Sponsored by

AAGLAdvancing Minimally Invasive Gynecology Worldwide

Radu Apostol, DO Aarathi Cholkeri-Singh, MDScott G. Chudnoff, MD, MS Mark D. Levie, MD

Malcolm G. Munro, MD, FRCS(c), FACOG Kirsten J. Sasaki, MD

Hervé Fernandez, MD, PhD Miriam Hanstede, MDMegan C. Lutz, MD, MPH Julia Kefalas Troncon, MD

Sebastiaan Veersema, MD, PhD Dabao Xu, MD

Plenary 3: Hysteroscopy

DISCUSSANTS

MODERATOR

Richard J. Gimpelson, MD

CO-MODERATOR

Jorge E. Dotto, MD

Professional Education Information   Target Audience This educational activity is developed to meet the needs of surgical gynecologists in practice and in training, as well as other healthcare professionals in the field of gynecology.  Accreditation AAGL is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.  The AAGL designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.   DISCLOSURE OF RELEVANT FINANCIAL RELATIONSHIPS As  a  provider  accredited  by  the Accreditation  Council  for  Continuing Medical  Education, AAGL must ensure balance, independence, and objectivity in all CME activities to promote improvements in health care and not proprietary interests of a commercial interest. The provider controls all decisions related to identification  of  CME  needs,  determination  of  educational  objectives,  selection  and  presentation  of content,  selection  of  all  persons  and  organizations  that will  be  in  a  position  to  control  the  content, selection  of  educational methods,  and  evaluation  of  the  activity.  Course  chairs,  planning  committee members,  presenters,  authors, moderators,  panel members,  and  others  in  a  position  to  control  the content of this activity are required to disclose relevant financial relationships with commercial interests related  to  the subject matter of  this educational activity. Learners are able  to assess  the potential  for commercial  bias  in  information  when  complete  disclosure,  resolution  of  conflicts  of  interest,  and acknowledgment of  commercial  support are provided prior  to  the activity.  Informed  learners are  the final safeguards in assuring that a CME activity is independent from commercial support. We believe this mechanism contributes to the transparency and accountability of CME.   

Table of Contents 

Course Description ........................................................................................................................................ 1  Disclosure ...................................................................................................................................................... 2  Hysteroscopic Proximal Tubal Occlusion versus Laparoscopic Salpingectomy as  Treatment for Hydrosalpinges Prior to IVF or ICSI: A RCT S. Veersema .................................................................................................................................................. 4  Tertiary Prevention of Morbus Asherman: A Randomized Controlled Trial Title M. Hanstede  ................................................................................................................................................. 7  Uterine Synechiae after Hysteroscopic Myomectomy: Should We Use Bipolar or  Monopolar Energy?    H. Fernandez  .............................................................................................................................................. 10  Analysis of the Differential Genetic Expression between Symptomatic and  Asymptomatic Endometrial Polyps  J.K. Troncon  ................................................................................................................................................ 13  Video: Myomectomy of Type II Submucous Uterine Myoma Using Hysteroscopy  Endo‐Operative System (HEOS) D. Xu  ........................................................................................................................................................... 16  Video: Effective Management of Essure Complications M. Lutz  ........................................................................................................................................................ 17  Cultural and Linguistics Competency  ......................................................................................................... 18  

Plenary 3: Hysteroscopy

Moderator: Richard J. Gimpelson Co-Moderator: Jorge E. Dotto

Discussants: Radu Apostol, Aarathi Cholkeri-Singh, Scott G. Chudnoff, Mark D. Levie,

Malcolm G. Munro, Kirsten Sasaki

Faculty: Hervé Fernandez, Miriam Hanstede, Megan Lutz, Julia Kefalas Troncon, Sebastiaan Veersema, Dabao Xu

This session will discuss advanced analysis and hysteroscopic surgical techniques, as well as effective management of complications. Learning Objectives: At the conclusion of this course, the participant will be able to: 1) Describe advanced indications; and 2) discuss additional surgical techniques to improve outcomes of Hysteroscopic surgery.

Course Outline 2:15 Hysteroscopic Proximal Tubal Occlusion versus Laparoscopic Salpingectomy as

Treatment for Hydrosalpinges Prior to IVF or ICSI: A RCT S. Veersema

2:21 Discussant A. Cholkeri-Singh

2:25 Tertiary Prevention of Morbus Asherman: A Randomized Controlled Trial M. Hanstede

2:31 Discussant S.G. Chudnoff

2:35 Uterine Synechiae after Hysteroscopic Myomectomy: Should We Use Bipolar or Monopolar Energy? H. Fernandez

2:41 Discussant M.G. Munro

2:45 Analysis of the Differential Genetic Expression between Symptomatic and Asymptomatic Endometrial Polyps J.K. Troncon

2:51 Discussant K.J. Sasaki

2:55 Video: Myomectomy of Type II Submucous Uterine Myoma Using Hysteroscopy Endo-Operative System (HEOS) D. Xu

3:01 Discussant R. Apostol

3:05 Video: Effective Management of Essure Complications M. Lutz

3:11 Discussant M.D. Levie

3:15 Adjourn

PLANNER DISCLOSURE The following members of AAGL have been involved in the educational planning of this workshop (listed in alphabetical order by last name). Art Arellano, Professional Education Manager, AAGL* R. Edward Betcher* Amber Bradshaw Speakers Bureau: Myriad Genetics Lab Other: Proctor: Intuitive Surgical Sarah L. Cohen Consultant: Olympus Erica Dun* Joseph (Jay) L. Hudgens Contracted Research: Gynesonics Frank D. Loffer, Medical Director, AAGL* Suketu Mansuria Speakers Bureau: Covidien Linda Michels, Executive Director, AAGL* Karen C. Wang* Johnny Yi* SCIENTIFIC PROGRAM COMMITTEE Sawsan As-Sanie Consultant: Myriad Genetics Lab Jubilee Brown* Aarathi Cholkeri-Singh Consultant: Smith & Nephew Endoscopy Speakers Bureau: Bayer Healthcare Corp., DySIS Medical, Hologic Other: Advisory Board: Bayer Healthcare Corp., Hologic Jon I. Einarsson* Suketu Mansuria Speakers Bureau: Covidien Andrew I. Sokol* Kevin J.E. Stepp Consultant: CONMED Corporation, Teleflex Stock Ownership: Titan Medical Karen C. Wang* FACULTY DISCLOSURE The following have agreed to provide verbal disclosure of their relationships prior to their presentations. They have also agreed to support their presentations and clinical recommendations with the “best available evidence” from medical literature (in alphabetical order by last name). Radu Apostol* Aarathi Cholkeri-Singh Consultant: Smith & Nephew Endoscopy Speakers Bureau: Bayer Healthcare Corp., DySIS Medical, Hologic Other: Advisory Board: Bayer Healthcare Corp., Hologic Scott G. Chudnoff* Jorge E. Dotto* Hervé Fernandez*

2

Richard J. Gimpelson Contracted Research: Minerva Surgical Other: Advisory Board: Mirabilis Medical Other: Clinical Events Committee: Halt Medical Royalty: CooperSurgical Miriam Hanstede* Mark D. Levie Consultant: Bayer Healthcare Corp. Megan C. Lutz* Malcolm G. Munro Consultant: Aegea Medical, Boston Scientific Corp., Inc., Gynesonics, Hologic Stock Ownership: Channel Medical Kirsten J. Sasaki* Julia Kefalas Troncon* Sebastiaan Veersema Consultant: Bayer Healthcare Corp. Royalty: Olympus Dabao Xu* Content Reviewer has no relationships. Asterisk (*) denotes no financial relationships to disclose.

3

Hysteroscopic Proximal Tubal Occlusion versus Laparoscopic Salpingectomy as Treatment for

Hydrosalpinges Prior to IVF or ICSI: A RCT

Presenter: Sebastiaan Veersema

AAGL 2016

UMC Utrecht

The Netherlands

Disclosures

Consultant: Bayer Healthcare Corp.Royalty: Olympus

Objective

Discuss whether hysteroscopic proximal tubal occlusion by Essure devices as treatment for hydrosalpinges results in comparable ongoing pregnancy rates following IVF/ICSI as compared to laparoscopic salpingectomy.

In- en exclusion criteria

• Hydrosalpinx visible onultrasound uni- or bilateral.

• Hydrosalpinx confirmed by HSG or laparoscopy

• 18-41 years

• Indication for IVF/ICSI

< 18 years

> 41 years

Pregnancy

PID recently (< 6months)

Declining Essure

Submucous myomastype 0 and 1

Patient characteristics

Essure® SalpingectomyAge (years)(mean with SD)

32.6  (± 4.5) 32.0  (± 4.5)

Duration of subfertility (months) (median with 25th to 75th percentile)

32.4  (18.4-50.9) 25.4  (16.1-38.9)

SubfertilityPrimarySecondary

64.3%

35.7%

53.5%

46.5%

HydrosalpinxUnilateralBilateral

42.9%

57.1%

37.2%

62.8%

BMI (kg/m2) 24.5 (22.0-27.2) 23.5  (21.0-25.3)

Cycle duration (days) 28.0 (28.0‐29.0) 28.0 (27.0‐29.0) 

Semen (TMSC) (x106 /ml) 29.0 (10.5‐59.3)  33.0 (12.0‐48.0)

4

IVF/ICSI treatment characteristicsPer protocolEssure® (N=27) Salpingectomy (N=32)

P-value

Time interval between treatment and

embryo transfer (months)

5.2 (4.5 – 6.2) 3.9 (3.1 – 5.3) (n= 31) 0.001

Units of gonadotrophins 2550 (1700 – 3788)  2138 (1725 – 3075) (n=25) 0.331

Duration of ovarian stimulation (days) 13.0 (12.0 – 14.3)  12.0 (11.0 – 12.0) (n=27) 0.009

No. of retrieved oocytes 10.0 (5.0 – 15.0)  12.5 (6.3 – 16.5) (n=28) 0.525

No. of fertilized oocytes 6.0 (4.0 – 10.0) 8.0 (3.3 – 11.0) 0.471

Fertilization methodIVFICSINo fresh treatmentMissing

21/27 (77.8%)

2/27 (7.4%)

4/27 (14.8%)

27/32 (84.4%)

1/32 (3.1%)

4/32 (12.5%)

0.774

Transferred embryos

Fresh

Frozen‐thawed

24

37

27

21

0.743

0.017

Embryo transferSETDET

53

4

44

2

0.021

0.488

Embryo qualityTQEMQEPQE

31

15

8

29

7

5

0.204

0.326

0.772

Essure®(n=27)

Salpingectomy(n=32)

Absolute difference(95% CI)

P- value(Chi-Square)

Relative Risks 95-% CI for the RR

Primary outcome

Ongoing pregnancyPer included patientPer embryo transferred

9/27 (33.3%)9/61 (14.8%)

19/32 (59.4%)19/48 (39.6%)

36.1% (-1.8 – 50.0)24.8% (6.9 – 41.8)

0.0670.004

0.560.37

0.31 – 1.030.19 – 0.75

Secondary outcome

Implantation ratePer embryo transferred 11/61 (18.0%) 20/48 (41.7%) 23.7% (5.3 – 41.1) 0.01 0.43 0.23 – 0.81

Clinical pregnancy ratePer included patient 11/27 (40.7%) 20/32 (62.5%) 21.8 (-6.0 – 46.4) 0.121 0.65 0.38 – 1.11

Miscarriage ratePer included patientPer embryo transferred

2/27 (7.4%)2/61 (3.3%)

1/32 (3.1%)1/48 (2.1%)

4.3% (-10.3 – 21.4)1.2% (-8.3 – 9.5)

0.5881.000

2.371.60

0.23 – 27.740.15 – 17.12

Ectopic pregnancy ratePer included patientPer embryo transferred

0/27 (0.0%)0/61 (0.0%)

0/32 (0.0%)0/48 (0.0%)

n/an/a

n/an/a

n/an/a

n/an/a

Live birth ratePer included patientPer embryo transferred

8/27 (29.6%)8/61 (13.1%)

16/32 (50.0%)16/48 (33.3%)

20.4% (-7.0 – 44.5)20.2% (3.2 – 36.9)

0.1430.007

0.590.39

0.30 - 1.170.18 – 0.84

Pregnancy outcomes, per protocol

P-value 0.006

Pregnancy outcomes; Intention to treatEssure®(n=42)

Salpingectomy(n=43)

Absolute difference(95% CI)

P- value(Chi-Square)

Relative Risks 95-% CI for the RR

Primary outcome

Ongoing pregnancyPer included patientPer embryo transferred

11/42 (26.2%)11/78 (14.1%)

24*/43 (55.8%)22*/60 (36.7%)

29.6% (7.1 – 49.1)22.6% (7.1 – 37.7)

0.0080.003

0.470.38

0.27 - 0.830.20 - 0.73

Secondary outcome

Implantation ratePer embryo transferred 13/78 (16.7%) 23/60 (38.3%) 21.6% (5.7 – 37.0) 0.006 0.43 0.24 - 0.79

Clinical pregnancy ratePer included patient 13/42 (31.0%) 25/43 (58.1%) 27.1% ( 4.4 – 47.0) 0.016 0.53 0.32 - 0.89

Miscarriage ratePer included patientPer embryo transferred

2/42 (4.8%)2/78 (2.6%)

1/43 (2.3%)1/60 (1.7%)

2.5% (-8.3 – 14.1)0.9% (-6.7 – 7.5)

0.6161.000

2.051.54

0.19 - 21.740.14 - 16.57

Ectopic pregnancy ratePer included patientPer embryo transferred

0/42 (0%)0/78 (0%)

0/43 (0%)0/60 (0%)

n/an/a

n/an/a

n/an/a

n/an/a

Live birth ratePer included patientPer embryo transferred

9/42 (21.4%)9/78 (11.5%)

20*/43 (46.5%)18*/60 (30.0%)

25.1% (3.4 – 44.5)18.5% (4.0 – 33.1)

0.0220.009

0.460.38

0.24 - 0.890.19 - 0.80

References

Practice Committee of American Society for Reproductive Medicine incollaboration with Society of Reproductive Surgeons. Salpingectomy for hydrosalpinx prior to in vitro fertilization. Fertil Steril. 2008 Nov;90 (5 Suppl):S66-8.

Mijatovic V, Veersema S, Emanuel MH, Schats R, Hompes PG. Essurehysteroscopic tubal occlusion device for the treatment of hydrosalpinx prior to in vitro fertilization-embryo transfer in patients with a contraindication forlaparoscopy. Fertil Steril. 2010 Mar 1;93(4):1338-42.

Mijatovic V, Dreyer K, Emanuel MH, Schats R, Hompes PG. Essure hydrosalpinx occlusion prior to IVF-ET as an alternative to laparoscopic salpingectomy. Eur J Obstet Gynecol Reprod Biol. 2012 Mar;161(1):42-5.

Dreyer K, Lier MC, Emanuel MH, Twisk JW, Mol BW, Schats R, HompesPG,Mijatovic V. Hysteroscopic proximal tubal occlusion versus laparoscopicsalpingectomy as a treatment for hydrosalpinges prior to IVF or ICSI: an RCT. Hum Reprod. 2016 Sep;31(9):2005-16.

Take to work message

In the treatment of hydrosalpinges prior to IVF/ICSI is Essure inferior to laparoscopic salpingectomy.

5

Acknowledgements

Mark Hans Emanuel

Kim Dreyer

Peter Hompes

Velja Mijatovic

Free University Amnsterdam, Spaarne Gasthuis HoofddorpUMC Utrecht

The Netherlands

6

Tertiary Prevention of Morbus Asherman,

a Randomized Controlled Trial

Miriam Hanstede M.D.

Spaarne Gasthuis Haarlem/Hoofddorp

The Netherlands

Plenary Session 3: Hysteroscopy on November 16, 2016

Disclosures

2

I have no financial relationships to disclose

Objective

3

Discuss the best way to treat an Asherman patient after successful adhesiolysis to prevent spontaneous recurrence of adhesions

Intra Uterine Adhesions

IUA

Trauma

to the endometrium

in a

gravid uterus

Trauma to the endometrium in a non

gravid uterus

Trauma to the

endometrium caused by infections

Asherman

Syndroom

Trauma to the endometrium

caused byhypoxia

Presence of symptoms

Recurrence and grade of adhesionsGrade ESGE %

1 20.8

2 25.0

2a 22.7

3 29.1

4 38.5

5 41.9

Grade AFS %

Mild 22.9

Moderate 22.7

Servere 36.5

Hanstede M et al. Results of centralized Asherman surgery, 2003-2013. Fertil Steril. 2015 Dec;104(6):1561,1568.

RCT, prevention of recurrence of adhesions

Singel center, single blind RCT

IRB approval

Power calculation

110 women were included in the study

60 were inlcuded in the hormone group of endogenous 60 were included in the controle group

Schedule

Day 1 to 10: 4 mg oestradiol

Day 11 to 15: 4 mg oestradiol en 10 mg noresthisteron

Day 16 to 20: geen medicatie

Day 21 to 35: 4 mg oestradiol

Day 36 to 40: 4 mg oestradiol 10 mg noresthisteron

7

Protocol Asherman Treatment

Hysteroscopy with

Fluoroscopy

After successful procedure

Cu-less IUD

Hysteroscopiccontrol

After 8-10weeks

Methods

InclusionWomen with M.Asherman whom underwent successful hysteroscopic adhesiolysis

Exclusion- Women with anovulation oligomenorrhea or amenorrhea prior to the development of Asherman syndrome

- Uterine congenital anomalies- Women who do not master the Dutch or English language

- Women younger than 18 years of age

- Women with contraindications of hormonal suppletion

- Women who use hormonal suppletion

Flow Chart

9

Succesfull TCA

Hormone group

60

8-10 weeks visit

- Hysteroscopy

-PBAC and questionnaire

6,9, 12 months contact

- PBAC and questionaire

- recurrence and re-intervention

- Pregnancy

Controle Group

60

8-10 weeks visit

- Hysteroscopy

-PBAC and questionnaire

6,9, 12 months contact

- PBAC and questionaire

- recurrence and re-intervention

- Pregnancy

Randomisation after informedconsent

Baseline Caracteristics

Hormones No-Hormones P

Total 60 60

Age 32.5 (22-41) 33.2 (23-43) 0.471

BMI 23.9 (18-40) 24.4 (18-36) 0.582    

Causal procedure 0.620    

First trimester 71% 76%

Post partum 30% 24%

Grade Adhesions 0.260

Mild 7% 8%

Moderate 45% 54%

Severe 48% 38% 0

Primary outcome

(OR (95% CI): 0.77 (0.30-1.98) p=0,590)

Secondary outcome

8

Secondary outcome

Endometrial thickness Hormone group 5,1±1,2mm

Control group 5,5±2,1mm

(Mann-Whitney test, p=0,894).

Secondary outcome

• Good outcome/Bad outcome combined 8 to10 weeksHormone group 80,0% Controle group 83,3% • 6 months Hormone group 57,6% Controle group 68,0%

9 monthsHormone group 90,5% Controle group 82,4%

12 monthsHormone group 95,5% Controle group 91,7%

Take to work message

15

Influence the chance of getting pregnant after adhesiolysis Influences the endometrial thicknessNot influence the chance of recurrence of adhesions

Weather or not women are treated with a hormone schedule in Asherman patients after a successful adhesiolysis, does:

Take to work message 2

16

The grade of adhesions tends to be higherThey are more difficult to restore uterine anatomyThey have more risk of spontaneous recurrence of adhesions They have a significant smaller chance of getting pregnant

If your causal procedure is a post partum curettage

Acknowledgments

17

Mark Hans EmanuelEls HijmansJolies van de Berg

References

18

1 Schenker JG, Margalioth EJ. Intrauterine adhesions: an updated appraisal. Fertil Steril. 1982;37:593–610 2 Hanstede MMF, van der Meij E, Goedemans L, Emanue MH. Centralized Asherman’s surgery 2003-2013: Ferti Steril 2015 3 K. Wamsteker and S. De Block, “Diagnostic hysteroscopy: technique and documentation,” in Endoscopic Surgery for Gynecologists, C. Sutton and M.

Diamond, Eds., pp. 511–524, Saunders, London, UK, 1998. 4 American Fertility Society classifications of adnexal adhesions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, mullerian

anomalies and intrauterine adhesions. Fertil Steril.1988;49:944–955 5 Yu D, Wong Y, Cheong Y, Xia E, Li T. Asherman syndrome: one century later. Fertil Steril, 2008;89. 759–779 6 Fedele L, Vercellini P, Viezzoli T, Ricciardiello O, Zamberletti D. Intrauterine adhaesions: current diagnostic and therapeutic trends. Acta Eur Fertil

1986;17:317. 7 Capella-Allouc S, Morsad F, Rongieres-Bertrand C, Taylor S, Fernandez H. Hysteroscopic treatment of severe Asherman’s syndrome and subsequent fertility.

Hum Reprod 1999;14:1230–3. 8 Pace S, Stentella P, Catania R, Palazzetti PL, Frega A. Endoscopic treatment of intrauterine adheiosn. Clin Exp Obstet Gynecol 2003;30:26-8. 9 Fernandez H, Al Najjar F, Chauvenaud-Lambling et al. (2006). "Fertility after treatment of Asherman's syndrome stage 3 and 4". J Minim Invasive Gynecol 13

(5): 398–402.

9

Uterine Synechiae after HysteroscopicMyomectomy: Should We Use Bipolar or 

Monopolar Energy? 

Presenter: Hervé FERNANDEZ

I have no financial relationships to disclose.

Disclosures

Objective

The main objective was to compare the rate of 

synechiae after resection of myomas FIGO type 

0, 1 and 2 using bipolar or monopolar energy

Design

Randomized controlled trial,

Single‐blind, two‐centre,

Superiority trial

WOMEN

Under 42 years,

With either symptomatic menometrorrhagiaand/or primary/secondary infertility,

One or more myoma type 0‐2 by 3D US,

Amenable to hysteroscopic surgery

Material & Methods

Pre operative visit: consent form and randomization

2D and 3D ultrasound by abdominal & vaginal way

Office hysteroscopy by vaginoscopy

Day surgery

Systematic control by office hysteroscopy at 6 weeks

10

HYSTEROSCOPIC SURGERY

• Hysteroscopic myomectomy was performed using a rigid (Karl Storz®) 26 Fr resectoscope with either monopolar or bipolar energy through an electrode with a cutting loop of 4mm

• All procedures were planned to occur during the follicular phase of the menstrual cycle

• No anti‐adhesion devices or hyaluronic acid were inserted into the uterine cavity after the resection

Main Results

• 58 patients randomized and analysed into two arms depending on the type of energy: monopolar (n = 27) vs. bipolar (n = 31).

• No statistically significant differences existed between the two treatment arms regarding women characteristics

– monopolar 25 ± 10.4 mm vs bipolar  29.2 ± 12.2 mm

Measurements and Main Results

The synechiae rate observed during the postoperative follow‐up visit at 6 weeks

in bipolar energy = 1/31 (3.2%)

versus 

monopolar energy = 7/27 (26.9%)

(p = 0.012)

Measurements and Main Results

4 synechiae were grade I, 2 were grade II and 1 was grade III.

The only case of synechiae observed in bipolar energy group, was grade I

Due to significative difference, the study

stopped for ethical reason to avoid a loss of 

opportunity for the women

Conclusion 

First randomized comparative clinical study that 

shows a significant superiority in reducing the 

synechiae rate using bipolar energy in the 

resection type fibroids 0‐2 compared to the 

monopolar energy

11

Conclusion 

• Office hysteroscopic control, 6 weeks after resection of myoma in order to treat iatrogenic, uncomplicated synechiae, using simple fluid distension techniques must become the gold standart

• Place of routine use of anti‐adhesionaltreatments or device on debate

Acknowledgements

André Nazac, M.Comtet, AG.Pourcelot, X. Deffieux, M. Vassilieff, C.Lalanne,

M. Duracinsky

Brugmann Hospital Brussels

12

Analysis of the Differential Genetic Expression between Symptomatic and

Asymptomatic Endometrial Polyps

Júlia Kefalás Troncon, M.D.

MSc Student in Obstetrics and Gynecology,

Assistant Physician - Department of Obstetrics and Gynecology, Faculty of

Medicine of Ribeirão Preto, University of São Paulo - USP, Ribeirão Preto (SP), Brazil

I have no financial relationships to disclose.

OBJECTIVES

• Discuss the association between endometrial polyps andendometrial cancer

• Evaluate if there is benefit in performing hysteroscopicpolypectomy in asymptomatic postmenopausal patients

BACKGROUND

• PATHOGENESIS OF ENDOMETRIAL POLYPS

-Differential hormonal receptor expression favouringhyperestrogenism

-Unbalance between cellular proliferation and apoptosisfavouring tissue growth

Association with type I endometrial cancer?

NOGUEIRA. 2005, RBGO.SANT’ANA DE ALMEIDA et al. 2004,MATURITAS.

MAIA et al. 2004, BJOG.

BACKGROUND

• RISK FACTORS FOR MALIGNANCY

-Age (> 60 years)

-Menopausal status

-Polyp size (> 15mm)

-Postmenopausal bleeding

Around 3,5% prevalence of endometrial hyperplasiaand cancer

ANTUNES et al. 2007, MATURITAS.BAIOCCHI et al. 2009, AJOG.BEN-ARIE et al. 2004, EUR J OBSTET GYNECOL REPROD BIOL.

METHODS

• Cross-sectional study

• Tertiary referral hospital

• Postmenopausal patients undergoing hysteroscopicpolypectomy

39 symptomatic

21 asymptomatic

• Exclusion: use of hormonal therapy or tamoxifen

• Signed informed consent

13

METHODS

• Sample of tissue from the extracted polyp

• DNA extraction and PCR (Polimerase Chain Reaction)

• Analysis of the differential genic expression: genesinvolved in endometrial carcinogenesis

GENES EVALUATED

• PTEN

Tumor-suppressor gene (favors apoptosis)

• MLH-1

Mismatch repair system (Microsatellite instability)

• CTNNB1

Beta-catenin protein (WNT pathway of cellulardifferentiation)

• BCL-2

Inhibits apoptosisABAL et al. 2006, HISTOL HISTOPATHOL.HECHT, MUTTER. 2006, J CLIN ONCOLKONOPKA et al. 2007, J CANCER RES CLIN ONCOL. MUTTER et al. 2000, J NATL CANCER I.SAKURAGI et al. 2002, GYNECOL ONCOL. SANSAL, SELLERS. 2004, J CLIN ONCOL. WANG et al. 2009, CLIN CANCER RES. YANG et al. 2015, CANCER CAUSES CONTROL

RESULTS

Variable Group N. Obs. Average Minimum Maximum P-value

AGE0 21 60,29 48 79

0,161 39 63,15 51 83

DURATION OF MENOPAUSE

0 21 11,48 2 240,13

1 38 14,79 2 37

BCL2__RQ_0 21 2,84 0,23 17,88

0,981 39 2,14 0,02 26,95

PTEN__RQ_0 21 2,93 0,1 31,28

0,741 39 4,37 0,06 71,68

MLH1__RQ_0 21 4,74 0,38 64,31

0,311 39 3,74 0,17 68,98

CTNNB1_RQ_0 21 2,01 0,52 18,7

0,741 39 1,65 0,18 11,17

POLYP SIZE0 21 2,55 1,5 4,8

0,881 39 2,51 0,8 6

DISCUSSION

• Lack of evidence estabilishing if endometrial polyps arein fact cancer precursors – DETECTION BIAS

• It can not be determined if the bleeding was trulyoriginated from the polyp – LESS THAN 1% OFCANCERS CONFINED TO THE POLYP

• EPIDEMIOLOGICAL ASSOCIATION?

SAVELLI et al. 2003, AJOG.

PERRI et al. 2010, AJOG.

CONCLUSIONS

• Evaluate the uterine cavity in its entirety

• Offer polypectomy in symptomatic patients wheneverpossible

• Individualize the conduct in asymptomatic polyps /Patient’s desire

• Further studies needed – are polyps only markers ofendometrial disease and not cancer precursors?

MITTAL, DA COSTA. 2008, INT J GYNECOLPATHOL.PERRI et al. 2010, AJOG.

REFERENCES1. Abal M, Planaguma J, Gil-Moreno A, Monge M, Gonzalez M, Baro T, et al. Molecular pathology of endometrial carcinoma: transcriptional

signature in endometrioid tumors. Histol Histopathol. 2006;21(2):197-204.2. Antunes A, Jr., Costa-Paiva L, Arthuso M, Costa JV, Pinto-Neto AM. Endometrial polyps in pre- and postmenopausal women: factors

associated with malignancy. Maturitas. 2007;57(4):415-21.3. Baiocchi G, Manci N, Pazzaglia M, Giannone L, Burnelli L, Giannone E, et al. Malignancy in endometrial polyps: a 12-year experience.

AJOG. 2009;201(5):462 e1-4.4. Ben-Arie A GC, Laviv Y, Levy R, Caspi B, Huszar M, et al. The malignant potential of endometrial polyps. Eur J Obstet Gynecol Reprod

Biol. 2004;115(2):206-10.5. Hecht JL, Mutter GL. Molecular and pathologic aspects of endometrial carcinogenesis. J Clin Oncol. 2006;24(29):4783-91.6. Konopka B, Janiec-Jankowska A, Czapczak D, Paszko Z, Bidzinski M, Olszewski W, et al. Molecular genetic defects in endometrial

carcinomas: microsatellite instability, PTEN and beta-catenin (CTNNB1) genes mutations. J Cancer Res Clin Oncol. 2007;133(6):361-71.7. Maia H, Jr., Maltez A, Studart E, Athayde C, Coutinho EM. Ki-67, Bcl-2 and p53 expression in endometrial polyps and in the normal

endometrium during the menstrual cycle. BJOG . 2004;111(11):1242-1247.8. Mittal K, Da Costa D. Endometrial hyperplasia and carcinoma in endometrial polyps: clinicopathologic and follow-up findings. Int J

Gynecol Pathol. 2008;27(1):45-8.9. Mutter GL, Lin MC, Fitzgerald JT, Kum JB, Baak JPA, Lees JA, et al. Altered PTEN expression as a diagnostic marker for the earliest

endometrial precancers. J Natl Cancer I. 2000;92(11):924-31.10. Nogueira AA. Pólipos endometriais. RBGO. 2005;27(5):289-92.11. Perri T, Rahimi K, Ramanakumar AV, Wou K, Pilavdzic D, Franco EL, et al. Are endometrial polyps true cancer precursors? AJOG.

2010;203(3):232 e1-6.12. Sakuragi N, Salah-eldin AE, Watari H, Itoh T, Inoue S, Moriuchi T, et al. Bax, Bcl-2, and p53 expression in endometrial cancer. Gynecol

Oncol. 2002;86(3):288-96.13. Sansal I, Sellers WR. The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol. 2004;22(14):2954-63.14. Sant'Ana de Almeida EC, Nogueira AA, Candido dos Reis FJ, Zambelli Ramalho LN, Zucoloto S. Immunohistochemical expression of

estrogen and progesterone receptors in endometrial polyps and adjacent endometrium in postmenopausal women. Maturitas.2004;49(3):229-233.

15. Savelli L, De Iaco P, Santini D, Rosati F, Ghi T, Pignotti E, et al. Histopathologic features and risk factors for benignity, hyperplasia, andcancer in endometrial polyps. AJOG. 2003;188(4):927-31.

16. Wang Y, Hanifi-Moghaddam P, Hanekamp EE, Kloosterboer HJ, Franken P, Veldscholte J, et al. Progesterone inhibition of Wnt/beta-catenin signaling in normal endometrium and endometrial cancer. Clin Cancer Res. 2009;15(18):5784-93.

17. Yang HP, Meeker A, Guido R, Gunter MJ, Huang GS, Luhn P, et al. PTEN expression in benign human endometrial tissue and cancer in relation to endometrial cancer risk factors. Cancer Causes Control. 2015;26(12):1729-36.

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ACKNOWLEDGEMENTS

Julio C. Rosa-e-Silva, MD, PhDJuliana Meola, PhD

Francisco J. Candido-dos-Reis, MD, PhDOmero B. Poli-Neto, MD, PhDAntonio A. Nogueira, MD, PhD

Department of Obstetrics and Gynecology, Faculty of Medicine of Ribeirão Preto, University of São Paulo - USP,

Ribeirão Preto (SP), Brazil

15

Myomectomy of Type II Submucous Uterine Myoma Using

Hysteroscopy Endo-Operative System (HEOS)

Presenter: Dabao Xu, MD Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China

Objective: This video demonstrates the advantages of using HEOS, a specially designed operative

hysteroscope with a 13 Fr working channel and 3mm cold instruments, to remove a type II myoma while

protecting the endometrium overlying the surface of the myoma in a single procedure.

Design: Step-by-step explanation of the technique using videos and pictures (educative video) (Canadian Task Force Classification III). Setting: Third Xiangya Hospital

Patient(s): A 37 yo, G2P0 underwent routine ultrasound revealed a 33mm*32mm*34mm myoma

located in the left uterine wall,and 1/5 of the myoma protruded into the uterine cavity.

Intervention: Myomectomy of type IIsubmucous uterine myona using HEOS (Sopro-comeg Company,

Bordeaux, France).

Measurement and Main Results: The type II submucous myoma was removed completely using HEOS

cold scissors and graspers in a single procedure. The operation time totaled 28 minutes. No

complications. Postoperative pathology: uterine myoma. The myoma bed appeared well-healed at the

follow up visit 2 months postoperatively.

Conclusion: When indicated, myomectomy of a submucous myoma using HEOS is safer than using

traditional resectoscopy.

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Effective Management of Essure Complications

Presenter: Megan Lutz, MD, MPH Women's Health Institute, Cleveland Clinic, Cleveland, Ohio

Objective: To demonstrate management of complications with Essure tubal sterilization.

Design: Narrated video of three case studies demonstrating surgical management of Essure

complications. Setting: After the introduction of Essure hysteroscopic tubal sterilization to the market in

2002, the first formal post-market FDA study on safety and effectiveness was published in September

2015. Because the conclusions from the study do not seem congruent with patient concerns for safety

and adverse events, the FDA is evaluating the need for further studies. Gynecologists currently seek

such substantiated studies to properly guide clinical counseling and patient consent for management of

under-documented Essure complications, as well as evidence based techniques for Essure complication

management. While techniques for removal have been described, this video aims to address common

factors encountered with management of Essure complications.

Interventions: Laparoscopic and hysteroscopic approach to adverse events from Essure with several key

points for successful removal.

1. Diagnostic laparoscopy revealing the malpositioned Essure insert when imaging modalities are

otherwise equivocal

2. Informed consent establishing the goal of the patient, addressing risk of retained fragments,

discussing desire to retain or remove uterus, and discussing exposure to fluoroscopy and

radiation

3. Visual inspection and routine intra-operative imaging evaluating for retained fragments with

fluoroscopy and KUB

Conclusion: Until larger studies are available, we demonstrate several safe and effective strategies to

navigate complications with Essure tubal sterilization.

Sources: 1. Chudnoff SG et al. Hysteroscopic Essure Inserts for Permanent contraception: Extended Follow-up Results of a Phase

III Multicenter International Study. JMIG. Sept-Oct 2015; 2. Dhruva SS, Ross JS, Gariepy AM et al. Revisiting Essure- Toward Safe

and Effective Sterilization. NEJM, Oct 8, 2015.

17

CULTURAL AND LINGUISTIC COMPETENCY Governor Arnold Schwarzenegger signed into law AB 1195 (eff. 7/1/06) requiring local CME providers, such as

the AAGL, to assist in enhancing the cultural and linguistic competency of California’s physicians

(researchers and doctors without patient contact are exempt). This mandate follows the federal Civil Rights Act of 1964, Executive Order 13166 (2000) and the Dymally-Alatorre Bilingual Services Act (1973), all of which

recognize, as confirmed by the US Census Bureau, that substantial numbers of patients possess limited English proficiency (LEP).

California Business & Professions Code §2190.1(c)(3) requires a review and explanation of the laws

identified above so as to fulfill AAGL’s obligations pursuant to California law. Additional guidance is provided by the Institute for Medical Quality at http://www.imq.org

Title VI of the Civil Rights Act of 1964 prohibits recipients of federal financial assistance from

discriminating against or otherwise excluding individuals on the basis of race, color, or national origin in any of their activities. In 1974, the US Supreme Court recognized LEP individuals as potential victims of national

origin discrimination. In all situations, federal agencies are required to assess the number or proportion of LEP individuals in the eligible service population, the frequency with which they come into contact with the

program, the importance of the services, and the resources available to the recipient, including the mix of oral

and written language services. Additional details may be found in the Department of Justice Policy Guidance Document: Enforcement of Title VI of the Civil Rights Act of 1964 http://www.usdoj.gov/crt/cor/pubs.htm.

Executive Order 13166,”Improving Access to Services for Persons with Limited English

Proficiency”, signed by the President on August 11, 2000 http://www.usdoj.gov/crt/cor/13166.htm was the genesis of the Guidance Document mentioned above. The Executive Order requires all federal agencies,

including those which provide federal financial assistance, to examine the services they provide, identify any

need for services to LEP individuals, and develop and implement a system to provide those services so LEP persons can have meaningful access.

Dymally-Alatorre Bilingual Services Act (California Government Code §7290 et seq.) requires every

California state agency which either provides information to, or has contact with, the public to provide bilingual

interpreters as well as translated materials explaining those services whenever the local agency serves LEP members of a group whose numbers exceed 5% of the general population.

~

If you add staff to assist with LEP patients, confirm their translation skills, not just their language skills.

A 2007 Northern California study from Sutter Health confirmed that being bilingual does not guarantee competence as a medical interpreter. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2078538.

US Population

Language Spoken at Home

English

Spanish

AsianOther

Indo-Euro

California

Language Spoken at Home

Spanish

English

OtherAsian

Indo-Euro

19.7% of the US Population speaks a language other than English at home In California, this number is 42.5%

18