Sponsored by

AAGLAdvancing Minimally Invasive Gynecology Worldwide

Plenary 3 - Hysteroscopy

MODERATORS

Philip G. Brooks, MDAngelos G. Vilos, MD

Attilio Di Spiezio Sardo, MDKarina M. Haber, MD Nicholas A. Ryan, MD

Simone Ferrero, MD, PhDTadeusz Issat, MD

Lennie van Hanegem, MD

GLOBAL CONGRESSON MINIMALLY INVASIVE GYNECOLOGYNOV. 17-21, 2014 | Vancouver, British Columbia

43rd AAGL

Professional Education Information   Target Audience This educational activity is developed to meet the needs of residents, fellows and new minimally invasive specialists in the field of gynecology.  Accreditation AAGL is accredited by the Accreditation Council for Continuing Medical Education 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  Safety, Efficacy and Reproductive Outcomes of Hysteroscopic Outpatient Metroplasty to Expand Dysmorphic Uteri (HOME‐DU Technique) A. Di Spiezio Sardo ........................................................................................................................................ 3  Office Essure in Septate Uterus and Double Cervix K.M. Haber .................................................................................................................................................... 5  Triptorelin, Letrozole and Ulipristal Acetate Treatment before Hysteroscopic Resection of Large Myomas: Prospective Comparative Study S. Ferrero ....................................................................................................................................................... 6  Resection of Retained Products of Conception with the Myosure XL N.A. Ryan ....................................................................................................................................................... 9  Diagnostic Work‐Up for Postmenopausal Bleeding – A Randomized Controlled Trial L. van Hanegem ................................................................................................................................ 10  A Randomized, Single Blind, Placebo‐Controlled Trial for the Pain Reduction during the Outpatient Hysteroscopy after Ketoprofen or Intravaginal Misoprostol T. Issat ......................................................................................................................................................... 13  Cultural and Linguistics Competency  ......................................................................................................... 16   

 

Plenary 3 ‐ Hysteroscopy  

Moderators: Philip G. Brooks, Angelos G. Vilos  

Faculty: Attilio Di Spiezio Sardo, Simone Ferrero, Karina M. Haber, Tadeusz Issat,  Nicholas A. Ryan, Lennie van Hanegem 

 This session is comprised of presentations by experienced hysteroscopists who will describe how hysteroscopy can be used safely and more effectively to  improve reproductive function and/or reduce symptoms of bleeding from retained  products  of  conception,  intracavitary  myomata  and/or  congenitally  deformed  uteri.  Studies  of medications to reduce myoma size or decrease operative pain from hysteroscopies will be reported.    Learning Objectives: At the conclusion of this course, the participant will be able to: 1) Describe the use of operative hysteroscopy in patients with various congenital uterine deformities, emphasizing the safety and efficacy of hysteroscopy in the management of abnormal uterine bleeding.  

Course Outline  2:15  Safety, Efficacy and Reproductive Outcomes of Hysteroscopic Outpatient  

Metroplasty to Expand Dysmorphic Uteri (HOME‐DU) Technique)  A. Di Spiezio Sardo   

2:25  Office Essure in Septate Uterus and Double Cervix  K.M. Haber 

2:31  Triptorelin, Letrozole and Ulipristal Acetate Treatment before Hysteroscopic  Resection of Large Myomas: Prospective Comparative Study  S. Ferrero 

2:41  Resection of Retained Products of Conception with the Myosure XL  N.A. Ryan 

2:48  Diagnostic Work‐Up for Postmenopausal Bleeding – A Randomized  Controlled Trial  L. van Hanegem 

2:58  A Randomized, Single Blind, Placebo‐Controlled Trial for the Pain Reduction during  the Outpatient Hysteroscopy after Ketoprofen or Intravaginal Misoprostol  T. Issat 

3:15  Adjourn  

Page 1

PLANNER DISCLOSURE The following members of AAGL have been involved in the educational planning of this workshop and have no conflict of interest to disclose (in alphabetical order by last name). Art Arellano, Professional Education Manager, AAGL* Viviane F. Connor* Kimberly A. Kho* Frank D. Loffer, Medical Director, AAGL* Linda Michels, Executive Director, AAGL* M. Jonathon Solnik* Johnny Yi* 

 SCIENTIFIC PROGRAM COMMITTEE Arnold P. Advincula Consultant: Blue Endo, Intuitive Surgical, SurgiQuest Other: Royalties: CooperSurgical William M. Burke* Rosanne M. Kho* Ted T.M. Lee Consultant: Ethicon Endo‐Surgery Javier F. Magrina* Ceana H. Nezhat  Consultant: Karl Storz  Other: Medical Advisor: Plasma Surgical Other: Scientific Advisory Board: SurgiQuest Kevin J.E. Stepp Consultant: CONMED Corporation, Teleflex Other: Stock Ownership: Titan Medical Robert K. Zurawin Consultant: Bayer Healthcare Corp., CONMED Corporation, Ethicon Endo‐Surgery, Hologic,  Intuitive Surgical  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). Philip G. Brooks* Attilio Di Spiezio Sardo* Simone Ferrero* Karina M. Haber* Tadeusz Issat* Nicholas A. Ryan* Nehalennia (Lennie) van Hanegem* Angelos Vilos*  Asterisk (*) denotes no financial relationships to disclose. 

Page 2

ATTILIO DI SPIEZIO SARDO, MD, PhDDepartment of Obstetrics and Gynecology

University “Federico II” of Naples

Diagnosing class U1 uteri…

Past

Present

“HOME-DU TECHNIQUE”

Ambulatory setting

Conscious sedation

5-mm hysteroscope

Vaginoscopic approach

5 Fr bipolar electrode

Polyethylene oxide-sodium carboxymethylcellulose gel

Population

T-shaped Tubular

I

IO

I

IO

Page 3

Anatomical results (1) Anatomical results (2)

Inclusion criteria Pregnancy Abortion rate

Term delivery rate

Live birth rate

Primaryinfertility (n=22)

12/22

(54%)

3/12

(25%)

9/12

(75%)

9/12

(75%)

Repeated earlyabortions ( 2)

(n=7)

5/7

(71%)

2/5

(40%)

2/5

(40%)

3/5

(60%)

Preterm delivery

(n=1)

0/1

(0,0%)

- - -

Total

(n=30)

17/30

(56%)

5/17

(29.4%)

11/17*

(64,7%)

12/17

(70.6%)

*only 1 case of preterm delivery (5,9%)

Functional results Perspectives

Further studies with a control group managed expectantly

Improvement of the uterine cavity morphology/volume vsendometrial injury

HOME-DU vs standard technique

Relevance of anti-adhesions treatment

The real voyage of discoveryconsists not in seeking newlandscapes, but having new

eyes

Proust

Page 4

Office Essure in Uterine Didelphys 

 

Karina Haber, M.D. 

Montefiore Medical Center, Bronx, New York 

 

Study Objective: To show a unique case of office essure placement  in a patient with a double vagina, 

double cervix, and uterine didelphys.  

 

Design: Step‐by‐step explanation of the technique using educative video. 

 

Setting: Müllerian duct anomalies (MDA’s) occur in approximately 1% of the general population and are 

associated with uterine, cervical, and vaginal abnormalities. Office based hysteroscopic sterilization has 

been shown to be a well tolerated  in women with normal female anatomy and has been concluded to 

be good option for those who desire permanent sterility. In women with MDA’s, office hysteroscopy can 

be used to confirm anatomical variations. In experienced hands, office based hysteroscopic sterilization 

should be considered as a feasible option in women with a double vagina, double cervix, and/or uterine 

anomalies. 

 

Interventions: Office hysteroscopic placement of Essure device in a woman with a rare MDA and desires 

permanent sterilization.  

 

Conclusions: This technique of office‐based hysteroscopic sterilization is a reasonable choice for women 

with Müllerian duct anomalies. 

Page 5

TRIPTORELIN, LETROZOLE AND ULIPRISTAL ACETATE TREATMENT

BEFORE HYSTEROSCOPIC RESECTION OF LARGE MYOMAS: PROSPECTIVE

COMPARATIVE STUDY

Simone Ferrero, MD, PhD

Department of Obstetrics and Gynecology, San Martino Hospital and National

Institute for Cancer Research, University of GenoaItaly

AUTHORS’ DISCLOSURE

I have no financial relationships to disclose

OBJECTIVES OF THE STUDY

- Primary objective: to investigate the usefulness of preoperativetreatment with triptorelin (gonadotropin releasing hormoneagonist), letrozole (aromatase inhibitor) and ulipristal acetate(selective progesterone receptor modulator) in patientsundergoing hysteroscopic removal of large uterine submucosalmyomas (20-35 mm)

- Secondary objective: to assess the changes in myoma volumecaused by the three hormonal therapies

After this lecture, the attendee should implement the preoperativehormonal treatment prior to hysteroscopic myomectomy.

BACKGROUND

• Hysteroscopic resection is the standard treatment of submucosalmyomas.

• Contradictory results have been reported on the usefulness ofpreoperative administration of gonadotropin releasing hormone agonistsprior to hysteroscopic myomectomy (Muzii et al., 2010; Mavrelos et al.,2010; Kamath et al., 2014).

• Letrozole (a non-steroidal aromatase inhibitor) and ulipristal acetate (aselective progesterone-receptor modulator) have been used to decreasethe volume of uterine myomas and control uterine bleeding (Gurates etal., 2008; Parsanezhad et al., 2010; Donnez et al., 2012; Duhan et al.,2013; Song et al., 2013; Leone Roberti Maggiore et al., 2014; Donnezet al., 2014).

MATERIALS AND METHODS

Study design: single center prospective non-randomized comparative study

Study patients underwent either direct surgery (group S) or received a 3-month preoperative treatment with one of the following drugs:

- triptorelin (3.75 mg intramuscular injection every 28 days; group T)

- letrozole (2.5 mg/day; group L) *

- ulipristal acetate (5 mg/day; group U)* Letrozole is not approved for the treatment of uterine myomas by the FDA and Italian Ministry of Health and, therefore, the use of these drugs should be considered experimental

The choice of treatment was not randomized; treatment allocation was decided on the basis of the preference of the patients. Patients were informed in details on the potential adverse effects and on the cost of treatment.

Inclusion criteria:

- premenopausal age

- myomas graded as type 0, type 1 or type 2 according to the FIGO classification (Munro et al., 2011) with diameter between 20 and 35 mm

Exclusion criteria:

- associated polyps

- associated non-hysteroscopic surgical procedures

- > 2 myomas requiring hysteroscopic resection

Page 6

Evaluation of myomas

• the largest diameter and volume of the submucosal myomas (VOCAL, GE Healthcare, Milwaukee, WI, USA) were assessed by transvaginal ultrasonography

• office diagnostic hysteroscopy was performed to verify that the characteristics of the myomas were compatible with the inclusion criteria of the study

• on the day of surgery, a second transvaginal ultrasonography was performed to evaluate the changes in volume of the myomas in the groups receiving preoperative medical treatments

Hysteroscopic resection of the myomas

• the procedures were performed under general anesthesia in a day-surgery setting

• two skilled senior gynecologic endoscopists performed the procedures

• the procedures were performed in the early follicular phase in patients included in group S and in the last week of treatment in patients included in the other study groups

• hysteroscopic resection was performed by the slicing technique using a continuous flow 8.5 mm 12° resectoscope with bipolar 24 Fr loop 0.2 mm wire electrodes (Olympus, Hamburg, Germany)

• intraoperative ultrasonography was used when required

Surgical outcomes

• Operative time, calculated from the introduction up to the extraction of the resectoscope

• Total surgical time, calculated from the dilatation of the cervical canal up to the complete extraction of the myomas

• Absorbed fluid, calculated by subtracting the fluid collected from the total fluid instilled

• Intraoperative and postoperative complications

• Operative difficulty, evaluated by surgeons using a 10-point linear visual analog scale (VAS)

• Postoperative patient pain and satisfaction, evaluated 5 hours after surgery by using two VAS scales

• Completeness of resection, assessed by ultrasonography performed and follow-up consultations (at 1 and 3 months from surgery)

Statistical analysis

• An interim-analysis was performed and the results are presented in the current study

• The chi-squared test was used to compare categorical variables

• The one way analysis of variance was used to compare normally distributed continuous variables between the four study groups; the Holm-Sidak method was used to perform pairwise multiple comparisons. The Kruskal-Wallis one-way analysis of variance on ranks was used for the comparison of continuous variable that were not normally distributed; the Dunn’s method was used to perform multiple comparisons

• Data were analyzed with SPSS software version 20.0 (SPSS Inc., Chicago, IL)

• A p < .05 was considered statistically significant.

RESULTS

FLOW CHART SHOWING RECRUITMENT AND WOMEN’S PROGRESS THROUGH THE STUDY

Group S(n = 23)

Group T(n = 20)

Group L(n = 11)

Group U(n = 7)

p Total(n = 61)

Age (years, mean ± SD) 35.0 ± 4.7 36.3 ± 5.4 36.8 ± 5.1 38.4 ± 4.3 .419 36.1 ± 5.0

Nulliparous (n,%) 7 (30.4%) 5 (25.0%) 3 (27.3%) 2 (28.6%) .984 17 (27.9%)

Abnormal uterine bleeding (n, %) * 16 (69.6%) 14 (70.0%) 7 (63.6%) 5 (71.4) .981 42 (68.9%)

Infertility (n, %) * 8 (34.8%) 5 (25.5%) 0 (0.0%) 1 (14.3%) .142 14 (23.0%)

Miscarriage (n, %) * 4 (17.4%) 1 (5.0%) 2 (18.2%) 0 (0.0%) .390 7 (11.5%)

Diameter of the largest myoma (cm, mean ± SD) 2.7 ± 0.5 2.8 ± 0.4 3.0 ± 0.4 2.9 ± 0.3 .254 2.8 ± 0.4

Volume of the largest myoma (cm3, mean ± SD) 7.4 ± 3.5 7.2 ± 3.2 8.0 ± 3.2 8.6 ± 2.4 .722 7.6 ± 3.2

Number of myomas (n, median, range) 1 (1-2) 1 (1-2) 1 (1-2) 1 (1-2) .900 1 (1-2)

Total myoma volume (cm3, mean ± SD) 8.8 ± 3.7 8.4 ± 3.9 9.8 ± 5.9 9.7 ± 3.6 .783 8.9 ± 4.1

* Sometimes more than one for the same patient

DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF THE STUDY POPULATION

All medical treatments caused a significant decrease in the volume of the largest myoma(group T, p < .001; group L, p < .001; group U, p = .006)

The percentage decrease in myoma volume was lower in group U (-21.0%) than in groupT (-37.1%; p = .001) and in group L (-34.5%; p = .010)

CHANGES IN THE VOLUME OF THE LARGEST MYOMA CAUSE BY 3-MONTH HORMONAL TREATMENT

OPERATIVE RESULTS

Group S(n = 23)

Group T(n = 20)

Group L(n = 11)

Group U(n = 7)

p Pairwise multiple comparison procedures

Operative time (minutes, mean ± SD) 29.7 ± 8.6 21.1 ± 6.4 20.9 ± 5.5 25.89 ± 3.0 < .001 p < .001 group S vsgroup T;

p < .001 group S vsgroup L *

Total surgical time (minutes, mean ±SD)

36.7 ± 8.4 26.4 ± 6.4 26.1 ± 5.5 31.1 ± 4.4 < .001 p < .001 group S vsgroup T;

p < .001 group S vsgroup L *

Volume of fluid infused during hysteroscopy (l, mean ± SD)

7.9 ± 2.5 6.2 ± 2.0 5.4 ± 2.0 7.2 ± 2.6 .017 .004 group S vs group L

Volume of fluid absorbed (ml, mean ±SD)

457 ± 139 340 ± 112 366 ± 111 371 ± 103 .019 p = .003 group S vsgroup T;

p = .048 group S vsgroup L *

Operative difficulty (VAS, median, range)

3.6

(1.2-6.5)

2.0

(1.0-4.3)

1.9

(0.7-5.7)

2.8

(0.79-6.6)

.004 p < .05 group S vsgroup T ^

Incomplete resection (n,%) 1 (4.3%) 0 (0.0%) 0 (0.0%) 0 (0.0%) .641

* Holm-Sidak method; ^ Dunn’s method

There was no case of uterine perforation or fluid overload.

Postoperative patient pain was minimal and non significantly different among the four study groups (p = .538).

Similarly, patient satisfaction was similar in the four study groups (p = .762).

Page 7

DISCUSSION

• Preoperative treatment with triptorelin and letrozole facilitates the hysteroscopic resection of large uterine submucosal myomas by decreasing the operative time and the volume of fluid absorbed.

• The surgical advantages of preoperative hormonal therapies should be balanced with the incidence of adverse effects and with the cost of treatments.

• The operative results obtained in group S demonstrate that hysteroscopic myomectomy can be safely performed in most of the patients without the administration of preoperative hormonal treatment.

• In selected cases with multiple myomas or in case of procedures performed by less experienced surgeons, the shrinking of the myomas may allow to perform hysteroscopic procedures in patients that would be candidate to more invasive surgical techniques or to obtain a complete myoma resection during a single surgical procedure.

DISCUSSION

LIMITATIONS OF THE STUDY:

- the study was not randomized, it is likely that economical issues and knowledge of thepotential adverse effects of treatment influenced the choice of the patients

- the different mode of drug administration

- the small number of patients assigned to treatment with letrozole and ulipristal acetate

- the surgeons performing hysteroscopy were not blinded to the treatment received by thepatients

FUTURE RESEARCH:

- to evaluate the efficacy of ulipristal acetate in the treatment of submucosal uterinemyomas

- to compare in randomized study with larger sample size the efficacy of treatment withletrozole and triptorelin prior to hysteroscopic resection of large submucosal myomas

- to assess the role of preoperative hormonal therapies in patients with > 2 large FIGOtype 2 myomas that are currently treated by multiple hysteroscopic procedures or bymore invasive surgical techniques

• Donnez J, Tatarchuk TF, Bouchard P, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. N Engl J Med.2012;366:409-20.

• Donnez J, Tomaszewski J, Vázquez F, et al. Ulipristal acetate versus leuprolide acetate for uterine fibroids. N Engl J Med.2012;366:421-32.

• Donnez J, Vazquez F, Tomaszewski J, et al. Long-term treatment of uterine fibroids with ulipristal acetate. Fertil Steril.2014;101:1565-73.

• Duhan N, Madaan S, Sen J. Role of the aromatase inhibitor letrozole in the management of uterine leiomyomas in premenopausalwomen. Eur J Obstet Gynecol Reprod Biol. 2013;171:329-32.

• Gurates B, Parmaksiz C, Kilic G, et al. Treatment of symptomatic uterine leiomyoma with letrozole. Reprod Biomed Online.2008;17:569-74.

• Kamath MS, Kalampokas EE, Kalampokas TE. Use of GnRH analogues pre-operatively for hysteroscopic resection of submucousfibroids: a systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2014;177:11-8.

• Leone Roberti Maggiore U, Scala C, Venturini PL, et al. Preoperative treatment with letrozole in patients undergoing laparoscopicmyomectomy of large uterine myomas: a prospective non-randomized study. Eur J Obstet Gynecol Reprod Biol. 2014;181C:157-162.

• Muzii L, Boni T, Bellati F, et al. GnRH analogue treatment before hysteroscopic resection of submucous myomas: a prospective,randomized, multicenter study. Fertil Steril. 2010;94:1496-9.

• Mavrelos D, Ben-Nagi J, Davies A, et al. The value of preoperative treatment with GnRH analogues in women with submucousfibroids: a double-blind, placebo-controlled randomized trial. Hum Reprod. 2010;25:2264-9.

• Munro MG, Critchley HO, Fraser IS; FIGO Menstrual Disorders Working Group. The FIGO classification of causes of abnormaluterine bleeding in the reproductive years. Fertil Steril. 2011;95:2204-8.

• Parsanezhad ME, Azmoon M, Alborzi S, et al. A randomized, controlled clinical trial comparing the effects of aromatase inhibitor(letrozole) and gonadotropin-releasing hormone agonist (triptorelin) on uterine leiomyoma volume and hormonal status. FertilSteril. 2010;93:192-8.

• Song H, Lu D, Navaratnam K, et al. Aromatase inhibitors for uterine fibroids. Cochrane Database Syst Rev. 2013;10:CD009505.

REFERENCES

Page 8

Resection of Retained Products of Conception with the Myosure XL 

 

Nicholas Ryan, MD 

Baylor College of Medicine, Houston, Texas 

 

Study Objective: To demonstrate a novel  technique  for  resection of  retained products of  conception 

using the MyoSure XL® (Hologic, Bedford, MA) device.  

 

Design: Step‐by‐step explanation of the technique using video. 

 

Setting:  A  33  year  old  G2P1001  had  a  missed  abortion  at  approximately  10  weeks  gestation  and 

underwent a dilatation and suction curettage at an outlying hospital. The procedure was complicated by 

a  2  liter  blood  loss  that  required  transfusion.  She  presented  two weeks  later with  recurrent  vaginal 

bleeding.  Ultrasound  confirmed  retained  products  of  conception  with  a  possible  arteriovenous 

malformation. Hematocrit at this time was 23.1%. She underwent bilateral uterine artery embolization 

(UAE)  using Gelfoam®  (Pfizer, New  York, NY).  Ten  days  following UAE,  she  underwent  hysteroscopic 

resection of the retained products of conception using the MyoSure XL device. 

 

Interventions: Hysteroscopic resection of retained products of conception using the MyoSure XL device.  

 

Conclusions:  In  certain  circumstances,  retained  products  of  conception  following  dilatation  and 

curettage can be safely and effectively resected under direct visualization using the MyoSure XL device. 

This technique could theoretically reduce the likelihood of perforation, confirm complete removal of the 

lesion, and  facilitate minimal dissection  into  the myometrium and disruption of  the opposing uterine 

walls to effectively reduce the risk of Asherman’s syndrome. 

 

Keywords: Retained products of conception; Operative hysteroscopy; MyoSure XL 

Page 9

Diagnostic work-up for postmenopausal bleeding

a randomized clinical trial

N. van Hanegem, MDMaastricht UMC+

The Netherlands

Disclosures

I have no financial relationships to disclose.

How to handle a patient with:

• a first episode of postmenopausal bleeding• an endometrial thickness of > 4 mm and • a benign histology after endometrial sampling.

Learning objectives Diagnostic work-up PMP bleeding1,2,3

Vaginal examination, Cervical cytology and TVS

Endometrium > 4 mm or non-measurable

Endometrialbiopsy

Benign histology

??

Insufficientsample

Hysteroscopy

(Pre)malignancy

Treatment

Endometrium ≤ 4 mm

Expectantmanagement

Recurrentbleeding

Histology(hysteroscopy)

• Regardless of endometrial thickness4,5:• No abnormalities 50%• Endometrial carcinoma 10%• Endometrial polyp 20%

• Sensitivity endometrial biopsy for endometrial cancer: 92-95%6,7

• Endometrial thickness > 4 mm8,9:• 40% endometrial polyps• No evidence that removal of polyps can reduce

recurrent bleeding

Patients with postmenopausal bleeding

Does further work-up for and treatment of benign endometrial lesions reduce the risk of recurrent

postmenopausal bleeding?

Scientific question

Page 10

Randomized clinical trial

P Women with postmenopausal bleeding

I Hysteroscopy

C Expectant management

O Recurrent bleeding within 1 year• Recurrent bleeding > 1 year• (Pre)malignancy

Study designInclusioncriteria: •Postmenopausal bleeding•Double endometrial thickness > 4 mm•Benign histology after endometrial biopsy

Exclusioncriteria:•Abnormal cervical cytology•Aromatase-inhibitor/anti-estrogen

Sample size: 50% reduction of recurrent bleeding (drop-out rate 20%; power 80%; α 5%)

N=200

Methods

Intervention:• Diagnostic hysteroscopy. In case of an

endometrial polyp, polypectomy was performed.

Comparison:• No further diagnostic work-up.

All patients were instructed to contact theoutpatient clinic in case of recurrent bleeding andcontacted for follow-up after 1 year.

Methods: Allocation Results: flow chart

200 women included

98 hysteroscopy 87 received assigned intervention

102 exp managementnobody had hysteroscopy

2 lost to follow-up 7 follow-up ongoing

3 follow-up ongoing

95 included in analysesMedian follow up 60 weeks

93 included in analysesMedian follow up 63 weeks

RR 0.91 (95% CI 0.63-1.3)

Results: Recurrent bleeding < 1 year

Recurrent bleeding

No recurrent bleeding

Hysteroscopy 14 (14%) 84 98

Expectantmanagement

16 (17%) 77 93

30 161 191

87 of 98 women received allocated intervention.

Results: (pre)malignancy in hysteroscopy-group

Hysteroscopy N=87Hysteroscopy N=87

Polyp N=46Polyp N=46

Benign N=38

Benign N=38

Hyperplasia+atypiaN=5

Hyperplasia+atypiaN=5

HysterectomyHysterectomy

Hyperplasia+atypiaN=3

Hyperplasia+atypiaN=3

CarcinomaN=2

CarcinomaN=2

Carcinoma N=1Carcinoma N=1No result

N=2No result

N=2

No polyp N=41No polyp N=41

Page 11

Results: Recurrent bleeding during complete FU

Hysteroscopy

Recurrentbleeding N=27

HysteroscopyN=17 Benign N=17

Endometrialbiopsy N=3

Carcinoma N=1 Benign N=2

Ultrasound, thinendometrium

N=3

No investigation,

N=4

Expectant management

Recurrentbleeding N=19

HysteroscopyN=8

Carcinoma N=2 Benign N=6

Endometrialbiopsy N=4 Benign N=4

Ultrasound, thinendometrium

N=3

No investigation

N=4

• Women with postmenopausal bleeding and benign endometrial biopsy have a 17% risk of recurrent bleeding within 1 year.

• Hysteroscopy does not reduce this risk.

• However, unexpected 3 endometrial carcinomas and 3 pre-malignancies (6%) were diagnosed after an initially benign endometrial biopsy.

Conclusions

Research group• N. van Hanegem MD*, Maastricht University Medical Center, Maastricht• M.C. Breijer MD PhD*, Erasmus MC, Rotterdam• S.A. Slockers, medical student, Maxima Medical Center, Veldhoven• M.H. Zafarmand PhD, Academic Medical Center, Amsterdam• P.M. Geomini MD PhD, Maxima Medical Center, Veldhoven• R. Catshoek MD, Maastricht UMC, Maastricht• J.M. Pijnenborg MD PhD, TweeSteden Ziekenhuis, Tilburg• L.F. van der Voet MD PhD, Deventer Hospital, Deventer• F.P. Dijkhuizen MD PhD, Rijnstate Hospital, Arnhem• G.C.R. van Hoecke MD, Albert Schweitzer Hospital, Dordrecht• N. Reesink MD PhD, Medical Spectrum Twente, Enschede• S. Veersema MD PhD, St. Antonius Hospital, Nieuwegein• M.H. van Hooff MD PhD, Sint Franciscus Gasthuis• P.J.M. van Kesteren MD PhD, OLVG, Amsterdam• J.A. Huirne MD PhD, VU Medical Center• M.Y. Bongers MD PhD, Maxima Medical Center, Veldhoven• B.W. Mol MD PhD, The Robinson Institute, Adelaide, Australia• A. Timmermans MD PhD, Academic Medical Center

References

1. Dutch Society of Obstetrics and Gynecology (NVOG). Diagnostics in abnormal vaginal blood loss in the postmenopausal period. 2003.

2. Epstein E. Management of postmenopausal bleeding in Sweden: a need for increased use of hydrosonography and hysteroscopy. Acta Obstet Gynecol Scand 2004 Jan;83(1):89-95.

3. Scottish Intercollegiate Guidelines Network. Investigation of postmenopausal bleeding. 2002. 4. Emanuel M, Verdel M, Wamsteker K, Lammes F. An audit of true prevalence of intrauterine

pathology: the hysteroscopic findings, controlled for patient selection in 1202 patients with abnormal uterine bleeding. Gynecol Endosc 1995;4:237-41.

5. Dijkhuizen FP, Brolmann HA, Potters AE, Bongers MY, Heinz AP. The accuracy of transvaginal ultrasonography in the diagnosis of endometrial abnormalities. Obstet Gynecol 1996 Mar;87(3):345-9.

6. Clark TJ, Mann CH, Shah N, Khan KS, Song F, Gupta JK. Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial hyperplasia. Acta Obstet Gynecol Scand 2001 Sep;80(9):784-93.

7. Dijkhuizen FP, Mol BW, Brolmann HA, Heintz AP. The accuracy of endometrial sampling in the diagnosis of patients with endometrial carcinoma and hyperplasia: a meta-analysis. Cancer 2000 Oct 15;89(8):1765-72.

8. Epstein E, Ramirez A, Skoog L, Valentin L. Dilatation and curettage fails to detect most focal lesions in the uterine cavity in women with postmenopausal bleeding. Acta Obstet GynecolScand 2001 Dec;80(12):1131-6.

9. Timmermans A, Veersema S. Office hysteroscopy in women with postmenopausal bleeding: see and treat of endometrial polyps using a duckbill polyp snare. Gyn Surg 2004;1:189-90.

Page 12

A randomized, single blind, placebo-controlled trial for the pain reduction

during the outpatient hysteroscopy after Ketoprofen or intravaginal Misoprostol

Tadeusz Issat, MD, PhD

Department of Reproductive Health, Institute of Mother and Child Warsaw, Poland

DisclosureI have no financial relationships to disclose.

Known factors that might reduce pain during office hysteroscopy

Pain reduction

Lidocaine gel

Tramadol iv.

Transcutaneous electrical nerve

stimulation

Intrauterine and intracervical

lidocaine

Sublingual buprenorphine

Reduction inwaiting time for

procedure

Guidelines

„..RCOG: women withoutcontraindications shouldbe advised to considertaking standard doses ofnon-steroidal anti-inflammatory agents(NSAIDs) around 1 hourbefore their scheduledoutpatient hysteroscopyappointment with the aimof reducing pain in theimmediate postoperativeperiod.. .”

Study design

RCTMisoprostol arm:

vaginal Misoprostol (400 μg) and 100 ml of 5% intravenous

glucose

Ketoprofen arm: iv Ketoprofen

(50mg/1ml) in 100 ml of 5% glucose and intravaginal

placebo

Placebo arm: intravaginal

placebo and 100ml of 5% iv glucose

Aim of the study was to assess the pain during and after outpatient hysteroscopy, depending on the use of intravaginal Misoprostol (400 μg), intravenous non-steroidal

anti-inflammatory agent Ketoprofen (1mg/1ml) or placebo

Inclusion and exclusion criteria

• aged over 18

• agreed to participate in the study and a written informed consent was obtained

• indications for office hysteroscopy

• women with a possible pregnancy

• lower genital tract infections • gestational trophoblastic disease • presence of endocervical polyps • asthma• acute porphyria • hepatitis • renal failure• lactation • oversensitivity to one of the

agents endometrial polyps measuring more than 30mm

Inclusion criteria Exclusion criteria

Page 13

Procedure• The procedure according to the RCOG Green-Top Guideline Nr 59

• The tablets (Misoprostol or placebo) in the posterior vaginal fornix approx. 4 h before hysteroscopy and after the randomisation

• The procedure approx. 30 min after Ketoprofen or 100 ml of 5% glucose in a placebo and Misoprostol arms

• The 3.2mm Versascope hysteroscope (Gynecare division of Ethicon, Inc., Somerville, New Jersey, US) with normal saline solution as a distension medium

• When appropriate, a Versapoint (Gynecare) used to cut the polyps or fibroids, the 5F forceps used to facilitate extraction of fragments. Only the 5F forceps used for the simple biopsy of endometrium. Vaginoscopy involved in all procedures, no dilators used

• 300 W xenon lamp and video camera

• Distension fluid pressure generated using an automated flow-meter pump set for 120 mmH2O of intrauterine pressure

• For one-dimensional assessment of pain, a visual analog scale (VAS) was used

• The patients were asked to mark VAS scale before, during, 5 minutes and 15 minutes after the procedure

• Secondary measures the following complications were investigated:

Measurements

No pain Worst painVAS scale

uterine perforation false cervical passage cervical laceration bleeding and pain after Misoprostol failure rate and the time of the

procedure were recorded

vaginal bleeding nausea vomiting diarrhea fever infection

163 Assessed for eligibility

11 Excluded:� 8 Not meeting criteria� 3 Declined

152 Randomized

50 Analyzed

51 in Misoprostol group� 50 Hysteroscopy� 1 Failure (Closed os)

50 in Ketoprofen group� 50 Hysteroscopy

51 in Placebo group� 50 Hysteroscopy� 1 Failure (Closed os)

50 Analyzed50 Analyzed

Randomization process Statistical analysis

• The statistical parameters for this calculation included a type I error of 0.05 and a power of 80%. Satisfactory pain reduction was set for 30% when compared between the arms, thus a sample of around 45 patients in each arm was calculated. The final number was set for 150 patients with 50 subjects in each arm.

• Patient characteristics were compared, using the Chi square test and Fisher exact test for categorical variables

• For the continuous variables the analysis of variance ANOVA and Kruskal-Wallis tests were used. The post hoc analysis was performed with the Tukey, Dunnett(Placebo group as a control) and Games-Howell tests

• The statistical software package SPSS 17.0 (SPSS Inc. Chicago, US) was used for data analyses.

Patients characteristics

Placebo (N=50) Ketoprofen (N=50) Misoprostol (N=50) p

Age (yrs); median (IQR) 43,50 (36,50 - 56,00) 49,00 (39,75 - 59,25) 51,30 (47,00 - 52,30) 0,398Weight (kg); median (IQR) 66,50 (61,50 - 76,00) 66,00 (60,00 - 75,50) 71,25 (67,10 - 72,30) 0,686

Height (cm); median (IQR)

164,00 (160,00 -168,00) 163,00 (157,50 - 167,50) 164,10 (162,40 - 165,70) 0,481

Parity; n(%)

Nulliparous 12 (24,00) 15 (30,00) 16 (32,00) 0,890

Multiparous 38 (76,00) 35 (70,00) 34 (78,00)

Postmenopausal; n(%) 19 (38,00) 26 (54,00) 25 (50,00) 0,159

Referral diagnosis n(%) 0,151Abnormal

endometrium on US 10 (20,00) 14 (28,00) 13 (26,00)Endometrial

polyps 29 (58,00) 17 (34,00) 24 (48,00)

Infertility 1 (2,00) 2 (4,00) 0

Uterine bleeding 9 (18,00) 16 (32,00) 12 (24,00)

Other 1 (2,00) 1 (2,00) 1 (2,00)

Procedure type; n(%) 0,159Operative

hysteroscopy 31 (62,00) 24 (48,00) 24 (48,00)Diagnostic

hysteroscopy 19 (38,00) 26 (54,00) 26 (52,00)

p>0.05

Placebo (N=50) Ketoprofen (N=50) Misoprostol (N=50) p

Procedure time (s); median (IQR)

255,00 (156,00 - 240,75)

190,00(130,00 - 304,00)

277,00 (150,00 - 370,00) 0,156

Pain assessment

VAS score before the procedure

0 0 0 0,666

VAS score during the procedure

4,00 (2,75 - 5,25) 3,00 (2,00 - 5,00) 3,00 (2,00 - 4,00)* 0,020

VAS score at the end of theprocedure

1,00 (0 - 2,00) 1,00 (0 - 2,00) 0 (0 - 1,00)* 0,006

VAS score 15 min. after the procedure

0 0 0 0,160

Need for additional oral analgesia; n(%)

0 2 (4,00) 2 (4,00) 0,153

* p<0.05

Results

Page 14

Results

The median VAS scores measured directly after the procedure

The median VAS scores measured during the procedure

Vaginal misoprostol reduces pain during and at the end of the outpatient hysteroscopy when compared to non-steroidal anti-inflammatory agents or

placebo

VAS score during and after the hysteroscopy and time of procedure

VAS scores measured during the procedure and the time

of hysteroscopy

VAS scores measured after the procedure and the time of

hysteroscopy

Objective

• 400 μg vaginal misoprostol administrated 4 hours before the procedure of outpatient hysteroscopy appears to be a better alternative to NSAID's in terms of pain reduction during and directly after the procedure.

• This observation does not depend on the patients’ age, hormonal status, parity or type of the procedure (operative or diagnostic).

Thank you

References:

• RCOG Green-top Guideline No.59 Best Practice in Outpatient Hysteroscopy March 2011 • Deffieux X, Gauthier T, Menager N, Legendre G, Agostini A, Pierre F. Hysteroscopy: guidelines for clinical

practice from the French College of Gynaecologists and Obstetricians. Eur J Obstet Gynecol Reprod Biol. 2014 Jul;178:114-22

• Van den Bosch T, Van Schoubroeck D, Daemen A, Domali E, Vandenbroucke V, De Moor B, Deprest J, Timmerman D. Lidocaine does not reduce pain perception during gel instillation sonography or subsequent office hysteroscopy: results of a randomized trial. Gynecol Obstet Invest. 2011;71(4):236-239

• Floris S, Piras B, Orrù M, Silvetti E, Tusconi A, Melis F, Tuveri M, Piga M, Paoletti AM, Melis GB. Efficacy of intravenous tramadol treatment for reducing pain during office diagnostic hysteroscopy. Fertil Steril. 2007 Jan;87(1):147-151

• De Angelis C, Perrone G, Santoro G, Nofroni I, Zichella L. Suppression of pelvic pain during hysteroscopy with a transcutaneous electrical nerve stimulation device. Fertil Steril. 2003 Jun;79(6):1422-1427.

• Munro MG, Brooks PG. Use of local anesthesia for office diagnostic and operative hysteroscopy. J Minim Invasive Gynecol. 2010 Nov-Dec;17(6):709-718

• Agdi M, Tulandi T. Outpatient hysteroscopy with combined local intracervical and intrauterine anesthesia. Gynecol Obstet Invest. 2010;69(1):30-2

• Lin YH, Hwang JL, Huang LW, Chen HJ. Use of sublingual buprenorphine for pain relief in office hysteroscopy. J Minim Invasive Gynecol. 2005 Jul-Aug;12(4):347-350.

Page 15

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%

Page 16