Hysteroscopic Sterilization in the Office Amy Garcia, MD Director, Center for Women’s Surgery Assistant Professor, University of New Mexico Department of Obstetrics and Gynecology Division of Urogynecology Albuquerque, New Mexico

Disclosure Conceptus, Inc Minerva Surgical Consultant Speaker Minerva Surgical Ethicon Women’s Health and Urology Ethicon EndoSurgery

Why Hysteroscopic Sterilization in the Office? Patient Comfort Patient Financial Burden Lessened Office co-pay vs. outpatient co-pay Co-insurance, self-pay Health System Financial Burden Lessened Improved reimbursement for physicians Reduced Risk No general anesthesia No incisions Patient Convenience Physician Convenience

What Women Want for Permanent Birth Control Safest Available Procedure Reliable Quick Recovery In-Office Availability Office Co-pay

Women Whose Families Are Complete Women >35 is the largest group of unintended pregnancy Family Planning Perspectives Volume 30, Number 1, January/February 1998 Unintended Pregnancy in the United States

Hysteroscopic Sterilization History

Female Sterilization Trend JMIG 2009;16:22-7

Essure in the Office With Local Anesthesia JMIG 2006;13:447-50

In-Office Hysteroscopic vs. LS TL JMIG 2005;12:318-22

Essure in the Office with Local Anesthesia Ketorolac 60 mg IM 30 min. pre Paracervical 10 mL 2% Lidocaine 10 Minutes

Essure System FDA Approved 2002 Fully deployed micro-insert delivery catheter micro-insert DryFlow® Introducer Nursing Presentation The Essure Permanent Birth Control System is comprised of the Essure micro-insert, a disposable delivery system and a disposable split introducer (not shown here). -The disposable delivery system (shown in this picture) consists of a delivery wire, a release catheter, a delivery catheter and an ergonomic handle. The delivery wire and release catheter are layered beneath the delivery catheter. -The ergonomically designed handle makes use of a rotatable wheel and gear system which provides for retraction of the outer delivery catheter followed by withdrawal of the inner release catheter causing the micro-insert to be fully deployed. -The outer delivery catheter is 1mm in diameter allowing it to be placed through a 5fr operating channel of any commercially available hysteroscope. ergonomic handle 11

Stainless Steel Innercoil Micro-insert Design PET Fiber Dynamic Expanding Superlastic Nitinol Outer Coil Device Length: 3.85 cm Wound Down Outer Diameter: 0.8 mm Expanded Outer Diameter: 1.5 – 2.0 mm Stainless Steel Innercoil

Essure Placement Gold Band 1. Ostia visualized 2. Delivery Catheter Positioned 3. Release Catheter with Gold Band 4. Micro-insert Positioned Takeaway: Key steps in device placement as viewed through the hysteroscope. Image 1 Uterus distended with physiologic saline Tubal ostium in center of visual field Identify and assess both ostiahysteroscopically before proceeding to micro-insert placement Image 2 Delivery catheter advanced until black positioning marker is at tubal ostium Delivery catheter withdrawn away from micro-insert into operating channel of hysteroscope Image 3 Gold band is aligned outside the tubal ostium, Green release catheter withdrawn to expand the micro-insert Image 4 Micro-insert properly positioned and deployed across utero-tubal junction References: N/A Rev history: Gold Band 13

Reports from 2001 through July 2010 JMIG 2011 18, 475-482 MAUDE Reports from 2001 through July 2010 436,927 kits 63 reports Phase ll and Pivotal Trials Manufacturer and User Facility Device Experience

Essure Nickel Sensitivity Change in FDA Contraindication July 2011 497,306 kits and 92 reports Removal of contraindication for known hypersensitivity to nickel confirmed by skin test Removal of warning for suspected hyper- sensitivity to pursue confirmatory skin test New warning for suspected hyper-sensitivity The removal of a contraindication for patients with known hypersensitivity to nickel as confirmed by skin test The removal of a warning for patients with a suspected hypersensitivity to nickel to pursue a confirmatory skin test The addition of a warning for patients with suspected hypersensitivity to nickel Given the clinical relevance of data gathered from the Essure clinical trials and a decade of commercial use, the following label modifications were approved by the US Food and Drug Administration on July 1, 2011. Removed Contraindications statement: “Known hypersensitivity to nickel confirmed by skin test (see Warnings section below for patients with hypersensitivity to nickel.)” Removed Warnings statement: “Patients with suspected hypersensitivity to nickel should undergo a skin test to assess hypersensitivity prior to an Essure placement procedure (see Contraindications section above for patients with known hypersensitivity to nickel).” New Warnings statement: “The Essure micro-insert includes nickel-titanium alloy, which is generally considered safe. However, in vitro testing has demonstrated that nickel is released from this device. Patients who are allergic to nickel may have an allergic reaction to this device, especially those with a history of metal allergies. In addition, some patients may develop an allergy to nickel if this device is implanted. Typical allergy symptoms reported for this device include rash, pruritus, and hives.” The new labeling was supported by the following information: Nickel sensitivity was not an exclusion criterion in the Essure clinical trials and no short-term adverse events occurred that suggested that the micro-insert was allergenic A review of nine years of commercial experience/adverse events reported did not demonstrate a causal relationship between nickel sensitivity and wearing the Essure micro-insert The number of reported adverse events related to possible allergic reaction to the Essure micro-insert is extremely low; less than 1 in 5,000

Essure Nickel Sensitivity New FDA Warning July 2011 “The Essure micro-insert includes nickel-titanium alloy, which is generally considered safe. However, in vitro testing has demonstrated that nickel is released from this device. Patients who are allergic to nickel may have an allergic reaction to this device, especially those with a history of metal allergies. In addition, some patients may develop an allergy to nickel if this device is implanted. Typical allergy symptoms reported for this device include rash, pruritus, and hives.” The removal of a contraindication for patients with known hypersensitivity to nickel as confirmed by skin test The removal of a warning for patients with a suspected hypersensitivity to nickel to pursue a confirmatory skin test The addition of a warning for patients with suspected hypersensitivity to nickel Given the clinical relevance of data gathered from the Essure clinical trials and a decade of commercial use, the following label modifications were approved by the US Food and Drug Administration on July 1, 2011. Removed Contraindications statement: “Known hypersensitivity to nickel confirmed by skin test (see Warnings section below for patients with hypersensitivity to nickel.)” Removed Warnings statement: “Patients with suspected hypersensitivity to nickel should undergo a skin test to assess hypersensitivity prior to an Essure placement procedure (see Contraindications section above for patients with known hypersensitivity to nickel).” New Warnings statement: “The Essure micro-insert includes nickel-titanium alloy, which is generally considered safe. However, in vitro testing has demonstrated that nickel is released from this device. Patients who are allergic to nickel may have an allergic reaction to this device, especially those with a history of metal allergies. In addition, some patients may develop an allergy to nickel if this device is implanted. Typical allergy symptoms reported for this device include rash, pruritus, and hives.” The new labeling was supported by the following information: Nickel sensitivity was not an exclusion criterion in the Essure clinical trials and no short-term adverse events occurred that suggested that the micro-insert was allergenic A review of nine years of commercial experience/adverse events reported did not demonstrate a causal relationship between nickel sensitivity and wearing the Essure micro-insert The number of reported adverse events related to possible allergic reaction to the Essure micro-insert is extremely low; less than 1 in 5,000

Adiana System FDA Approved 2009 Radio Frequency Generator Monopolar electrosurgery – Position Detection Array Requires non-electrolyte fluid medium Consideration for hyponatremia Step-by-step guidance Time and temperature of energy controlled No reported injuries due to RF in clinical trial

Adiana Delivery Catheter No Perforations in Clinical Trial Diameter 1.34 mm Inserted 1.4 cm into Tube Matrix at Distal Tip Position Detection Array (PDA) Confirms position of catheter Aids matrix placement ~ 1 cm RF Electrode -- Bipolar Delivers energy 60 seconds 5 mm in length PDA Matrix The adiana sterilization method is a combination of controlled thermal damage to the lining of the fallpian tube followed by insertion of a biocompatible matrix. Under hysteroscopic guidance, the catheter is placed into the fallopian tube. Once in the intramural portion of the tube, position is confirmed with the position detection array. This is designed to monitor uniform contact with the tissue throughout the energy delivery portion of the procedure. The radio frequency electrode array delivers energy to the fallopian tube for approximately 1 minute over a distance of 5 mm. The catheter is withdrawn and the matrix is deployed within the area of thermal injury which is 3.5 mm in length. Thermal injury to the tubal epithelium which aids epithelial ingrowth into the matrix. RF Electrode 1 Cytyc Surgical Products Panel Adiana Briefing Information for December 14, 2007 , FDA Panel Page 88-89 2 Cytyc Surgical Products Panel Adiana Briefing Information for December 14, 2007 FDA Executive Summary, Page 5

Adiana Biocompatible Implant The matrix is a non-absorbable biocompatible silicone elastomer that facilitates epithelial ingrowth and tubal occlusion. Inert Silicone Matrix Epithelial In-growth

Technology Comparison Overview Essure1 Adiana2 Potential Occlusion Length 20 mm 3.5 mm Distention Media Saline Glycine, Sorbitol, Mannitol Generator Required No Yes Pregnancies in Clinical Trial 12 Confirmation Test HSG tubal occlusion & device placement HSG tubal occlusion Visible on X-Ray/HSG Device within Uterine Cavity Visual Confirmation of Placement Product Shelf Life 3 Years 1 Year Adiana no instruction for device placement confirmaiton 1 Essure Instructions for Use 2 Vancaille et al, A 12-Month Prospective Evaluation of Transcervical Sterilization Using Implantable Polymer Matrices, Obstetrics & Gynecology . 112(6):1270-1277, December 2008 3 Cytyc Surgical Products Panel Adiana Briefing Information for December 14, 2007 FDA Panel, Page 905

Reported Pregnancies in Clinical Trials Among Subjects Who Completed Evaluation Year One Two Three Four Five 6 - 9 Total Pregnancies Essure1 (N=745) 02 trial complete Year One Two Three Four Five 6 - 9 Pregnancies to date Adiana3,4 (N=645) 65 1 ectopic 3 2* 1* ?? 12 The five year effectiveness rate for the essure is 99.84% (failure rate of .16%). This makes the Essure the most reliable of the permanent birth control methods available. The 2 year cumulative 2 year failure rate for the adiana is 1.82% (second only to the spring clip in the CREST trial data at 2.38%) Essure - Number of patients completing follow up visits (page 15 of Phase II and of Pivotal): 1 year    2 year    3 year    4 year    5 year Phase II    196       194         182         176         60 Pivotal      461       435         423         403         386 1 Phase II Trial Final Report, Page 33 and Pivotal Trial Final Report, Page 75 2 4 patients were pregnant at the time of Essure placement (luteal phase). Ref: Final Pivotal Study Report, page 54 3 Cytyc Surgical Products Panel Adiana Briefing Information for December 14, 2007 FDA Panel, Page 596 4Adiana Instructions for Use, AW-03216-001 Rev 3 5 5 additional Adiana pregnancies in patients who were told not to rely on the device. Cytyc Surgical Products Panel Adiana Briefing Information for December 14, 2007 FDA Panel, FDA Executive Summary, Page 51 *Based on patients that have completed follow up. Not all patients have completed 4 and 5 year follow up. 21

Adiana Black Box Warning The black box warning refers to the five additional pregnancies that occurred in the Adiana pivotal trial in patients who were told NOT to rely on the device. These 5 pregnancies were not included in the 12 pregnancies reported in the trial in patients who were told to rely on the device. If included, failure rate would be 2.81% 5 Additional Pregnancies in Clinical Trial Women told NOT to rely on the device for contraception NOT included in the 12 pregnancies reported Adiana Instructions for Use, AW-03216-001 Rev 3

Essure Confirmation Test HSG 3 Months Bilateral Placement Bilateral Occlusion

Adiana Confirmation Test HSG 3 Months Bilateral Occlusion

HSG Patency Rate (%) 3 month HSG 6 month Essure1 3.5% 0% Adiana2 8.8% 5.6% Same as slide 16 but a table versus a graph, pick your preferred format and hide/delete the other. Essure: n=656 3 mos: 23 6 mos: 0 Final: 0 Adiana: n = 604 3 mos: 53 6 mos: 26 (not all tubes were re-evaluated at 6 months Final: 34 1 Essure Instructions for Use 2 Adiana data from Panel Briefing Information for December 14, 2007 FDA Panel, Clinical Report page 586

Tubal Occlusion Confirmation Test Hysterosalpingogram (HSG) Positive and valuable part of the Essure/Adiana Bilateral placement and occlusion for Essure Bilateral occlusion for Adiana Provides patient piece of mind Provides physician piece of mind Covered by insurance Every patient knows of a story in which someone got pregnant after a tubal ligation or vasectomy. The confirmation test is a valuable part of the essure procedure and reassures them that they will not have an unplanned pregnancy. You can compare this to the three month wait for a vasectomy or the three to six month wait for spotting to subside following the placement of an IUD.

Two Year Failure Rates Pregnancies/1000 women (1.82%) (.07%) 1 2 2 2 3 1 Essure Effectiveness Report (data December 16, 2004), page 14 2 Peterson, H.B., et al, The risk of pregnancy after tubal sterilization: findings from the U.S. Collaborative Review of Sterilization. Am J Obstet Gynecol. 1996 Apr;174(4):1161-8 3 Cytyc Surgical Products Panel Adiana Briefing Information for December 14, 2007 FDA Panel Executive Summary, Pages 32, 34

Essure Typical Use Pregnancy Rate = .12% Non- Compliance 44% 74% No ECT 44% No Info. Pending 26% Prior to ECT 8% Luteal Phase 7% Physician Off Label 7% Pregnancy Rate = .12% Non- Compliance 44% 74% Education & Follow-up As reported to the FDA in the 2008 PMA annual report (1998 through Dec 2008) there have been 305 reported pregnancies out of 259,746 procedures.

Successful Hysteroscopic Sterilization Continuous Distention of the Uterine Cavity Clear Visualization Uterine cavity Tubal ostia Confident Hysteroscopist Supportive Staff Under cont distention add 119 content It begins with hysteroscopy basics!

Optimize Visualization Cycle Timing Early proliferatve phase Cycle day 4 – 10 Decreased risk of luteal pregnancy Reduced endometrial tissue Enhanced visualization of ostia Hormonal Effect OCP’s, Depo Provera, Mirena

Distention Medium Saline Pressure bag 3 liters (1 liter) Warm Cystoscopy tubing Back-up available

Instruments

Instruments

Pre-Procedure Medication Misoprostil 200 microgram per vagina 10-12 hrs. prior If cervical softening is needed NSAIDS Ibuprofen 800 mg PO hs and am prior Ketoralac 30 mg IM 15 – 30 min. prior Anxiolytic Diazepam 10 mg PO 1 hour prior Narcotic Hydrocodone 5/500 mg 1 hour prior

Pre-Procedure Local Anesthesia Tenaculum Site 1% lidocaine (w or w/o epi) 2 cc at 12 o’clock Paracervical Block 4 and 8 o’clock Intrauterine 1% lidocaine Placed with insemination catheter Approximately 10 cc

RCT 1% Lidocaine vs Saline for PCB Significant Lower Pain Scores Obstetrics & Gynecology Vol. 115, NO.1, January 2010 RCT 1% Lidocaine vs Saline for PCB Significant Lower Pain Scores Tenaculum placement Traversing external cervical os Traversing internal cervical os No Difference for Device Placement

Vaginoscopic Hysteroscopy Procedure Consideration for misoprostil No Speculum Needed Betadine Vagina No Anesthesia Fill Posterior Fornix with Saline Consider the patient!!

Post-Procedure Medication NSAID’s Ibuprofen prn Narcotic Extra given if cervix is dilated

Procedure Moderate Lithotomy Bimanual Exam Open-Sided Speculum Boot stirrups Bimanual Exam Open-Sided Speculum Pederson Clean Cervix Bedadine swabs Single Toothed Tenaculum Vaginoscopy is possible Placement of Local Anesthesia Assure Cervical Diameter Cervical dilation to 5 mm (6 mm for nulliparous) Parous cervix seldom needs dilation

Procedure Place Hysteroscope Remove Speculum Access Cavity Remove Tenaculum Assess Ostia Prior to opening device package Place Devices Photo document Check Cervix Assess Patient Comfort

Additional Tips Minimize Movement Do Not Sound Do Not Over Dilate Cervix Vocal Anesthesia Atmosphere Music Soft Lighting Warm Blanket Position Monitor for Patient Viewing Provide Photo for Patient

Post-Procedure Documentation Number of Visible Coils Scope/Procedure Time Fluid Deficit Unusual Anatomy Difficult Placement Patient Comfort Patient Counseling

Avoid Pregnancies Contraception Avoid Luteal Phase Before and after procedure Avoid Luteal Phase Cycle timing Pre-procedure Urine hCG 3 Month HSG Bilateral placement/occlusion Essure Bilateral occlusion Adiana Follow-up Protocol 08/2011 330 procedures 1 had a hysterectomy 8 never able to contact 12 have received 2nd letter 9 have received 1st letter 90% Completed HSG

Hysteroscopic Sterilization Coding ICD-9 V25.2 Interruption of fallopian tubes or vas deferens CPT 58565 Bilateral fallopian tube cannulation to induce occlusion by placement of permanent implants

Reimbursement 90 Day Global 2011 Essure $1,250.00 Adiana $ 800.00 In-Patient (21), Out-Patient (22), ASC (24) Hysteroscopic Sterilization 58565 2011 RVU Medicare CF 34.01 125% CF 42.5125 12.9 $ 438.73 $ 548.41 Non-Facility/Office (11) 56.66 $ 1,927.00 $ 2,408.76 Essure $1,250.00 Adiana $ 800.00

HSG Coding ICD-9 CPT V26.51 Tubal ligation status V67.09 Follow-up exam following other surgery CPT 58340 Catheterization and introduction of saline or contrast media for sonohysterography or hysterosalpingogram 74740 Hysterosalpingogram radiologic supervision interpretation 74740-26 Professional component only

Training Office Personnel Train with Equipment Reprocessing and handling of hysteroscope Set-up of equipment Know How to Trouble-shoot Be Comfortable with Procedure Arrange for Staff Observation Patient counseling Actual procedure Have a Written Protocol