Transcervical Sterilization: Past, Present, and Future Tony Ogburn, MD * , Eve Espey, MD, MPH Department of Obstetrics and Gynecology, MSC 10-5580, 1 University of New Mexico, Albuquerque, NM 87131-5286, USA Sterilization is one of the most common forms of contraception in the United States (US), used by 18% of reproductive-aged women currently us- ing contraception [1]. Only oral contraceptive pills, used by 19% of women contraceptors in the US, are more commonly used. It is estimated that over 10 million reproductive-aged women have been sterilized in the US [2]. Female sterilization is typically performed by way of minilaparotomy in the postpartum period or via laparoscopy for interval procedures. When performed via laparotomy, sterilization techniques usually involve the re- moval of a segment of tube for pathologic examination and confirmation of complete resection. Laparoscopic tubal sterilization became widespread in the 1970s and remains the most common approach for female steriliza- tion. Various techniques include cautery, bands, and clips. All are highly ef- fective with typical failure rates of less than 1% [3]. Though tubal sterilization by minilaparotomy or laparoscopy is safe and effective, several disadvantages are associated with the transabdominal ap- proach. Both techniques are usually performed in an operating room and require general or regional anesthesia. Serious complications that occur in approximately 1% of laparoscopic tubal sterilizations and may be cata- strophic include anesthetic complications and vascular or intestinal injuries [4]. Patients who are morbidly obese or have coexisting serious medical con- ditions may be poor candidates for sterilization by either of these approaches. Transcervical sterilization is an alternative to the transabdominal ap- proach and has several benefits. The transcervical approach has been in- vestigated for many years with various materials and techniques used to occlude or block the tubes. Access to the tubes is most often through the * Corresponding author. E-mail address: [email protected](T. Ogburn). 0889-8545/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.ogc.2007.02.003 obgyn.theclinics.com Obstet Gynecol Clin N Am 34 (2007) 57–72
Tony Ogburn, MD*, Eve Espey, MD, MPHDepartment of Obstetrics and Gynecology, MSC 10-5580,
1 University of New Mexico, Albuquerque, NM 87131-5286, USA
Sterilization is one of the most common forms of contraception in theUnited States (US), used by 18% of reproductive-aged women currently us-ing contraception [1]. Only oral contraceptive pills, used by 19% of womencontraceptors in the US, are more commonly used. It is estimated that over10 million reproductive-aged women have been sterilized in the US [2].
Female sterilization is typically performed by way of minilaparotomy inthe postpartum period or via laparoscopy for interval procedures. Whenperformed via laparotomy, sterilization techniques usually involve the re-moval of a segment of tube for pathologic examination and confirmationof complete resection. Laparoscopic tubal sterilization became widespreadin the 1970s and remains the most common approach for female steriliza-tion. Various techniques include cautery, bands, and clips. All are highly ef-fective with typical failure rates of less than 1% [3].
Though tubal sterilization by minilaparotomy or laparoscopy is safe andeffective, several disadvantages are associated with the transabdominal ap-proach. Both techniques are usually performed in an operating room andrequire general or regional anesthesia. Serious complications that occur inapproximately 1% of laparoscopic tubal sterilizations and may be cata-strophic include anesthetic complications and vascular or intestinal injuries[4]. Patients who are morbidly obese or have coexisting serious medical con-ditions may be poor candidates for sterilization by either of these approaches.
Transcervical sterilization is an alternative to the transabdominal ap-proach and has several benefits. The transcervical approach has been in-vestigated for many years with various materials and techniques used toocclude or block the tubes. Access to the tubes is most often through the
cervix and uterus using hysteroscopy for direct visualization, or by blindplacement of materials into the uterus.
Potential advantages to the transcervical approach are many. Because in-cisions are not used with this approach, major complications, such as vascu-lar or bowel injury, are avoided. Recovery may be shorter and less painful.Transcervical sterilization can usually be performed using only local anes-thesia and/or sedation, making anesthetic complications a rarity, as wellas reducing the costs associated with anesthesia. Such procedures may beperformed in an office setting, further reducing overall costs and increasingconvenience for patients and practitioners. Patients who may not be goodcandidates for laparoscopic sterilization, including the morbidly obese andthose who have major medical conditions, may be good candidates fortranscervical sterilization.
Disadvantages to the transcervical approach include a delay to sterilityand the need for a test to document that the tubes are blocked. With thetransabdominal approach, sterilization is immediately effective. Special andexpensive equipment may be necessary and providers need specific trainingto master the techniques. Because the techniques are new, long-term comp-lications may arise that are not currently identified.
In this article, the history of transcervical sterilization techniques are re-viewed as well as the current Food and Drug Administration (FDA)-approved method, Essure (Conceptus Inc., San Carlos, California), andother methods that are under investigation or used internationally.
History of transcervical sterilization
The transcervical route for female sterilization has been considered sincethe mid nineteenth century. One of the earliest reports was in 1849 whenchemical cautery was reported with instillation of silver nitrate into theuterus [5]. As early as 1878, electrocautery was reported as a potentialway to block the proximal portion of the tube [6]. Additional reportsfrom the early 1900s commonly described chemical and electrical cauteryprocedures [7–9].
Hysteroscopy was first described as a diagnostic tool in 1869 [10] and wasused to gain access to the tubes in some of the earliest reports of transcer-vical sterilization. The use of distending media, such as CO2, enabling bettervisualization of the endometrial cavity in the 1920s, fostered increased inter-est in this approach [11]. Despite improved visualization, these techniquesfell from favor because they were plagued by high failure rates and associ-ated morbidities.
The development of fiber optics allowed laparoscopy to become the pre-dominant method of female sterilization in the 1960s and 1970s. This tech-nology also allowed improved visualization of the endometrial cavity withhysteroscopy. Technical improvements in hysteroscopy combined with the
59TRANSCERVICAL STERILIZATION: PAST, PRESENT, AND FUTURE
desire to develop a safe, effective, and less-invasive form of female steriliza-tion resulted in a renewed interest in the transcervical approach.
Many approaches have been described, including instillation of sclerosingagents, thermal occlusion, and mechanical occlusive devices. These tech-niques may be performed either blindly or with hysteroscopic guidance.Though several methods held promise, until recently, none provided thecombination of efficacy, safety, and feasibility needed to become widely ac-cepted as a means of female sterilization.
Mechanical methods
Various mechanical methods have undergone human trials. Preformeddevices placed under direct hysteroscopic visualization include the hydro-gelic plug [12], Hamou’s intratubal device [13], and the Craft ceramic plug[14]. Several reports describe silicone plugs formed in situ in the tube. Oneof the more notable is the Ovabloc (Fame Medical Products, Nijmegen,Netherlands) system that uses liquid siloxane injected under direct hystero-scopic visualization into the tube. The liquid polymerizes forming a siliconeplug that blocks each tube. Silver is added to the mixture to make the plugsvisible on radiograph. Though success rates approached those obtained withstandard laparoscopic procedures, reports of pelvic pain, plug fracture andmigration, extravasation of the silicone liquid into the peritoneal cavity, andperforation of the uterine wall made this technique less desirable [15,16].Also the authors reported that tubal spasm precluded completion of the pro-cedure in up to 20% of cases. The most recent study of the technique wasperformed in Belgium in 1999 and involved 392 women [17]. Placementwas unsuccessful in 17% of women, and plug retention, as determined byradiograph, occurred in 93.8% of the women in whom it was successfullyplaced. The Ovabloc is currently available in the Netherlands and Belgium,but no efforts have been made for FDA approval in the US.
Thermal methods
Various thermal methods of tubal occlusion have been described. Afterthe first report in 1916 [9], only sporadic interest in transcervical thermaltubal sterilization occurred until the 1970s when improved hysteroscopictechnology sparked renewed interest in electrocoagulation of the tubes forsterilization [18,19]. Reports of high failure rates and significant morbidity,such as bowel injury and in associated with the procedures, resulted in aban-donment of this approach [20,21].
Sclerosing methods
Chemicalmethods are appealing as ameans of sterilization because they of-fer the best hope for amethod that canbe performedblindlywith a nonsurgical
60 OGBURN & ESPEY
approach. Several obstacles have impeded the development of many of thesemethods. The substances are caustic, and spillage through the tubes andinto the peritoneal cavitymay result in damage to other structures. Several ap-plications of the agent over time may be necessary, making the methods lessconvenient. Some agents have toxicities that preclude their safe use. Finally,failure rates are higher than with standard methods of sterilization.
Many substances have been investigated including phenol [22], tetracy-cline [23], and polidocanol [24]. Each is plagued by one of the problems pre-viously listed, and none is approvable. The Femcept device, initiallydescribed in 1977 [25], was used to instill a tissue adhesive, methyl cyanoac-rylate, into the tubes. It polymerized on contact with water and occluded thetubes. It then underwent degradation releasing chemicals, such as formalde-hyde, that induced a tissue reaction causing permanent occlusion. After ini-tial enthusiasm for the device, it was abandoned when bilateral tubalocclusion rates of only 85% to 90% were reported even with two applica-tions [26]. Failure to occlude the tubes was likely due to tubal spasm duringthe procedure, preventing instillation of the methyl cyanoacrylate into thetube in many patients. Two other agents, quinacrine and erythromycin, con-tinue to be studied and are discussed in detail later. Currently no sclerosingagent is available for use for female sterilization in the US.
Current status of transcervical sterilization in the United States
Recently, the focus in transcervical sterilization has been on hystero-scopic approaches and sclerosing agents. The Essure device is FDA-ap-proved and currently in use. Other methods under investigation includesclerosing agents, primarily quinacrine and erythromycin; and a hystero-scopic approach called Adiana (Adiana, Redwood City, California) that in-volves a combination of thermal injury and implant placement.
Essure
The Essure device was approved for use by the FDA in 2002 and by theEuropean Union in 2001. It is currently used in the US, Australia, and Eu-rope. The device is delivered into the fallopian tube under direct visualiza-tion with hysteroscopy. The insert comes loaded in a single-use deliverysystemdone device for each tube (Fig. 1). It consists of an inner coil ofstainless steel and an outer coil of a nickel–titanium (Nitinol, NDC, Fre-mont, California) alloy. Fibers of polyethylene terephthalate are wound inand around the inner coil (Figs. 2 and 3). The device is placed in the prox-imal tube in a wound-down state with a diameter of 0.8 mm. When de-ployed, the outer coil expands up to 2.0 mm to anchor the device in thetube. Proper placement results in 3 to 8 coils emanating into the uterine cav-ity with the remainder of the device in the lumen of the tube (Fig. 4). Afterplacement, polyethylene terephthalate fibers stimulate an immediate
61TRANSCERVICAL STERILIZATION: PAST, PRESENT, AND FUTURE
inflammatory response characterized by macrophages, fibroblasts, foreignbody giant cells, and plasma cells [27]. The reaction peaks within 2 to 3weeks and resolves by approximately 10 weeks, leaving dense fibrosis withocclusion of the tube and anchoring of the device. During this time, the pa-tient must use an alternate form of contraception, because the tube may notbe fully occluded until the process is complete. At 3 months, a hysterosalpin-gogram (HSG) is performed to confirm occlusion of the tubes (Fig. 5).
Food and Drug Administration approval studies for Essure
The approval process for Essure involved an initial Phase IA perihyster-ectomy trial that demonstrated feasibility of microinsert placement, evalu-ated introducer devices, and assessed initial blockage of the tubes. Asubsequent Phase IB posthysterectomy trial involved placement of microin-serts in patients who subsequently underwent hysterectomy up to 7 monthsafter placement [27]. The study, which involved 33 women, confirmed theproposed mechanism of action of an in-growth of tissue into the tube result-ing in complete blockage. It also demonstrated patient tolerance and accept-ability of placement of the device as well as safety and comfort duringrecovery after placement. Eighty five percent of inserts were successfullyplaced in this initial report.
Fig. 1. The Essure delivery system. (Courtesy of Conceptus, Inc., Mountain View, CA; with
permission.)
Fig. 2. The Essure microinsert component. (Courtesy of Conceptus, Inc., Mountain View, CA;
with permission.)
62 OGBURN & ESPEY
A Phase II trial to assess the safety and efficacy of the device in the in-tended patient population followed [28]. This multicenter trial involved227 women at centers in the US, Australia, and Europe. Successful place-ment of the device was achieved in 86% of patients on the first attemptand 88% after a second attempt. No serious adverse events occurred. In24 months of follow-up, 98% of patients reported very good or excellent tol-erance of the implants. No pregnancies were reported in 6015 women-months of exposure to intercourse.
The pivotal, or Phase III, trial for Essure involved 518 women in a multi-centered international trial. Bilateral placement was achieved in 464 (90%)of women. All procedures were performed in an outpatient setting, and 88%reported tolerance of device placement as good to excellent. Four hundredand fifty six of the 464 returned for follow-up at 3 months. On HSG, 92%had bilateral tubal occlusion. Sixteen (3.5%) had tubal patency with the in-serts in the correct location. All had bilateral tubal occlusion on HSG at 6months. Twenty-one women (4.5%) did not have correct placement of the
Fig. 3. The Essure microinsert dimensions. (Courtesy of Conceptus, Inc., Mountain View, CA;
with permission.)
Fig. 4. Appearance of Essure after proper placement. (Courtesy of Conceptus, Inc., Mountain
View, CA; with permission.)
63TRANSCERVICAL STERILIZATION: PAST, PRESENT, AND FUTURE
inserts on HSG, including 14 who had expulsion. Nine of those who had ex-pulsion underwent successful bilateral placement with occlusion docu-mented at 3 months postprocedure. Ultimately 87% of the original 518women were able to rely on Essure for permanent sterilization [29]. Therewere no reported pregnancies in this trial.
Essure remains the only transcervical method of sterilization approvedfor use in the US. Since the Phase II and pivotal trials, other studies haveconfirmed reasonable bilateral placement rates, high patient acceptance,a good safety profile in performing the procedure in the outpatient settingusing local anesthesia and/or sedation, applicability in various practice set-tings, and efficacy [30–35].
Advantages and disadvantages of Essure
Feasibility of incorporating EssureSeveral other issues must be considered when assessing Essure as an op-
tion for sterilization. One is the need for operative hysteroscopy skills andequipment. Many gynecologists are familiar and skilled with laparoscopictechniques but have less familiarity and skill with hysteroscopy. Althoughone of the main advantages of this technique is the ability to perform it inan office setting, many physicians do not have hysteroscopic equipment intheir offices and may not be willing or able to invest the significant fundsnecessary to obtain it.
Cost of EssureAnother issue is the cost-effectiveness of the approach. Two inserts are
required for a single procedure and currently cost $1150. Depending onthe practice setting, the expense of the inserts may be offset by savingsfrom avoidance of operating room use and the need for an anesthesiologist,
Fig. 5. HSG appearance 3 months after Essure placement. (Courtesy of Conceptus, Inc., Moun-
tain View, CA; with permission.)
64 OGBURN & ESPEY
as well as avoiding the costs of disposable materials typically used for lap-aroscopy. Third party coverage and reimbursement for the procedure varyamong private insurers as well as among state Medicaid programs andmay have an impact on the decision to use this technique.
Reversibility of EssureThough all sterilization procedures should be considered permanent, it is
well known that some women desire childbearing after being sterilized. Todate, no reports document successful reversal of the Essure procedure. Asingle case report describes successful in vitro fertilization with a resultanttwin pregnancy after placement of Essure coils in a patient who had hydro-salpinx [36]. The coils in this case were placed to block the tubes to improvethe chance of successful in vitro fertilization and to prevent ectopic preg-nancy. Additional evidence that in vitro fertilization may be feasible afterEssure sterilization derives from a report of patients undergoing hystero-scopy an average of 20 months following Essure placement [37]. The authornoted that the length of coils exposed in the uterine cavity was an average of1.9 mm compared with 5.5 mm at the time of placement. He proposed thata progressive tissue encapsulation occurs that, over time, excludes the coilsfrom the intrauterine cavity.
Diagnostic workup for abnormal bleeding and EssureAnother consideration is the evaluation and management of patients who
have abnormal bleeding after Essure placement. No reports have examinedthe safety of performing blind diagnostic procedures, such as dilation andcurettage or endometrial biopsy. Theoretically, the inserts could be damagedor inadvertently removed. The encapsulation phenomenon described previ-ously may make such events unlikely. The product Web site recommends ei-ther a direct visualization procedure, such as hysteroscopy, or an imagingstudy, such as HSG or ultrasound, to document continued appropriateplacement of the inserts after a blind procedure is performed [38].
Endometrial ablation and EssureThe feasibility and safety of concomitant Gynecare Thermchoice (Ethi-
con Inc., Somerville, New Jersey) thermal balloon ablation has been docu-mented [39]. This report included 40 patients in a feasibility study and 9 ina safety study. In the feasibility trial, women underwent bilateral placementof Essure coils followed by thermal balloon ablation immediately beforehysterectomy. Inspection of the coils and uterus after hysterectomy detectedno damage to the coils and satisfactory endometrial destruction. The bal-loon was undamaged. In the safety study, thermocouples were placed inthe tubal serosa to measure heat transmission in the tube during balloon ab-lation with the Essure coils in place. Temperatures ranged from 37.1 to37.5�C and did not reach the critical threshold of 45 C. Based on this infor-mation, the FDA approved the use of Essure and Thermachoice ablation for
65TRANSCERVICAL STERILIZATION: PAST, PRESENT, AND FUTURE
concomitant use. However, in a letter dated October 2006 sent by Conceptusto physicians trained in Essure placement, this approval was rescinded. Theletter stated that information presented to the FDA in the postapproval‘‘Essure System Combined with Gynecare Thermachoice Uterine BalloonTherapy HSG Evaluation Study’’ indicated that 5 of 30 women who had un-dergone both procedures concomitantly developed intrauterine synechiaethat prevented assessment of tubal patency by HSG. The option remainsto perform Thermachoice ablation with the Essure inserts in place after oc-clusion has been documented.
There are no data on the feasibility and safety of using other thermal en-dometrial ablation methods, cryo-ablation, or laser ablation techniqueswhen Essure sterilization has been performed. The use of techniques usingmicrowave or radiofrequency should not be used with Essure coils in placebecause of the risk of heat transmission by the coils and subsequent damageto surrounding tissues.
In summary, Essure is a new option for permanent female sterilization. It isideal for patients who are not good candidates for laparoscopic sterilization,including obese women and those who have significant medical conditions.Because it is safe, is effective, requires no incisions, and can be performed inan outpatient setting without general anesthesia, it may be the best optionformost patients.Where Essure is available, it is appropriate to offer this tech-nique to all patients desiring permanent sterilization, discussing the advan-tages and disadvantages of both Essure and laparoscopic tubal sterilization.
Transcervical methods under investigation
Adiana
Research is ongoing with this method and it is not yet approved for use inthe US. Like Essure, this method uses a hysteroscopic approach and may beperformed in an office setting under local anesthesia with sedation as needed.The system has three components: a delivery catheter, a radiofrequency gen-erator, and a polymer matrix (Figs. 6–8). A hysteroscope is entered into theuterine cavity where the tubal ostia are visualized. The delivery catheter isadvanced into the proximal 1.5-cm interstitial portion of the fallopiantube. The radiofrequency generator is then activated, and the proximal por-tion of the tube is heated to a temperature of 64� C creating a thermal lesion.The polymer matrix is then released into the tube through the same deliverycatheter. The thermal lesion removes the surface epithelium and stimulatesin-growth of healthy vascularized tissue into the matrix pores. Once thein-growth is completed, the matrix and tissue form a permanent occlusivebarrier in each tube (Figs. 9 and 10). Patients must use alternative contracep-tion for 3 months until an HSG is performed and confirms bilateral tubalblockage. The matrix is highly echogenic and can be localized using ultra-sound, although tubal occlusion cannot be confirmed in this manner.
66 OGBURN & ESPEY
Potential advantages of this technique over Essure sterilization includethe lack of material projecting into the uterine cavity and the lack of metalremaining in the tube. Because only the proximal 1.5 cm of tube is cannu-lated, the risk of uterine perforation may be reduced.
As of November 2006, Adiana remained under investigation with nopublished reports in the literature. However, data from 509 patients enrolledin a multicenter US trial are available on the company Web site. The datareveal a 94.8% successful bilateral placement rate with a 1-year pregnancyprevention rate of 99.7%. Over 50% of procedures were performed with lo-cal anesthesia, and the rest required only ‘‘minimal IV sedation.’’ Womenwere ‘‘highly satisfied,’’ and no serious adverse events were reported. It isanticipated that the method will be FDA-approved and available on theUS market in late 2007 or 2008.
Quinacrine
Quinacrine chloride, an antimalarial drug, was first described by Zipperand colleagues [40] in 1970 as a sclerosing agent for sterilization. The initialreport described instillation of quinacrine paste injected blindly into the
Fig. 6. The Adiana system. (Courtesy of Adiana, Inc., Redwood City, CA; with permission.)
Fig. 7. Implantable matrix. (Courtesy of Adiana, Inc., Redwood City, CA; with permission.)
67TRANSCERVICAL STERILIZATION: PAST, PRESENT, AND FUTURE
uterine cavity. This approach was abandoned because of rapid absorptionwith systemic effects and a high failure rate. Subsequently, quinacrine wasintroduced into the uterus in pellet form using a device similar to a copperintrauterine device inserter. Family Health International (FHI, ResearchTriangle Park, North Carolina) received an investigational exemption foran Investigational New Drug to study quinicrine pellets for sterilization.A Phase I trial of 10 prehysterectomy patients in 1983 to 1984 collectedsafety and pharmacokinetic data. It found that quinacrine levels were sim-ilar to those obtained with oral administration [41]. Because of concernsabout the need for multiple insertions to achieve adequate scarring of theuterine cavity as well as potential mutagenicity that had not been thor-oughly investigated, FHI cancelled the Investigational New Drug applica-tion and did not pursue Phase II trials.
The largest trial to date was performed in Vietnam with 31,781 women[42]. Subjects enrolled in the study underwent quinacrine sterilization using
Fig. 8. Delivery catheter. (Courtesy of Adiana, Inc., Redwood City, CA; with permission.)
Fig. 9. Cross-sectional view through the matrix shows the porous architecture surrounding the
solid central core. (Courtesy of Adiana, Inc., Redwood City, CA; with permission.)
68 OGBURN & ESPEY
252 mg in pellet form. The pregnancy rate at 24 months for all women un-dergoing quinacrine sterilization was 5.9%. There were only eight seriouscomplications and no deaths reported. Following publication of this study,ethical concerns were raised about the conduct of the study and about themethod itself. The public health community believed inadequate clinicaland/or toxicologic evaluations had been performed before testing quinacrinesterilization in such a large number of patients. As a result, the WorldHealth Organization recommended halting use of the method until suchstudies were completed [43].
A review by Sokal and colleagues [44] in 1995 summarized the work onquinacrine and concluded that quinacrine sterilization is likely safer in theshort term than surgical sterilization, that potential carcinogenicity shouldbe studied, and that efficacy is lower than that of surgical sterilization. De-spite lower efficacy, quinacrine sterilization remains an appealing methodbecause of its widespread availability and low cost, especially in developingcountries. Sokal further concluded that insertions should be performed inthe proliferative phase of the menstrual cycle, at least two insertions are nec-essary, and that the optimal dose is 216 to 324 mg per insertion. Failurerates are lower in women over age 35 at the time of quinacrine sterilization.
Since Sokal’s review, several studies have assessed the short-term safetyand efficacy of quinacrine sterilization. Feldblum and colleagues [45] re-ported on Chilean women who had undergone quinacrine sterilization anaverage of 9.6 years previously. The 10-year cumulative pregnancy
Fig. 10. Cross-sectional view shows the tissue ingrowth into the pores of the matrix. Space fill-
ing, healthy vascularized ingrowth is seen. (Courtesy of Adiana, Inc., Redwood City, CA; with
permission.)
69TRANSCERVICAL STERILIZATION: PAST, PRESENT, AND FUTURE
probability, the cumulative number of women per 100 that would get preg-nant over 10 years after the procedure, was 8.9 in patients who had under-gone two insertions with 252-mg pellets. Women over age 35 were 0.3 timesas likely to become pregnant compared with women under age 35. Ectopicpregnancy rates are similar to those with laparoscopic tubal sterilization. Nomajor complications or deaths were reported.
In 2003, the International Federation of Gynecology and Obstetrics helda session at their triennial meeting devoted to quinacrine sterilization.Proceedings were published in a supplement to the International Journalof Gynecology and Obstetrics. The 25 reports in the supplement camefrom 14 different countries and documented over 40,000 cases of quinicrinesterilization with no serious adverse events or deaths [46].
Despite a substantial body of literature on the use of quinacrine steriliza-tion, concerns about lack of long-term safety and toxicology data have pre-vented this method from being adopted in the US. Additional toxicitystudies have been undertaken to address these concerns. Mice studieshave revealed no increases in tumor incidence [47], but have revealed an in-crease in benign uterine endometrial polyps and endometrial hyperplasia infemale mice. The significance of these findings remains unclear as do theirapplicability to humans.
Even if adequate reassuring data are obtained, quinacrine sterilizationwill likely not play a major role in the US because currently available ster-ilization methods are more effective. In developing countries where access tosurgical sterilization is minimal, quinacrine sterilization may provide a safe,inexpensive, and accessible option. Most recently, in December 2006, FHI,a leader in prior investigations of quinacrine, has cancelled plans for a clin-ical study of quinacrine sterilization and has stopped working to developquinacrine as a method of nonsurgical sterilization. (D. Sokal, FHI, per-sonal communication, December 2006). The reasons for discontinuingwork on this method have been shared with the FDA, but are not yet pub-lished in the peer-reviewed literature. This pullback from the method mayhave a dramatic impact on the continued investigation and availability ofquinacrine sterilization.
Erythromycin
Erythromycin, a macrolide antibiotic, has been used as a sclerosing agentin other anatomic sites and is currently under consideration for female ster-ilization. An animal trial comparing the efficacy of transcervical administra-tion of erythromycin lactiobionate to quinacrine hydrochloride in ratsfound it to be more effective at preventing pregnancy [48]. In contrast,a study of 790 cases of women undergoing erythromycin sterilizations in In-dia using a 500-mg crushed tablet or pellet reported failure rates of 35.8%and 28.6%, respectively, at 12 months. Although no serious complicationswere reported, the authors concluded that the failure rate with this
70 OGBURN & ESPEY
technique was too high to consider it an acceptable option [49]. Potential ad-vantages of erythromycin include experience with the agent as a sclerosingagent in other anatomic locations and a reassuring safety profile. FHI hasobtained a patent for the use of macrolide antibiotics for female sterilizationand is currently investigating appropriate formulations. FHI believes thatthe powder formulations used in the India trial are not indicative of the re-sults that could be obtained with a better-designed formulation (D. Sokal,FHI, personal communication, March 2007).
Summary
After multiple attempts at developing transcervical sterilization tech-niques over the past 150 years, US women now have the option of a trans-cervical method, Essure, which can be performed without an incision underlocal anesthesia. It is feasible in most patients and highly effective once oc-clusion has been confirmed with HSG. Another method, Adiana, is likely tobe approved and enter the market in the near future. Expanded choices forsterilization are a positive development for women’s health because moreoptions may decrease unintended pregnancy. The Essure procedure providesa safe effective choice for women in the US and other developed countries.In addition, it provides an option for women who might not be candidatesfor traditional sterilization methods.
The future looks promising for the development of options that are equallysafe and effective yet less expensive and less technology-dependent. A nonsur-gical method, such as quinacrine or erythromycin, that could be inserted aseasily as an intrauterine device with little or no specialized equipment wouldbe a tremendous advance for women around the world, especially those in lessdeveloped areas where sterilization is not typically available.
It is expected that the world population will approach 12 billion by 2100,a doubling from the current six billion [50]. Improving the ability to controlfertility, permanently if a woman desires, may help slow the rapid popula-tion growth that contributes too many socioeconomic problems for both de-veloped and developing nations.
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