The accumulation of evidence suggesting the fallopian tube as the site of origin for the majority of epithelial ovarian cancers provides promise that salpingectomy may be an effective prevention strategy.1,2 Both the Society of Gynecologic Oncology and the American College of Obstetricians and Gynecologists have published statements supporting consideration of salpingectomy at the time of benign gynecologic surgery based on population data that suggest significant ovarian cancer risk reduction.3,4 Multiple studies have reported the safety and feasibility of salpingectomy at the time of hysterectomy, with no difference in operative time or complications.5,6
Sterilization at the time of cesarean delivery is an ideal opportunity to increase the utilization and potential effect of salpingectomy. Approximately 650,000 postpartum sterilizations are performed annually, the majority at the time of cesarean delivery.7,8 However, this setting for complete salpingectomy is not well studied prospectively and theoretical concerns exist regarding the potential for longer operative time and higher rates of complications given the increased blood flow to the gravid uterus. A retrospective cohort study reported no increase in complications, but found a longer total operative time when salpingectomy compared with standard tubal ligation was performed at the time of cesarean delivery.8
We designed a prospective randomized controlled trial to assess whether salpingectomy compared with standard tubal ligation at the time of cesarean delivery results in increased sterilization procedure time. Secondary outcomes included successful completion of salpingectomy, total operative time, blood loss, and postoperative complications.
MATERIALS AND METHODS
We conducted a randomized controlled noninferiority trial to assess operating time for sterilization procedures at the time of cesarean delivery. Women undergoing planned cesarean delivery and sterilization at the University of Virginia Medical Center were screened for eligibility on presenting to the labor and delivery unit. Eligibility criteria included age older than 21 years, a primary language of English or Spanish, and ability to provide informed consent. Women were excluded if they had a known placenta accreta, a known congenitally or surgically absent fallopian tube, required cesarean delivery after experiencing labor, or had a known hereditary cancer syndrome.
Randomization was performed in a one-to-one ratio using a random number generator with Microsoft Excel. This was completed by a member of the clinical research staff and the assignments were then transferred to numbered, sealed opaque envelopes. After written informed consent, enrolling physicians then opened the envelopes and revealed the intervention group, either standard tubal ligation or salpingectomy. Assignment was not blinded to either the physician surgeon or the study participant.
The method of standard tubal ligation procedure (Pomeroy or Parkland method) was at the discretion of the attending physician. All standard tubal ligation procedures were performed with suture and without any occlusive or cautery devices. Salpingectomy procedures were performed with the Covidien small jaw LigaSure device. All health care providers on labor and delivery underwent a training session on use of this device and the method for performing salpingectomy before study initiation.
The sterilization time was recorded as starting when the first fallopian tube was identified and grasped and as ending when the procedure had been completed bilaterally and hemostasis from the sterilization was achieved. This was called out by a member of the surgical team and recorded by an operating room nurse. Additionally, total surgical time was recorded from the time of skin incision to the time of completed skin closure. Salpingectomy completion rates for each group were determined by the number of salpingectomies performed in women randomized to salpingectomy. Demographic variables and clinical outcomes were collected from the electronic medical record. Change in hematocrit was assessed using a preoperative value (obtained 1 day before or on the day of surgery) and a postoperative day 1 value. Infection was defined as documented infection in the medical record and treatment with either intravenous or oral antibiotics. Postdischarge complications were assessed at either the routine postpartum clinic visit or by telephone if the patient did not attend the follow-up visit.
The primary outcome was a per-protocol analysis of sterilization procedure time. Literature estimates for tubal sterilization time during cesarean delivery were not available. Thus, all standard tubal ligation procedures during cesarean delivery were timed for a 2-month period before study initiation to derive estimates of the average time and SD. Using these data, an average sterilization time of 5 minutes with an SD of 5 minutes was used. The noninferiority margin was set at 5 minutes for salpingectomy given this was outside 1 SD and deemed a clinically significant difference in procedure time. Using a noninferiority design with a one-sided independent-sample t test, to achieve a power of 90% with an α of 0.05, 18 women needed to complete each intervention.
Secondary outcomes were assessed with t tests or Wilcoxon rank-sum tests for continuous variables and χ2 or Fisher exact tests for categorical variables as appropriate. Statistical analysis was performed with SAS 4.0, with a P value of .05 determining significance. The study was approved by the University of Virginia institutional review board for Health Sciences Research (19517) and registered on clinicaltrials.gov (NCT 03028623).
From May 2017 to January 2018, there were 44 women enrolled and randomized. During this time period, 81 women planned to undergo cesarean delivery and sterilization. Within this group, two women did not meet eligibility criteria, 17 were not approached, and 18 declined to participate in the study. Of the 22 women randomized to each intervention, 19 salpingectomies and 20 standard tubal ligations were performed. The final analysis included 19 salpingectomies and 18 standard tubal ligations (Fig. 1).
Bilateral salpingectomy was successfully completed in 95% (19/20, 95% CI 0.75–0.99) of the women assigned to the intervention who underwent a sterilization procedure. One procedure was converted to standard tubal ligation as a result of adhesions, although this participant was not included in the final analysis as a result of failed recording of procedural time. In the three total patients in whom time was not recorded, the times were called out by the surgical team and not recorded by operating room staff. Two women in the salpingectomy group underwent hysterectomy for unsuspected placenta accreta with no additional tubal sterilization performed.
The intervention groups were balanced with regard to demographic and clinical characteristics (Table 1). Salpingectomy procedure time was noninferior to standard tubal ligation, with a mean difference of 0.5 minutes, with a mean sterilization procedure time of 5.6 minutes in the salpingectomy group and 6.1 minutes in the standard tubal ligation group (P<.05, one-sided 95% CI upper bound 1.8 minutes) (Fig. 2; Table 2). Total operative time was not different between intervention groups, with a median time of 60 minutes for cesarean delivery with salpingectomy compared with 68 minutes for cesarean delivery with standard tubal ligation (P=.34) (Table 2). The majority of surgeries were performed by a junior and senior resident with attending supervision in both groups (68% salpingectomy vs 83% standard tubal ligation, P=.45). The remaining procedures were performed jointly by a single resident and attending physician. The primary outcome of tubal procedure time was stratified by whether there was a junior and senior resident pair or resident and attending pair. There remained no difference in tubal procedure time between the salpingectomy and standard tubal ligation cohorts in the stratified subanalysis (resident pair 5.8 vs 5.7 minutes, P=.88; resident and attending pair 5.0 vs 7.9 minutes, P=.22).
There was also no difference in estimated blood loss, change in hematocrit, need for transfusion, wound infection, length of stay, or readmission between the two intervention cohorts (Table 2). Surgical pathology was reviewed for all tubal specimens. The only abnormalities noted were a benign paratubal cyst in a patient undergoing salpingectomy and a benign adenomatoid tumor in a patient undergoing standard tubal ligation.
This trial demonstrates that salpingectomy is noninferior to standard tubal ligation during cesarean delivery with respect to procedural time. Salpingectomy was completed in 95% of participants. This was accomplished in the context of an academic training program and a population with a median body mass index (calculated as weight (kg)/[height (m)]2) of 37.
Although there is suggestive evidence from large retrospective cohort studies, the ovarian cancer risk-reduction benefit of salpingectomy remains theoretical, with the true degree of benefit unknown.2,9 Madsen et al9 report a 42% ovarian cancer risk reduction for salpingectomy compared with 13% for tubal ligation in a large Danish case control study. Greater benefit has been shown for bilateral salpingectomy, with up to 65% decrease in risk reported by Falconer et al2 in a large Swedish cohort. Benefits of salpingectomy extend beyond that of cancer prevention. Although pregnancy rates after standard tubal ligation (through postpartum partial salpingectomy) are the lowest of any method, failures do occur.10 Because complete salpingectomy is more extirpative, it may be more effective because pregnancies after bilateral complete salpingectomy are limited to case reports.11–13 Given the potential advantages of complete salpingectomy, introduction into standard practice should follow as long as harms are not increased.
Although limited by small numbers, there was no apparent increase in complications in the current study. Notably, there was no need for transfusion or reoperation in the salpingectomy cohort. A large retrospective cohort study including more than 6,000 sterilizations at the time of cesarean delivery also did not demonstrate any difference in complication rates between salpingectomy and tubal ligation. This included 206 salpingectomies and total operating time was 9.5 minutes longer compared with cesarean delivery with tubal ligation.8 This study did not report on sterilization procedure times, and approach of salpingectomy was nonstandardized using either sutures or bipolar cautery. In another study, neither operating time nor complication rates were increased in 149 cesarean sterilization procedures that included 50 salpingectomies after a practice change of instituting salpingectomy at a tertiary medical center in Israel.14
Another theoretical harm is whether there is a greater decrease in ovarian reserve compared with standard tubal ligation. This has been evaluated during cesarean delivery, with a trial of 46 patients demonstrating no difference in anti-Müllerian hormone levels between salpingectomy and standard tubal ligation 6–8 weeks after surgery.15 Long-term effects remain unknown.
Given the low rate of serious complications that would require a large population to detect a significant difference, the current study was powered based on an outcome of sterilization operating time. Because prior studies have assessed total operating time, the aim of this study was to specifically determine whether the method of the tubal sterilization procedure itself added length to the case. A LigaSure device was used in this study, which may contribute to the high success rate and short sterilization procedure times. Other techniques using clamps and suture ligature have been described with a 91% success rate.16
Limitations of the current study include the small sample size, making it difficult to adequately assess for differences between groups in infrequent outcomes. Although groups appeared similar, there were more resident and attending pairs in the salpingectomy compared with the standard tubal ligation group, which could theoretically affect times and outcomes. However, in a stratified analysis of the primary outcome based on staffing, there remained no difference in tubal procedure time. In addition, all procedures were performed with the LigaSure device and cost-effectiveness of this method has not yet been evaluated. The cost of the LigaSure device, which is a one-time use instrument, was $439.
In conclusion, salpingectomy for sterilization during cesarean delivery was successfully completed in 95% of participants, and the salpingectomy procedure time was noninferior to standard tubal ligation with no apparent increase in complications. These promising results support the safety and feasibility of replacing standard tubal ligation with bilateral salpingectomy at the time of planned cesarean delivery.
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