Transcript Global Endometrial Ablation

Global Endometrial Ablation
Robert D. Auerbach, M.D. FACOG
Senior Vice President & Chief Medical Officer
CooperSurgical, Inc.
The Endometrium
Endometrium
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Endometrial Ablation Therapy Goals
Endometrial ablation is
 Indicated for the treatment of menorrhagia or patient-perceived heavy
menstrual bleeding
 Premenopausal women with normal endometrial cavities
 No desire for future fertility
Patients who choose endometrial ablation should be willing to accept
normalization of menstrual flow, not necessarily amenorrhea, as an
outcome.*
* ACOG Practice Bulletin Clinical Management, Guidelines for ObstetricianGynecologists; Number 81, May 2007
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The Menstrual Cycle… and Beyond
 Normal menses
 Menarche: 12 yo
 Menopause: 51 yo
 35-40 ml/cycle
 Abnormalities
 Menorrhagia: an abnormally heavy
and prolonged menstrual period
bleeding at regular intervals
 Metrorrhagia: uterine bleeding at
irregular intervals
 Meno-metrorrhagia: irregular heavy
and prolonged uterine bleeding
 Polymenorrhea: menstrual cycles
more frequent than 21 days
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Menorrhagia
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PBAC (Pictorial Bleeding Assessment Chart)
 PBAC - Menorrhagia
 Simple non-laboratory method for
semi-objective diagnosis
 Sensitivity: 86% (doesn’t miss the
Dx)
 Specificity: 89% (doesn’t overcall
the Dx)
 FDA studies
 Menorrhagia: PBAC>150
 Normal menses: PBAC≤75
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Etiology: Things to Consider
 AUB can be caused by a wide variety of local and systemic diseases.
 Most cases are related to pregnancy, structural uterine pathology (e.g., fibroids,
polyps), anovulation, a disorder of clotting, or neoplasia.
 Questions to ask:
 What is the woman's age?
 Is she sexually active? Could she be pregnant?
 What is her normal menstrual cycle like? Are there symptoms of ovulation?
 What is the nature of the abnormal bleeding (frequency, duration, volume,
relationship to activities such as coitus)?
 Are there any associated symptoms?
 Does she have a systemic illness or take any medications?
 History of a bleeding disorder?
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AUB: Making a Diagnosis
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AUB: Making a Diagnosis
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The Workup
 History and Physical Exam
 Laboratory Studies
 HCG to rule-out pregnancy and rare
conditions (molar disease)
 Blood count to assess for anemia
 Other blood studies based on history (i.e.,
coagulation profile, thyroid etc.)
 Hysteroscopy (alternative SIS)
 Direct visualization of the endometrial cavity
 Requires anesthesia
 Allows for targeted biopsy
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The Workup
 Ultrasound and SIS (alternative hysteroscopy)
 Sterile saline is instilled into the endometrial cavity and a transvaginal ultrasound
examination is performed
 Allows for careful architectural evaluation can detect small lesions which may be
missed or poorly defined by transvaginal sonography
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The Workup
 Endometrial biopsy
 After pregnancy has been excluded
 Endometrial biopsy should be performed in all women >35 to rule out
endometrial cancer or a premalignant lesion (endometrial hyperplasia)
 Endometrial biopsy in women between the ages of 18 and 35 who have risk
factors for endometrial cancer: family or personal history of ovarian, breast,
colon or endometrial cancer; PCO, obesity, diabetes
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Menorrhagia: Rx Should Be Individualized
Etiology:
 Anatomic
 Submucosal fibroids
 Endometrial polyps
 Adenomyosis
 Functional
 Bleeding diatheses
 Anovulation
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Menorrhagia Rx
 Menorrhagia unrelated to malignancy variety of therapeutic options:
 Watchful waiting
 Medical therapy
 Oral hormonal therapy (OCP, E2/P, P)
 Injection (Depo-Provera)
 IUD (Mirena)
 Surgical therapy
 Endometrial resection/ablation
- 1st generation
- 2nd generation
 Hysterectomy
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Menorrhagia without organic pathology is the primary
indication for endometrial ablation
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Continuing on with the Procedure…
 H&P
 Items to consider
 Cycle timing
 Lab studies
 Endometrial thinning
 SIS or hysteroscopy
 Cervical priming
 Endometrial bx
 Pre-op antibiotics
 Patient counseling
 Not routine
 Informed consent
 Certain cases would be indicated such
as h/o PID
 Schedule procedure
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Endometrial Thinning
 Endometrial thinning
 Benefit: reduction in lining thickness with closer exposure to basal layer
 Recommended for all Global Endometrial Ablation – not required for NovaSure
 Methods
 Cycle timing
 GnRH (Lupron – 3.75mg one month prior to procedure)
 Uterine curettage immediately prior to procedure
Proliferative Endometrium
Atrophic Endometrium
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Cervical Priming: Her Option Probe is 5.5 mm
 Cervical dilation can be painful
 6 mm or less diameter may not require dilation (Thermachoice and Her Option)
 8 mm or greater diameter will require dilation (HTA, NovaSure, MEA)
 Physician will determine need for dilation during the workup of AUB
during the examination and endometrial biopsy. Options include:
 Hygroscopic dilation - Laminaria
 Paracervical block followed by manual cervical dilation
 Pharmaceutical
 Prostaglandins such as Cytotec are most common
 The optimal Cytotec dose has not been established (most studies used 200-400 mcg)
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Endometrial Ablation
The Technologies
Standard versus Global Endometrial Ablation
 Rollerball Standard Endometrial Ablation (RB)
 Utilizes operative hysteroscope and energy source
 Considered the “Gold Standard” and used as the comparator in FDA
approvals
 All Global Endometrial Ablation must be approved in the US via a PMA that
requires substantial scientific investigation
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Standard Versus Global Endometrial Ablation
Global Endometrial Ablation
 Do not require an operative
hysteroscope – heating and
freezing
 Goal is to simplify the
procedure and increase
adoption rates
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Standard Versus Global Endometrial Ablation
 Rollerball and global techniques (GEA) have similar success rates –
used in PMA process
 Global methodologies tended to take less time and are more readily
performed
 Patients undergoing global techniques had a lower incidence of
complications
Lethaby, A, Hickey, M, Garry, R, Lethaby, A. Endometrial destruction techniques for heavy
menstrual bleeding. Cochrane Database Syst Rev 2005; :CD001501.
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Global Endometrial Ablation: Devices
 NovaSure®
 RF heat
 HTA®
 Circulating hot saline
 Thermachoice®
 Heated fluid-filled balloon
 MEA™
 Microwave heat
 Her Option®
 Cryotherapy/Freezing
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Thermachoice
 Hot liquid silicone balloon
 5 mm probe
 Balloon is inflated with 5%
dextrose in water
 Pressure of 160-180 mmHg
 Heated to approximately 87 degrees
Celsius for 8 minutes
 Circulating device within the balloon
that provides more even distribution
of the hot water
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NovaSure
 3-D bipolar mesh
 8 mm probe
 Suction is applied to the
endometrial cavity and up to 180
watts of bipolar power applied
 System will shut down with
complete desiccation or after a
total treatment time of 2 minutes
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HTA
 8 mm hysteroscope sheath is inserted
into the uterus
 Ablation under direct vision
 Uterine cavity is distended by heated
saline
 Treatment phase lasts for 10 minutes
 Total time approximately 17 minutes
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MEA™
 9.2 GHz, 30 watt microwave
system
 8 mm probe
 Produce a tissue temp of 75-85
degrees Celsius at a depth of
6 mm
 Treat the entire cavity - surgeon
moves the probe from cornu to
cornu and across the lower
uterine segment
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Her Option: A Twist on Cryotherapy
 Cryoprobe - 5.5 mm
 Elliptical ice ball approximately 3.5 by 5 cm forms around the probe
 At the edge of the ice ball the temperature is not destructive
 Number of ice balls that must be created is dependent upon the size
of the cavity
 Procedure takes 10 to 20 minutes
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Device Comparisons
Thermal Technology
Devices available in the US
Heat Injury and Scarring
Pathology of Heat
 Intense areas of necrosis with
acute and chronic inflammatory
cells
Post-NovaSure
 Foreign body giant cells
common
 Fibroblasts proliferate
 Scarring develops
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Post-Thermachoice
Her Option and Cryobiology
 Three mechanisms of cell death
 Intracellular ice formation
 Dehydration
 Ischemia
 Potential benefits of cold
 Cold has a natural analgesic affect,
reducing pain
 Post-op tissue may have less scarring
 Less risk of adhesion in cavity
 May not mask future pathologies
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Uterine Cavity Integrity
Why is it important?
Normal Menstrual Flow
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Why is it important?
Tubal Ligation
Normal Menstrual Flow
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Why is it important?
hematosalpinx
Tubal Ligation
Occluded Uterine Cavity
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hematosalpinx
Why is it important?
Desired post GEA
uterine cavity remains open
Tubal Ligation
Normal Menstrual Flow or Less
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Cavity Integrity: Hematometra
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Other Issues Regarding Cavity Integrity
 Advantages of an open uterine
cavity
 Ability to investigate later pathology
 Endometrial biopsy
 Hysteroscopy
 Ability to perform hysteroscopic
procedures
 Trans-cervical sterilization
 Reduction in pain-associated failures
of GEA
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Inability to Perform Endo Bx or SIS: from the Literature
Devices – NovaSure, thermal balloon
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Cryoablation May Cause Less Scarring
 Lahey Clinic study
 Subjects: 112 women with menometrorrhagia
 Amount and duration of bleeding recorded
 All underwent pretreatment hysteroscopy and endometrial sampling
 Contour and depth of cavity noted
 Her Option procedure performed
 Following Cryoablation patients were evaluated at one, three, six and 12 months
 Hysteroscopy was carried out between three and 12 months post-op
Duane Townsend, MD, FACOG, Innovative Technologies in Operative Gynecology For
the 21st Century.
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Lahey Clinic Study
Duane Townsend, MD, FACOG, Innovative Technologies in
Operative Gynecology For the 21st Century.
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Lahey Clinic Study
Duane Townsend, MD, FACOG, Innovative Technologies in Operative
Gynecology For the 21st Century.
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Pain Associated with Global
Endometrial Ablation
Procedure Discomfort: Every Patient is Unique
 Physician will individualize pain
management strategy
 Anxiety
 Anxiolytic medication is used to treat the symptoms
of anxiety
 Common medications: Valium, Xanax, Ativan
 Pain
 Local Anesthetics
 Block pain fibers
 Common medications: Lidocaine, Bupivacaine,
Mepivacaine
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Procedure Discomfort: Pain Medications (cont.)
 Analgesic known as “painkillers”
 Non-narcotic: NSAID
 Non-addicting, anti-inflammatory, anti-pyretic
 Common medications: Toradol, Ibuprophin, Naproxen
 Narcotic: Opioid
 Effects of opioids are due to decreased perception of pain, decreased reaction to pain
as well as increased pain tolerance
 Sedation and respiratory depression are side-effects
 Common medications: Percocet (acetaminophen and oxycodone), Vicodin
(acetaminophen and hydrocodone)
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Global Endometrial Ablation and Pain
 Cervical dilation
 sacral plexus
 Uterine distension
 thoracic plexus
 Tissue destruction
 thoracic plexus
 Time to perform procedure
 Combined sacral and thoracic plexus
plus anxiety
 Vasovagal
 Syncope may occur in women who have
pain during the gynecological procedure
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Important for patient and staff
Paracervical and Intracervical Block (deep cervical block)
 Para and Intracervical infiltration of a local anesthetic interrupts the
visceral sensory fibers of:
 lower uterus
 cervix
 upper vagina
 Procedure
 Equipment
 Sterile gloves
 Local anesthetic
 Syringe with appropriate needle
 Prepare cervix with antiseptic
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Paracervical and Intracervical Block (deep cervical block)
 Procedure (cont.)
 Injections at 10 mm deep at 2, 4, 8 and 10 positions
 lateral cervical margin (paracervical)
 mid-stroma (intracervical)
 1% Lidocaine (10 to 20 ml) commonly used
 Two randomized trials that compared the
analgesic effects of paracervical and intracervical
block - no statistically significant differences
between the two blocks in pain levels
 Onset within 5 minutes and peak plasma levels
10-15 minutes
Risk - seizure activity related to inadvertent intravascular injection
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Global Endometrial Ablation and Pain
 Cervical dilation
 Paracervical block
 Uterine distension
 Significant: narcotic
 Minimal: NSAID
 Tissue destruction
 Significant: narcotic
 Minimal: NSAID
 Time to perform procedure
 Anxiolytic, paracervical block,
analygesic
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Important for patient and staff
Pain Associated with Global Endometrial Ablation Procedures
 Cervical dilation
 Minimal dilation (if any) required: Her Option, Thermachoice
 Dilation required: NovaSure, HTA, MEA
 Uterine distension
 Minimal cavity distention: Her Option, MEA
 Mechanism requires distention: Thermachoice, NovaSure, HTA
 Tissue destruction
 Freezing-based treatment: Her Option
 Heat-based treatment: NovaSure, Thermachoice, HTA, MEA
 Time to perform procedure
 Shortest: NovaSure, MEA
 Intermediate: Thermachoice
 Longest: HTA, Her Option
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Visual Analogue Scores (VAS) of Pain
 One of the most important aspects of
performing a Global Endometrial
Ablation procedure in the office is
patient comfort
 Patients that easily tolerate
procedures such as endometrial or
colposcopic-directed biopsy are
usually excellent office candidates
 Patients many times are motivated to
have a procedure performed in a
familiar setting
 VAS is a measurement instrument for
subjective characteristics
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Visual Analogue Scores (VAS) of Pain
 VAS Studies:
 Thermachoice: VAS scores of 2.6 (intraoperative) to 6.0 (post-operative); subjects
used a fentanyl (narcotic) patch
 Hector O. Chapa et al. In-Office Thermachoice III Ablation: A Comparison of Two Anesthetic
Techniques. Gynecol Obstet Invest 2010;69:140–144
 HTA: VAS score of 6.4
 Martin Farrugia. Hysteroscopic endometrial ablation using the Hydro ThermAblator in an
outpatient hysteroscopy clinic: Feasibility and acceptability. Journal of Minimally Invasive
Gynecology (2006) 13, 178–182
 NovaSure: VAS 2 to 3 range with intravenous narcotic sedation
 P. Y. Labergeet al. Assessment and Comparison of Intraoperative and Postoperative Pain
Associated with NovaSure and ThermaChoice Endometrial Ablation Systems. May 2003, Vol.
10, No. 2 The Journal of the American Association of Gynecologic Laparoscopists
 Her Option: VAS pain scores of 1.1 without narcotic sedation
 Herbst SJ, Roy KH, Manjon JM, Lukes AS, Bruno R. An Extended Treatment Regimen Using
the Her Option Office Cryoablation Therapy for AUB is Well-Tolerated. AAGL 2007
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Outcomes
ACOG Practice Bulletin
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ACOG Practice Bulletin
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FDA and Global Endometrial Ablation Devices
 FDA decided on PBAC score comparison between Global
Endometrial Ablation devices and first generation endometrial
treatment as the basis of approval
 Criteria for enrollment
 Menorrhagia defined as PBAC >150
 Endometrial ablation success defined as PBAC <75
 All approved GEA devices were found to be equal to first generation
endometrial ablation for the treatment of menorrhagia
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Why not amenorrhea as a measuring stick?
 Some studies have a stricter interpretation of amenorrhea than
others; this dramatically affects Global Endometrial Ablation
amenorrhea outcomes
 Rare controlled comparisons in the literature
 Unless two devices are compared head/head in a randomized controlled trial
(RCT), it is impossible to reliably compare amenorrhea rates
 Most published studies that present amenorrhea rates are single-arm (no
comparison group) case series
 Wide swings in amenorrhea rates as compared to RCT data
 Bias introduced into results
 Population bias
 Provider bias
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Why not amenorrhea as a measuring stick?
 “Hidden” menstruation: Heat-ablation technologies cause an
Asherman-like syndrome with obliteration of the endometrial cavity
 Hormone levels are unaffected by endometrial ablation
 “Trapped” areas of functional endometrial tissue can result in a hematometra or
post ablation tubal syndrome (PATS) leading to cyclic pain - 10% with heat
based procedures
 Hysterectomy rates in patients utilizing heat technology are reported as:
 Up to 8% NovaSure
 Up to 13% Thermachoice
 Up to 9% HTA
 Cryoablation affects the endometrium via intracellular ice formation, dehydration
and ischemia to cause ablation
 Cavity remaining patent and without significant scarring - Lahey clinic study 0f 112
patients with intact cavity*
 Hysterectomy rate: up to 8%
* Duane Townsend, MD, FACOG, Innovative Technologies in Operative Gynecology For the 21st
Century
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“Hidden” Menstruation and Pain: Clinical Evidence
Devices – NovaSure, thermal balloon
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“Hidden” Menstruation and Pain: Clinical Evidence
Devices – NovaSure, thermal balloon
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Other Benefits
Improvements in Pain Associated with AUB
100%
90%
80%
very severe
severe
moderate
mild
very mild
none
70%
60%
50%
40%
30%
20%
10%
0%
baseline
3 months
6 months
12 months
87% of patients experienced moderate to severe pain at baseline
85% of patients reported mild to no pain at 12 months
Example – Her Option data
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Improvements in Mood Associated with AUB
100%
90%
80%
70%
Often
Sometimes
Rarely
Never
60%
50%
40%
30%
20%
10%
0%
Baseline
3 months
6 months
12 months
93% of patients reported mood complaints sometimes to often at baseline
90% of patients never or rarely had mood complaints at 12 months
Example – Her Option data
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Endometrial Ablation and
Transcervical Sterilization
Endometrial Ablation and Transcervical Sterilization
 Hysteroscopic sterilization has become an important alternative for
women deciding to undergo a permanent contraceptive procedure
 Gynecologists have explored combining these procedures with
endometrial ablation:
 Thermachoice: Valle, RF. Concomitant Essure tubal sterilization and
Thermachoice endometrial ablation: feasibility and safety. Fertil Steril 2006;
86:152
 NovaSure: Hopkins, MR. Radiofrequency global endometrial ablation followed
by hysteroscopic sterilization. J Minim Invas Gynecol 2008; 14:494
 Her Option: Presthus JB. Gynecology, Minnesota Gynecology and Surgery,
Edina, Minnesota. A Preliminary Study of the Safety of Her Option Office
Cryoablation Therapy System in Women with Implanted Essure Contraceptive
Inserts. Abstracts / Journal of Minimally Invasive Gynecology 15 (2008) S2
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ACOG’s Position
 “DO NOT perform the Essure procedure concomitantly with endometrial
ablation. Ablation causes intrauterine synechiae, which can compromise
(i.e., prevent) the 3-month Essure confirmation test (HSG). Women who
have inadequate 3-month confirmation tests cannot rely on Essure for
contraception”
 “Health care providers should follow the manufacturers’ instructions and
not perform same-day endometrial ablation and hysteroscopic sterilization.”
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Confirming Occlusion: Ultrasound???
 Pelvic radiography or transvaginal ultrasound as an initial test for
appropriate placement following Essure:
1. 150 women underwent Essure procedures followed at 12 weeks by pelvic
ultrasound, pelvic radiograph and HSG
 A "satisfactory" pelvic radiograph or ultrasound had high predictive values for HSGconfirmed tubal occlusion (100 and 99% respectively)
2. Case series of approximately 6,000 Essure procedures, 4 of 10 women who
became pregnant after the procedure had post-procedure confirmation of
placement with ultrasound alone
1.
Veersema, S, Vleugels, MP, Timmermans, A, Brolmann, HA. Follow-up of successful
bilateral placement of Essure microinserts with ultrasound. Fertil Steril 2005; 84:1733.
2.
Veersema, S, Vleugels, MP, Moolenaar, LM, et al. Unintended pregnancies after Essure
sterilization in the Netherlands. Fertil Steril 2008
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HSG: FDA Standard for Confirming Bilateral Tubal Occlusion
 “According to the U.S. device labeling, HSG is the only method to be used for
confirmation of tubal occlusion.”
 “…rates of adherence with HSG, rates varied from as high as 86.4% to as low as
12.7%”
 Essure: “Out of the 64 pregnancies that occurred…47% appeared to result from
nonadherence to use of interim contraception or return for HSG.”
 Adiana: “Out of the six pregnancies that occurred in the first 12 months…three
were attributed by the manufacturer to improper interpretation of the HSG.”
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Safety of Global Endometrial
Ablation
Complications
 Complications do occur with Global Endometrial Ablation - the rates
of adverse events are relatively rare
 Global Endometrial Ablation devices enhance safety in unique
manner compared to standard endometrial ablation:
 NovaSure: checking for uterine cavity pressure
 Thermachoice: monitoring balloon pressure
 HTA: monitoring fluid loss
 MEA: pre-op check of myometrial thickness
 Her Option: cryoablation under ultrasound guidance
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Complications: Studies
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Reimbursement
Reimbursement for Global Endometrial Ablation in an
Office Setting
 CMS has assigned CPT codes and associated Relative Value Units
(RVU) for performing endometrial ablation in the office
 CPT codes now reimburse for the cost of the disposable probes as well as a
significant facility fee
 Advantage
 Patient: having the procedure done with local anesthesia in the familiar setting
of the office environment
 Physician: ability to perform the procedure without having to deal with operating
room schedules, wait times, delays and paperwork
 CPT codes
 58353: Thermal ablation without hysteroscopic guidance
 58563: Thermal ablation under hysteroscopic guidance
 58356: Endometrial cryoablation
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Summary
Endometrial Ablation Therapy Goals
Endometrial ablation is
 Indicated for the treatment of menorrhagia or patient-perceived heavy
menstrual bleeding
 Premenopausal women with normal endometrial cavities
 No desire for future fertility
Patients who choose endometrial ablation should be willing to accept
normalization of menstrual flow, not necessarily amenorrhea, as an
outcome
Key tool:
• ACOG Practie Bulletin Clinical Management, Guidelines for ObstetricianGynecologists; Number 81, May 2007
• Part Number: 21200030
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Quality of life outcomes may be the preferred outcome
measure for patients undergoing treatment for DUB
Example – Her Option data
100%
90%
80%
70%
Moderate to extreme affect on QOL
60%
50%
Moderate to severe dysmenorrhea
40%
30%
Bleeding through clothing
Moderate to severe PMS symptoms
20%
10%
0%
Baseline
12 months
Satisfaction is highly correlated with significant improvement in quality of life and not
necessarily reduction in menstrual blood loss.
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Considerations for Performing Global Endometrial Ablation
in the Office
 Type of patient
 Not overly anxious
 Able to tolerate minor office procedures such as endometrial biopsy
 Motivated to NOT go to the hospital or ambulatory surgery center
 Procedure
 Comfortable for an office procedure
 Low risk of complications
 Equipment
 Size: compatible with standard exam rooms
 Easy to perform/utilize without OR-type staff
 Financial
 Adequate reimbursement for the physician
 Patient Co-pay
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