A less invasive transcervical approach to permanent birth control is making something of a comeback--with one new method already FDA-approved and others waiting in the wings.
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A less invasive transcervical approach to permanent birth control is making something of a comebackwith one new method already FDA-approved and others waiting in the wings.
For some 11 million American women, tubal sterilization is currently the birth control method of choice. Of the estimated 700,000 bilateral tubal sterilizations performed annually in the United States, 50% are ambulatory interval procedures (i.e., not related in time to a pregnancy).1 And of these, nearly nine out of every 10 are performed laparoscopically.2 Conventional incisional approaches to interval sterilization such as laparoscopy and minilaparotomy are safe for most women. But they do carry risks associated with general anesthesia andalbeit rarelycan cause vascular damage, injury to the bowel, bladder, or uterus, or result in unintended laparotomy.3 Laparoscopic tubal sterilization may also cause postoperative pain and necessitate a multi-day recovery, possibly leading to reduced satisfaction with and acceptability of this elective procedure.
A transcervical approach to tubal sterilization, on the other hand, offers a nonincisional alternative requiring no general anesthesia that can be readily adapted to an outpatient or office setting. Benefits of this less invasive approach include reduced postprocedure pain, allowing a patient to resume normal activities more quickly. A transcervical approach could be especially valuable for those women for whom laparoscopic surgery is contraindicated. Examples are obese women, those with severe cardiopulmonary dysfunction or diaphragmatic hernia, or patients who've previously undergone abdominal/pelvic surgery.
Possible advantages of the transcervical approach were suspected as long ago as the 1970s and early 1980s when concerted efforts were made to develop widely applicable transcervical sterilization methods. Until recently, the potential of this approach has remained unfulfilled. In the past few years, recent technological innovations seem to be converging with improved hysteroscopic techniques, instrumentation, and training to rekindle interest in hysteroscopic sterilization. Many feel this approach warrants a second look.
Recently the Association of Reproductive Health Professionals (ARHP) met to identify current efforts to develop transcervical sterilization procedures.4 Historically, hysteroscopic sterilization methods have been based on three main strategies for blocking the fallopian tubes: (1) mechanical occlusive devices or plugs to block the oviduct, (2) injection techniques for the delivery of sclerosing substances or tissue adhesives, and (3) destruction of the interstitial portion of the oviduct by thermal energy. Although thermal destruction has been abandoned, as detailed in the ARHP proceedings, both occlusive and chemical approaches are still being pursued. My goal in this article is to review the state of development of transcervical hysteroscopic approaches.
The Essure micro-insert (Conceptus, Inc., San Carlos, Calif.) has recently (November 4, 2002) been approved by the Food and Drug Administration. The method is already used routinely in Australia, the European Union, Canada, and Singapore.
The safety and efficacy of the micro-insert has been rigorously studied in a total of almost 750 women in prospective, international, multicenter, single-arm Phase II and pivotal trials. In both of these studies, the micro-insert placement procedure was well-tolerated and resulted in rapid recovery, high patient satisfaction, and effective permanent contraception.
I've had extensive experience with this technology in my role, along with Prof. John F. Kerin of the University of Adelaide and Ashford Hospital, Adelaide, South Australia, as a principal investigator in the Phase II and pivotal clinical trials of the device. The results of both trialsheld at clinical sites in the US, Australia, Spain, the United Kingdom, and Belgiumhave been submitted for publication. Dr. Kerin has already published his single-center experience with the Essure device during the Phase II trial.5
Design of the micro-insert. This occlusive device consists of a flexible stainless steel inner coil, an expandable outer coil made of nickel titanium alloy (Nitinol), and a layer of polyethylene terephthalate (PET) fibers running along and through the inner coil (Figure 1). Medical devices composed of Nitinol are not new, having been implanted in humans since the early 1980s and used in vascular and nonvascular stents since the early 1990s. PET (Dacron) fibers have been in widespread clinical use, primarily as vascular grafts, for more than 40 years.
The 4-cm-long micro-insert is delivered through the 5F (1.7-mm internal diameter) operative channel of a standard 5-mm outer diameter hysteroscope. Physiologic saline is used to distend the uterine cavity. The micro-insert delivery system is attached to a handle that permits one-handed release of the intratubal device. To improve access to the fallopian tube, the micro-insert is maintained in a wound-down configuration (that is, its pre-expanded diameter of 0.8 mm) by a narrow release catheter, which is itself inserted by using a release catheter sheathed in a hydrophilic delivery catheter.
Aided by a guidewire attached to the device's inner coil, the insert attains its ideal positioning when 5 to 10 mm of the trailing end of the micro-insert is visible at the ostium. When disengaged from the release catheter, the outer coil of the micro-insert expands up to 2.0 mm in diameter to span the intramural and proximal isthmic portions of the fallopian tube. This expansion anchors the device in the tubal lumen at the utero-tubal junction (Figure 1).
The PET fibers elicit an initial moderate foreign-body inflammatory reaction, which peaks between 2 and 3 weeks. Over the next 3 months, the PET fibers cause localized tissue ingrowth from the surrounding tubal wall into and around the device; that completely occludes the tubal lumen and permanently anchors the micro-insert.6 The tissue response is confined to the region of the tube where the device has been placed and does not involve the serosal surface or the tubal mucosa distal to the device.6 After bilateral device placement is achieved, a woman is required to continue on an alternative form of contraception for 3 months and until complete tubal occlusion is confirmed with the performance of a hysterosalpingogram (HSG). Only at this point can the woman discontinue her alternative contraceptive method. For a small percentage of women, it takes between 3 and 6 months postprocedure for the tubal lumen to become completely occluded.
Placement success rate. In the past, a major obstacle to hysteroscopic tubal sterilization has been a low bilateral placement or occlusion rate.7 Placement failure can result from several circumstances: unsuspected intrauterine or tubal pathology, unremitting tubal spasm, laterally positioned tubal ostia, endometrial bleeding or fragmentation, or device expulsion.7 In contrast to earlier attempts, the participating investigators in both Essure clinical trials achieved a high bilateral placement rate. In the Phase II study, bilateral micro-insert placement was successful in 88% of women, while in the larger pivotal trial, it was ultimately successful in 464 (92%) of 507 women.
The chief cause of placement failure was stenotic or previously occluded tubes. The second most common anatomic cause was compromise of the visual field by the endometrium. Of the women in the pivotal trial for whom bilateral devices could not be placed, 18 elected to undergo a diagnostic HSG as a prerequisite to possibly reattempting the procedure. HSG findings identified 15 of these 18 women as already sterile. Even though 14 of the 20 pivotal trial investigators had no previous experience with the micro-insert, all participating physicians achieved high success rates. Training for placement of the device includes a 1-day instructional session, practice with device placement in a uterine simulator, three to five proctored cases, and five assisted cases.
Typically, the procedure can be completed in 30 minutes. In the pivotal trial, the time elapsed from hysteroscope insertion to its removal averaged 13 minutes. Following the procedure, women were quickly discharged from the recovery room (on average, after 44 minutes). Average time from arrival to discharge from the facility was 80 minutes. In contrast, laparoscopic tubal sterilization requires on average 4 to 5 hours of hospital recovery time.8,9
A chief attraction of this technique is the high marks it receives from both patients and participating physicians. In the pivotal trial, local anesthesia with or without IV sedation was used in all but one case. Most women reported that the pain they experienced during the procedure was either the same or less than expected, and 90% rated tolerance of the placement procedure as "good to excellent." More than two thirds rated the postprocedure pain during recovery as mild or nonexistent, and only 24% of patients requested a prescription for narcotic-type analgesics afterwards.
Women were able to resume normal activities quickly. In the pivotal trial 60% of women said they returned to normal function within 1 day or less, and more than three quarters had resumed normal activities by day 2. Roughly nine of 10 (92%) women had returned to work in 1 day or less. In contrast, women undergoing laparoscopic tubal sterilization can require up to 6 days postsurgery to resume regular activities and an average of 3 days to return to work.8-10
Following the procedure, vaginal bleeding was usually reported as light flow or spotting, persisting an average of 3 days. Although roughly one in three women said they had pain during the first postprocedure day, almost no one did on subsequent days.
Effectiveness and tolerability. Long-term tolerance of the micro-insert was closely evaluated, through both interviews and diaries kept by the women. At follow-up visits, women consistently rated their tolerance for wearing the micro-insert device as "high." In the pivotal trial, 99% of women at all follow-up visits rated comfort as "good to excellent." More than 98% of women were "satisfied" or "very satisfied" at all follow-up visits.
Three months after micro-insert placement, correct device placement and bilateral tubal occlusion could be confirmed in 96% of women participating in the pivotal trial. No pregnancies have been reported in either the Phase II or pivotal trials, which taken together have now amassed more than 10,000 women-months of follow-up. Women in the pivotal trial will be followed for 5 years to determine long-term efficacy.
Another transcervical sterilization approach is being developed by Adiana, Inc. (Redwood City, Calif.), but this technology is at an earlier stage of development than Essure (Figure 2). Clinical trials to demonstrate efficacy were initiated late last year and enrollment is expected to be completed by early 2004. In the two-step procedure, a superficial lesion in the surface epithelium is first created in the intramural portion of the fallopian tube using low-level bipolar radiofrequency energy. Then a porous nonbiodegradable matrix implant constructed from medical-grade silicone is placed into the tubal lumen. Like Essure, the Adiana implant is designed to encourage tissue ingrowth to occlude the fallopian tube. The company has completed studies demonstrating the ability of this procedure to occlude fallopian tubes as determined by (a) HSG, (b) an in vitro-dye-pressure test, and (c) histological analysis of the implant. A small number of women who wore the devices for up to 12 weeks reported little or no discomfort.
Currently under development at Biomedical Engineering Solutions, Inc., the Intratubal Ligation Device (ILD) is still in the preclinical research stage. This device consists of triple-layer co-axial catheters in which the retracted tip of the inner lumen forms a deflated balloon, the middle lumen houses an O-ring, and the outer lumen is designed to deploy the O-ring over an invaginated tissue pedicle. It is anticipated that this device will be inserted either hysteroscopically or by blind placement. Once the device is positioned in the ampullary region of the fallopian tube, the balloon of the inner catheter, which is coated with adhesive, is extended beyond the leading edge of the middle catheter lumen, and inflated. The coated balloon adheres to the fallopian tube lumen. When it is withdrawn back into the tip of the middle catheter lumen, it produces an invagination of the fallopian tube wall. The O-ring is pushed over the tissue with the outer actuator sleeve, creating a sphincter that provides temporary occlusion of the fallopian tube. Formation of scar tissue at the site of the sphincter is necessary to create permanent tubal occlusion.
A concept still in the research and development stage at Berkeley Applied Science and Engineering (San Francisco, Calif.) is that of a reversible tubal occlusion device. The goal is to design this nickel-titanium stent to provide enough radial strength to occlude the fallopian tube and to do so with minimum tissue injury, so that reversal, if desired, would be an option.
Recent clinical trials have clearly demonstrated that hysteroscopic tubal sterilization can result in minimal pain, rapid recovery, and high patient satisfaction, while affording effective permanent birth control. With the recent FDA approval of Essure, the promise of a transcervical hysteroscopic approach has become a reality.
Although adequate hysteroscopic skills are essential to cannulate and manipulate the micro-insert within the tubal lumen, the procedure is among the simplest of operative hysteroscopic interventions. After receiving appropriate training, nine out of 10 physicians in Australia described the placement procedure as either "simple" or "moderately simple."
Hysteroscopic sterilization has a notable limitation: It may be impossible to place the micro-inserts bilaterally in up to one in 10 women; anatomical impediments or unsuspected intrauterine or tubal pathology is most often offered as an explanation. Nevertheless, hysteroscopic sterilization could provide an attractive option for women, especially those who are poor candidates for laparoscopy, because the transcervical route eliminates the risks of general anesthesia and incisional surgery. In the Essure micro-insert clinical trials, obese women and those with prior abdominal or pelvic surgery or both had very high bilateral placement rates. Other women likely to be poor candidates for incisional surgery, such as those taking warfarin or with multiple sclerosis, also had successful micro-insert placement. When considering the placement failure rate, one must keep in mind that physicians do not offer laparoscopic tubal ligation to every woman who requests it, due to peritoneal access issues and the perceived risks of complications.
The avoidance of general anesthesia and an invasive incisional procedure makes hysteroscopic tubal sterilization suitable for a broad range of women and could increase the overall use of tubal sterilization. Few would deny that more contraceptive options are neededand hysteroscopic permanent birth control represents a promising new option. I anticipate that the availability of this approach will further emphasize the usefulness of hysteroscopy in ob/gyn practice.
In the early 1970s, gynecologists widely adopted laparoscopy because it made tubal sterilization easier. Just as laparotomy gave way to laparoscopy some three decades ago, so too might hysteroscopy supplant laparoscopy in the next 10 years as the preferred method for tubal sterilization.
Dr. Cooper is a shareholder in Conceptus, a publically traded company.
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Jay Cooper. New approaches to hysteroscopic sterilization.