for stage II disease. Olive and Martin 9 found estimated cure rates of 45.2% and 71.4% for 59 stage I and 48 stage II patients with monthly fecundity rates of 2.8% and 3.35%, respectively. There are no studies comparing the use of the CO2 laser with other conventional techniques. Murphy et al. Laparoscopic cautery for endometriosis 249

Only one published study offers cure rates or monthly probability of pregnancy with use of danazol or conservative surgery.1 Guzick and Rock calculated these parameters for treatment with danazol or conservative surgery in stage I and II patients with no additional infertility factors. Their results gave cure rates of 68.3% and 74.%, with monthly probabilities of pregnancy of 4.% and 5.7%, respectively. The purpose of our study was to better analyze the effectiveness of laparoscopic cautery, a relatively inexpensive, easy, and complication-free procedure in the treatment of endometriosis-related infertility. This was accomplished by better definition of factors and by using more effective statistical tools including life table analysis, estimated cure rates, and monthly probability ofpregnancy and fecundity. Our data suggest that crude PRs for AFS stage I or II endometriosis treated with laparoscopic cautery alone are comparable with other surgical and medical therapy modalities. After the endometriosis was treated, women with corrected ovulatory dysfunction had a similar crude PR, although a somewhat lower cure rate than women with endometriosis alone. Only with more than one infertility factor present was a marked decrease in estimated cure compared with women with endometriosis alone seen. The monthly probability of pregnancy, a reflection of the rapidity with which the assigned therapy was successful, was significantly higher only for women with stage II disease. This may well be because of the fact that these women have more implants or adhesions and that cautery and destruction of lesions provide greater incremental benefit than in women with only stage I disease. Monthly fecundity rate represents the overall likelihood of any patient so treated to conceive in any given month. Although there is no statistically significant difference among the four groups as shown in Table 2, a trend toward lower fecundity rates can be seen with increasing disease or compounding factors. Although the monthly probability of pregnancy for those cured was significantly greater for stage II, the average fecundity was lower than stage 1. This probably reflf cts the fact that >5% ofthe pregnancies with stage II disease occurred in the 1st month in contrast to stage 1. This appears to be an inherent problem of the models used. Interestingly, the monthly fecundity rates for both stage I and II patients compare very favorably with those observed after treatment with danazol, laser vaporization, and conservative surgery.3,1,11,17 We conclude that laparoscopic cauterization is an effective mode of therapy for the treatment of infertility associated with endometriosis, at least for stage I and stage II disease. 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