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Outcome of laparoscopic versus traditional surgery for ectopic pregnancies*
Pacific Coast Fertility Society April 10 to 14, 1991 Stouffer Esmeralda Resort. Indian Wells, California Selectedpapel's-Robert Israel, M.D., G~st Editor
Vol. 57, No.2, February 1992
FERTILITY AND STERILITY
Printed on acid-free paper in U.S.A.
Copyright 0 1992 The American Fertility Society
Outcome of laparoscopic versus traditional surgery for ectopic pregnancies*
Carmen J. Sultana, M.D.t Kirk Easley, M.S.:J: Robert L. Collins, M.D.t§ Cleveland Clinic Foundation, Cleveland, Ohio
Objective: To compare pregnancy rates after three surgical procedures for ectopic pregnancy (EP) over a 9-year period for normal and infertility patients. Design: In a retrospective analysis, we examined crude pregnancy rates and life-table analysis of cumulative pregnancy rates. A proportional hazard regression model was used to examine relative risk of type of surgery and fertility rates. Patients, Participants: One hundred twenty-six cases of EPs were reviewed at the Cleveland Clinic Foundation, a tertiary institution. Main Outcome Measures: Comparisons of rates of viable term deliveries were calculated between three types of surgery and were stratified according to the status of infertility. Confidence intervals for relative risk of surgery and fertility status on future pregnancy were calculated. Results: No difference in pregnancy rates was observed after the three procedures (P = 0.08). Normals had a significantly higher (4 times higher) pregnancy rate than infertility patients, independent of surgical procedure. Conclusion: Successful pregnancy after EP is related to history of infertility rather than type of surgery to treat ectopic event. More randomized study is needed to examine laparoscopic salpingostomy, especially in patients with other infertility problems. Fertil Steril 1992;57:285-9 Key Words: Ectopic pregnancy, infertility, pregnancy, pregnancy rates, laparoscopy, salpingostomy, salpingectomy.
Ectopic pregnancy (EP) is a condition that can have severe effects on fertility. Risk factors such as pelvic inflammatory disease (PID), surgical sterilization, intrauterine device (IUD) use, endometriosis, in vitro fertilization (IVF), diethylstilbestrol exposure, and progesterone contraceptive pills are known to increase the relative risk ofEP. It is commonly quoted that only 30% of women treated with salpingectomy subsequently experience a term
Received May 2, 1991; revised and accepted November 20, 1991.
* Presented at the Annual Meeting of the Pacific Coast Fertility Society, Indian Wells, California, April 11 to 14, 1991. t Department of Gynecology. :\: Department of Biostatistics. § Reprint requests: Robert L. Collins, M.D., The Cleveland Clinic Foundation, Department of Gynecology (A-81), One Clinic Center, Cleveland, Ohio 44195-5037. Vol. 57, No.2, February 1992
pregnancy (1, 2). According to Schenker and Evron (3), more recent studies give postectopic delivery rates of 23% to 72%. The first successful surgical treatment of a tubal gestation by total salpingectomy was reported by Lawson Tait in 1884 (3, 4). Since then, attempts have been made to improve future fertility by more conservative surgical techniques. Stromme (5) described the first successful salpingotomy in 1953. The laparoscopic treatment of tubal ectopics is now advocated by many as leading to high subsequent pregnancy rates (6, 7). A review of the data is provided by Schenker and Evron (3). Few studies have used life-table analysis to determine outcome (8). The purpose of this paper is to examine the relationship between three types of surgical procedure and the chance of future successful delivery after EP in a mixed patient population, using both crude Sultana et a1.
Surgery for ectopic pregnancies
285
pregnancy rate and cumulative rate. Because surgical procedure is not the only variable affecting future outcome, each patient's reproductive history was also examined to determine how this would influence the chances of live birth after surgery for EP. MATERIALS AND METHODS
The medical records of all patients carrying a discharge diagnosis of extrauterine pregnancy or EP at the Cleveland Clinic Foundation between 1982 and 1990 were reviewed. The Clinic is a tertiary referral center for gynecology and infertility, but no obstetrical care is offered. The single-chart system at the Foundation collects all inpatient and outpatient data for each patient in a single record, allowing long continuity of follow-up in many cases. Out of 151 such discharge diagnoses generated by the Medical Records Department, 126 cases from 113 patients were found to have the diagnosis confirmed by pathology and were included in the review. Each ectopic gestation was coded as a separate event. All outpatient notes, laboratory results, emergency room visits, and operative reports pertinent to each case were reviewed. Data were collected on the following patient variables: (1) age, (2) race, (3) obstetrical history, (4) risk factors, (5) history oftreatment for infertility at the Foundation, (6) surgical procedure, and (7) future pregnancies. The risk factors included a history of PID, previous EP, previous tubal surgery including sterilization, endometriosis, IUD use, an IVF or exogenous gonadotropin-induced pregnancy, tubal blockage, or pelvic adhesions. Cases that had no comment on history were coded as no risk. Patients who had sought evaluation for infertility in our clinic were categorized as infertile; all others were labeled normal. Surgical procedures were divided into three categories: laparoscopic salpingotomy, laparotomy with salpingostomy, or laparotomy with salpingectomy. Laparoscopic salpingectomy was counted as salpingectomy (one case). Intraoperative and postoperative complications were noted. The occurrence and outcome of any future pregnancies were obtained by reviewing the entire chart subsequent to the surgery and by phone confirmation when possible. These were divided into categories: (1) live birth/intrauterine pregnancy (IUP) (excluding miscarriage), (2) no viable intrauterine pregnancy (including miscarriage), and (3) sterilizations (including voluntary procedures and those secondary to undesired bilateral salpingectomy). 286
Sultana et al.
Surgery for ectopic pregnancies
The number of patients who had repeat ectopic gestations was noted. In vitro fertilization pregnancies were not counted as pregnancies (n = 1). The number of months to pregnancy and the number of months followed after surgery were used in life-table analysis. Nine patients were completely lost to follow-up and contributed no data; 11 were sterilized at time of surgery and also contributed no data. However, these were not excluded from the crude pregnancy rate data because the numbers were small. Descriptive statistics were tabulated as frequency counts and percentages for discrete data and as the mean and SD for continuous measures. Categorical data were analyzed using Fisher's Exact Test or x2 , depending on expected cell frequencies. Estimates of cumulative pregnancy rates were obtained using the Kaplan-Meier method (9). The equality of survival curves between groups was tested with the generalized Wilcoxon test (10). The Cox (11) proportional hazards linear-regression model was used to determine which factors were simultaneously associated with pregnancy. A forward stepwise procedure was used to first identify factors that were most highly significant and then add factors that were significant in the presence of previously entered factors. Estimates of relative risk and 95% confidence intervals (CIs) were generated from the parameter estimates of regression coefficients and associated SEs. SAS was used for all statistical testing and management of the database (12). RESULTS
One hundred twenty-six cases of pathologically confirmed EPs that occurred between 1982 and 1990 at the Cleveland Clinic Foundation were reviewed. Operative notes or discharge summaries confirming the procedure were obtained for all cases except 1. Seven additional charts with seven possible admissions for EP could not be located through Medical Records by the investigator for review. The demographic patient data include a mean age of 30.5 ± 4.6 (±SD) years. White women made up 69.0% of the cases; 31.0% were black. The majority (55.6%) of the cases occurred in patients who had never delivered a live child before the EP. Over 84 % of the cases had known risk factors for ectopic gestations. Ectopics occurred in 54.0% of the infertility clinic patients (n = 67), and 46.0% occurred in routine gynecology patients (n = 59). The operative notes indicate that the majority of ectopic gestations occurred in the fallopian tube. Location was specified for 63.7%; ampullary ectopics Fertility and Sterility
Table 1
Cumulative Pregnancy Rates by Surgical Procedure
Type of surgery
Pregnant
Patients
12 mo
24mo
36mo
Pvalue
4 10 13
43 38 33
5.9 ± 4.1* 6.3 ± 4.3 13.4 ± 6.3
9.7 ± 5.4 22.4 ± 8.2 31.8 ± 9.6
18.7 ± 9.8 32.5 ± 9.8 36.7 ± 10.1
0.08
Laparoscopic/Salpingotomy Laparotomy/Salpingostomy Laparotomy/Salpingectomy
* Values are means ± SD.
made up 77.2% of these. Of the remammg, 8.9% were isthmic, 8.9% infundibular, and 1.3% ovarian. The 37.3% with no specified location were also tubal. No outcome was available for 9 of the 113 patients (8.0%), i.e., the patient did not return to the clinic after her postoperative visit, and she could not be reached by phone. The mean number of months of follow-up was 22.5 ± 20.6; the median was 19 months. Eleven patients were sterilized at the time of surgery. Our life-table rates include these 20 patients. Complications of surgery included four patients treated laparoscopically who required a repeat surgical procedure for persistently elevated or rising titers of human chorionic gonadotropin. One patient had inadvertent salpingectomy during attempted laparoscopic salpingostomy. One patient originally treated with laparotomy had two repeat procedures before the ectopic was found. No patients died as a result of the ectopic gestation, and none required admission to intensive care. The repeat ectopic rate per patient was 13.3% (n = 15). The mean number of months to pregnancy was 21.8 ± 16.6; the median was 19 months. The overall crude pregnancy rate was 22.2%. The totals in Table 1 indicate the successful IUP rate according to surgical procedure (laparotomy
with full or partial salpingectomy, laparotomy with salpingostomy, and laparoscopic salpingotomy). Life-table analysis showed no difference (P = 0.08) between cumulative pregnancy rates for the three procedures (Fig. 1), with cumulative rates at 12, 24, and 36 months presented in Table 1. Likewise, X2 analysis showed no significant difference between the crude pregnancy rates for the three procedures (P = 0.054), although it approached significance. When the procedures were compared with each other, two at a time, the difference between laparoscopic and laparotomy salpingostomies was significant (P = 0.043). All salpingostomies did not have better outcome than salpingectomies (17.3% vs. 29.5%, P = 0.11). The crude pregnancy rate for laparotomy with salpingectomy (29.5%) was similar to that of laparotomy with salpingostomy (26.3%). Patients were subdivided further according to their status as infertility or normal patients to see how this affected the outcome per procedure (Table 2). Infertility patients were approximately twice as likely to have laparoscopic attempts at salpingostomy, whereas normal patients were almost twice as likely to have salpingostomy via laparotomy. Patients with a history of infertility had a lower crude delivery rate (IUP). In the group of infertility
Table 2 Pregnancy Rates Among Procedures by History of Infertility*
1.0 0.9 f-
Type of Surgery ............ Surgery 1 - - - - _. Surgery 2 - - Surgery3
z 0.8 «z 0.7 ~
w a: 0.6
a.
z 0.5
0
i= 0.4
a: 0 a. 0
.-------
0.3
a: 0.2 a.
---- - -.--_ ............... I
0.1
•...••.••••••..•....•••••••••••••:
:
0.0 0
12
24
36
MONTHS
Figure 1 Cumulative pregnancy rates by surgical procedure. Surgery 1, laparoscopic salpingotomy; surgery 2, laparotomy salpingostomy; surgery 3, laparotomy salpingectomy. Vol. 57, No.2, February 1992
Pregnant
Not Pregnant
Total
Infertilet Laparotomy/Salpingostomy Laparotomy/Salpingectomy Laparoscopic/Salpingotomy Total
2 5 0 7
12 19 29 60
14 24 29 67
Normal:j: Laparotomy/Salpingostomy Laparotomy/Salpingectomy Laparoscopic/Salpingotomy Total
8 8 4 20
16 12 10 38
24 20 14 58
* Overall X2
= 5.98; P = 0.054. t Fisher's Exact test, P = 0.03. :j: Fisher's Exact test, P = 0.8.
Sultana et al.
Surgery for ectopic pregnancies
287
patients (n = 67),7 (10.4%) conceived and delivered, whereas 60 did not (89.6%). In contrast, more patients conceived in the group without a history of infertility (n = 59). Twenty-one patients conceived (35.6%), whereas, 38 did not (64.4%). The difference between infertility and normal patients was highly significant (P < 0.01). Table 3 shows that the difference observed is mainly due to the difference between these two groups after laparoscopic salpingotomy (P = 0.008). The difference in pregnancy rates between procedures for infertile patients was significant (P = 0.03, Table 2). Pooling salpingostomies for infertility patients altered the relationship between salpingostomy and salpingectomy (P = 0.038), with salpingectomy significantly more successful. Infertility patients appeared to have better outcomes with all laparotomies, regardless of whether the procedure was salpingostomy or salpingectomy. For normal patients, the rate of delivery (IUP) was similar for all three procedures, although slightly higher for laparotomy salpingectomy (28.6%, 33.3%, and 40.0%, P = 0.8, Table 3). Finally, Cox's (11) proportional hazard regression model was used to test the simultaneous importance of both factors on pregnancy rate. Results of this analysis found infertility history as significant (P = 0.002) but not type of surgery (P = 0.14). The estimate of relative risk was 3.9 (95% CI: 1.6, 9.3) for infertility history and 2.3 (95% CI: 0.8, 6.7) for type of surgery. Patients with normal fertility history were almost four times as likely as patients with a history of infertility to become pregnant after surgery for EP. Because the CI for relative risk due to surgery includes 1.0, we conclude no difference in the likelihood of becoming pregnant on the basis of surgical procedure. The difference between nulliparous and parous patients as to chance of future delivery (IUP) was not significant (P = 0.53). DISCUSSION
The overall delivery rate for laparoscopic procedures was quite low, although the repeat ectopic rate was similar to another published report (13). Why should cases with laparotomy be more successful? We conclude that outcome depends more on the history of infertility than on the procedure; previous parity was not important. Our crude pregnancy rate was lower than quoted in the literature (14), although the cumulative rates in normal patients were similar. The fact that patients may return to the Clinic for gynecological care but must go elsewhere 288
Sultana et al.
Surgery for ectopic pregnancies
Table 3 Pregnancy Rates for Infertile Versus Normal Patients by Type of Surgery* Not Pregnant
Total
4 0 4
10 29 39
14 29 43
8 2 10
16 12 28
24 14 38
8
12 19 31
20 24 44
Pregnant Laparoscopic/Salpingotomyt Normal Infertile Total Laparotomy /Salpingostomy:j: Normal Infertile Total Laparotomy /Salpingectomy§ Normal Infertile Total
5
13
* Overall X2 = 10.6; P = 0.002. t Fisher's Exact test, P = 0.008. :j: Fisher's Exact test, P = 0.3. § Fisher's Exact test, P = 0.2.
for obstetrical care partially may explain this. We did not include miscarriages as pregnancies. All patients may not have been attempting pregnancy. We also did not exclude patients who were sterilized or lost to follow-up. Franklin and Ziederman (15) noted only 38% IUP rate after salpingectomy in a population with 72% follow-up, whereas Shenker and Evron (3) noted a 26% subsequent pregnancy rate. Other authors have provided data on outcome after "conservative surgery" (i.e., laparotomy/salpingotomy) (14, 16, 17). Langer et al. (18) presents a 71 % crude live birth rate and 12% repeat ectopic rate in 49 unrandomized patients (excluding those using contraception). Sixty-six percent were nulliparous (similar to our patient population). Timonen and Nieminen (19) found similar rates (29.2% vs. 36.1 %) between salpingectomy and salpingostomy, whereas those of Ploman and Wicksell (20) favored salpingotomy (52% of 31 patients vs. 32% of those who had salpingectomy). Jarvinen et al. (16) noted 68.8% (22/32) of his patients had term pregnancy after salpingotomy. DeCherney and Kase (17) noted, as we did, no difference between patients with salpingectomy versus salpingostomy (42% vs. 39%). The introduction of laparoscopic techniques for removal of tubal EP has introduced another factor into the outcome equation. DeCherney et al. (7) noted a 50% pregnancy rate at 1 year in 18 patients treated in this way. It is important to note that patients with abnormal tubes were excluded. This population differs from our infertility patients. Bruhat et al. (6) treated 60 cases laparoscopically. Of the 25 who later attempted pregnancy, 18 conceived Fertility and Sterility
normally (72%), whereas 12% had repeat ectopics. A high number (23 patients) were lost to follow-up or were sterilized. Our trends confirm those of Sherman et al. (21), who noted an 85% IUP rate in normal patients regardless of salpingotomy or salpingectomy. Those with an infertility history or abnormal findings at surgery had a 76% rate with salpingotomy versus 44% with salpingectomy. Our data demonstrate similar trends but lower overall rates and much lower rates with infertility patients. Even though it seems intuitive that infertility patients with possible damage to the contralateral tube would benefit from salpingostomy, our study did not support this; the opposite was seen. The degree to which the severity ofthe patient's pathology at surgery influenced the surgeon in the choice of procedure was not randomized and cannot be determined from our data. Perhaps the more conservative laparoscopic salpingostomy was selected for more severe cases that would have done poorly at any rate. From this data, there appears to be no significant benefit to laparoscopic procedures versus laparotomy in terms of future pregnancy in the normal patient. Clearly, a randomized prospective study is needed.
REFERENCES 1. Grant A. The effect of ectopic pregnancy on infertility. Clin Obstet Gynecol 1962;55:861-74. 2. Vehaskari A. The operation of choice for ectopic pregnancy with reference to subsequent fertility. Acta Obstet Gynecol Scand SuppI1960;39:1-41. 3. Schenker JG, Evron S. New concepts in the surgical management of tubal pregnancy and the consequent postoperative results. Fertil Steril 1983;40:709-23. 4. Weckstein LN. Current perspectives on ectopic pregnancy. Obstet Gynecol Surv 1985;40:259-72.
Vol. 57, No.2, February 1992
5. Stromme WB. Salpingotomy for tubal pregnancy. Obstet GynecoI1953;1:472-5. 6. Bruhat MA, Manhes M, Mage G, Pouly TL. Treatment of ectopic pregnancy by means of laparoscopy. Fertil Steril 1980;33:411-4. 7. DeCherney AM, Romero R, Naftolin F. Surgical management of unruptured ectopic pregnancy. Fertil Steril1981;35:21-4. 8. Tulandi T, Guralnick M. Treatment of tubal ectopic pregnancy by salpingotomy with or without tubal suturing and salpingectomy. Fertil Steril 1991;55:53-5. 9. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81. 10. Breslow N. A generalized Kruskal-Wallis test for comparing K samples subject to unequal patterns of censorship. Biometrika 1970;57:579-94. 11. Cox DR. Regression models and life tables (with discussion). J R Stat Soc B 1972;34:187-220. 12. SAS Institute. SAS/STAT user's guide. 4th ed. Cary, NC: SAS Institute Inc., 1989. 13. Pauerstein CJ, editor. Ectopic pregnancy. In: The fallopian tube: a reappraisal. Philadelphia: Lea & Febiger, 1974:99. 14. Stromme WB. Conservative surgery for ectopic pregnancy. Obstet GynecoI1973;41:215-23. 15. Franklin EW, Ziederman AM. Tubal ectopic pregnancy: etiology and obstetric & gynecologic sequelae. Am J Obstet Gynecol 1973;117:220-5. 16. Jarvinen PA, Nummi S, Pretola N. Conservative operative therapy of tubal pregnancy with post-op daily hydrotubation. Acta Obstet Gynecol Scand 1972;51:169-70. 17. DeCherney A, Kase N. The conservative surgical management of unruptured ectopic pregnancy. Obstet Gynecol 1979;54: 451-5. 18. Langer R, Bukovsky I, Herman A, Sherman D, Sadovsky G, Caspi E. Conservative surgery for tubal pregnancy. Fertil Steril 1982;38:427-30. 19. Timonen S, Nieminen V. Tubal pregnancy: choice of operative method of treatment. Acta Obstet Gynecol Scand 1967;46: 327-39. 20. Ploman L, Wicksell F. Fertility after conservative surgery in tubal pregnancy. Acta Obstet Gynecol Scand 1960;39:14352. 21. Sherman D, Langer R, Sadovsky G, Bukovsky I, Caspi I. Improved fertility following ectopic pregnancy. Fertil Steril 1982;37:497-502.
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289
Vol. 57, No.2, February 1992
FERTILITY AND STERILITY
Printed on acid-free paper in U.S.A.
Copyright 0 1992 The American Fertility Society
Outcome of laparoscopic versus traditional surgery for ectopic pregnancies*
Carmen J. Sultana, M.D.t Kirk Easley, M.S.:J: Robert L. Collins, M.D.t§ Cleveland Clinic Foundation, Cleveland, Ohio
Objective: To compare pregnancy rates after three surgical procedures for ectopic pregnancy (EP) over a 9-year period for normal and infertility patients. Design: In a retrospective analysis, we examined crude pregnancy rates and life-table analysis of cumulative pregnancy rates. A proportional hazard regression model was used to examine relative risk of type of surgery and fertility rates. Patients, Participants: One hundred twenty-six cases of EPs were reviewed at the Cleveland Clinic Foundation, a tertiary institution. Main Outcome Measures: Comparisons of rates of viable term deliveries were calculated between three types of surgery and were stratified according to the status of infertility. Confidence intervals for relative risk of surgery and fertility status on future pregnancy were calculated. Results: No difference in pregnancy rates was observed after the three procedures (P = 0.08). Normals had a significantly higher (4 times higher) pregnancy rate than infertility patients, independent of surgical procedure. Conclusion: Successful pregnancy after EP is related to history of infertility rather than type of surgery to treat ectopic event. More randomized study is needed to examine laparoscopic salpingostomy, especially in patients with other infertility problems. Fertil Steril 1992;57:285-9 Key Words: Ectopic pregnancy, infertility, pregnancy, pregnancy rates, laparoscopy, salpingostomy, salpingectomy.
Ectopic pregnancy (EP) is a condition that can have severe effects on fertility. Risk factors such as pelvic inflammatory disease (PID), surgical sterilization, intrauterine device (IUD) use, endometriosis, in vitro fertilization (IVF), diethylstilbestrol exposure, and progesterone contraceptive pills are known to increase the relative risk ofEP. It is commonly quoted that only 30% of women treated with salpingectomy subsequently experience a term
Received May 2, 1991; revised and accepted November 20, 1991.
* Presented at the Annual Meeting of the Pacific Coast Fertility Society, Indian Wells, California, April 11 to 14, 1991. t Department of Gynecology. :\: Department of Biostatistics. § Reprint requests: Robert L. Collins, M.D., The Cleveland Clinic Foundation, Department of Gynecology (A-81), One Clinic Center, Cleveland, Ohio 44195-5037. Vol. 57, No.2, February 1992
pregnancy (1, 2). According to Schenker and Evron (3), more recent studies give postectopic delivery rates of 23% to 72%. The first successful surgical treatment of a tubal gestation by total salpingectomy was reported by Lawson Tait in 1884 (3, 4). Since then, attempts have been made to improve future fertility by more conservative surgical techniques. Stromme (5) described the first successful salpingotomy in 1953. The laparoscopic treatment of tubal ectopics is now advocated by many as leading to high subsequent pregnancy rates (6, 7). A review of the data is provided by Schenker and Evron (3). Few studies have used life-table analysis to determine outcome (8). The purpose of this paper is to examine the relationship between three types of surgical procedure and the chance of future successful delivery after EP in a mixed patient population, using both crude Sultana et a1.
Surgery for ectopic pregnancies
285
pregnancy rate and cumulative rate. Because surgical procedure is not the only variable affecting future outcome, each patient's reproductive history was also examined to determine how this would influence the chances of live birth after surgery for EP. MATERIALS AND METHODS
The medical records of all patients carrying a discharge diagnosis of extrauterine pregnancy or EP at the Cleveland Clinic Foundation between 1982 and 1990 were reviewed. The Clinic is a tertiary referral center for gynecology and infertility, but no obstetrical care is offered. The single-chart system at the Foundation collects all inpatient and outpatient data for each patient in a single record, allowing long continuity of follow-up in many cases. Out of 151 such discharge diagnoses generated by the Medical Records Department, 126 cases from 113 patients were found to have the diagnosis confirmed by pathology and were included in the review. Each ectopic gestation was coded as a separate event. All outpatient notes, laboratory results, emergency room visits, and operative reports pertinent to each case were reviewed. Data were collected on the following patient variables: (1) age, (2) race, (3) obstetrical history, (4) risk factors, (5) history oftreatment for infertility at the Foundation, (6) surgical procedure, and (7) future pregnancies. The risk factors included a history of PID, previous EP, previous tubal surgery including sterilization, endometriosis, IUD use, an IVF or exogenous gonadotropin-induced pregnancy, tubal blockage, or pelvic adhesions. Cases that had no comment on history were coded as no risk. Patients who had sought evaluation for infertility in our clinic were categorized as infertile; all others were labeled normal. Surgical procedures were divided into three categories: laparoscopic salpingotomy, laparotomy with salpingostomy, or laparotomy with salpingectomy. Laparoscopic salpingectomy was counted as salpingectomy (one case). Intraoperative and postoperative complications were noted. The occurrence and outcome of any future pregnancies were obtained by reviewing the entire chart subsequent to the surgery and by phone confirmation when possible. These were divided into categories: (1) live birth/intrauterine pregnancy (IUP) (excluding miscarriage), (2) no viable intrauterine pregnancy (including miscarriage), and (3) sterilizations (including voluntary procedures and those secondary to undesired bilateral salpingectomy). 286
Sultana et al.
Surgery for ectopic pregnancies
The number of patients who had repeat ectopic gestations was noted. In vitro fertilization pregnancies were not counted as pregnancies (n = 1). The number of months to pregnancy and the number of months followed after surgery were used in life-table analysis. Nine patients were completely lost to follow-up and contributed no data; 11 were sterilized at time of surgery and also contributed no data. However, these were not excluded from the crude pregnancy rate data because the numbers were small. Descriptive statistics were tabulated as frequency counts and percentages for discrete data and as the mean and SD for continuous measures. Categorical data were analyzed using Fisher's Exact Test or x2 , depending on expected cell frequencies. Estimates of cumulative pregnancy rates were obtained using the Kaplan-Meier method (9). The equality of survival curves between groups was tested with the generalized Wilcoxon test (10). The Cox (11) proportional hazards linear-regression model was used to determine which factors were simultaneously associated with pregnancy. A forward stepwise procedure was used to first identify factors that were most highly significant and then add factors that were significant in the presence of previously entered factors. Estimates of relative risk and 95% confidence intervals (CIs) were generated from the parameter estimates of regression coefficients and associated SEs. SAS was used for all statistical testing and management of the database (12). RESULTS
One hundred twenty-six cases of pathologically confirmed EPs that occurred between 1982 and 1990 at the Cleveland Clinic Foundation were reviewed. Operative notes or discharge summaries confirming the procedure were obtained for all cases except 1. Seven additional charts with seven possible admissions for EP could not be located through Medical Records by the investigator for review. The demographic patient data include a mean age of 30.5 ± 4.6 (±SD) years. White women made up 69.0% of the cases; 31.0% were black. The majority (55.6%) of the cases occurred in patients who had never delivered a live child before the EP. Over 84 % of the cases had known risk factors for ectopic gestations. Ectopics occurred in 54.0% of the infertility clinic patients (n = 67), and 46.0% occurred in routine gynecology patients (n = 59). The operative notes indicate that the majority of ectopic gestations occurred in the fallopian tube. Location was specified for 63.7%; ampullary ectopics Fertility and Sterility
Table 1
Cumulative Pregnancy Rates by Surgical Procedure
Type of surgery
Pregnant
Patients
12 mo
24mo
36mo
Pvalue
4 10 13
43 38 33
5.9 ± 4.1* 6.3 ± 4.3 13.4 ± 6.3
9.7 ± 5.4 22.4 ± 8.2 31.8 ± 9.6
18.7 ± 9.8 32.5 ± 9.8 36.7 ± 10.1
0.08
Laparoscopic/Salpingotomy Laparotomy/Salpingostomy Laparotomy/Salpingectomy
* Values are means ± SD.
made up 77.2% of these. Of the remammg, 8.9% were isthmic, 8.9% infundibular, and 1.3% ovarian. The 37.3% with no specified location were also tubal. No outcome was available for 9 of the 113 patients (8.0%), i.e., the patient did not return to the clinic after her postoperative visit, and she could not be reached by phone. The mean number of months of follow-up was 22.5 ± 20.6; the median was 19 months. Eleven patients were sterilized at the time of surgery. Our life-table rates include these 20 patients. Complications of surgery included four patients treated laparoscopically who required a repeat surgical procedure for persistently elevated or rising titers of human chorionic gonadotropin. One patient had inadvertent salpingectomy during attempted laparoscopic salpingostomy. One patient originally treated with laparotomy had two repeat procedures before the ectopic was found. No patients died as a result of the ectopic gestation, and none required admission to intensive care. The repeat ectopic rate per patient was 13.3% (n = 15). The mean number of months to pregnancy was 21.8 ± 16.6; the median was 19 months. The overall crude pregnancy rate was 22.2%. The totals in Table 1 indicate the successful IUP rate according to surgical procedure (laparotomy
with full or partial salpingectomy, laparotomy with salpingostomy, and laparoscopic salpingotomy). Life-table analysis showed no difference (P = 0.08) between cumulative pregnancy rates for the three procedures (Fig. 1), with cumulative rates at 12, 24, and 36 months presented in Table 1. Likewise, X2 analysis showed no significant difference between the crude pregnancy rates for the three procedures (P = 0.054), although it approached significance. When the procedures were compared with each other, two at a time, the difference between laparoscopic and laparotomy salpingostomies was significant (P = 0.043). All salpingostomies did not have better outcome than salpingectomies (17.3% vs. 29.5%, P = 0.11). The crude pregnancy rate for laparotomy with salpingectomy (29.5%) was similar to that of laparotomy with salpingostomy (26.3%). Patients were subdivided further according to their status as infertility or normal patients to see how this affected the outcome per procedure (Table 2). Infertility patients were approximately twice as likely to have laparoscopic attempts at salpingostomy, whereas normal patients were almost twice as likely to have salpingostomy via laparotomy. Patients with a history of infertility had a lower crude delivery rate (IUP). In the group of infertility
Table 2 Pregnancy Rates Among Procedures by History of Infertility*
1.0 0.9 f-
Type of Surgery ............ Surgery 1 - - - - _. Surgery 2 - - Surgery3
z 0.8 «z 0.7 ~
w a: 0.6
a.
z 0.5
0
i= 0.4
a: 0 a. 0
.-------
0.3
a: 0.2 a.
---- - -.--_ ............... I
0.1
•...••.••••••..•....•••••••••••••:
:
0.0 0
12
24
36
MONTHS
Figure 1 Cumulative pregnancy rates by surgical procedure. Surgery 1, laparoscopic salpingotomy; surgery 2, laparotomy salpingostomy; surgery 3, laparotomy salpingectomy. Vol. 57, No.2, February 1992
Pregnant
Not Pregnant
Total
Infertilet Laparotomy/Salpingostomy Laparotomy/Salpingectomy Laparoscopic/Salpingotomy Total
2 5 0 7
12 19 29 60
14 24 29 67
Normal:j: Laparotomy/Salpingostomy Laparotomy/Salpingectomy Laparoscopic/Salpingotomy Total
8 8 4 20
16 12 10 38
24 20 14 58
* Overall X2
= 5.98; P = 0.054. t Fisher's Exact test, P = 0.03. :j: Fisher's Exact test, P = 0.8.
Sultana et al.
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287
patients (n = 67),7 (10.4%) conceived and delivered, whereas 60 did not (89.6%). In contrast, more patients conceived in the group without a history of infertility (n = 59). Twenty-one patients conceived (35.6%), whereas, 38 did not (64.4%). The difference between infertility and normal patients was highly significant (P < 0.01). Table 3 shows that the difference observed is mainly due to the difference between these two groups after laparoscopic salpingotomy (P = 0.008). The difference in pregnancy rates between procedures for infertile patients was significant (P = 0.03, Table 2). Pooling salpingostomies for infertility patients altered the relationship between salpingostomy and salpingectomy (P = 0.038), with salpingectomy significantly more successful. Infertility patients appeared to have better outcomes with all laparotomies, regardless of whether the procedure was salpingostomy or salpingectomy. For normal patients, the rate of delivery (IUP) was similar for all three procedures, although slightly higher for laparotomy salpingectomy (28.6%, 33.3%, and 40.0%, P = 0.8, Table 3). Finally, Cox's (11) proportional hazard regression model was used to test the simultaneous importance of both factors on pregnancy rate. Results of this analysis found infertility history as significant (P = 0.002) but not type of surgery (P = 0.14). The estimate of relative risk was 3.9 (95% CI: 1.6, 9.3) for infertility history and 2.3 (95% CI: 0.8, 6.7) for type of surgery. Patients with normal fertility history were almost four times as likely as patients with a history of infertility to become pregnant after surgery for EP. Because the CI for relative risk due to surgery includes 1.0, we conclude no difference in the likelihood of becoming pregnant on the basis of surgical procedure. The difference between nulliparous and parous patients as to chance of future delivery (IUP) was not significant (P = 0.53). DISCUSSION
The overall delivery rate for laparoscopic procedures was quite low, although the repeat ectopic rate was similar to another published report (13). Why should cases with laparotomy be more successful? We conclude that outcome depends more on the history of infertility than on the procedure; previous parity was not important. Our crude pregnancy rate was lower than quoted in the literature (14), although the cumulative rates in normal patients were similar. The fact that patients may return to the Clinic for gynecological care but must go elsewhere 288
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Table 3 Pregnancy Rates for Infertile Versus Normal Patients by Type of Surgery* Not Pregnant
Total
4 0 4
10 29 39
14 29 43
8 2 10
16 12 28
24 14 38
8
12 19 31
20 24 44
Pregnant Laparoscopic/Salpingotomyt Normal Infertile Total Laparotomy /Salpingostomy:j: Normal Infertile Total Laparotomy /Salpingectomy§ Normal Infertile Total
5
13
* Overall X2 = 10.6; P = 0.002. t Fisher's Exact test, P = 0.008. :j: Fisher's Exact test, P = 0.3. § Fisher's Exact test, P = 0.2.
for obstetrical care partially may explain this. We did not include miscarriages as pregnancies. All patients may not have been attempting pregnancy. We also did not exclude patients who were sterilized or lost to follow-up. Franklin and Ziederman (15) noted only 38% IUP rate after salpingectomy in a population with 72% follow-up, whereas Shenker and Evron (3) noted a 26% subsequent pregnancy rate. Other authors have provided data on outcome after "conservative surgery" (i.e., laparotomy/salpingotomy) (14, 16, 17). Langer et al. (18) presents a 71 % crude live birth rate and 12% repeat ectopic rate in 49 unrandomized patients (excluding those using contraception). Sixty-six percent were nulliparous (similar to our patient population). Timonen and Nieminen (19) found similar rates (29.2% vs. 36.1 %) between salpingectomy and salpingostomy, whereas those of Ploman and Wicksell (20) favored salpingotomy (52% of 31 patients vs. 32% of those who had salpingectomy). Jarvinen et al. (16) noted 68.8% (22/32) of his patients had term pregnancy after salpingotomy. DeCherney and Kase (17) noted, as we did, no difference between patients with salpingectomy versus salpingostomy (42% vs. 39%). The introduction of laparoscopic techniques for removal of tubal EP has introduced another factor into the outcome equation. DeCherney et al. (7) noted a 50% pregnancy rate at 1 year in 18 patients treated in this way. It is important to note that patients with abnormal tubes were excluded. This population differs from our infertility patients. Bruhat et al. (6) treated 60 cases laparoscopically. Of the 25 who later attempted pregnancy, 18 conceived Fertility and Sterility
normally (72%), whereas 12% had repeat ectopics. A high number (23 patients) were lost to follow-up or were sterilized. Our trends confirm those of Sherman et al. (21), who noted an 85% IUP rate in normal patients regardless of salpingotomy or salpingectomy. Those with an infertility history or abnormal findings at surgery had a 76% rate with salpingotomy versus 44% with salpingectomy. Our data demonstrate similar trends but lower overall rates and much lower rates with infertility patients. Even though it seems intuitive that infertility patients with possible damage to the contralateral tube would benefit from salpingostomy, our study did not support this; the opposite was seen. The degree to which the severity ofthe patient's pathology at surgery influenced the surgeon in the choice of procedure was not randomized and cannot be determined from our data. Perhaps the more conservative laparoscopic salpingostomy was selected for more severe cases that would have done poorly at any rate. From this data, there appears to be no significant benefit to laparoscopic procedures versus laparotomy in terms of future pregnancy in the normal patient. Clearly, a randomized prospective study is needed.
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5. Stromme WB. Salpingotomy for tubal pregnancy. Obstet GynecoI1953;1:472-5. 6. Bruhat MA, Manhes M, Mage G, Pouly TL. Treatment of ectopic pregnancy by means of laparoscopy. Fertil Steril 1980;33:411-4. 7. DeCherney AM, Romero R, Naftolin F. Surgical management of unruptured ectopic pregnancy. Fertil Steril1981;35:21-4. 8. Tulandi T, Guralnick M. Treatment of tubal ectopic pregnancy by salpingotomy with or without tubal suturing and salpingectomy. Fertil Steril 1991;55:53-5. 9. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81. 10. Breslow N. A generalized Kruskal-Wallis test for comparing K samples subject to unequal patterns of censorship. Biometrika 1970;57:579-94. 11. Cox DR. Regression models and life tables (with discussion). J R Stat Soc B 1972;34:187-220. 12. SAS Institute. SAS/STAT user's guide. 4th ed. Cary, NC: SAS Institute Inc., 1989. 13. Pauerstein CJ, editor. Ectopic pregnancy. In: The fallopian tube: a reappraisal. Philadelphia: Lea & Febiger, 1974:99. 14. Stromme WB. Conservative surgery for ectopic pregnancy. Obstet GynecoI1973;41:215-23. 15. Franklin EW, Ziederman AM. Tubal ectopic pregnancy: etiology and obstetric & gynecologic sequelae. Am J Obstet Gynecol 1973;117:220-5. 16. Jarvinen PA, Nummi S, Pretola N. Conservative operative therapy of tubal pregnancy with post-op daily hydrotubation. Acta Obstet Gynecol Scand 1972;51:169-70. 17. DeCherney A, Kase N. The conservative surgical management of unruptured ectopic pregnancy. Obstet Gynecol 1979;54: 451-5. 18. Langer R, Bukovsky I, Herman A, Sherman D, Sadovsky G, Caspi E. Conservative surgery for tubal pregnancy. Fertil Steril 1982;38:427-30. 19. Timonen S, Nieminen V. Tubal pregnancy: choice of operative method of treatment. Acta Obstet Gynecol Scand 1967;46: 327-39. 20. Ploman L, Wicksell F. Fertility after conservative surgery in tubal pregnancy. Acta Obstet Gynecol Scand 1960;39:14352. 21. Sherman D, Langer R, Sadovsky G, Bukovsky I, Caspi I. Improved fertility following ectopic pregnancy. Fertil Steril 1982;37:497-502.
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