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Comparability of perioperative morbidity between abdominal myomectomy and hysterectomy for women with uterine leiomyomas
Comparability of perioperative morbidity between abdominal myomectomy and hysterectomy for women with uterine leiomyomas Stephen W. Sawin, MD,a Nicole D. Pilevsky, MD,a Jesse A. Berlin, ScD,b and Kurt T. Barnhart, MD, MSCEa, b Philadelphia, Pennsylvania OBJECTIVE: The aim of this study was to compare the perioperative morbidity associated with abdominal myomectomy with that of hysterectomy. STUDY DESIGN: This was a retrospective cohort study of 394 women at an academic medical center. Main outcome measured was perioperative morbidity, with the following secondary outcomes: febrile morbidity, hemorrhage, unintended major surgical procedures, life-threatening events, and rehospitalization. RESULTS: Morbidity was associated with myomectomy and hysterectomy in 39% and 40% of cases, respectively. The crude odds ratio for morbidity of myomectomy with respect to hysterectomy was 0.93 (95% confidence interval, 0.63-1.40). Women who underwent myomectomy were significantly younger, weighed less, and had a smaller preoperative uterine size. In a multivariable analysis that accounted for these differences the odds ratio increased to 1.46 (95% confidence interval, 0.77-2.77) but still was not statistically elevated. The study had >90% power to detect a clinically relevant 15% absolute difference in overall morbidity between the 2 groups. CONCLUSION: No clinically significant difference in perioperative morbidity between myomectomy and hysterectomy was detected. Myomectomy should be considered a safe alternative to hysterectomy. (Am J Obstet Gynecol 2000;183:1448-55.)
Key words: Hysterectomy, morbidity, myomectomy, uterine myomas
Hysterectomy is among the most common major surgical procedures performed today.1 Uterine leiomyomas (myomas) are the most common pelvic tumors found among women2, 3 and the most frequent indication for abdominal hysterectomy.4, 5 Approximately 20% to 50% of women are estimated to have myomas,2 and myoma accounts for 40% of abdominal hysterectomies performed in the United States.4 Although most myomas are considered to be asymptomatic, 20% to 50% produce symptoms that include menorrhagia, pelvic pain or pressure, infertility, recurrent pregnancy loss, and impingement on adjacent organs that causes constipation, urinary frequency, or hydronephrosis.2 The incidence and severity of myomas increase with premenopausal age,5, 6 which makes this a common clinFrom the Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center,a and the Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania.b Received for publication November 12, 1999; revised February 29, 2000; accepted April 7, 2000. Reprint requests: Kurt T. Barnhart, MD, MSCE, University of Pennsylvania Medical Center, Department of Obstetrics and Gynecology, 106 Dulles, 3400 Spruce St, Philadelphia, PA 19104. Copyright © 2000 by Mosby, Inc. 0002-9378/2000 $12.00 + 0 6/1/107730 doi:10.1067/mob.2000.107730
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ical condition encountered among women of advanced reproductive age. Recent trends of delayed childbearing and an increase in the number of women in the latter reproductive years have increased the demand for conservative treatment of uterine myomas for preservation of reproductive potential.5, 7 New advances in assisted reproductive techniques, including the use of donor oocytes, now permit women in the later reproductive years to carry a child if the uterus is still intact. In addition, there is a growing population of women who desire uterine conservation after completion of childbearing because of concerns about sexual dysfunction and dyspareunia after hysterectomy.7 Although hysterectomy has been traditionally offered to women of advanced reproductive age with symptomatic myomas, alternative therapies are now being given greater attention.5, 7-9 For many years it was believed that abdominal myomectomy was associated with greater operative blood loss, longer surgical time, and higher risk of postoperative hemorrhage than hysterectomy.3 Some gynecologists consider hysterectomy to be a simpler, less time-consuming, and less complicated procedure,9 whereas others have found the two procedures to carry comparable complication rates.10 Abdominal myomectomy is successful in alleviating symptoms in approximately 80% of cases2 and
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therefore should be considered a viable alternative to hysterectomy for symptomatic myomas. We undertook a retrospective review of women who underwent abdominal myomectomy and hysterectomy performed in our institution for myomas during the course of 3 years to compare the intraoperative and postoperative morbidities of the procedures and to aid in counseling patients who are considering these two options. Methods Subjects. Hospital charts were reviewed by 2 of the authors (Stephen W. Sawin, MD, and Nicole D. Pilevsky, MD) for all women who underwent abdominal myomectomy and an equal number of women who underwent abdominal hysterectomy at the University of Pennsylvania Medical Center from 1994 through 1996. Charts were identified by a computerized search of medical records under the procedure codes abdominal myomectomy and abdominal hysterectomy and the diagnosis code uterine leiomyoma. All charts identified were available for direct review. Patients were included if the abdominal myomectomy or hysterectomy was the primary procedure and not incidental to a more involved operation. Patients were excluded if the surgery involved a malignancy, pregnancy, or gynecologic infection or if it was performed on an emergency basis. The service that performed the surgery was noted (reproductive endocrinology, gynecologic oncology, general gynecology, or resident service) but was not used to exclude any patients. The Hospital of the University of Pennsylvania is an inner-city tertiary referral center; the subspecialty and general gynecology services mostly treat privately insured patients from the greater Philadelphia area, and the resident service mostly treats patients with public assistance or no insurance from the inner city. Approximately 3 times as many women underwent hysterectomy as myomectomy during this period, and none of the procedures were supracervical hysterectomies. The sample of subjects who underwent hysterectomy was selected by reviewing the chart of the first woman who had a hysterectomy performed after the date of each myomectomy identified. The patients were not otherwise matched. Institutional review board approval for this project was obtained from the committee on studies involving human beings at the University of Pennsylvania Medical Center. Information collected. The 2 groups were compared with respect to age, parity, weight, previous myomectomy, uterine size, preoperative use of gonadotropin-releasing hormone (GnRH) agonists, prophylactic use of antibiotics, presence of adhesions, surgical time, estimated blood loss, febrile morbidity, maximum postoperative white blood cell count, postoperative use of antibiotics, length of hospital stay, blood transfusions, and other complications of surgery. Uterine size was determined from examination with the patient under anesthesia;
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when this figure was unavailable, it was determined from the admission notes. Surgical time was defined as the time of skin incision to the time of skin closure. All other intraoperative procedures were recorded. Estimated blood loss was obtained from the operative notes as assessed by the surgical team. It was calculated by measuring the volume of blood in the suction containers minus the volume of irrigation used, plus the amount of blood in the sponges as determined by weight. The surgical technique used for reducing blood loss at the time of myomectomy (surgical tourniquet or vasopressin injection) was noted. The presence of adhesions was scored in a semiquantitative fashion as follows: mild (filmy and transparent), moderate (dense, bands between organs but with mobility of the organ maintained, opaque), and severe (fixation of organs to pelvic sidewall or other organs). The number of myomas removed, as documented in the pathology report, was also noted, as were the weights of hysterectomy specimens. Definition of morbidity. The largest series analyzing surgical morbidity after hysterectomy was the Collaborative Review of Sterilization study coordinated by the Centers for Disease Control.4 This study has set the standard definition for morbidity after hysterectomy, which includes the following 5 categories: febrile morbidity, hemorrhage, unintended major surgical procedures, life-threatening events, and rehospitalization. The overall morbidity associated with an abdominal hysterectomy was 42.8%. Febrile morbidity (32.3%) and hemorrhage (15.4%) accounted for most of the morbidity identified.4 A recent review of the literature demonstrated that overall morbidity has remained stable since the Collaborative Review of Sterilization study.11 Recently The American College of Obstetricians and Gynecologists published a set of gynecologic quality assurance clinical indicators for hysterectomy, including 12 indicators that address surgical morbidity.12 These 12 indicators, which are grouped into 5 categories (Table I), have been found to be 99% accurate in identifying morbidity after hysterectomy.13 We used this classification scheme to identify cases of perioperative morbidity in women who underwent either hysterectomy or myomectomy. Sample size and power. To calculate the sample size required for this study we made the following assumptions. Approximately 40% of women who undergo hysterectomy were assumed to have morbidity.4 A 15% absolute increase or decrease in the rate of morbidity was assumed to be clinically significant. With a probability of a type I statistical error (2-sided) of .05 and a probability of a type II statistical error of .1, a sample size of 173 patients who underwent each procedure would be necessary to detect that difference. To achieve that sample size we reviewed the clinical course of all women who underwent an abdominal myomectomy and an equal number of women
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Table I. Classification of perioperative morbidity associated with hysterectomy and myomectomy Morbidity indicator* Febrile morbidity Hemorrhage Unintended procedure Life-threatening events Readmission
Definition Occurrence of infection not present on admission or initiation of antibiotics >24 h after surgery Gynecologic surgery with ≥2 units of blood, postoperative hematocrit of <24%, or postoperative hemoglobin concentration of <8 g/dL Unplanned removal, injury, or repair of organ during operative procedure or unplanned return to operating room for surgery during the same admission Cardiopulmonary arrest, resuscitation, unplanned admission to special (intensive) care unit, or death Unplanned readmission within 14 d or admission after return visit to the emergency department for the same problem
Adapted from Dicker et al,4 The American College of Obstetricians and Gynecologists,12 and Gambone et al.13 *The presence of any category defines the presence of morbidity.
who underwent hysterectomy in 3 consecutive years. This resulted in our final sample size of 197 women who underwent each procedure. Data analysis. The primary outcome of this study was the percentage of women considered to have perioperative morbidity according to the previously stated criteria. The subtypes of morbidity were noted, and these subtypes were analyzed as secondary outcomes. Descriptive analyses were first conducted in the total eligible cohort to examine baseline associations and to assess whether the distributions of continuous variables were consistent with the assumption of normality required for parametric statistical tests. Comparison of women who underwent myomectomy with those who underwent hysterectomy was conducted with the independent sample t test for continuous variables and the ordinary χ2 test for categoric variables. Results for the continuous variables were confirmed with the Wilcoxon rank sum test. Associations between outcome and procedure type and between outcome and other variables were assessed with both relative risks and odds ratios. Because these measures gave similar results, only the odds ratio was estimated in subsequent multivariable logistic regression models. We performed both unadjusted and stratified analyses to determine potential confounding variables and to identify possible modifiers of the association between procedure type and outcome (interactions between procedure type and other variables; see Table IV). Multivariable logistic regression was then used to estimate the odds ratio for procedure type after adjustment for all potential confounders. Variables were included in the logistic regression model (1) if they were biologically plausible, (2) if they demonstrated P < .20 for the association with outcome in the unadjusted analyses, or (3) if adjustment for the given variable changed the odds ratio for myomectomy versus hysterectomy by ≥10%.14, 15 The assumption of linearity of the relationship between continuous variables and outcome was checked by testing significance of quadratic terms (variable squared). If the squared term was significant, the variable was categorized and fitted with a series of indicator variables. The only
variable for which the quadratic term was significant was the presence of adhesions noted at the time of surgery, which was subsequently categorized as none, mild, moderate, or severe on the basis of clinical considerations without looking at the category-specific associations with outcome. The percentage of missing data ranged from 9% (uterine size) to 0% (age, history of previous myomectomy, preoperative use of a GnRH agonist, preoperative use of antibiotics, and presence of adhesions at the time of surgery). Complete data on all variables were available for 83% of subjects. Analyses were conducted both on the subset of subjects with no missing data and after imputation of missing data with the impute command in the STATA software package (Stata Corporation, College Station, Tex), with no dramatic change in results. Results Table II shows the demographic and preoperative characteristics of the patients stratified according to the type of surgical procedure performed. Patients who underwent myomectomy were significantly younger, weighed less, were of lower parity, and had a smaller preoperative uterine size than those who underwent hysterectomy. The most common reason for surgery among the women who underwent hysterectomy was vaginal bleeding or pain, whereas reasons such as recurrent miscarriage, infertility, or enlarged uterine size without symptoms were more common indications for surgery among those who underwent myomectomy. Indications other than pain or bleeding were grouped together to allow statistical analysis. Preoperative antibiotics use was more frequent in the myomectomy group. The rates of preoperative use of a GnRH agonist were similar in the two groups. In 29% of the myomectomy procedures the endometrial cavity was entered, and on average 9.2 myomas were removed. The surgical techniques used to reduce blood loss at the time of myomectomy included the use of either a surgical tourniquet (73%) or vasopressin (14%), both of these (10%), or neither of these(3%). In only 1 case was a myomectomy converted to a hysterectomy be-
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Table II. Demographic and baseline characteristics of patients who underwent myomectomy or hysterectomy Myomectomy (n = 197) Hysterectomy (n = 197) Statistical significance Continuous variables Age (y, mean ± SD) Weight (lb, mean ± SD) Parity (mean ± SD) Preoperative uterine size (gestational wk equivalent, mean ± SD) Categoric variables (%) Preoperative use of antibiotics Preoperative use of GnRH agonists Previous myomectomy Adhesions present at surgery Indication for surgery‡ Bleeding Pain Other
36.1 ± 5.5 156.1 ± 36.5 0.5 ± 0.9 14.4 ± 5.0
43.9 ± 5.9 174.4 ± 43.7 1.6 ± 1.3 15.6 ± 4.9
P < .0001* P < .0001* P < .0001* P < .0001*
99.5% 9.1% 7.1% 36.5%
96.5% 10.2% 11.7% 43.6%
35.6% 38.7% 25.6%
61.9% 30.8% 7.3%
P = .03† P = .73† P = .11† P = .51† P < .0001† P < .0001† P = .10† P < .0001†
*By t test. †By χ2 test. ‡n = 191.
Table III. Unadjusted analysis of outcomes of myomectomy versus hysterectomy Odds ratio
Outcome
Myomectomy (n = 197)
95% Hysterectomy Confidence (n = 197) Unadjusted interval
Morbidity Overall morbidity 38.6% 40.1% Febrile morbidity 33.0% 25.9% Hemorrhage 9.6% 14.2% Unintended procedure 4.5% 9.6% Life-threatening event* 1.5% 1.0% Readmission* 1.5% 2.5% Other outcomes Operative time (min, mean ± SD) 200.9 ± 68.1 175.5 ± 56.2 Estimated blood loss (mL, mean ± SD) 226.7 ± 190.5 483.6 ± 375.8 Length of stay in hospital (d, mean ± SD) 3.96 ± 2.1 4.42 ± 2.4 Maximum white blood cell count (103 cells/µL, mean ± SD) 13.12 ± 3.7 11.67 ± 3.7 Maximum drop in hemoglobin concentration (g/dL) 2.49 ± 1.4 2.11 ± 1.2 Patients transfused (No.) 18/197 (9.1%) 25/197 (12.8%) Patients transfused with autologous blood§ 16/18 (88.9%) 13/25 (52.0%)
0.93 1.41 0.46 0.45 1.51 0.59
0.63-1.40 0.91-2.17 0.26-0.83 0.20-0.99 0.17-18.00 0.09-3.10
Statistical significance
P = .75 P = .12 P = .009 P = .049 P = 1.00 P = .72 P = .00002† P = .00001† P = .048† P = .022† P = .51† P = .25‡ P < .0001ll
*Exact P value and 95% confidence interval. †By t test. ‡By χ2 test. §This variable represents a subset of the number of subjects transfused. llBy Fisher exact test.
cause of difficulty in completing the surgical procedure. A previous myomectomy had been performed in 7% of myomectomy cases and 12% of hysterectomy cases. The average uterine weight after hysterectomy was 654.5 g. Operative complications in the myomectomy group included 1 cystotomy, 1 case of pulmonary edema, 2 smallbowel obstructions that necessitated reoperation, 6 cases of ileus, and 1 incision breakdown. Operative complications in the hysterectomy group included 1 cystotomy, 1 patient with congestive heart failure, 8 cases of ileus, 3 bowel injuries, 5 incision breakdowns (1 of which included dehiscence), 1 rectus muscle hematoma, 1 ureteral injury, and 6 pelvic abscesses.
Table III shows the results of the unadjusted analysis of morbidity and other outcomes among the women who underwent myomectomy versus those who underwent hysterectomy. The overall morbidity associated with abdominal myomectomy was similar to that of abdominal hysterectomy. There were significantly lower prevalences of hemorrhage and the performance of an unintended procedure among women who underwent myomectomy than among those who underwent hysterectomy. Febrile morbidity was more common among women who underwent myomectomy, but this trend was not statistically significant. Life-threatening events and readmissions were rare in both groups.
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Table IV. Odds ratios of morbidity among those who underwent myomectomy with respect to those who underwent hysterectomy stratified according to potential confounding variables Odds ratio Variable adjusted for Analysis on entire sample (N = 394) None (unadjusted, crude) Age† Weight† Uterine size† Previous myomectomy Parity† GnRH analog Indication Service‡ Adhesions† Preoperative antibiotics Analysis restricted to those with complete data on all variables None (unadjusted, crude) Age† Weight† Uterine size Previous myomectomy Parity† Leuprolide acetate Indication Service‡
No.
Adjusted
95% Confidence interval
Unadjusted statistical significance
394 394 384 360 394 375 394 383 393 394 394
0.94 1.01 1.02 1.21 0.97 0.95 0.94 0.99 1.02 1.03 0.93
0.63-1.49 0.61-1.64 0.67-1.55 0.78-1.87 0.64-1.45 0.59-1.52 0.63-1.41 0.64-1.55 0.65-1.58 0.68-1.56 0.62-1.40
P = .436* P = .042* P = .037* P = .72* P = .054* P = .6* P = .5* P = .3* P = .072* P = .93*
326 326 326 326 326 326 326 326 326
1.05 1.08 1.10 1.19 1.08 1.02 1.06 1.07 1.18
0.68-1.64 0.65-1.82 0.70-1.72 0.74-1.88 0.69-1.68 0.62-1.67 0.68-1.65 0.68-1.67 0.74-1.89
P = .6§ P = .085§ P = .021§ P = .57§ P = .068§ P = .21§ P = .73§ P = .79§
*P value for test of interaction. †Interaction P value tests for linear trend in log odds ratio for myomectomy versus hysterectomy across values of the continuous variable. ‡Medical service that performed the surgery—general gynecology, gynecologic oncology, reproductive endocrinology, resident service. §P value for test of heterogeneity.
Abdominal myomectomy was a lengthier procedure than abdominal hysterectomy but was associated with significantly less blood loss. Approximately equal numbers of subjects in each group required blood transfusions; among those who did, however, patients who underwent myomectomy were significantly more likely to receive a transfusion with autologous blood. The average hospital stay was significantly shorter among the women who underwent myomectomy. To examine the confounding effects of patient characteristics, surgical indication, and findings at surgery on the association between risk of morbidity and procedure type, stratified analyses were performed. A comparison of the overall morbidity between women who underwent myomectomy and hysterectomy stratified according to potential confounding variables is listed in the top half of Table IV. Adjustment for any single variable did not substantially change the unadjusted odds ratio for morbidity among women who underwent abdominal myomectomy with respect to hysterectomy; therefore none of the variables were considered to be strong confounders. The odds ratio for morbidity among those who underwent myomectomy with respect to hysterectomy was not significantly elevated after adjustment for any variable. The bottom half of Table IV restricts the same analysis to only those patients for whom a complete data set was
available. The overall odds ratio was not materially changed by adjustment for any single variable, nor was it significantly elevated among those who underwent myomectomy with respect to those who underwent hysterectomy. Table V presents the multivariable-adjusted odds ratio for overall morbidity comparing hysterectomy with myomectomy and according to each potential confounding variable. After the adjustment of all potential confounding variables the odds ratio for morbidity increased to 1.46 (95% confidence interval, 0.77-2.77) compared with the unadjusted odds ratio of 0.94 (95% confidence interval, 0.63-1.49). Although this adjusted odds ratio was not statistically significant, this trend may suggest that there were characteristics of the patients in the myomectomy group independent of the procedure performed that tended to lower the overall morbidity. For the remaining variables in Table V the odds ratio represents the association with morbidity independent of the procedure performed. Only uterine size and the presence of adhesions at the time of surgery were significantly associated with increased perioperative morbidity. Analysis of the association of severity of adhesions with morbidity demonstrated that only the presence of severe adhesions was significantly associated with increased morbidity. Nonsignificant trends noted included an in-
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Table V. Logistic regression model Odds ratio Variable Procedure Age Weight Uterine size Previous myomectomy GnRH agonist use Parity Adhesions None Mild Moderate Severe Service General gynecology Reproductive endocrinology Gynecologic oncology Resident service Indication Bleeding Pain Other
Value
95% Confidence interval
Statistical significance
1.46 1.01 1.00 1.10 1.44 1.44 1.01
0.77-2.77 0.96-1.05 0.99-1.01 1.04-1.15 0.60-3.41 0.66-3.14 0.79-1.29
P = .25 P = .72 P = .60 P = .0002 P = .41 P = .36 P = .91 P = .044
1.00 1.10 1.16 3.12
Referent 0.56-2.13 0.52-2.57 1.38-7.02
1.00 0.81 1.28 1.36
Referent 0.43-1.52 0.53-3.11 0.65-2.80
1.00 1.48 1.05
Referent 0.70-3.15 0.60-1.83
P = .78 P = .71 P = .006 P = .44 P = .51 P = .58 P = .41 P = .57 P = .31 P = .16
Table VI. Logistic regression model for overall morbidity and subtypes of morbidity comparing surgical procedure of myomectomy with hysterectomy Odds ratio
Overall morbidity Febrile morbidity Hemorrhage Unintended procedure Life-threatening event* Readmission*
Value
95% Confidence interval
Statistical significance
1.46 1.89 0.62 0.84 — —
0.77-2.77 0.97-3.72 0.24-1.63 0.25-2.81 — —
P = .25 P = .063 P = .34 P = .78 — —
*Values are not given because there were too few events to permit fitting of a multiple variable logistic regression model.
crease in perioperative morbidity among women with previous myomectomy and an increase when surgery was conducted for the indication of pain. Risk of morbidity changed only modestly depending on the surgical service, with reproductive endocrinologists having the lowest morbidity rate and the resident service having the highest morbidity rate. Table VI presents the multivariable-adjusted odds ratio of each subtype of morbidity for women who underwent myomectomy with respect to those who underwent hysterectomy. After adjustment for confounding variables none of the morbidity subtypes differed significantly between the myomectomy and hysterectomy groups, although there was a trend toward a higher incidence of febrile morbidity among those who underwent myomectomy. There were not enough cases of life-threatening events or readmission to permit appropriate statistical analyses.
Comment Many women have to face the decision between myomectomy and hysterectomy for the treatment of symptomatic leiomyoma. They rely heavily on their physicians to inform them of the risks and benefits associated with these surgical options. Although there are no controlled trials in the literature that demonstrate that abdominal myomectomy is associated with greater morbidity than hysterectomy, some gynecologic educational bulletins, textbooks, and review articles support this assertion.3, 9, 16 Febrile morbidity and hemorrhage have been the most common complications noted to be increased after myomectomy with respect to hysterectomy.10, 16-21 The results of our study do not support this conclusion. Previous case series have lacked control groups and have used different definitions of morbidity, which makes comparisons difficult. We chose to rigorously define morbidity according to a standardized and validated system13
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that used The American College of Obstetricians and Gynecologists quality assurance indicators as outcome variables grouped according to the categories used in the Collaborative Review of Sterilization study. Several recent case series have suggested that abdominal myomectomy is a safe procedure with acceptable morbidity.10, 16-21 This is the first study to use a such a rigorous definition of morbidity to evaluate abdominal myomectomy and should allow accurate comparisons between institutions and with future studies. Only one previous study, that of Iverson et al,10 directly compared the morbidity associated with abdominal myomectomy with that of hysterectomy, and it found that myomectomy was associated with no greater risk of blood loss or febrile morbidity and with no significant differences in other morbidity variables. Similar to that study, we found that myomectomy was associated with less operative blood loss but that this finding lost statistical significance after multivariable logistic regression analysis with correction for uterine size. Both studies demonstrated that uterine size was an independent risk factor for morbidity in either procedure, consistent with the findings of other studies.18 We saw a trend toward higher febrile morbidity in the myomectomy group, whereas Iverson et al10 found a trend toward higher febrile morbidity in the hysterectomy group. It is interesting that a recent reanalysis of their data including the first 48 postoperative hours found a significantly higher rate of fever in the myomectomy group.22 The original study by Iverson et al10 did not report a sample size calculation and has the potential for insufficient power to detect a significant difference in morbidity. Our study had >90% power to detect a 15% difference in morbidity. To our knowledge this is the largest comparative study of these 2 procedures in the literature, and it is the first to document adequate power to detect a clinically significant difference. The American College of Obstetricians and Gynecologists Technical Bulletin on uterine leiomyoma states, “Although intraoperative blood loss, operative time and risk for postoperative hemorrhage appear to be slightly higher than with hysterectomy, these risks are somewhat offset by the lower rates of infectious morbidity and ureteral injury associated with myomectomy.”3 Although we did see a statistically significantly longer operative time and a nonsignificant trend toward less operative injury, we were not able to demonstrate more blood loss or lower infectious morbidity associated with myomectomy. Iverson et al10 found no differences in operative time, blood loss, hemorrhage, or infectious morbidity after they controlled for uterine size. It is possible that the high uses of tourniquets in our study (83%) and vasopressin in the study by Iverson et al10 (95%) significantly reduced the risk of hemorrhage previously ascribed to abdominal myomectomy. Our estimated blood loss from myomec-
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tomy was 226 mL, and only 9% of our patients had hemorrhage necessitating transfusion. Transfusion has been reported to be necessary in as many as 52% of cases in other series.10, 16-21 Two studies reported a statistically significant reduction in operative blood loss during myomectomy when a tourniquet or vasopressin injection was used,17, 23 and another study found vasopressin injection and tourniquet use to be equally effective in controlling blood loss.18 Some authors have suggested that the preoperative use of GnRH agonists reduces operative blood loss,21 whereas others have not demonstrated any benefit.20 The rate of use of GnRH agonists among the women who underwent myomectomy in our study was low (9.1%) and similar to the rate in the hysterectomy group (10.2%), and GnRH agonist use is therefore unlikely to have been a confounding factor. It appears that previous concerns regarding the increased risk of operative blood loss with myomectomy have been tempered by the modern use of adjuvant measures to reduce hemorrhage. We also demonstrated that women who underwent myomectomy were different from those who underwent hysterectomy. Women who elected to undergo myomectomy were approximately 8 years younger, had fewer children, and were less likely to have the surgery performed for the indication of vaginal bleeding. These differences probably reflect the desire among younger and less parous women to preserve fertility even with significant uterine pathologic conditions. In addition, myomectomy is commonly offered to women who wish to preserve future fertility, whereas hysterectomy is commonly offered to treat vaginal bleeding after a woman has completed childbearing. Other differences between the 2 groups were that women who underwent hysterectomy were approximately 18 lb heavier, had a slightly larger preoperative uterine size, and were less likely to receive preoperative antibiotics. The clinical significance of these differences is doubtful, because the absolute differences between the two groups in these variables were small. The absolute difference in uterine size between the 2 groups was only slightly more than the equivalent of 1 week of gestation (14.4 vs 15.6 weeks’ gestation equivalent) and was certainly within the range of error for a bimanual examination. More than 96% of all women who underwent a surgical procedure received preoperative antibiotics, which means that the statistically significant difference between groups is unlikely to have been clinically significant. The differences between women in the 2 groups were adjusted for by means of multivariable analysis. After adjustment, the odds ratios for overall morbidity and febrile morbidity among women who underwent myomectomy with respect to those who underwent hysterectomy did increase but still were not statistically significant. In light of the width of the confidence interval (upper confidence
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limit of 2.77 for the odds ratio) we are unable to completely rule out a clinically important difference in morbidity between the groups. In addition, after adjustment the odds ratios for hemorrhage and the occurrence of an unintended procedure were no longer significantly lower among women who underwent myomectomy. These trends demonstrate that, although only uterine size and the presence of severe adhesions were significantly and independently associated with surgical morbidity, in aggregate women who underwent myomectomy in this study period were at lower surgical risk than were those who underwent hysterectomy. It is important that after adjustment for these factors the morbidity detected among women who underwent myomectomy was not significantly higher than among women who underwent hysterectomy. Our study design restricted our analysis to intraoperative and short-term postoperative morbidity. Other important considerations, such as long-term morbidity, recurrence, and success in alleviating symptoms were not addressed, because such was not the goal of this study. In conclusion, we did not find any evidence to suggest that abdominal myomectomy was associated with a clinically significantly elevated risk of morbidity with respect to abdominal hysterectomy performed for the same diagnosis. Although every case is unique and factors other than short-term morbidity should also be addressed, myomectomy should be considered a safe alternative to hysterectomy for the treatment of uterine fibroids. REFERENCES
1. Graves EJ. Detailed diagnoses and procedures, national hospital discharge survey, 1990. Vital Health Stat 13 1992;113:1-225. 2. Buttram VC, Reitter RC. Uterine leiomyomata: etiology, symptomatology and management. Fertil Steril 1981;36:433-45. 3. American College of Obstetricians and Gynecologists. Uterine leiomyomata. Washington: The College; 1994. p. 1-9. ACOG Technical Bulletin No.: 192. 4. Dicker RC, Greenspan JR, Strauss LT, Cowart MR, Scally MJ, Peterson HB, et al. Complications of abdominal and vaginal hysterectomy among women of reproductive age in the United States. The Collaborative Review of Sterilization. Am J Obstet Gynecol 1982;144:841-8. 5. Verkauf BS. Changing trends in treatment of leiomyomata uteri. Curr Opin Obstet Gynecol 1993;5:301-10.
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6. Marshall LM, Spiegelman D, Barbieri RL, Goldman MB, Manson JE, Colditz GA, et al. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet Gynecol 1997;90:967-73. 7. Garcia CR. Management of the symptomatic fibroid in women older than 40 years of age: hysterectomy or myomectomy? Obstet Gynecol Clin North Am 1993;20:337-48. 8. Altchek A. Management of fibroids. Curr Opin Obstet Gynecol 1992;4:463-71. 9. Wallach EE. Myomectomy. In: Thompson JD, Rock JA, editors. TeLinde’s operative gynecology. Philadelphia: JB Lippincott; 1992. p. 647-61. 10. Iverson RE Jr, Chelmow D, Strohbehn K, Waldman L, Evantash EG. Relative morbidity of abdominal hysterectomy and myomectomy for management of uterine leiomyomas. Obstet Gynecol 1996;88:415-9. 11. Harris WJ. Early complications of abdominal and vaginal hysterectomy. Obstet Gynecol Surv 1995;50:795-805. 12. American College of Obstetricians and Gynecologists. Establishment of a departmental monitoring and evaluation program. In: American College of Obstetricians and Gynecologists. Quality assessment and improvement in obstetrics and gynecology. Washington: The College; 1994. p. 16. 13. Gambone JC, Reiter RC, Lench JB. Quality assurance indicators and short-term outcome of hysterectomy. Obstet Gynecol 1990; 76:841-5. 14. Mickey RM, Greenland S. The impact of confounder selection criteria on effect estimation. Am J Epidemiol 1989;129:125-37. 15. Maldonado G, Greenland S. Simulation study of confounder selection strategies. Am J Epidemiol 1993;138:923-36. 16. Verkauf BS. Myomectomy for fertility enhancement and preservation. Fertil Steril 1992;58:1-15. 17. LaMorte AI, Lalwani S, Diamond MP. Morbidity associated with abdominal myomectomy. Obstet Gynecol 1993;82:897-900. 18. Ginsburg ES, Benson CB, Garfield JM, Gleason RE, Friedman AJ. The effect of operative technique and uterine size on blood loss during myomectomy: a prospective randomized study. Fertil Steril 1993;60:956-62. 19. Smith DC, Uhlir JK. Myomectomy as a reproductive procedure. Am J Obstet Gynecol 1990;162:1476-82. 20. Friedman AJ, Rein MS, Harrison-Atlas D, Garfield JM, Doubilet PM. A randomized, placebo-controlled, double-blind study evaluating leuprolide acetate depot treatment before myomectomy [published erratum appears in Fertil Steril 1990;54:749]. Fertil Steril 1989;52:728-33. 21. Golan A, Bukovsky I, Pansky M, Schneider D, Weinraub Z, Caspi E. Pre-operative gonadotrophin-releasing hormone agonist treatment in surgery for uterine leiomyomata. Hum Reprod 1993;8:450-2. 22. Iverson RE, Chelmow D, Strohbehn K, Waldman L, Evantash EG, Aronson MP. Myomectomy fever: testing the dogma. Fertil Steril 1999;72:104-8. 23. Frederick J, Fletcher H, Simeon D, Mullings A, Hardie M. Intramyometrial vasopressin as a haemostatic agent during myomectomy. Br J Obstet Gynaecol 1994;101:435-7.
Key words: Hysterectomy, morbidity, myomectomy, uterine myomas
Hysterectomy is among the most common major surgical procedures performed today.1 Uterine leiomyomas (myomas) are the most common pelvic tumors found among women2, 3 and the most frequent indication for abdominal hysterectomy.4, 5 Approximately 20% to 50% of women are estimated to have myomas,2 and myoma accounts for 40% of abdominal hysterectomies performed in the United States.4 Although most myomas are considered to be asymptomatic, 20% to 50% produce symptoms that include menorrhagia, pelvic pain or pressure, infertility, recurrent pregnancy loss, and impingement on adjacent organs that causes constipation, urinary frequency, or hydronephrosis.2 The incidence and severity of myomas increase with premenopausal age,5, 6 which makes this a common clinFrom the Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center,a and the Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania.b Received for publication November 12, 1999; revised February 29, 2000; accepted April 7, 2000. Reprint requests: Kurt T. Barnhart, MD, MSCE, University of Pennsylvania Medical Center, Department of Obstetrics and Gynecology, 106 Dulles, 3400 Spruce St, Philadelphia, PA 19104. Copyright © 2000 by Mosby, Inc. 0002-9378/2000 $12.00 + 0 6/1/107730 doi:10.1067/mob.2000.107730
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ical condition encountered among women of advanced reproductive age. Recent trends of delayed childbearing and an increase in the number of women in the latter reproductive years have increased the demand for conservative treatment of uterine myomas for preservation of reproductive potential.5, 7 New advances in assisted reproductive techniques, including the use of donor oocytes, now permit women in the later reproductive years to carry a child if the uterus is still intact. In addition, there is a growing population of women who desire uterine conservation after completion of childbearing because of concerns about sexual dysfunction and dyspareunia after hysterectomy.7 Although hysterectomy has been traditionally offered to women of advanced reproductive age with symptomatic myomas, alternative therapies are now being given greater attention.5, 7-9 For many years it was believed that abdominal myomectomy was associated with greater operative blood loss, longer surgical time, and higher risk of postoperative hemorrhage than hysterectomy.3 Some gynecologists consider hysterectomy to be a simpler, less time-consuming, and less complicated procedure,9 whereas others have found the two procedures to carry comparable complication rates.10 Abdominal myomectomy is successful in alleviating symptoms in approximately 80% of cases2 and
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therefore should be considered a viable alternative to hysterectomy for symptomatic myomas. We undertook a retrospective review of women who underwent abdominal myomectomy and hysterectomy performed in our institution for myomas during the course of 3 years to compare the intraoperative and postoperative morbidities of the procedures and to aid in counseling patients who are considering these two options. Methods Subjects. Hospital charts were reviewed by 2 of the authors (Stephen W. Sawin, MD, and Nicole D. Pilevsky, MD) for all women who underwent abdominal myomectomy and an equal number of women who underwent abdominal hysterectomy at the University of Pennsylvania Medical Center from 1994 through 1996. Charts were identified by a computerized search of medical records under the procedure codes abdominal myomectomy and abdominal hysterectomy and the diagnosis code uterine leiomyoma. All charts identified were available for direct review. Patients were included if the abdominal myomectomy or hysterectomy was the primary procedure and not incidental to a more involved operation. Patients were excluded if the surgery involved a malignancy, pregnancy, or gynecologic infection or if it was performed on an emergency basis. The service that performed the surgery was noted (reproductive endocrinology, gynecologic oncology, general gynecology, or resident service) but was not used to exclude any patients. The Hospital of the University of Pennsylvania is an inner-city tertiary referral center; the subspecialty and general gynecology services mostly treat privately insured patients from the greater Philadelphia area, and the resident service mostly treats patients with public assistance or no insurance from the inner city. Approximately 3 times as many women underwent hysterectomy as myomectomy during this period, and none of the procedures were supracervical hysterectomies. The sample of subjects who underwent hysterectomy was selected by reviewing the chart of the first woman who had a hysterectomy performed after the date of each myomectomy identified. The patients were not otherwise matched. Institutional review board approval for this project was obtained from the committee on studies involving human beings at the University of Pennsylvania Medical Center. Information collected. The 2 groups were compared with respect to age, parity, weight, previous myomectomy, uterine size, preoperative use of gonadotropin-releasing hormone (GnRH) agonists, prophylactic use of antibiotics, presence of adhesions, surgical time, estimated blood loss, febrile morbidity, maximum postoperative white blood cell count, postoperative use of antibiotics, length of hospital stay, blood transfusions, and other complications of surgery. Uterine size was determined from examination with the patient under anesthesia;
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when this figure was unavailable, it was determined from the admission notes. Surgical time was defined as the time of skin incision to the time of skin closure. All other intraoperative procedures were recorded. Estimated blood loss was obtained from the operative notes as assessed by the surgical team. It was calculated by measuring the volume of blood in the suction containers minus the volume of irrigation used, plus the amount of blood in the sponges as determined by weight. The surgical technique used for reducing blood loss at the time of myomectomy (surgical tourniquet or vasopressin injection) was noted. The presence of adhesions was scored in a semiquantitative fashion as follows: mild (filmy and transparent), moderate (dense, bands between organs but with mobility of the organ maintained, opaque), and severe (fixation of organs to pelvic sidewall or other organs). The number of myomas removed, as documented in the pathology report, was also noted, as were the weights of hysterectomy specimens. Definition of morbidity. The largest series analyzing surgical morbidity after hysterectomy was the Collaborative Review of Sterilization study coordinated by the Centers for Disease Control.4 This study has set the standard definition for morbidity after hysterectomy, which includes the following 5 categories: febrile morbidity, hemorrhage, unintended major surgical procedures, life-threatening events, and rehospitalization. The overall morbidity associated with an abdominal hysterectomy was 42.8%. Febrile morbidity (32.3%) and hemorrhage (15.4%) accounted for most of the morbidity identified.4 A recent review of the literature demonstrated that overall morbidity has remained stable since the Collaborative Review of Sterilization study.11 Recently The American College of Obstetricians and Gynecologists published a set of gynecologic quality assurance clinical indicators for hysterectomy, including 12 indicators that address surgical morbidity.12 These 12 indicators, which are grouped into 5 categories (Table I), have been found to be 99% accurate in identifying morbidity after hysterectomy.13 We used this classification scheme to identify cases of perioperative morbidity in women who underwent either hysterectomy or myomectomy. Sample size and power. To calculate the sample size required for this study we made the following assumptions. Approximately 40% of women who undergo hysterectomy were assumed to have morbidity.4 A 15% absolute increase or decrease in the rate of morbidity was assumed to be clinically significant. With a probability of a type I statistical error (2-sided) of .05 and a probability of a type II statistical error of .1, a sample size of 173 patients who underwent each procedure would be necessary to detect that difference. To achieve that sample size we reviewed the clinical course of all women who underwent an abdominal myomectomy and an equal number of women
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Table I. Classification of perioperative morbidity associated with hysterectomy and myomectomy Morbidity indicator* Febrile morbidity Hemorrhage Unintended procedure Life-threatening events Readmission
Definition Occurrence of infection not present on admission or initiation of antibiotics >24 h after surgery Gynecologic surgery with ≥2 units of blood, postoperative hematocrit of <24%, or postoperative hemoglobin concentration of <8 g/dL Unplanned removal, injury, or repair of organ during operative procedure or unplanned return to operating room for surgery during the same admission Cardiopulmonary arrest, resuscitation, unplanned admission to special (intensive) care unit, or death Unplanned readmission within 14 d or admission after return visit to the emergency department for the same problem
Adapted from Dicker et al,4 The American College of Obstetricians and Gynecologists,12 and Gambone et al.13 *The presence of any category defines the presence of morbidity.
who underwent hysterectomy in 3 consecutive years. This resulted in our final sample size of 197 women who underwent each procedure. Data analysis. The primary outcome of this study was the percentage of women considered to have perioperative morbidity according to the previously stated criteria. The subtypes of morbidity were noted, and these subtypes were analyzed as secondary outcomes. Descriptive analyses were first conducted in the total eligible cohort to examine baseline associations and to assess whether the distributions of continuous variables were consistent with the assumption of normality required for parametric statistical tests. Comparison of women who underwent myomectomy with those who underwent hysterectomy was conducted with the independent sample t test for continuous variables and the ordinary χ2 test for categoric variables. Results for the continuous variables were confirmed with the Wilcoxon rank sum test. Associations between outcome and procedure type and between outcome and other variables were assessed with both relative risks and odds ratios. Because these measures gave similar results, only the odds ratio was estimated in subsequent multivariable logistic regression models. We performed both unadjusted and stratified analyses to determine potential confounding variables and to identify possible modifiers of the association between procedure type and outcome (interactions between procedure type and other variables; see Table IV). Multivariable logistic regression was then used to estimate the odds ratio for procedure type after adjustment for all potential confounders. Variables were included in the logistic regression model (1) if they were biologically plausible, (2) if they demonstrated P < .20 for the association with outcome in the unadjusted analyses, or (3) if adjustment for the given variable changed the odds ratio for myomectomy versus hysterectomy by ≥10%.14, 15 The assumption of linearity of the relationship between continuous variables and outcome was checked by testing significance of quadratic terms (variable squared). If the squared term was significant, the variable was categorized and fitted with a series of indicator variables. The only
variable for which the quadratic term was significant was the presence of adhesions noted at the time of surgery, which was subsequently categorized as none, mild, moderate, or severe on the basis of clinical considerations without looking at the category-specific associations with outcome. The percentage of missing data ranged from 9% (uterine size) to 0% (age, history of previous myomectomy, preoperative use of a GnRH agonist, preoperative use of antibiotics, and presence of adhesions at the time of surgery). Complete data on all variables were available for 83% of subjects. Analyses were conducted both on the subset of subjects with no missing data and after imputation of missing data with the impute command in the STATA software package (Stata Corporation, College Station, Tex), with no dramatic change in results. Results Table II shows the demographic and preoperative characteristics of the patients stratified according to the type of surgical procedure performed. Patients who underwent myomectomy were significantly younger, weighed less, were of lower parity, and had a smaller preoperative uterine size than those who underwent hysterectomy. The most common reason for surgery among the women who underwent hysterectomy was vaginal bleeding or pain, whereas reasons such as recurrent miscarriage, infertility, or enlarged uterine size without symptoms were more common indications for surgery among those who underwent myomectomy. Indications other than pain or bleeding were grouped together to allow statistical analysis. Preoperative antibiotics use was more frequent in the myomectomy group. The rates of preoperative use of a GnRH agonist were similar in the two groups. In 29% of the myomectomy procedures the endometrial cavity was entered, and on average 9.2 myomas were removed. The surgical techniques used to reduce blood loss at the time of myomectomy included the use of either a surgical tourniquet (73%) or vasopressin (14%), both of these (10%), or neither of these(3%). In only 1 case was a myomectomy converted to a hysterectomy be-
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Table II. Demographic and baseline characteristics of patients who underwent myomectomy or hysterectomy Myomectomy (n = 197) Hysterectomy (n = 197) Statistical significance Continuous variables Age (y, mean ± SD) Weight (lb, mean ± SD) Parity (mean ± SD) Preoperative uterine size (gestational wk equivalent, mean ± SD) Categoric variables (%) Preoperative use of antibiotics Preoperative use of GnRH agonists Previous myomectomy Adhesions present at surgery Indication for surgery‡ Bleeding Pain Other
36.1 ± 5.5 156.1 ± 36.5 0.5 ± 0.9 14.4 ± 5.0
43.9 ± 5.9 174.4 ± 43.7 1.6 ± 1.3 15.6 ± 4.9
P < .0001* P < .0001* P < .0001* P < .0001*
99.5% 9.1% 7.1% 36.5%
96.5% 10.2% 11.7% 43.6%
35.6% 38.7% 25.6%
61.9% 30.8% 7.3%
P = .03† P = .73† P = .11† P = .51† P < .0001† P < .0001† P = .10† P < .0001†
*By t test. †By χ2 test. ‡n = 191.
Table III. Unadjusted analysis of outcomes of myomectomy versus hysterectomy Odds ratio
Outcome
Myomectomy (n = 197)
95% Hysterectomy Confidence (n = 197) Unadjusted interval
Morbidity Overall morbidity 38.6% 40.1% Febrile morbidity 33.0% 25.9% Hemorrhage 9.6% 14.2% Unintended procedure 4.5% 9.6% Life-threatening event* 1.5% 1.0% Readmission* 1.5% 2.5% Other outcomes Operative time (min, mean ± SD) 200.9 ± 68.1 175.5 ± 56.2 Estimated blood loss (mL, mean ± SD) 226.7 ± 190.5 483.6 ± 375.8 Length of stay in hospital (d, mean ± SD) 3.96 ± 2.1 4.42 ± 2.4 Maximum white blood cell count (103 cells/µL, mean ± SD) 13.12 ± 3.7 11.67 ± 3.7 Maximum drop in hemoglobin concentration (g/dL) 2.49 ± 1.4 2.11 ± 1.2 Patients transfused (No.) 18/197 (9.1%) 25/197 (12.8%) Patients transfused with autologous blood§ 16/18 (88.9%) 13/25 (52.0%)
0.93 1.41 0.46 0.45 1.51 0.59
0.63-1.40 0.91-2.17 0.26-0.83 0.20-0.99 0.17-18.00 0.09-3.10
Statistical significance
P = .75 P = .12 P = .009 P = .049 P = 1.00 P = .72 P = .00002† P = .00001† P = .048† P = .022† P = .51† P = .25‡ P < .0001ll
*Exact P value and 95% confidence interval. †By t test. ‡By χ2 test. §This variable represents a subset of the number of subjects transfused. llBy Fisher exact test.
cause of difficulty in completing the surgical procedure. A previous myomectomy had been performed in 7% of myomectomy cases and 12% of hysterectomy cases. The average uterine weight after hysterectomy was 654.5 g. Operative complications in the myomectomy group included 1 cystotomy, 1 case of pulmonary edema, 2 smallbowel obstructions that necessitated reoperation, 6 cases of ileus, and 1 incision breakdown. Operative complications in the hysterectomy group included 1 cystotomy, 1 patient with congestive heart failure, 8 cases of ileus, 3 bowel injuries, 5 incision breakdowns (1 of which included dehiscence), 1 rectus muscle hematoma, 1 ureteral injury, and 6 pelvic abscesses.
Table III shows the results of the unadjusted analysis of morbidity and other outcomes among the women who underwent myomectomy versus those who underwent hysterectomy. The overall morbidity associated with abdominal myomectomy was similar to that of abdominal hysterectomy. There were significantly lower prevalences of hemorrhage and the performance of an unintended procedure among women who underwent myomectomy than among those who underwent hysterectomy. Febrile morbidity was more common among women who underwent myomectomy, but this trend was not statistically significant. Life-threatening events and readmissions were rare in both groups.
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Table IV. Odds ratios of morbidity among those who underwent myomectomy with respect to those who underwent hysterectomy stratified according to potential confounding variables Odds ratio Variable adjusted for Analysis on entire sample (N = 394) None (unadjusted, crude) Age† Weight† Uterine size† Previous myomectomy Parity† GnRH analog Indication Service‡ Adhesions† Preoperative antibiotics Analysis restricted to those with complete data on all variables None (unadjusted, crude) Age† Weight† Uterine size Previous myomectomy Parity† Leuprolide acetate Indication Service‡
No.
Adjusted
95% Confidence interval
Unadjusted statistical significance
394 394 384 360 394 375 394 383 393 394 394
0.94 1.01 1.02 1.21 0.97 0.95 0.94 0.99 1.02 1.03 0.93
0.63-1.49 0.61-1.64 0.67-1.55 0.78-1.87 0.64-1.45 0.59-1.52 0.63-1.41 0.64-1.55 0.65-1.58 0.68-1.56 0.62-1.40
P = .436* P = .042* P = .037* P = .72* P = .054* P = .6* P = .5* P = .3* P = .072* P = .93*
326 326 326 326 326 326 326 326 326
1.05 1.08 1.10 1.19 1.08 1.02 1.06 1.07 1.18
0.68-1.64 0.65-1.82 0.70-1.72 0.74-1.88 0.69-1.68 0.62-1.67 0.68-1.65 0.68-1.67 0.74-1.89
P = .6§ P = .085§ P = .021§ P = .57§ P = .068§ P = .21§ P = .73§ P = .79§
*P value for test of interaction. †Interaction P value tests for linear trend in log odds ratio for myomectomy versus hysterectomy across values of the continuous variable. ‡Medical service that performed the surgery—general gynecology, gynecologic oncology, reproductive endocrinology, resident service. §P value for test of heterogeneity.
Abdominal myomectomy was a lengthier procedure than abdominal hysterectomy but was associated with significantly less blood loss. Approximately equal numbers of subjects in each group required blood transfusions; among those who did, however, patients who underwent myomectomy were significantly more likely to receive a transfusion with autologous blood. The average hospital stay was significantly shorter among the women who underwent myomectomy. To examine the confounding effects of patient characteristics, surgical indication, and findings at surgery on the association between risk of morbidity and procedure type, stratified analyses were performed. A comparison of the overall morbidity between women who underwent myomectomy and hysterectomy stratified according to potential confounding variables is listed in the top half of Table IV. Adjustment for any single variable did not substantially change the unadjusted odds ratio for morbidity among women who underwent abdominal myomectomy with respect to hysterectomy; therefore none of the variables were considered to be strong confounders. The odds ratio for morbidity among those who underwent myomectomy with respect to hysterectomy was not significantly elevated after adjustment for any variable. The bottom half of Table IV restricts the same analysis to only those patients for whom a complete data set was
available. The overall odds ratio was not materially changed by adjustment for any single variable, nor was it significantly elevated among those who underwent myomectomy with respect to those who underwent hysterectomy. Table V presents the multivariable-adjusted odds ratio for overall morbidity comparing hysterectomy with myomectomy and according to each potential confounding variable. After the adjustment of all potential confounding variables the odds ratio for morbidity increased to 1.46 (95% confidence interval, 0.77-2.77) compared with the unadjusted odds ratio of 0.94 (95% confidence interval, 0.63-1.49). Although this adjusted odds ratio was not statistically significant, this trend may suggest that there were characteristics of the patients in the myomectomy group independent of the procedure performed that tended to lower the overall morbidity. For the remaining variables in Table V the odds ratio represents the association with morbidity independent of the procedure performed. Only uterine size and the presence of adhesions at the time of surgery were significantly associated with increased perioperative morbidity. Analysis of the association of severity of adhesions with morbidity demonstrated that only the presence of severe adhesions was significantly associated with increased morbidity. Nonsignificant trends noted included an in-
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Table V. Logistic regression model Odds ratio Variable Procedure Age Weight Uterine size Previous myomectomy GnRH agonist use Parity Adhesions None Mild Moderate Severe Service General gynecology Reproductive endocrinology Gynecologic oncology Resident service Indication Bleeding Pain Other
Value
95% Confidence interval
Statistical significance
1.46 1.01 1.00 1.10 1.44 1.44 1.01
0.77-2.77 0.96-1.05 0.99-1.01 1.04-1.15 0.60-3.41 0.66-3.14 0.79-1.29
P = .25 P = .72 P = .60 P = .0002 P = .41 P = .36 P = .91 P = .044
1.00 1.10 1.16 3.12
Referent 0.56-2.13 0.52-2.57 1.38-7.02
1.00 0.81 1.28 1.36
Referent 0.43-1.52 0.53-3.11 0.65-2.80
1.00 1.48 1.05
Referent 0.70-3.15 0.60-1.83
P = .78 P = .71 P = .006 P = .44 P = .51 P = .58 P = .41 P = .57 P = .31 P = .16
Table VI. Logistic regression model for overall morbidity and subtypes of morbidity comparing surgical procedure of myomectomy with hysterectomy Odds ratio
Overall morbidity Febrile morbidity Hemorrhage Unintended procedure Life-threatening event* Readmission*
Value
95% Confidence interval
Statistical significance
1.46 1.89 0.62 0.84 — —
0.77-2.77 0.97-3.72 0.24-1.63 0.25-2.81 — —
P = .25 P = .063 P = .34 P = .78 — —
*Values are not given because there were too few events to permit fitting of a multiple variable logistic regression model.
crease in perioperative morbidity among women with previous myomectomy and an increase when surgery was conducted for the indication of pain. Risk of morbidity changed only modestly depending on the surgical service, with reproductive endocrinologists having the lowest morbidity rate and the resident service having the highest morbidity rate. Table VI presents the multivariable-adjusted odds ratio of each subtype of morbidity for women who underwent myomectomy with respect to those who underwent hysterectomy. After adjustment for confounding variables none of the morbidity subtypes differed significantly between the myomectomy and hysterectomy groups, although there was a trend toward a higher incidence of febrile morbidity among those who underwent myomectomy. There were not enough cases of life-threatening events or readmission to permit appropriate statistical analyses.
Comment Many women have to face the decision between myomectomy and hysterectomy for the treatment of symptomatic leiomyoma. They rely heavily on their physicians to inform them of the risks and benefits associated with these surgical options. Although there are no controlled trials in the literature that demonstrate that abdominal myomectomy is associated with greater morbidity than hysterectomy, some gynecologic educational bulletins, textbooks, and review articles support this assertion.3, 9, 16 Febrile morbidity and hemorrhage have been the most common complications noted to be increased after myomectomy with respect to hysterectomy.10, 16-21 The results of our study do not support this conclusion. Previous case series have lacked control groups and have used different definitions of morbidity, which makes comparisons difficult. We chose to rigorously define morbidity according to a standardized and validated system13
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that used The American College of Obstetricians and Gynecologists quality assurance indicators as outcome variables grouped according to the categories used in the Collaborative Review of Sterilization study. Several recent case series have suggested that abdominal myomectomy is a safe procedure with acceptable morbidity.10, 16-21 This is the first study to use a such a rigorous definition of morbidity to evaluate abdominal myomectomy and should allow accurate comparisons between institutions and with future studies. Only one previous study, that of Iverson et al,10 directly compared the morbidity associated with abdominal myomectomy with that of hysterectomy, and it found that myomectomy was associated with no greater risk of blood loss or febrile morbidity and with no significant differences in other morbidity variables. Similar to that study, we found that myomectomy was associated with less operative blood loss but that this finding lost statistical significance after multivariable logistic regression analysis with correction for uterine size. Both studies demonstrated that uterine size was an independent risk factor for morbidity in either procedure, consistent with the findings of other studies.18 We saw a trend toward higher febrile morbidity in the myomectomy group, whereas Iverson et al10 found a trend toward higher febrile morbidity in the hysterectomy group. It is interesting that a recent reanalysis of their data including the first 48 postoperative hours found a significantly higher rate of fever in the myomectomy group.22 The original study by Iverson et al10 did not report a sample size calculation and has the potential for insufficient power to detect a significant difference in morbidity. Our study had >90% power to detect a 15% difference in morbidity. To our knowledge this is the largest comparative study of these 2 procedures in the literature, and it is the first to document adequate power to detect a clinically significant difference. The American College of Obstetricians and Gynecologists Technical Bulletin on uterine leiomyoma states, “Although intraoperative blood loss, operative time and risk for postoperative hemorrhage appear to be slightly higher than with hysterectomy, these risks are somewhat offset by the lower rates of infectious morbidity and ureteral injury associated with myomectomy.”3 Although we did see a statistically significantly longer operative time and a nonsignificant trend toward less operative injury, we were not able to demonstrate more blood loss or lower infectious morbidity associated with myomectomy. Iverson et al10 found no differences in operative time, blood loss, hemorrhage, or infectious morbidity after they controlled for uterine size. It is possible that the high uses of tourniquets in our study (83%) and vasopressin in the study by Iverson et al10 (95%) significantly reduced the risk of hemorrhage previously ascribed to abdominal myomectomy. Our estimated blood loss from myomec-
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tomy was 226 mL, and only 9% of our patients had hemorrhage necessitating transfusion. Transfusion has been reported to be necessary in as many as 52% of cases in other series.10, 16-21 Two studies reported a statistically significant reduction in operative blood loss during myomectomy when a tourniquet or vasopressin injection was used,17, 23 and another study found vasopressin injection and tourniquet use to be equally effective in controlling blood loss.18 Some authors have suggested that the preoperative use of GnRH agonists reduces operative blood loss,21 whereas others have not demonstrated any benefit.20 The rate of use of GnRH agonists among the women who underwent myomectomy in our study was low (9.1%) and similar to the rate in the hysterectomy group (10.2%), and GnRH agonist use is therefore unlikely to have been a confounding factor. It appears that previous concerns regarding the increased risk of operative blood loss with myomectomy have been tempered by the modern use of adjuvant measures to reduce hemorrhage. We also demonstrated that women who underwent myomectomy were different from those who underwent hysterectomy. Women who elected to undergo myomectomy were approximately 8 years younger, had fewer children, and were less likely to have the surgery performed for the indication of vaginal bleeding. These differences probably reflect the desire among younger and less parous women to preserve fertility even with significant uterine pathologic conditions. In addition, myomectomy is commonly offered to women who wish to preserve future fertility, whereas hysterectomy is commonly offered to treat vaginal bleeding after a woman has completed childbearing. Other differences between the 2 groups were that women who underwent hysterectomy were approximately 18 lb heavier, had a slightly larger preoperative uterine size, and were less likely to receive preoperative antibiotics. The clinical significance of these differences is doubtful, because the absolute differences between the two groups in these variables were small. The absolute difference in uterine size between the 2 groups was only slightly more than the equivalent of 1 week of gestation (14.4 vs 15.6 weeks’ gestation equivalent) and was certainly within the range of error for a bimanual examination. More than 96% of all women who underwent a surgical procedure received preoperative antibiotics, which means that the statistically significant difference between groups is unlikely to have been clinically significant. The differences between women in the 2 groups were adjusted for by means of multivariable analysis. After adjustment, the odds ratios for overall morbidity and febrile morbidity among women who underwent myomectomy with respect to those who underwent hysterectomy did increase but still were not statistically significant. In light of the width of the confidence interval (upper confidence
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limit of 2.77 for the odds ratio) we are unable to completely rule out a clinically important difference in morbidity between the groups. In addition, after adjustment the odds ratios for hemorrhage and the occurrence of an unintended procedure were no longer significantly lower among women who underwent myomectomy. These trends demonstrate that, although only uterine size and the presence of severe adhesions were significantly and independently associated with surgical morbidity, in aggregate women who underwent myomectomy in this study period were at lower surgical risk than were those who underwent hysterectomy. It is important that after adjustment for these factors the morbidity detected among women who underwent myomectomy was not significantly higher than among women who underwent hysterectomy. Our study design restricted our analysis to intraoperative and short-term postoperative morbidity. Other important considerations, such as long-term morbidity, recurrence, and success in alleviating symptoms were not addressed, because such was not the goal of this study. In conclusion, we did not find any evidence to suggest that abdominal myomectomy was associated with a clinically significantly elevated risk of morbidity with respect to abdominal hysterectomy performed for the same diagnosis. Although every case is unique and factors other than short-term morbidity should also be addressed, myomectomy should be considered a safe alternative to hysterectomy for the treatment of uterine fibroids. REFERENCES
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