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Reproductive Surgery in the Era of ART

(Didactic)

PROGRAM CHAIR

William W. Hurd, MD

G. David Adamson, MD Victor Gomel, MD Keith B. Isaacson, MD

Professional Education Information Target Audience Educational activities are developed to meet the needs of surgical gynecologists in practice and in training, as well as, other allied healthcare professionals 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 3.75 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 ...................................................................................................................................................... 3 Tubal Reconstructive Surgery vs. ART V. Gomel ....................................................................................................................................................... 5 Hydrosalpinx and Other Indications for Laparoscopy for the Infertile Patient G.D. Adamson ............................................................................................................................................ 16 When and How to Evaluate the Uterine Cavity: HSG vs. Sonohysterography vs Office Hysteroscopy K.B. Isaacson ............................................................................................................................................... 23 When and How to Removal Intramural Fibroids to Improve Fertility W.W. Hurd ................................................................................................................................................. 32 Tubal Ligation Reversal vs. IVF V. Gomel ..................................................................................................................................................... 39 Ovarian Surgery: Endometriomas and Ovarian Drilling W.W. Hurd ................................................................................................................................................. 47 Surgical Treatment of Uterine Anomalies: Indications and Techniques K.B. Isaacson ............................................................................................................................................... 53 Does Treating Endometriosis Improve infertility? G.D. Adamson ............................................................................................................................................ 58 Cultural and Linguistics Competency ......................................................................................................... 65

PG 216 Reproductive Surgery in the Era of ART (Didactic)

William W. Hurd, Chair

Faculty: G. David Adamson, Victor Gomel, Keith B. Isaacson

Course Description The development of Assisted Reproductive Technologies (ART), particularly in vitro fertilization (IVF), has dramatically changed the surgical approach to the infertile patient. At the same time, advances in minimally invasive surgery have allowed a broad range of pelvic procedures to be performed as outpatient surgery or in the office. As a result, surgical indications and approaches continue to evolve based on new information about the effects of pelvic pathology on infertility and new surgical and non-surgical technology. This course is a candid discussion by four reproductive surgeons who specialize in infertility about the important and shifting roles of reproductive surgery in the era of ART and IVF. The course will describe the most recent advances and recommendations for the diagnosis and surgical treatment of common causes of infertility, including endometriosis, hydrosalpinx, fibroids, pelvic adhesions, tubal occlusion, intra-uterine pathology and polycystic ovary syndrome.

Course Objectives At the conclusion of this course, the participant will be able to: 1) List the fertility effects of common gynecologic conditions, including leiomyoma, hydrosalpinx, endometriosis and uterine septum; 2) evaluate the relative merits of the different methods for detecting intrauterine pathology in the infertile patient; 3) compare the advantages and disadvantages of the various surgical methods for diagnosing and treating endometriosis in infertile women; 4) demonstrate knowledge of when and how best to remove intramural fibroids in the infertile patient; and 5) distinguish and compare various surgical methods for treating hydrosapinx in infertile women.

Course Outline

1:30 Welcome, Introductions and Course Overview W.W. Hurd 1:35 Tubal Reconstructive Surgery vs. ART V. Gomel 2:00 Hydrosalpinx and Other Indications for Laparoscopy for the Infertile Patient G.D. Adamson 2:25 When and How to Evaluate the Uterine Cavity:

HSG vs. Sonohysterography vs Office Hysteroscopy K.B. Isaacson 2:50 When and How to Removal Intramural Fibroids to Improve Fertility W.W. Hurd 3:15 Questions & Answers All Faculty 3:25 Break 3:40 Tubal Ligation Reversal vs. IVF V. Gomel

1

4:05 Ovarian Surgery: Endometriomas and Ovarian Drilling W.W. Hurd 4:30 Surgical Treatment of Uterine Anomalies: Indications and Techniques K.B. Isaacson 4:55 Does Treating Endometriosis Improve infertility? G.D. Adamson 5:20 Questions & Answers All Faculty 5:30 Course Evaluation

2

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 Consultant: Conceptus Incorporated Frank D. Loffer, Executive Vice President/Medical Director, AAGL* Linda Michels, Executive Director, AAGL* Jonathan Solnik Other: Lecturer - Olympus, Lecturer - Karl Storz Endoscopy-America SCIENTIFIC PROGRAM COMMITTEE Arnold P. Advincula Consultant: CooperSurgical, Ethicon Women's Health & Urology, Intuitve Surgical Other: Royalties - CooperSurgical Linda Bradley Grants/Research Support: Elsevier Consultant: Bayer Healthcare Corp., Conceptus Incorporated, Ferring Pharmaceuticals Speaker's Bureau: Bayer Healthcare Corp., Conceptus Incorporated, Ferring Pharm Keith Isaacson Consultant: Karl Storz Endoscopy Rosanne M. Kho Other: Honorarium - Ethicon Endo-Surgery C.Y. Liu* Javier Magrina* Ceana H. Nezhat Consultant: Intuitve Surgical, Lumenis, Karl Storz Endoscopy-America Speaker's Bureau: Conceptus Incorporated, Ethicon Women's Health & Urology William H. Parker Grants/Research Support: Ethicon Women's Health & Urology Consultant: Ethicon Women's Health & Urology Craig J. Sobolewski Consultant: Covidien, CareFusion, TransEnterix Stock Shareholder: TransEnterix Speaker's Bureau: Covidien, Abbott Laboratories Other: Proctor - Intuitve 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). William W. Hurd* G. David Adamson Consultant: LabCorp Other: CEO and Founder - Advanced Reproductive Care Victor Gomel* Keith B. Isaacson

3

Consultant: Karl Storz Endoscopy Joseph S. Sanfilippo* Asterisk (*) denotes no financial relationships to disclose.

4

TUBAL

RECOSTRUCTIVE SURGERY

VERSUS ART

Victor Gomel

Professor Victor Gomel

DISCLOSURE

• I have no financial relationships to disclose.

• The presence of a credible alternative with IVF, permits to operate in cases with better prognosis and obtain better results.

• Most cases can be done by laparoscopyy p pyas part of initial diagnostic procedure.

• Complex cases may require use of a minilap, performed on day care basis.

Gomel V. Reproductive Surgery in Reconstructive & Reproductive Surgery, Informa, London 2010

Victor Gomel

REPRODUCT. SURGERY-DEVELOPMENTS

• Microsurgery

• Surgical access by laparoscopy

• Surgical access by minilaparotomy• Surgical access by minilaparotomy

• Hysteroscopic surgical access

• Prevention of postoperative adhesions

Victor Gomel

ART- USA: 2000- 2009

Victor Gomel

SURGERY VERSUS IVF

SURGERY*

Victor Gomel

COMMERCIALIZATION OF IVF SERVICES IVF

*Both practice and teaching of surgery

5

NO. EMBRYO TRANSFERRED- USA 2008

4.6%4.6%

13.0%13.0%

DAY 5DAY 5

1515..55%%

9.7%

9.7%19.2%19.2%

DAY DAY 33

Victor Gomel

67.0%67.0%31.1%31.1% 40.0%40.0%

CDC Reproductive Health; www.cdc.gov/art/ART 2008

ASSISTED REPRODUCTION- USA 2008

1.7%1.7%

34.0%34.0%

Victor Gomel

64.3%64.3%


13,892 Live Births

Singletons Twins Triplets +

Delivery/OPU IVF ICSI Multi preg

Europe 21.1 20.2 22.3

France 19.2 20.5 19.3

ART- EUROPE: 2008

Victor Gomel

Germany 16.0 16.1 21.8

Itay 15.2 14.3 23.4

U. Kingdom 26.4 27.5 17.9

de Mouzon et al. Hum Reprod. 201; 27: 954‐ 966

IMPACT OF MULTIPLE BIRTHS

• Increased obstetrical complications

• Increased neonatal complications/ deaths

• Responsible for major societal costs

• Significant financial burden and emotional

costs for the parents.

Victor Gomel

FIRST IVF BABYMADE IN CANADA

Victor Gomel

Born December 25, 1983

IVF AS PRIMARY TREATMENT

• Male factor infertility

• Age of female partner

• Tubal disease + Male factorTubal disease Male factor

• Inoperable tubal disease

• Others: ie. need for PGD

Victor Gomel


6

INFERTILITY- INVESTIGATION

• Clinical assessment*

• Semen analysis

• Assessment of ovulation

Victor GomelLe Toucher, in Maygrier JP. Paris,1822

• Assess tubal factors- HSG

* Sonography is part of clinical assessment

HSG

PHIMOSIS

Victor Gomel

HYDROSALPINX

PHIMOSIS

HSG

Victor Gomel

HYDROSALPINX


• Clinical assessment*

• Semen analysis




• Laparoscopy ± hysterocopy


DISTAL TUBAL

DISEASE

Victor Gomel

DISEASE

Victor Gomel

LAPAROSCOPY

7

LAPAROSCOPY

Victor Gomel

SALPINGO-OVARIOLYSIS

LAPAROSCOPY

Victor Gomel



Victor Gomel

LIVEBIRTHRATE>50%

SALPINGOSTOMY

Victor GomelGomel V, McComb PF. J Reprod Med. 2006; 51: 177‐84.

LIVE BIRTH RATE ±30%

SALPINGOSTOMY BY MICROSURGERY

AFS Score* Patients # Pregn. %

Mild ¤ 17 12 71

Victor Gomel

Severe 73 15 21

Total 90 27 30

* AFS Classification Gomel V., Erenus M.; 1990¤ p < 0.05

Victor Gomel

8

“The evidence is fair to recommend laparos-

Victor Gomel

Fertil Steril. 2012; 97: 539‐ 459

copic fimbrioplasty and neosalpingostomy for the treatment of mild hydrosalpinges in young women with no other significant infertility factors.”

y ra

tes

y ra

tes

p=0.083p=0.083p=0.057p=0.057

p=0.040p=0.040

p=0.019p=0.019

**

**

INFLUENCE OF SALPINGOSTOMYFOR HYDROSALPINX ON IVF OUTCOMES

n=185n=185 n=97n=97 n=75n=75 n=39n=39

Del

iver

yD

eliv

ery **

Strandel A. et al. Hum Reprod. 2001; 16: 2403-10

ASRM

PRACTICE

COMMITTEE

Fertil Steril. 2008; 90: S66-8

SALPINGOSTOMY FOR HYDRO BEFORE IVF

GR I GR II GR III GR IV

IMP/ET 2.8% 18.8% 16.7% 27.3%

Victor Gomel

PR/ET 8.5% 39.0% 43.0% 60.0%

GROUP I: Hydrosalpinx untreatedGROUP II: SalpingectomyGROUP III: SalpingostomyGROUP IV: Proximal tubal occlusion

Murray DL. et al. Fertil Steril. 1998; 69: 41‐5

TUBO-TUBAL

ANASTOMOSIS

Victor Gomel

REVERSAL OF STERILIZATION

Victor Gomel

9

TUBO-CORNUAL

ANASTOMOSIS

Victor Gomel

PROXIMAL TUBAL DISEASE

HSG

PROXIMAL TUBAL

DISEASE

Victor Gomel

CORNUAL OCCLUSION

HSG

Victor Gomel

SELECTIVE SALPINGOGRAPHY

SELECTIVE SALPINGOGRAPHY

Victor Gomel

TUBAL CANNULATION

HSG

Victor Gomel

TUBO-CORNUAL ANASTOMOSIS

Victor Gomel

10

Victor Gomel

Excision of diseased isthmic segment

Victor Gomel

Placement of the first anastomotic suture

TUBO-CORNUAL ANASTOMOSIS

LIVEBIRTHRATE± 50%

Victor Gomel

Musculo-epithelial layer approximted

± 50%

Gomel V. Fertil Steril. 1997; 28: 59- 67

MINI-LAPAROTOMY

MINI-LAPAROTOMY PROTRACTOR®

Combines functions of wound protector

and retractor

11

TUBO-CORNUAL ANASTOMOSIS*

Patients (n=48) No. %

Spontaneous abortion 3∞

Ectopic pregnancy 3° 6.2%

* For proximal disease, by microsurgery.∞ Two of these patients had viable births as well.° One of these patients had a viable birth as well.

Gomel V. Microsurgery in Female Infertility. Little Brown. Boston. 1983

Victor Gomel

Ectopic pregnancy 3 6.2%

Viable birth 27 56.2%

“Unless the proximal blockage on HSG is clearly due to SIN, selective salpingography or tubal

l b d ”

Victor GomelFertil Steril. 2012; 97: 539‐ 459

cannulation can be attempted.”

“Before performing this procedure , there should be confirmation of normal distal tubal anatomy.”

“... IVF is preferred to resection and microsurgical anastomosis.”


“… microsurgery may be considered after failed tubal cannulation if IVF is not an option for the patient, but it should be only by those with appropriate training.”

UNUSUAL

MICROSURGICAL

PROCEDURES

Victor Gomel

PROCEDURES

Victor GomelGomel V. Fertil Steril 1985; 43: 804‐ 8

Ovary and occluded ampullary stump

Victor Gomel

Mobilization of

adnexa with its

vascular pedicle

12

Intramural segment

Victor Gomel Victor GomelGomel V. Fertil Steril 1985; 43: 804‐ 8

Ampullary stump

Ampullary-intramural anastomosis

Victor Gomel Victor Gomel


Successful surgery offers the couple multiple cycles in which

to achieve conception naturally,

REPRODUCTIVE SURGERY

Victor Gomel

p y,and the opportunity to have

more than one pregnancy after a single surgical intervention.

13

RATE OF BIRTHS USA 2001 -9

Delivery/cycle initiated 28.5 %

Delivery/ 3 cycles initiated 54.0 %

Victor Gomel


> 50% of IVF Cycles were ICSI cycles.

?

IVF: TREATMENT CYCLES

Several studies have shown conclusively

that the majority of couples

undergoing IVF-ET

do not whish to complete

3 cycles of IVF.

Victor Gomel

Land JA, Coultar DA, Evers JL. Fertil Steril. 1997; 68: 278-81Olivius K et al. Fertil Steril. 2002; 77: 505-10

Frydman R. Convictions 2010. Bayard ; Paris

THE WAY IN WHICHHUMAN LIFE NORMALLY BEGINS…

Victor Gomel

ENDOMETRIOSIS* ‐ IVFCumulative III+IV Endo I+II TubalPregnancy° (n=67) (n=31) (n=87)

Fresh Embryo % 22.6 40.0 36.6Not successful

Victor Gomel

Fresh + Frozen % 56.7 67.7 81.6

Fre + Fro Birth % 40.3 55.8 43.7

* Endometriosis associated infertility; 98 consecutive women treated with IVF or ICSI

° Cumulative pregnancy after 1‐ 4 cycles of IVF/ICSI treatment.

. Kuivasaari P et al. Human Reprod. 2005

>50%

Victor Gomel

TUBO-CORNUAL ANASTOMOSIS- RESULTS

Outcome no. Patients %

Total patients 59

Viable births 27 45.8%

Victor Gomel

Of 32 with no births 21 treated 66 ē cycles IVF

Viable births 12

Viable births total 39/ 59 66.1%

Tomazevic T et al. Hum Reprod 1996; 11: 2613

14

“The assimilation of microsurgical techniques and principles into our specialty

made the gynecologist much more conscious of avoiding peritoneal trauma and more careful in tissue handling and tissue

Victor Gomel

f gcare. It made the gynecologist more

conscious of conservation, and overall a better surgeon.”

Gomel V. Fertil Steril. 1983; 39: 144‐ 156

• Reproductive surgery has a significant role in infertility.

• The cost of IVF is prohibitive for many.

• Refuse IVF for religious/ethical reasons.

Victor Gomel

g

• ±50% fail to obtain a baby with IVF.

• A percentage need surgery before IVFfor myomas, adnexal tumors, endometriosis, etc.

•Training in reproductive surgery is essential- to improve IVF outcome- to ensure gynecologists remain refined surgeons

• Surgery and ART are complementary

Victor Gomel

Surgery and ART are complementary.

• Selection of treatment should be based on the clinical findings and the circumstances of each couple.

Gomel V. Minerva Gynecol. 2005; 57: 21‐ 8

THANK YOUMERCIGRACIAS

ありがとう

OBRIGADO

Victor Gomel

TEŞEKÜRLER

GRAZZIEEYXAPIΣТΩ

شكرا

Victor Gomel

TRANSPOSITION OF TUBE & OVARY


15

Hydrosalpinx and Other Indications for Laparoscopy

in the Infertile Patient

Las Vegas, NVTuesday, November 6, 2012

David Adamson, MDDirector, Fertility Physicians of Northern California

Clinical Professor, Stanford University

Associate Clinical Professor, UCSF

Disclosures• Grants/Research Support: Auxogyn, Bayer‐Sherring, EMD‐

Serono

• Consultant: LabCorp

• Other: CEO and Founder ‐ Advanced Reproductive Care

Objectives

• List the indications and contraindications for performing salpingectomy in an infertile patient.

• Describe pathological pelvic anatomical conditions that are potentially mitigated by surgery.

• Compare the relative advantages and disadvantages of laparoscopy vs. ART in the infertile patient.

Patient Selection

Clinical Application of Laparoscopy• Younger women (?<37 years of age)• Short duration of infertility (<4 years)• Prior pregnancy• Normal male factor• Normal or treatable uterus• Normal ovarian reserve and

N l l ti il t t bl l ti di d• Normal ovulation or easily treatable ovulation disorder• Limited prior treatment• Appropriate candidate for laparoscopy

– “Treatable” disease reasonably suspected (NNT)– No contraindications/risks for laparoscopy, pregnancy– Patient accepts 9 to 15 months interval to IVF

Factors That Will Affect theChoice of Treatment

• Family

– Current socioeconomic status

– Current size

• Desire for diagnosis

• Perspective on use of technology for reproduction

– Future plans

– Time frame

• Treatment

– Financial resources

– Insurance coverage

p

• Perspective on risks

– Surgery

– Multiple pregnancy

• Religious beliefs

16

Phimosis and HydrosalpinxHydrosalpinx

ASRM Practice Guidelines, 2001. ASRM Practice Guidelines.

Surgery for Distal Tubal Disease—Good Prognosis

• Hydrosalpinges and fimbrial phimosis

• PID, Peritonitis, Prior surgery

• Good prognosis

Li it d fil d l dh i– Limited filmy adnexal adhesions

– Mildly dilated tubes (<3 cm) with thin, pliable walls

– Lush endosalpinx with preservation of the mucosal folds (1)

(1) American Fertility Society. Fertil Steril 1988;49:944–55.

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Surgery for Distal Tubal Disease—Good Prognosis

• Intrinsically normal tubes

– Peritubal adhesions

– Endometriosis

May mechanically impair oocyte capture– May mechanically impair oocyte capture

• Treatment outcomes

– Laparotomy adhesiolysis at 12 months 40%

– Untreated 8% (1) (1) Tulandi Am J Obstet Gynecol 1990;162:354–7.

Fimbrioplasty and Neosalpingostomy

• Pregnancy rates depend

– Degree of tubal disease

– More favorable with good‐prognosis patients (1,2)

• Hydrosalpinges (1) Mild Severey p g ( )

– IUP 58‐77% 0‐22%

– Ectopic 2% to 8% 0‐17%

• Irreversible deciliation(1) Nackley. Fertil Steril 1998;69:373–84.

(2) Milingos. J Am Assoc Gynecol Laparosc 2000;7:355–61.

Fimbrioplasty and Neosalpingostomy

• Fimbrioplasty similar to neosalpingostomy

• Perform laparoscopically; results same, risk less (1,2)

• IVF preferred over neosalpingostomy– Older women, male factor, other factors

– Salpingostomy may improve IVF success and allow spontaneous conceptionSalpingostomy may improve IVF success and allow spontaneous conception

– Tuboplasty is not appropriate for severe or both proximal & distal obstruction

– Consented both salpingostomy and salpingectomy

• Postoperative reocclusion may occur, necessitating more surgery

(1) ASRM Practice Committee. Fertil Steril 2006;86:S264–7.

(2)Bontis. Ann NY Acad Sci 2006;1092:199–210.

Surgical Treatment of Hydrosalpinges and IVF

• Hydrosalpinges

– Blocked tube at end secretes fluid faster than it is reabsorbed

– Becomes enlarged sac of secretionsBecomes enlarged sac of secretions

• Inflammatory/toxic fluid leaks back into uterus

– Direct mechanical flushing effect on embryo(s)

– Direct embryotoxic effect

– Effect on endometrial receptivityASRM Practice Committee. Fertil Steril 2008;90:S66–8.

Does Hydrosalpinx AffectIVF‐ET Outcome?

• Retrospective analysis

• Hydrosalpinx with US evidence of dilated tubes

– 60 patients had 116 initiated cycles and 106 ET

• Tubal Factor Controls

– 940 patients had 1428 initiated cycles and 1150 ET

• Outcomes

– Implantation 16% vs. 21% (P = 0.013)

– Preclinical Loss 37% vs. 14% (P=0.001)

– Miscarriage 25% vs. 20% (P=0.28)

– Ectopic 8% vs. 3% (P=0.04)

– Delivery/ET 26% vs. 34% (P=0.066)Barmat. JARG 1999;16(7):350-4.

Hydrosalpinges and IVFCochrane Meta‐Analysis

• 14 different studies of IVF

• 5592 women

– 1004 unilateral or bilateral hydrosalpinges

4 88 b l bl k h d l i– 4588 tubal blockage no hydrosalpinx

– 8703 IVF embryo transfers

Camus. Hum. Reprod 1999;14 (5):1243‐9.

18

Effect of Hydrosalpinges onIVF Outcomes

• PR 19.7% vs. 31.2% (OR=0.64; 95% CI 0.56, 0.74).

• IR 8.5% vs. 13.7%

• SAB (miscarriage) 43.7% vs. 31.1% (OR 0.58; 95% CI, 0 49 0 69)0.49–0.69)

• Delivery rate 13.4% vs. 23.4%

Camus. Hum Reprod 1999;14 (5):1243‐9.

Effect of Hydrosalpinges onIVF Outcomes

• 2 Meta‐analyses– 6700 cycles in 11 studies & 4 abstracts

• Pregnancy Rate– Tubal infertility PR 31.2%– Hydrosalpinges PR 16.4%Hydrosalpinges PR 16.4%

• PR 49% lower

– Fresh and FET

• Miscarriage– 2.3‐fold (95% CI, 1.6–3.5)

Zeyneloglu. Fertil Steril 1998;70:492–932.

Camus. Hum Reprod 1999;14:1243–9.

Impact of Ultrasound Appearance of Hydrosalpinges

• Hydrosalpinx is Ultrasound‐visible

– Implantation and Ongoing Implantation

• OR=0.33‐0.46, C.I. 0.21‐0.96

– Cumulative chance ongoing pregnancy after 1+ cyclesg g p g y y

• Relative hazard 0.36, C.I. 0.22‐0.59

• Hydrosalpinx not visible by ultrasound

– IVF outcome not reduced

Strandell. Hum Reprod 1999;14:2762–9.de Wit.Hum Reprod 1998;13:1696–701.

Indications for Salpingectomy or Tubal Occlusion

• Indication

– Fallopian tube is damaged beyond repair by infection, endometriosis, or ectopic pregnancy

• Poor prognosisp g

– Extensive, dense peritubal adhesions

– Massively dilated tubes

– Thick fibrotic walls, and/or

– Sparse or absent luminal mucosaASRM Practice Cmttee. Fertil Steril 2012 Mar;97(3):539-45.

Does Treatment + IVF Work? • 3 RCT

• Pilot study of 90

– Hydro or SIN

– LS and treatment vs LS look only

– PR per cycle 23 7% tx vs 16 3% none– PR per cycle 23.7% tx vs 16.3% none

• 204 patients with hydrosalpinges tx vs no

– delivery rate 28.6% vs 16.3% (P=.045)

– If seen on U/S 40.0% vs 17.5% (P=.038)

Strandell, Hum. Reprod 1999;14 (11):2762‐9.

Effect of Treating HydrosalpingesBefore IVF

ASRM Practice Committee. Fertil Steril 2012;97:539–45.

19

Surgical Treatment for Tubal Disease in Women Due to Undergo IVF (1)

• 5 RCT comparing surgical treatment vs. control group

– N=646

– Salpingectomy vs. No Treatment, 4 trials

– Salpingectomy vs. Tubal occlusion, 2 trials

– Aspiration vs. No Treatment, 1 trial

• Outcomes Laparoscopic Salpingectomy

– Ongoing Pregnancy: Peto OR 2.14, 95%CI 1.23 to 3.73

– Clinical pregnancy: Peto OR 2.31, 95%CI 1.48 to 3.62

Johnson. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD002125.

Surgical Treatment for Tubal Disease in Women Due to Undergo IVF (2)

• Laparoscopic occlusion vs. no intervention

– Ongoing Pregnancy: Peto OR 7.24, 95%CI 0.87 to 59.57

– Clinical Pregnancy: Peto OR 4.66, 95%CI 2.47 to 10.01

• Tubal occlusion to salpingectomy– Ongoing Pregnancy: Peto OR: 1.65, 95%CI 0.74, 3.71

Clinical Pregnancy: Peto OR 1 28 95%CI 0 76 to 2 14– Clinical Pregnancy: Peto OR 1.28, 95%CI 0,76 to 2.14

• US‐guided aspiration (1 RCT)– Clinical Pregnancy: Peto OR 1.97, 95%CI 0.62 to 6.29

• No significant differences in adverse effects of surgical treatments


Proximal Tubal Occlusion by Hysteroscopic Approach

• Essure coil inserts

– Data on IVF success rates are limited to a few very small case series (1,2).

– ? Trailing coils have potential to act as an IUD intrauterine

– Complete tissue encapsulation coils 17% of patients within 1 year & 25% at 13–43 months (3).

• Adiana: no data

– Radiofrequency energy to stimulate interstitial scarring followed by insertion of a small silicone elastomer matrix

(1) Mijatovic. Fertil Steril 2010;93:1338–42.

(2) Darwish. Acta Obstet Gynecol Scand 2007;86:1484–9.

(3) Kerin. J Min Invas Gynecol 2007;14:202–4.

Aspiration and NeosalpingostomyBefore IVF

• Ultrasound‐guided aspiration of hydrosalpinges at the time of oocyte retrieval yielded conflicting results in two small retrospective studies (1,2)

• A randomized study comparing ultrasound‐guided aspiration with a nontreated control reported significantly higher clinical pregnancy rates with aspiration (3).

• Intuitively it makes sense that laparoscopic neosalpingostomy before IVF• Intuitively, it makes sense that laparoscopic neosalpingostomy before IVF should improve the pregnancy rate, but there are still no confirmatory studies.

(1) Sowter. Hum Reprod 1997;12:2147–50.

(2) Van Voorhis. Hum Reprod 1998;13:736‐9.

(3) Hammadieh. Hum Reprod 2008;23:1113–17.

Conclusions: Surgical Treatment for Tubal Disease in Women Due to Undergo IVF (3)

• Surgical treatment should be considered for all women with hydrosalpinges prior to IVF treatment.

• Laparoscopic tubal occlusion is an alternative to laparoscopic salpingectomy in improving IVF PR.

F h h i i d h l f• Further research is required to assess the value of aspiration of hydrosalpinges prior to or during IVF procedures and also the value of tubal restorative surgery as an alternative (or as a preliminary) to IVF.


Effect of Unilateral Hydrosalpingeson IVF Pregnancy Rates

• Even patients with a unilateral hydrosalpinx have been shown to have lower pregnancy rates with IVF (1,2)

• Unilateral salpingectomy resulted in a significant improvement in IVF pregnancy rates in these patients (3)

• Salpingectomies for bilateral hydrosalpinges yielded higher IVF pregnancy rates than for unilateral hydrosalpinges (4)

(1) Kassabji. Eur J Obstet Gynecol Reprod Biol 1994;56:129–32.

(2) Murray. Fertil Steril 1998;69:41–5.

(3) Shelton. Hum Reprod 1996;11:523–5.

(4) Strandell. Hum Reprod 1999;14:2762–9.

20

Chances for Pregnancy After Unilateral Salpingectomy

• 25 women with one hydrosalpinx

– 18 salpingectomy or 7 tubal ligation

– pregnancy rates naturally without IVFp g y y

• 88% women achieved pregnancy

– Salpingectomy quicker

• Mean time to pregnancy 5.6 months

Sagoskin. Hum Rerod 2003 Dec;18(12):2634‐7.

Technical Aspects of Salpingectomy

• Coagulate and divide tube close to cornua

• Serially coagulate and cut the mesosalpinx

• Stay close to the tube to avoid

– thermal injury to the ovary

– Vascular injury of ovarian blood supply

• Ovarian injury possible but avoidable (1‐3)(1) Chan. Hum Reprod 2003;18:2175–80.(2) Dar. Hum Reprod 2000;15:142–4.(3) Strandell. Hum Reprod 2001;16:1135–9.

Summary and Conclusions1. The live birth rate achieved with IVF among women with hydrosalpinges is approximately one half that observed in women without hydrosalpinges.

2. In women with hydrosalpinges, preliminary laparoscopic salpingectomy or proximal tubal occlusion improves subsequent pregnancy and live birth rates

achieved with IVF. For every six women with hydrosalpinges, one more ongoing pregnancy will be achieved if salpingectomy or tubal occlusion is performed before IVFperformed before IVF.

3. Data are insufficient to permit recommendations regarding the effectiveness of alternative treatments such as laparoscopic neosalpingostomy, transvaginal aspiration of hydrosalpingeal fluid, hysteroscopic tubal occlusion, or antibiotic treatment.

SRS and ASRM Practice Committees. Fertil Steril 2008;90:S66–8.

Adhesions

Significance of Peritubal Adhesions

• 433 infertile women had laparoscopy

• Peritubal adhesion effect equal to unilateral b l b itubal obstruction

• 25% reduction

Nordenskjold, Acta Obstet Gynecol Scand. 1983;62(6):609‐15.

Effectiveness of Adhesiolysis

• Improved Pregnancy Rates Following Adhesiolysis

12 months 24 months

Not treated 11% 16%

Treated 32% 45%

p~0.000

Tulandi. AJOG 1990;162:354‐7.

21

Conclusions

• Advantages of Laparoscopy– More than one pregnancy

– Fewer multiple pregnancies

– Repair pathology

– Mitigate problems in addition to infertilityMitigate problems in addition to infertility

• Disadvantages of laparoscopy– Time required to attempt pregnancy

– Risks of surgery

– Costs of surgery

– Not all conditions are treatable or improved

THANKOYOU!

References (1)

American Fertility Society. Fertil Steril 1988;49:944–55. ASRM Practice Committee. Fertil Steril 2006;86:S264–7. ASRM Practice Committee. Fertil Steril 2008;90:S66–8. ASRM Practice Committee. Fertil Steril 2012 Mar;97(3):539–45. Barmat. JARG 1999;16(7):350‐4. Bontis. Ann NY Acad Sci 2006;1092:199–210. Camus. Hum Reprod 1999;14 (5):1243‐9. Chan. Hum Reprod 2003;18:2175–80. Dar. Hum Reprod 2000;15:142–4. Darwish. Acta Obstet Gynecol Scand 2007;86:1484–9. de Wit.Hum Reprod 1998;13:1696–701. Hammadieh. Hum Reprod 2008;23:1113–17. Johnson. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD002125. Kassabji. Eur J Obstet Gynecol Reprod Biol 1994;56:129–32. Kerin. J Min Invas Gynecol 2007;14:202–4.

References(2)

Mijatovic. Fertil Steril 2010;93:1338–42.Milingos. J Am Assoc Gynecol Laparosc 2000;7:355–61. Murray. Fertil Steril 1998;69:41–5. Nackley. Fertil Steril 1998;69:373–84. Nordenskjold, Acta Obstet Gynecol Scand. 1983;62(6):609‐15. Sagoskin. Hum Rerod 2003 Dec;18(12):2634‐7. Shelton Hum Reprod 1996;11:523–5Shelton. Hum Reprod 1996;11:523 5.Sowter. Hum Reprod 1997;12:2147–50. SRS and ASRM Practice Committees. Fertil Steril 2008;90:S66–8. Strandell. Hum Reprod 1999;14:2762–9. Strandell. Hum Reprod 2001;16:1135–9. Tulandi Am J Obstet Gynecol 1990;162:354–7. Van Voorhis. Hum Reprod 1998;13:736‐9. Zeyneloglu. Fertil Steril 1998;70:492–932.

22

When and How to When and How to Evaluate the Uterine Evaluate the Uterine Cavity: HSG vs. Cavity: HSG vs. Sonohysterography vs Sonohysterography vs Office HysteroscopyOffice Hysteroscopy

Keith Isaacson MD Keith Isaacson MD Director MIGS and Infertility, NWHDirector MIGS and Infertility, NWHAssociate Prof Ob/Gyn Associate Prof Ob/Gyn Harvard Medical SchoolHarvard Medical [email protected]@partners.org

DisclosuresDisclosures

Consultant Consultant –– Karl Storz Karl Storz EndoscopyEndoscopy

Learning ObjectivesLearning Objectives

-- At At the conclusion of this presentation, the conclusion of this presentation, the participant will be familiar with:the participant will be familiar with:

-- The indications to evaluate the uterine The indications to evaluate the uterine ititcavitycavity

-- The strengths and limitations of HSG, The strengths and limitations of HSG, sonohysterogramsonohysterogram and office hysteroscopyand office hysteroscopy

Indications for Uterine Indications for Uterine Cavity EvaluationCavity Evaluation Evaluation of Abnormal Uterine Evaluation of Abnormal Uterine

Bleeding (AUB)Bleeding (AUB) Infertility evaluationInfertility evaluation Location of foreign bodies/lost IUDLocation of foreign bodies/lost IUD Identification of focal endometrial Identification of focal endometrial

cancerscancers Complications of pregnancyComplications of pregnancy Cervical examinationCervical examination

Indications for Uterine Indications for Uterine Cavity AssessmentCavity Assessment

Pre and postPre and post--surgical evaluationsurgical evaluation Evaluation of PostEvaluation of Post--menopausal menopausal

bl dibl dibleedingbleeding

Indications for Cavity Indications for Cavity AssessmentAssessment

Evaluation of Abnormal Uterine Evaluation of Abnormal Uterine BleedingBleeding

InfertilityInfertility Location of foreign bodies/lost IUDLocation of foreign bodies/lost IUD Identification of focal endometrial Identification of focal endometrial


23

Evaluation of AUBEvaluation of AUBEvaluation of AUBEvaluation of AUB

Normal Menstrual Normal Menstrual CyclesCyclesCycle length Cycle length -- 28 +/28 +/-- 7days7daysDuration of flow Duration of flow -- 4 +/4 +/-- 2days2daysBlood loss/cycle Blood loss/cycle -- 40 +/40 +/-- 20ml20ml

Excessive Uterine Excessive Uterine BleedingBleeding

Cycle length Cycle length << 21days21daysf ff fDuration of flow Duration of flow >> 7days7days

Blood loss/cycle Blood loss/cycle >> 80ml80ml––67% develop anemia67% develop anemia11

Hallberg L et al. Acta Obstet Gynaecol Scand, 1966

Clinical IndicatorsClinical Indicators

Increase in >2 sanitary pads/dayIncrease in >2 sanitary pads/day Duration lasting > 3 days more than Duration lasting > 3 days more than

usualusualusualusual Intermenstrual bleedingIntermenstrual bleeding Cycles > 2 days shorter than usualCycles > 2 days shorter than usual Blood clots and socially embarrassing Blood clots and socially embarrassing

bleedingbleeding

Subjective AssessmentSubjective Assessment

One third of women with >80 One third of women with >80 ml/cycle feel their bleeding is ml/cycle feel their bleeding is normalnormalnormalnormal

15% of women with a flow <15 15% of women with a flow <15 ml/cycle feel their flow is heavyml/cycle feel their flow is heavy

Causes of abnormal Causes of abnormal uterine bleeding (AUB)uterine bleeding (AUB)

DysfunctionalDysfunctionalI t iI t i Iatrogenic Iatrogenic

OrganicOrganic

24

Dysfunctional Uterine Dysfunctional Uterine BleedingBleeding(anovulatory bleeding)(anovulatory bleeding)

Abnormal uterine bleeding with no Abnormal uterine bleeding with no identifiable organic diseaseidentifiable organic diseasegg

Bleeding due to irregular ovulation Bleeding due to irregular ovulation with periods of unopposed estrogenwith periods of unopposed estrogen–– perimenarcheperimenarche–– perimenopauseperimenopause–– PCOPCO

Iatrogenic AUBIatrogenic AUB

IUD’sIUD’s Steroid contraceptivesSteroid contraceptives

–– NorplantNorplant–– NorplantNorplant–– Depot ProveraDepot Provera–– OCPOCP

Other medicationsOther medications–– TranquilizersTranquilizers

Organic Conditions and Organic Conditions and AUBAUB

Complications of pregnancyComplications of pregnancy–– Retained placentaRetained placenta

MalignancyMalignancy InfectionInfection Systemic diseasesSystemic diseases

–– coagulopathiescoagulopathies–– hypothryoidismhypothryoidism–– liver diseaseliver disease

Organic lesions and AUBOrganic lesions and AUB

Benign pelvic lesionsBenign pelvic lesions–– submucous myomatasubmucous myomata–– intramural myomata (less common)intramural myomata (less common)intramural myomata (less common)intramural myomata (less common)–– endometrial and endocervical polypsendometrial and endocervical polyps–– adenomyosisadenomyosis

Evaluation of AUB: Step IEvaluation of AUB: Step I

History History –– Past medical history (systemic disease)Past medical history (systemic disease)–– MedicationsMedicationsMedicationsMedications–– Contraceptive useContraceptive use–– Age of AUB onsetAge of AUB onset–– LMP LMP -- r/o pregnancyr/o pregnancy–– Cycle regularityCycle regularity–– Abnormal bleeding from other sites Abnormal bleeding from other sites

Evaluation of AUB:Step IIEvaluation of AUB:Step II

Ovulatory vs AnovulatoryOvulatory vs Anovulatory–– Regular cycle Regular cycle -- 95% ovulatory95% ovulatory–– BBTBBTBBTBBT–– LH kitLH kit–– Luteal ProgesteroneLuteal Progesterone–– U/SU/S

25

Anovulatory AUBAnovulatory AUB

Hormonal evaluation Hormonal evaluation –– PCO (FSH, LH, E2)PCO (FSH, LH, E2)–– Hypothalamic amenorrhea (FSH, E2)Hypothalamic amenorrhea (FSH, E2)–– ProlactinProlactin–– TSHTSH

Hormonal therapy Hormonal therapy –– ProgestinsProgestins, E2/P4, , E2/P4, OCPsOCPs, , thryoidthryoid

replacement, replacement, parlodelparlodel–– MirenaMirena IUD IUD -- continuous release of local continuous release of local

levonorgestrellevonorgestrel

Ovulatory AUBOvulatory AUB

Coagulopathies (15Coagulopathies (15--20% of 20% of adolescents with excessive regular adolescents with excessive regular uterine bleeding)uterine bleeding)g)g)–– primary hemostasis (formation of platelet primary hemostasis (formation of platelet

plug)plug)–– secondary hemostasis (stabilization of secondary hemostasis (stabilization of

platelet plug with fibrin deposition)platelet plug with fibrin deposition)–– orderly dissolution of clot (fibrinolysis)orderly dissolution of clot (fibrinolysis)

Evaluation of Evaluation of CoagulopathiesCoagulopathies

CBC and Platelet countCBC and Platelet count PT PT -- factors II, V, VII, X, fibrinogenfactors II, V, VII, X, fibrinogen APTTAPTT-- factors VIII, IX, XII, II, V, Xfactors VIII, IX, XII, II, V, X Bleeding time Bleeding time -- platelet function, platelet number, platelet function, platelet number,

von Willebrand factor, vascular integrity.von Willebrand factor, vascular integrity. Platelet function test Platelet function test -- replace bleeding timereplace bleeding time vWF screen vWF screen –– vWFAg, vWF:RCo (marker for vWF vWFAg, vWF:RCo (marker for vWF

activity, Factor VIII:C coagulant capacity activity, Factor VIII:C coagulant capacity –– Type O have low nl vWF and high E2 elevates vWF Type O have low nl vWF and high E2 elevates vWF

Evaluation of the Evaluation of the Reproductive TractReproductive Tract Rule out malignancyRule out malignancy

–– Endometrial biopsy (> 35 y/o)Endometrial biopsy (> 35 y/o)–– Vaginal U/S if post menopausalVaginal U/S if post menopausalVaginal U/S if post menopausalVaginal U/S if post menopausal–– Pap smear +/Pap smear +/-- colposcopy and biopsycolposcopy and biopsy–– GuiacGuiac

Rule out infectionRule out infection–– cervical culturescervical cultures–– EB to rule out chronic endometritisEB to rule out chronic endometritis

Rule out adenomyosis Rule out adenomyosis -- MRI, ?hysteroscopyMRI, ?hysteroscopy

Indications for Uterine Indications for Uterine Cavity Evaluation Cavity Evaluation Premenopausal and ovulatoryPremenopausal and ovulatory Premenopausal and anovulatory but Premenopausal and anovulatory but

fails hormonal therapyfails hormonal therapyfails hormonal therapyfails hormonal therapy Postmenopausal bleeding off HRTPostmenopausal bleeding off HRT Unexpected postmenopausal bleeding Unexpected postmenopausal bleeding

on HRTon HRT

Evaluation of the Uterine Evaluation of the Uterine CavityCavity D&CD&C HysterosalpingogramHysterosalpingogram UltrasoundUltrasound UltrasoundUltrasound SonohysterographySonohysterography Office hysteroscopyOffice hysteroscopy

26

D&CD&C

Will miss up to 40% of focal lesions Will miss up to 40% of focal lesions such as polyps and fibroids.such as polyps and fibroids.

Equal to Pipelle office biopsy forEqual to Pipelle office biopsy for Equal to Pipelle office biopsy for Equal to Pipelle office biopsy for detecting diffuse endometrial detecting diffuse endometrial carcinoma.carcinoma.

Only indicated when office biopsy can Only indicated when office biopsy can not be obtained.not be obtained.

Loffer FD Obstet Gynecol 73(1): 16-20 1989

Vaginal Probe UltrasoundVaginal Probe Ultrasound

Useful for post menopausal bleedingUseful for post menopausal bleeding > 5 > 5 mm endometrium risk of CA is <3%mm endometrium risk of CA is <3%–– Sensitivity and specificity 56% and 49% (hysteroscopy Sensitivity and specificity 56% and 49% (hysteroscopy

100% and 50%)100% and 50%)100% and 50%)100% and 50%)–– PPV 83%, NPV PPV 83%, NPV --83% 83%

Can evaluate intramural and subserosal Can evaluate intramural and subserosal fibroids. fibroids.

Not helpful for focal endometrial lesions Not helpful for focal endometrial lesions such as polyps, myomas or focal cancers. such as polyps, myomas or focal cancers.

Litta P et al. Maturitas 50:117-23, 2005

33--D UltrasoundD Ultrasound

As sensitive and specific for congenital As sensitive and specific for congenital uterine anomalies as MRIuterine anomalies as MRI–– ArcuateArcuate uteriuteriArcuateArcuate uteriuteri–– SeptumSeptum–– BicornuateBicornuate uteriuteri–– DidelphysDidelphys

SIS Vs Hysteroscopy for SIS Vs Hysteroscopy for cavity evaluationcavity evaluation Similar time requirements Similar time requirements

–– 296 sec for SIS296 sec for SIS–– 255 sec for flexible OH255 sec for flexible OH

Significantly lower pain via VAS with OHSignificantly lower pain via VAS with OH Patient tolerancePatient tolerance

–– 78% preferred flexible OH78% preferred flexible OH

No significant difference in detecting No significant difference in detecting pathologypathology

Senapita S et al. O-105 Fertil Steril Vol 90 Suppl 1, Sept 2008

Hysteroscopic findings in Hysteroscopic findings in women with AUBwomen with AUB Menstrual blood loss >60 mlMenstrual blood loss >60 ml

–– 64% with lesion at hysteroscopy (Fraser 64% with lesion at hysteroscopy (Fraser IS Am J Obstet Gynecol, 162:1264, 1990IS Am J Obstet Gynecol, 162:1264, 1990y , ,y , ,

Post menopausal bleedingPost menopausal bleeding–– PPV 78%PPV 78%–– Negative predictive value 99.4% (Clark T Negative predictive value 99.4% (Clark T

et al. JAMA. 288:1610, Oct 2002et al. JAMA. 288:1610, Oct 2002

Indications for Office Indications for Office HysteroscopyHysteroscopy




27

Uterine Conditions Uterine Conditions Affecting FertilityAffecting Fertility Uterine fibroidsUterine fibroids

–– submucoussubmucous–– intramural?intramural?intramural?intramural?

Endometrial polypsEndometrial polyps Intrauterine synechiaIntrauterine synechia Congenital defectsCongenital defects Adenomyosis?Adenomyosis?

Submucosal MyomaSubmucosal Myoma

Submucus fibroids block or decrease Submucus fibroids block or decrease the normal vascular supply to the the normal vascular supply to the trophoblastic tissue.trophoblastic tissue.pp

Present in 8% of infertile womenPresent in 8% of infertile women Present in >50% of ovulatory women Present in >50% of ovulatory women

with menorrhagiawith menorrhagia

Valle FR. Am J Ob Gyn 1980:37:425-31

Narayan et al. Narayan et al. (JAAGL, 1994)(JAAGL, 1994)

100 failed IVF cycles with good 100 failed IVF cycles with good embryosembryos–– 73 normal cavity (control group)73 normal cavity (control group)73 normal cavity (control group)73 normal cavity (control group)–– 27 SM myomata27 SM myomata

16/27 had myomectomy, rest shrunk with 16/27 had myomectomy, rest shrunk with GnRHaGnRHa

–– Take home baby rateTake home baby rate 37% 37% -- myomectomy group myomectomy group 19% 19% -- controlscontrols

Bernard et al. Bernard et al. (Eu J Gyn/OB, Jan (Eu J Gyn/OB, Jan 2000)2000)

Retrospective study of 31 infertile Retrospective study of 31 infertile patients with SM myoma undergoing patients with SM myoma undergoing myomectomymyomectomyy yy y–– Followed for 3 yearsFollowed for 3 years–– 11/31 pregnant (35%)11/31 pregnant (35%)–– Lower pregnancy rate with >1 myoma Lower pregnancy rate with >1 myoma

and with concurrent intramural myomataand with concurrent intramural myomata

Submucous Myoma Submucous Myoma TherapyTherapy

30% 30% -- 60% pregnancy rates60% pregnancy rates–– Bernard et al, 2000Bernard et al, 2000–– Vercillini et al, 1999Vercillini et al, 1999Vercillini et al, 1999Vercillini et al, 1999–– Giatras et al, 1999 Giatras et al, 1999

Endometrial PolypsEndometrial Polyps

Impact on fertility?Impact on fertility? Present in 24% of infertile womenPresent in 24% of infertile women Present in >50% of ovulatory womenPresent in >50% of ovulatory women Present in >50% of ovulatory women Present in >50% of ovulatory women

with midcycle spotting with midcycle spotting

Valle FR. Am J Ob Gyn 1980:37:425-31

28

Intrauterine synechiaIntrauterine synechia

Increasing incidence worldwideIncreasing incidence worldwide–– D & C after delivery or missed abortionD & C after delivery or missed abortion–– TuberculosisTuberculosisTuberculosisTuberculosis–– Uterine insult in immunocompromised Uterine insult in immunocompromised

patientspatients

Schenker JG,. European J Obstet Gynecol & Repr Endocrinol 1996:65:109-113

Intrauterine AdhesionsIntrauterine Adhesions

Impact on fertility proportional to Impact on fertility proportional to degree of scarringdegree of scarring–– density of adhesionsdensity of adhesionsdensity of adhesionsdensity of adhesions–– degree of cavity occlusiondegree of cavity occlusion–– scarring on the uterine wallscarring on the uterine wall

Wamsteker K. Endoscopic Surgery for gynecologists. London: Saunders, 1993. 263-76

Congenital Uterine Congenital Uterine Abnormalities Abnormalities 0.2% 0.2% -- 10% of general population10% of general population

–– Septum Septum -- decrease vascularity decrease vascularity --recurrent Abrecurrent Ab

–– BicornuateBicornuate–– DidelphysDidelphys–– TT--shapeshape

Prevalence of Uterine Abnormalities in Prevalence of Uterine Abnormalities in Asymptomatic Patients Undergoing IVFAsymptomatic Patients Undergoing IVF

– Shamma et al (1992) - 12/28 (42%)– Giovanni et al (1998) - 18/100 (18%) all

had a normal HSG and 2 failed cycles– Kim et al (1999) - 8/72 (11%)– Ayida et al (1997) - 16/47 (34%)

37.5% clinical pregnancy rate without 37.5% clinical pregnancy rate without intrauterine lesions intrauterine lesions

8.3% clinical pregnancy rate with 8.3% clinical pregnancy rate with lesionslesions Shamma et al (1992)





Office Based Detection of Office Based Detection of Endometrial CAEndometrial CA

Vaginal probe ultrasound + office Vaginal probe ultrasound + office h t Pi ll d t i lh t Pi ll d t i lhysteroscopy + Pipelle endometrial hysteroscopy + Pipelle endometrial biopsy = Hysteroscopy and D&C for biopsy = Hysteroscopy and D&C for the detection of endometrial cancer.the detection of endometrial cancer.

Tahir M et al. BJOG 107:1058 Aug 2000

29

Does hysteroscopy influence Does hysteroscopy influence the prognosis of early stage the prognosis of early stage Endometrial Cancer?Endometrial Cancer? Means of diagnosis compared Means of diagnosis compared

–– Endometrial biopsyEndometrial biopsy–– HysteroscopyHysteroscopyHysteroscopy Hysteroscopy

ResultsResults–– Higher recurrence with endometrial Higher recurrence with endometrial

biopsybiopsy–– No difference in peritoneal cytology or 5 No difference in peritoneal cytology or 5

yr. survival rates. yr. survival rates.

Ben-Arie et al. Int J Gynecol CA July 2008






Pre and postPre and post--surgical evaluationsurgical evaluation Evaluation of PostEvaluation of Post--menopausal menopausal

bl dibl dibleedingbleeding Minor surgical proceduresMinor surgical procedures

–– Visual biopsyVisual biopsy–– Insertion of tubal occlusion deviceInsertion of tubal occlusion device–– AdhesiolysisAdhesiolysis–– PolypectomyPolypectomy

Information Changes Information Changes ManagementManagement Submucous Submucous

myomatamyomata–– Type 0 Type 0 -- 100% 100%

w/in cavityw/in cavity–– Type I Type I -- > >

50% w/in 50% w/in cavitycavity

–– Type II Type II -- < < 50% w/in 50% w/in cavitycavity

deBlok S, et al: Gynaecol Enosc 4:243-246, 1995

Office hysteroscopy nonOffice hysteroscopy non--disposable equipmentdisposable equipment HysteroscopeHysteroscope

–– FlexibleFlexible–– RigidRigid

12, 25, 30 degree angled lenses12, 25, 30 degree angled lenses Operative instrumentsOperative instruments

CartCart–– Light source, light cable, monitor, camera Light source, light cable, monitor, camera

(on cart or built into scope, image (on cart or built into scope, image capture)capture)

30

Costs and ReimbursementsCosts and Reimbursements

Capital equipment Capital equipment -- $12,000$12,000--$15,000$15,000–– Flexible scopeFlexible scope–– MonitorMonitorMonitorMonitor–– Light sourceLight source–– CameraCamera–– CartCart

QuestionsQuestions

Appropriate modalities to evaluate the Appropriate modalities to evaluate the uterine cavity include all of the uterine cavity include all of the following exceptfollowing exceptg pg pa)a) Vaginal probe ultrasoundVaginal probe ultrasoundb)b) 33--D ultrasoundD ultrasoundc)c) HSGHSGd)d) Office hysteroscopyOffice hysteroscopye)e) Saline Saline sonographysonography

QuestionsQuestions

Indications for evaluation of the Indications for evaluation of the uterine cavity include which of the uterine cavity include which of the followingfollowinggga)a) Pelvic painPelvic painb)b) Recurrent yeast infectionRecurrent yeast infectionc)c) DyspareuniaDyspareuniad)d) Recurrent miscarriageRecurrent miscarriage

QuestionsQuestions

SonohysterographySonohysterography has a better has a better sensitivity and specificity than HSG for sensitivity and specificity than HSG for detecting endometrial polypsdetecting endometrial polypsg p ypg p yp–– TrueTrue–– FalseFalse

QuestionsQuestions

Office hysteroscopy is a procedure Office hysteroscopy is a procedure that most often requires local that most often requires local anesthesia for pain managementanesthesia for pain managementp gp g

TrueTrue FalseFalse

31

When and How to Remove Intramural Fibroids to

Improve Fertility William W. Hurd, MD

Professor of Gynecology and Obstetrics

University Hospitals Case Medical CenterCase Western Reserve University School of Medicine

Disclosures

I have no financial relationships to disclose.

Learning Objectives

At the conclusion of this presentation, the participant should be able to:

1.Discuss what is known about the relationship b fib id d i f ilibetween fibroids and infertility

2.List guidelines for when to perform myomectomies in patients with infertility

3.Distinguish the relative advantages of the various surgical approaches for myomectomy

Incidence of Fibroids

Hysterectomy specimens 70%

Reproductive-age women 40%

Infertility women 10%

U l i d i f ili ?Unexplained infertility ?

Fibroids and Infertility

Some fibroids:

• Decrease fertility

• Increase spontaneous abortions

• Increase pregnancy complications• Increase pregnancy complications

Questions

1. When should we remove fibroids

in infertile women?

2. How?

Types of Fibroids

• Intracavitary

• Submucosal(Distorts cavity)

• Intramural

• Subserosal

• Pedunculated

32

Fibroids and Infertility:Possible Mechanisms

1. Interference with sperm/embryo transport

– Occlusion of the tubal ostea

– Changes in uterine contractility

– Elongation of the uterine cavity– Elongation of the uterine cavity

2. Impair implantation

– Intracavitary/Submucosal

– Intramural?

Do Submucosal and IntracavitaryFibroids Decrease Fertility?

Compared with infertile women without fibroids:

↓ Implantation rate ↓ Clinical pregnancy rate↓ Ongoing↓ Ongoing↓ Pregnancy/live birth rate ↑ Spontaneous abortion rate

(Pritts 2009)

Do Intramural Fibroids Decrease Fertility?

Effects of intramural fibroids on IVF:

Fibroids Control ORImplantation rate 16% 28% .62 (.48-.80)Delivery rate 31% 41% .69 (.50-.95)

(Benecke 2005)

Do Intramural Fibroids Decrease Fertility?

Intramural Fibroids <7 cm(Not Compressing Uterine Cavity)

60% IVF ICSI Results (n=245)

(Oliveira 2004)

0%

20%

40%

60%

Pregnancy Miscarriage

ControlFibroid

IVF-ICSI Results (n=245)

Effects of Size and Position on IVF-ICSI

Pregnancy

0%10%20%30%40%50%60%

(Oliveira 2004)

Miscarriage

0%10%20%30%40%50%60%

Control Subserosal 0.2 - 2.0 cm 2.0 - 4.0 cm 4.0 - 6.9 cm

Control Subserosal 0.2 - 2.0 cm 2.0 - 4.0 cm 4.0 - 6.9 cmIntramural

Intramural

Do Fibroids Increase Pregnancy Complications?

Obstetric and delivery outcomes for women with and without leiomyomas

(Stout 2010)

33

Fibroids >5 cm and Pregnancy Complications

Obstetric outcomes comparing women with leiomyomas <5 cm to those with leiomyomas >5 cm

(Stout 2010)

Does MyomectomyImprove Fertility or Miscarriage Rates?

Hysteroscopic Myomectomy:

– Retrospective (n= 29):

– 25 with intracavitary fibroids

– 4 with submucosal fibroids <5 mm

– No Pregnancy complications

(Shokeir 2005)

0%

10%

20%

30%

40%

50%

60%

70%

80%

ClinicalPregnancy

Spont Abortion Term Pregnancy

Before

After

Myomectomy and Pregnancy Rate

30%40%50%60%

Control

The only RCT

n=181

(Casini 2006)

0%10%20%30%

Intramural- Subserosal-

Submucosal Intramural submucosal intramural

Myomectomy

Myomectomy and Spontaneous Abortion Rates

• Intramural or Subserosal Fibroids >5 cm

• Retrospective, n = 51

Spontaneous Abortion Rates

(Li TC 1999)

0%

20%

40%

60%

Before After

Uterine Evaluation for Infertility

• Transvaginal Ultrasound

• Hysterosalpingogram

• Sonohysterogram

• 3-D ultrasound?

• MRI?

Ultrasonography

Measure:

• Location

• Number• Number

• Size

34

Hysterosalpingogram

Determines

• Tubal patency

• Distortion of the uterine cavityuterine cavity

Sonohysterogram

Determines

• Size

• Location relative to the• Location relative to theuterine cavity

3-D Ultrasonography

Uncertain role

Future:Future: 3-D sonohysterogram

MRI

• Most accurate

• Most expensive

• Offers little more informationinformation

When to Remove Fibroids

1. Symptomatic fibroids– Menorrhagia– Pressure symptoms related to size

3. Infertile patients – All Intracavitary or Submucosal fibroids – Intramural Fibroids >5 cm – Infertility unresponsive to therapy?

Surgical Approaches to Fibroids in the Infertile Patient

1. Hysteroscopic

• Intracavitary

• Some Submucosal

2 L i

3. Robotic

• Single Intramural

4. Open2. Laparoscopic

• Pedunculated

• Subserosal

• Intramural

• Submucosal?

• Large Submucosal

• Intramural

35

Hysteroscopic Approach

• Intracavitary

• Submucosal

I d i k fIncreased risk of

– Uterine perforation

– Infertility related to Asherman’s adhesions

– Placenta accrete

Brazil ClassificationPoint Penetration Size Base Location Lateral

0 0 <2 cm <1/3 lower No

1 <50% 2-5 cm 1/3-2/3 middle Yes

3 >50% >5 cm >2/3 upper

Suggested Approach

0-4 Hysteroscopic: Low complexity

5-6 Hysteroscopic: High complexity

7-9 Non-hysteroscopic

(Lasmar 2005)

Hysteroscopic Approaches1. Resectoscope

Advantage

– Deeper resection

– Reaches corners

– Less ExpensiveLess Expensive

2. Intra-uterine morcellator (Myosure®) (TrueClear®)

Advantages

– No electrosurgery

– Normal saline

– Easier

Hysteroscopic Myomectomy Pearls

• Preoperative GnRH agonist if >2 cm

• Vasopressin injection into cervix(10 u/50 cc NS)

• Careful Is & OsCareful Is & Os

– Good adhesion of bag to perineum

– Weighing device

– Know when to quit

Laparoscopic Approach

Fibroids involving myometrium

• SubmucosalSubmucosal

• Intramural

• Submucosal

Robotically Assisted Laparoscopic Approach

• Single submucosal/intramural fibroids

Indman

36

Risk of Laparoscopic Approach for the Infertility Patient

•Uterine rupture during pregnancy

ASRM Guideline:

“the inability to effectivelythe inability to effectively

close the myometrium laparoscopically could contribute to a higher incidence of this

complication”

(ASRM 2004)

Laparoscopic MyomectomyPearls

• Vasopressin injection(10 u/50 cc NS)

• V-lock® sutureV lock® sutureCover with adhesion barrier

• Adhesions Barrier

Laparotomy Myomectomy

Decreased • Blood Loss? • Subsequent uterine rupture?• Recurrence?

Increased• Discomfort• Wound infection• Adhesions

Laparotomy MyomectomyPearls

• Preoperative GnRH agonist

• Vasopressin

• Tourniquets

• Adhesion barrier• Adhesion barrier

Adhesion Prevention after Myomectomy

• Proven to decrease adhesions:– Oxidized regenerated cellulose

Interceed® – Hyaluronatecarboxymethycellulose

film Seprafilm® (laparotomy only)

• No data on subsequent fertility or other long-term outcomes

• No benefit:– 4% icodextrin solution: Adept®

(Robertson 2010) (Trew 2011)

SummaryFibroids in Infertile Women

1. All infertility patients are evaluated for fibroids

2. Fibroids should be removed in infertile patients when they are• IntracavitaryIntracavitary• Submucosal • Intramural fibroids >5 cm

3. Surgical approach depends on location, size, equipment, and training

37

Q ti ?Questions?

ReferencesBenecke C, Kruger TF, Siebert TI, Van der Merwe JP, Steyn DW. Effect of fibroids on fertility in patients undergoing assisted

reproduction. A structured literature review. Gynecol Obstet Invest. 2005;59(4):225-30. Casini ML, Rossi F, Agostini R, Unfer V. Effects of the position of fibroids on fertility. Gynecol Endocrinol. 2006 Feb;22(2):106-9. Lasmar RB, Barrozo PR, Dias R, Oliveira MA. Submucous myomas: a new presurgical classification to evaluate the viability of

hysteroscopic surgical treatment--preliminary report. J Minim Invasive Gynecol. 2005 Jul-Aug;12(4):308-11. Li TC, Mortimer R, Cooke ID. Myomectomy: a retrospective study to examine reproductive performance before and after

surgery. Hum Reprod. 1999 Jul;14(7):1735-40.Oliveira FG, Abdelmassih VG, Diamond MP, Dozortsev D, Melo NR, Abdelmassih R. Impact of subserosal and intramural

uterine fibroids that do not distort the endometrial cavity on the outcome of in vitro fertilization-intracytoplasmic sperm injection. Fertil Steril. 2004 Mar;81(3):582-7.

Parker WH, Olive DL, Pritts EA. Fibroids and pregnancy outcomes. Fertil Steril. 2012 Jul;98(1):e13. Practice Committee of the American Society for Reproductive Medicine. Myomas and reproductive function. Fertil Steril. 2004

Sep;82 Suppl 1:S111 6:Sep;82 Suppl 1:S111-6:Pritts EA, Parker WH, Olive DL. Fibroids and infertility: an updated systematic review of the evidence. Fertil Steril. 2009

Apr;91(4):1215-23. Robertson D, Lefebvre G, Leyland N, Wolfman W, Allaire C, Awadalla A, Best C, Contestabile E, Dunn S, Heywood M, Leroux

N, Potestio F, Rittenberg D, Senikas V, Soucy R, Singh S; Society of Obstetricians and Gynaecologists of Canada. Adhesion prevention in gynaecological surgery. J Obstet Gynaecol Can. 2010 Jun;32(6):598-608.

Shokeir TA. Hysteroscopic management in submucous fibroids to improve fertility. Arch Gynecol Obstet. 2005 Nov;273(1):50-4.Stout MJ, Odibo AO, Graseck AS, Macones GA, Crane JP, Cahill AG. Leiomyomas at routine second-trimester ultrasound

examination and adverse obstetric outcomes. Obstet Gynecol 2010;116:1056–63.Trew G, Pistofidis G, Pados G, Lower A, Mettler L, Wallwiener D, Korell M, Pouly JL, Coccia ME, Audebert A, Nappi C, Schmidt

E, McVeigh E, Landi S, Degueldre M, Konincxk P, Rimbach S, Chapron C, Dallay D, Röemer T, McConnachie A, Ford I, Crowe A, Knight A, Dizerega G, Dewilde R. Gynaecological endoscopic evaluation of 4% icodextrin solution: a European, multicentre, double-blind, randomized study of the efficacy and safety in the reduction of de novo adhesions after laparoscopic gynaecological surgery. Hum Reprod. 2011 Aug;26(8):2015-27.

38

TUBAL LIGATION

REVERSAL

VERSUS IVF

Victor Gomel

Professor Victor Gomel

DISCLOSURE


• The first option (reversal) is designed

to restore tubal function.

• Wh th d (IVF) l

Victor Gomel

• Whereas, the second (IVF), replaces

it.

• The advantages and drawbacks of IVFhave been discussed in my earlierpresentation and will not be repeatedhere.

• H ill i th i t t

Victor Gomel

• However, we will review the importantfactors that must be taken intoaccount in recommending the propertreatment modality..

Although performed less frequently thanbefore, reversal procedures have as yetnot suffered the abandonment otheranastomotic tubal procedures haveexperienced.

Yet, microsurgery finds its ultimateapplication in tubo-tubal anastomosis.

Victor Gomel

The precision afforded by the

microsurgical technique and use of

magnification allow precise dissection of

the occluded ends, proper alignment of

Victor Gomel

p p g

the proximal and distal segments of tube,

and excellent apposition of each layer

with very fine non-reactive sutures.

39

Furthermore since in the vast majority of

reversal cases the available tubal

segments are normal, the outcome is an

Victor Gomel

g ,

anatomically and physiologically normal,

albeit shortened fallopian tube.

Gomel V. McComb PF. J Reprod Med. RBM Online. 2006; 51: 177‐ 184


• Clinical assessment**

• Semen analysis





* Obtain the operative report of the prior tubal sterilization.

IVF AS PRIMARY TREATMENT

• Male factor infertility

• Age of female partner

• Tubal disease + Male factorTubal disease Male factor

• Inoperable tubal disease

• Others: ie. need for PGD

Victor Gomel


FURTHER CONSIDERATIONS

• Report of the prior tubal sterilization

• Size of remaining tubal segments?

• Need for HSG and/or laparoscopy?Need for HSG and/or laparoscopy?

• Health insurance coverage, costs, etc.

• Wishes of the patient/ couple…

Victor Gomel

Gomel V. RBM Online. 2007; 15: 403‐ 407

ISTHMIC-ISTHMIC

ANASTOMOSIS

Victor Gomel

ISTHMIC-ISTHMICANASTOMOSIS

Victor Gomel

40


Victor Gomel


Victor Gomel

ISTHMIC-ISTHMIC

ANASTOMOSIS

Victor GomelGomel V. RBMOnline. 2007; 15: 403-7

ISTHMIC-AMPULLARY

ANASTOMOSIS


PREPARATION OFAMPULLAY STUMP


PREPARATION OFAMPULLAY STUMP

Victor Gomel

41

ISTHMIC-AMPULLARY

ANASTOMOSIS

Victor Gomel

ISTHMIC-AMPULLARY

ANASTOMOSIS

Victor Gomel

CALCIFIEDTUBAL

PREGNANCY


IFFS 1974: 8TH WORLD CONGRESS

BUENOS AIRESARGENTINA


42

STERILIZATION REVERSAL- LAPAROSCOPY

Patients*(n=118) No. %

Not pregnant 20 16.9%


** Long term follow up.

Gomel V. Fertil Steril. 1980; 33: 587-97

Victor Gomel

p p g y

Intrauterine pregn. 96 81.4%


Total followed 922/ 1118 35/ 387Total I.U. pregn. 463 (50%) 329 (90%)Viable births 366 (40%) 295 (82%)

Total followed 922/ 1118 35/ 387Total I.U. pregn. 463 (50%) 329 (90%)Viable births 366 (40%) 295 (82%)

Authors Kim SY* Kim JD°

STERILIZATION REVERSAL- MICROSURGERY

Viable births 366 (40%) 295 (82%) Ongoing pregn. 31 ( 3%) 8 ( 2%)Spontaneous abort 90 (10%) 14 ( 4%)

Ectopic pregn. 42 ( 5%) 6 ( 2%)

Viable births 366 (40%) 295 (82%) Ongoing pregn. 31 ( 3%) 8 ( 2%)Spontaneous abort 90 (10%) 14 ( 4%)

Ectopic pregn. 42 ( 5%) 6 ( 2%)

*Followed more than 5 years. °Followed more than 2 years.Kim SY et al Fertil Steril 1997;68:865‐70Kim JD et al Fertil Steril 1997;68:875‐80

Patients (n=164/261*) %

Viable births 60.0%

Spontaneous abortion 18.0%

STERILIZATION REVERSAL- MICROSURGERY✪

✪ Procedures performed between Jan 1985- Dec 2005.Post-op hospital stay 2-3 days

*89 (34%) patients lost to follow–up, 8 did not try to conceive.

Gordts Sylvie. Fertil Steril.2009;92: 1198-202Victor Gomel

Spontaneous abortion 18.0%

Ectopic pregnancy 7.7%



Total IU. Pregnancy 17/32 53%

** Single suture tubal anastomosis.

Dubuisson JB, Chapron C. Curr Opin Obstet Gynecol 1998;10: 307-13

Victor Gomel

IU> pregn <38 years 10/17 59%

Viable births 13 41%

Total patients∞ 102

I.U. pregnancy 64 62.7%

Total patients∞ 102

I.U. pregnancy 64 62.7%


Outcome No. Patients %

p g y



p g y



**Single suture tubal anastomosis.∞Pre-selected by laparoscopy for length of tube: proximal > 3 cm, distal > 4cm.

Bissonette F et al.Fertil Steril 1999;72: 549

Victor Gomel

Total followed † 186 93%I.U. pregnancy 154 83%Viable births 98 53%

Total followed † 186 93%I.U. pregnancy 154 83%Viable births 98 53%



Viable births 98 53%Ongoing pregn. 31 17%Spontan abort. 25 13%Ectopic pregn. 5 3%

Viable births 98 53%Ongoing pregn. 31 17%Spontan abort. 25 13%Ectopic pregn. 5 3%

**Lost to follow up (n=15), not attempting pregn.(n=1). †Follow up >12 m

Yoon TK et al. Fertil Steril 1999; 72:1121‐26

43



Spontaneous abortion 3

Viable birth 12 23 5%

• Retrospective study.• Single 5-0 Vicryl suture to mesosalpinx and single 7-0 Vicryl suture

to approximate the two segments of tube at 12 o’clock position.

Ayoubi JM. In print. 2012

Victor Gomel



10 mm

8 mm X 2

12 mm

ROBOTIC TUBAL ANASTOMOSIS

Victor Gomel

15Dharia Patel SP et al. Fertil Steril. 2008; 90: 1175‐ 79

OUTCOME ROBOT (n=18) OPEN (n=10)

IU pregnancy 5 3


Victor Gomel

Spont. abortion 2

Tubal pregnancy 4 1

Dharia Patel SP et al. Fertil Steril. 2008; 90: 1175‐ 79


Victor Gomel


• “Robotic-assisted surgery appears to provide the same surgical outcomes and cost effectiveness when compared with traditional open tubal anastomoses.


traditional open tubal anastomoses.

• The high patency rates provide optimism for the role of robotics in trining programs.”

Victor Gomel


FACTORS AFFECTING OUTCOME

• AGE OF FEMALE PARTNER

Victor Gomel


44

PREGNANCY OUTCAME AFTERMICROSURGICAL STERILIZATION REVERSAL

50

60

70

80

90

<36 years

Victor Gomel

0

10

20

30

40

0 mo 6 12 18 24 36 months

y

36‐39 years

40‐43 years

Gordts Sylvie et al. Fertil Steril.2009;92: 1198-202

FACTORS AFFECTING OUTCOME

• AGE OF FEMALE PARTNER

• SURGICAL TECHNIQUE

• LENGTH OF RECONSTRUCTED TUBE

• OTHERS

Victor Gomel


Microsurgical tubal anastomosis yields abirth rate that exceeds 60%, withoutincreased risk of multiple pregnancy.

It offers the couple multiple cycles in

Victor Gomel

which to achieve conception naturally, andthe opportunity to have more than onepregnancy from a single intervention.


The real dilemma lies with the‘commercialization’ of IVF, and itsfrequent use as primary treatment forinfertility.

The dilemma is heightened by the factth t t ti t b l i i

Victor Gomel

that reconstructive tubal microsurgery isbeing taught and practiced less and less,thereby eliminating this credible surgicaloption in most centers.


Victor Gomel

“There is good evidence to support the recommendation for microsurgical anastomosis for t b l li ti l ”

Victor Gomel

Fertil Steril. 2012; 97: 539‐ 459

tubal ligation reversal.”

“…it can be accomplished by mini-laparotomy as an outpatient procedure.”

45

Comparable results may be obtained by laparoscopy if the procedure is performed “in an identical fashion to open microsurgical tubal


identical fashion to open microsurgical tubal anastomosis.” Operating times are prolonged.

“Only surgeons who are very facile with laparoscopic suturing and who have extensive training in conventional tubal microsurgery should attempt this procedure.”

THANK YOUMERCIGRACIAS

ありがとう

OBRIGADO

Victor Gomel

TEŞEKÜRLER

GRAZZIEEYXAPIΣТΩ

شكرا

46

Ovarian Surgery to Improve Fertility: Endometriomas and Ovarian Drilling

William W. Hurd, MDProfessor of Obstetrics and Gynecology

University Hospitals Case Medical CenterCase Western Reserve University School of Medicine

DISCLOSURES


LEARNING OBJECTIVES

At the conclusion of this presentation, the participant should be able to:

1. Discuss what is known about the relationship between endometriomas and infertility

2. Distinguish the relative advantages of the various surgical approaches to endometriomas

3. List guidelines for when to treat polycystic ovaries with ovarian drilling

ENDOMETRIOMA

• A “chocolate cyst” arising from growth of ectopic endometrial tissue within the ovary

• Often adherent to surrounding structuresOften adherent to surrounding structures, (peritoneum, fallopian tubes, bowel)

• Chocolate fluid: menstrual debris from the shedding and bleeding from implants

INCIDENCE

Endometriosis• 10% of all women• 30% of women with chronic pelvic pain• 20-40% of infertile women

Endometriomas• 10% of all women with endometriosis• 60% of women with moderate/severe

endometriosis

(Stepniewska 2009)

How Does Endometrial TissueGet into the Ovary?

Hypothetical possibilities:

1. Retrograde menstruation

• Progressive invagination of ovarian cortex

• Invades ovary

• Enters ovarian cysts at the time of ovulation

2. Embryonic Rests

3. Metaplasia of epithelial inclusions in the ovary (“coelomic metaplasia”)

47

Ultrasound Appearance of Endometriomas

• Ground glass appearance:

homogeneous low to medium level echoes

• Thick walled cystic mass• Thick walled, cystic mass

• Uni- or multi-locular

• Can have a solid,

nodular component

Differential Diagnosis

1. Hemorrhagic functional cyst (resolves over time)

2. Ovarian malignancies – Develop in <1% of women with endometriosis– Cell types: clear cell and endometrioid Ca– CA-125 is of little help (usually elevated)– Always send tissue for histopathology

diagnosis

(Kobayashi 2007)

SYMPTOMS

• Symptoms of endometriosis • Often asymptomatic• Ruptured endometrioma

= PID or appendicitis: ppPeritonitis ↑WBCFever

• What should we do when we puncture a cyst and find chocolate fluid?

Endometrioma Treatment Options

• Observation

• Medical Therapy

• Surgery• Surgery

Observation

Candidates:

• Previous histological diagnosis of endometriosis

• Recurrent asymptomatic adnexal mass consistent with an endometriomaconsistent with an endometrioma

• Size <4 cm

(Hurd 2012)

Observation Management Plan

• Ultrasound every 6 months x 1 year, then annually

• Repeat surgery for changes in:Repeat surgery for changes in:

– Symptoms

– Cyst size or complexity

48

Medical therapy

Medical options:

– GnRH Agonists

– Progestins

– OCPs

• Treatment for endometriosis symptoms

• Will not resolve endometrioma

Surgical Management of Endometriomas

Indications:

• Pain

• Exclusion of malignancy

• Infertility• Infertility

– Prior to IVF?

Endometriomas and Infertility

Endometrioma removal is controversial!

• Advantage:

Treatment of pelvic endometriosis (outside theTreatment of pelvic endometriosis (outside the ovary) improves fertility

• Disadvantage:

Endometrioma resection damages the ovary

Risk of Endometrioma Resection

• Decreased “ovarian reserve”

• Mechanism: Follicles adjacent to the cyst destroyed

• Measurable changes after resection:

– Increased ovarian resistance to ovulation induction

– Decreased oocyte number and quality for IVF

– Premature ovarian failure (2% if bilateral)

(Tsoumpou 2009) (Busacca 2006)

Should Endometriomas be Resected Prior to IVF?

Endometrioma resection results in :

• Slower follicle growth (longer stimulation)

• ↑FSH requirements↑FSH requirements

• ↓ Mature oocytes

• No change in rates of

– Fertilization

– Pregnancy

(Tsoumpou 2009)

Recommendation Prior to IVF

Remove endometriomas >4 cm prior to IVF

Rationale:• Confirm the diagnosis histologically• Improve access to follicles

(Kennedy 2005)

49

Surgical Approaches

• Oophorectomy

• Aspiration

• Cyst wall resection

(stripping technique)

• Fenestration and ablation

Oophorectomy

• Best Approach After childbearing completed

• Recurrence uncommon

• Most likely to relieve painMost likely to relieve pain

• Removing attached peritoneum with ovary might minimize the risk of ovarian remnant syndrome

Aspiration

• Puncture without aspiration can result in peritonitis

• Cyst should be completely drained and rinsed

• Recurrence rate: 88%

Cyst wall resection

• Remove entire cyst wall using a stripping technique

• Recurrence rate: 6%Recurrence rate: 6%

Fenestration and ablation

• Technique:

– Remove section of the cyst wall

– Irrigate cyst

– Coagulate (or laser vaporization) inside of– Coagulate (or laser vaporization) inside of cyst

• Less symptom relief

• Lower pregnancy rate

• Recurrence rate: 30%

(Hart 2005)

Why are Recurrence Rates so High?

Cyst wall resection: 6%

Fenestration/ablation: 30%

Aspiration: 88%

Reason: endometrial glands and stroma involves 60% (10-90%) of cyst wall for a depth of <2 mm

(Muzii 2007)

50

How to Decrease Recurrence

• Pregnancy • Breast Feeding• Estrogen-progestin OCPs

(Protective effect disappears after OCP cessation)

(Muzii 2000) (Seracchioli 2010)

Bottom Line: Endometriomas

• Most endometriomas should be removed

• Cyst wall resection is the goal

• Recurrence is always a risk

• OCPs after surgery for those not attempting pregnancy

Ovarian Drilling for PCOS: Ovarian Diathermy

• Laparoscopic “wedge resection” equivalent for PCOS

• Electrocautery or a laser is used to destroy partsElectrocautery or a laser is used to destroy parts of the ovaries

• Ovulation temporarily resumes in most women

Indications

• Women with PCOS who do not ovulate with

fertility medicines:

Metformin

Clomiphene citrateClomiphene citrate

FSH

• Women with PCOS who do not respond to clomiphene citrate and cannot afford FSH or IVF

Ovarian Drilling Technique

(No standard technique)

• Laparoscopy

• Puncture ovary 4-10 times using electrosurgical needle (or laser fiber)electrosurgical needle (or laser fiber)

• Probe: 8 mm distal stainless steel needle with insulated shaft

• Electrosurgical setting: 30 watts for 5 seconds

• Stay on side away from tube and peritoneum

(Amer 2002)

Results

• Androgens decrease within days

• Spontaneous ovulation occurs in most women

51

How Well doe it Work?No randomized controlled trials

Based on several series totaling >1,000 women:• 80% ovulate • 50% become pregnant50% become pregnant

(in women with no other fertility problems)

Best Prognosis:• Younger women • BMI < 25 Kg/M2

(Stegmann 2003)

Risks of Ovarian Drilling

1.Risks of related to laparoscopy (< 1/1,000)

2.Risk specific to ovarian drilling

– Peri-ovarian adhesions (usually mild)– Peri-ovarian adhesions (usually mild)

– Premature ovarian failure?

Bottom Line: Ovarian Drilling

• Relatively safe surgical treatment for women with PCOS resistant to fertility drugs

• Spontaneous pregnancy rates within 6 months ofSpontaneous pregnancy rates within 6 months of surgery are remarkable

• Ovarian adhesions are the primary concern

Questions?

REFERENCESAmer SAK, Li TC, Cooke ID. Laparoscopic ovarian diathermy in women with polycystic ovarian syndrome: a retrospective

study on the influence of the amount of energy used on the outcome. Hum Reprod 2002; 17 (4): 1046-51. Busacca M, Chiaffarino F, Candiani M, et al. Determinants of long-term clinically detected recurrence rates of deep,

ovarian, and pelvic endometriosis. Am J Obstet Gynecol 2006; 195:426.Hart RJ, Hickey M, Maouris P, et al. Excisional surgery versus ablative surgery for ovarian endometriomata. Cochrane

Database Syst Rev 2005; :CD004992.Hurd WW, Redwine DB. Chapter 13. Endometriosis. In: Bieber E, Sanfilippo J, Horowitz I, Shafi F, Eds. Clinical

Gynecology, 2nd Ed, Philadelphia: Elsevier Publishing, 2012.Kennedy S, Bergqvist A, Chapron C, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum

Reprod 2005; 20:2698.Kobayashi H, Sumimoto K, Moniwa N, Imai M, Takakura K, Kuromaki T, Morioka E, Arisawa K, Terao T. Risk of

developing ovarian cancer among women with ovarian endometrioma: a cohort study in Shizuoka Japan Int Jdeveloping ovarian cancer among women with ovarian endometrioma: a cohort study in Shizuoka, Japan. Int J Gynecol Cancer. 2007 Jan-Feb;17(1):37-43.

Muzii L, Bellati F, Palaia I, et al. Laparoscopic stripping of endometriomas: a randomized trial on different surgical techniques. Part I: clinical results. Hum Reprod 2005; 20:1981.

Seracchioli R, Mabrouk M, Frascà C, et al. Long-term cyclic and continuous oral contraceptive therapy and endometrioma recurrence: a randomized controlled trial. Fertil Steril 2010; 93:52.

Stegmann BJ, Craig HR, Bay RC, Coonrod DV, Brady MJ, Garbaciak JA Jr. Characteristics predictive of response to ovarian diathermy in women with polycystic ovarian syndrome. Am J Obstet Gynecol. 2003 May;188(5):1171-3.

Stepniewska A, Pomini P, Bruni F, Mereu L, Ruffo G, Ceccaroni M, Scioscia M, Guerriero M, Minelli L. Laparoscopic treatment of bowel endometriosis in infertile women. Hum Reprod. 2009 Jul;24(7):1619-25.

Tsoumpou I, Kyrgiou M, Gelbaya TA, Nardo LG. The effect of surgical treatment for endometrioma on in vitro fertilization outcomes: a systematic review and meta-analysis. Fertil Steril 2009; 92:75.

52

Surgical Treatment of Surgical Treatment of Uterine Anomalies: Uterine Anomalies: Indications and Indications and TechniquesTechniques

Keith Isaacson, MDKeith Isaacson, MDAssociate Professor of Obstetrics and Associate Professor of Obstetrics and GynecologyGynecologyHarvard Medical School Harvard Medical School Boston, MA Boston, MA USAUSA

DisclosuresDisclosures

Consultant Consultant –– Karl Storz Karl Storz EndoscopyEndoscopy

ObjectivesObjectives

Identify uterine pathology that impacts Identify uterine pathology that impacts fertilityfertility

DefineDefine the uterine surgical techniquesthe uterine surgical techniques Define Define the uterine surgical techniques the uterine surgical techniques that will enhance fertilitythat will enhance fertility

Review Review the complications and the the complications and the success rates of uterine surgery that success rates of uterine surgery that enhances fertility enhances fertility

Infertility EvaluationInfertility Evaluation

Semen AnalysisSemen Analysis Ovarian Reserve AssessmentOvarian Reserve Assessment Tubal patencyTubal patency Tubal patencyTubal patency Uterine assessmentUterine assessment

–– Vaginal probe ultrasoundVaginal probe ultrasound–– HSGHSG–– Saline sonographySaline sonography–– Office hysteroscopyOffice hysteroscopy

Should OH be a routine part Should OH be a routine part of the infertility evaluation?of the infertility evaluation? Lorusso, F et al 2008 (866 cycles)Lorusso, F et al 2008 (866 cycles)

–– 555 pts before first IVF555 pts before first IVF–– 311 after 2 or more failed IVF311 after 2 or more failed IVF–– 40% with intrauterine pathology40% with intrauterine pathology40% with intrauterine pathology40% with intrauterine pathology

Hinkley MD JSLS 2004 (Stanford Med)Hinkley MD JSLS 2004 (Stanford Med)–– 1000 patients prior to IVF1000 patients prior to IVF

32% with polyps32% with polyps3% submucous myomas3% submucous myomas3% adhesions3% adhesions0.5% septum0.5% septum0.3% retained POCs 0.3% retained POCs 0.3% bicornuate0.3% bicornuate

Intrauterine pathology Intrauterine pathology impacting fertilityimpacting fertility Uterine fibroidsUterine fibroids Intrauterine AdhesionsIntrauterine Adhesions Intrauterine polypsIntrauterine polyps Intrauterine polypsIntrauterine polyps Proximal Tubal occlusionProximal Tubal occlusion Uterine septumUterine septum AdenomyosisAdenomyosis

53

Information Changes Information Changes ManagementManagement Submucous Submucous

myomatamyomata–– Type 0 Type 0 -- 100% 100%

w/in cavityw/in cavity–– Type I Type I -- > >

50% w/in 50% w/in cavitycavity

–– Type II Type II -- < < 50% w/in 50% w/in cavitycavity

deBlok S, et al: Gynaecol Enosc 4:243-246, 1995

Myomas and reproductive Myomas and reproductive functionfunction

1. Cervical displacement can reduce exposure to sperm2. Enlargement or deformity of the uterine cavity that may

interfere with sperm migration and transport3. Obstruction of the proximal fallopian tubes4. Altered tubo-ovarian anatomy, interfering with ovum

capture5. Increased or disordered uterine contractility that may

hinder sperm or embryo transport or nidation6. Distortion or disruption of the endometrium and implantation

due to atrophy or venous ectasia over or oppositea submucous myoma

7. Impaired endometrial blood flow8. Endometrial inflammation or secretion of vasoactive

substances

Ed Bulliten, Fertil Steril 2008;90:S125–30

SM myomata and SM myomata and infertilityinfertility Pritts reported significantly lower pregnancy

rates (risk ratio, 0.32), implantation rates (risk ratio, 0.28), and delivery rates (risk ratio, 0.75) in patients with submucosal myomas and abnormal uterine cavities, in comparison with infertile control women without myomas.

Donnez and Jadoul also confirmed that only submucous myomas have a negative impact on embryo implantation.

Fertility after Hysteroscopic Resection ofSubmucous Myomas

No prospective randomized trialsNo prospective randomized trials Giatras et al. 1999 JMIGGiatras et al. 1999 JMIG

–– 41 infertile patients41 infertile patients61% t61% t–– 61% pregnancy rate61% pregnancy rate 56% delivery rate56% delivery rate

Betocchi et al F&S 2008Betocchi et al F&S 2008–– Beneficial treatment of SM myomata <1.5 cm in IVF Beneficial treatment of SM myomata <1.5 cm in IVF

patients. patients. Shokeir TA (Arch of Gynecol Obstet 2005) Shokeir TA (Arch of Gynecol Obstet 2005)

–– 3% to 63% after resection del rate3% to 63% after resection del rate–– Ab rate reduced from 61% to 26% after resectionAb rate reduced from 61% to 26% after resection

Intrauterine adhesions Intrauterine adhesions and fertilityand fertility 6%6%--20% of women with primary infertility20% of women with primary infertility 25% of women with recurrent Ab25% of women with recurrent Ab 25%25%--40% after post partum D&C40% after post partum D&Cp pp p 6% of women with 2 or more failed IVF with 6% of women with 2 or more failed IVF with

good embryo qualitygood embryo quality Found after myomectomy, UAE, InfectionFound after myomectomy, UAE, Infection 43% of women with Asherman’s present 43% of women with Asherman’s present

with infertiltiywith infertiltiy

Yu et al. Fertil Steril 2008;89:759–79

Therapy for Asherman’sTherapy for Asherman’s

Recurrence of adhesionsRecurrence of adhesions–– 20%20%--60% depending on severity60% depending on severity

Methods to prevent recurrenceMethods to prevent recurrence–– OCPsOCPs–– IUDIUD–– Foley balloonFoley balloon–– HAHA–– EstrogenEstrogen–– Second look hysteroscopySecond look hysteroscopy

54

Success of Asherman’s Success of Asherman’s therapytherapy Pace et al, pregnancy rate improved from 28.7% before

surgery to 53.6% after hysteroscopic treatment. Women with two or more previous unsuccessful pregnancies,

the live birth rate improved from 18.3% preoperatively to 68.6% postoperatively. The pregnancy rate after hysteroscopic lysis of intrauterine The pregnancy rate after hysteroscopic lysis of intrauterine adhesions in women who wanted to have a child has been about 74% (468 out of 632), which is much higher than found in untreated women (46%).

The pregnancy rate after treatment in women with infertility is about 45.6% (104 out of 228); the successful pregnancy rate after treatment in severe cases is reported to be consistently lower (18 out of 55 or 33%). For women with previous pregnancy wastage, both the pregnancy rate and the live birth rate after treatment are reasonably high (121 out of 135 or 89.6% and 104 out of 135 or 77.0%, respectively).

Clin Exp Obstet Gynecol 2003;30:26–8.

Recurrent IVF failureRecurrent IVF failure

421 pts 421 pts -- randomizedrandomized–– 211 with no OH 211 with no OH –– 21% PR21% PR–– 210 with OH210 with OH210 with OH210 with OH

154 normal cavities 154 normal cavities –– 32% PR32% PR 56 abnormal cavities (26%) repaired at 56 abnormal cavities (26%) repaired at

diagnosisdiagnosis–– 30% PR P=0.04430% PR P=0.044

Dimirol A, Gurgan T Reproductive Med Online 8:590 2004

Pregnancy rates after Pregnancy rates after PolypectomyPolypectomyStametellos L et al. Arch Gynecol Obstet

277:395-9 2008–– 83 patients with primary infertility and 83 patients with primary infertility and

endometrial polyps by hysteroscopyendometrial polyps by hysteroscopyendometrial polyps by hysteroscopyendometrial polyps by hysteroscopy–– 61% pregnancy rate, 52% delivery rate post 61% pregnancy rate, 52% delivery rate post

polypectomy in 3polypectomy in 3--18 mos post procedure18 mos post procedure Lass A et al J Assist Repro and Genet 1999 Lass A et al J Assist Repro and Genet 1999

(Bourne Hall)(Bourne Hall)–– 24 cases 24 cases –– reduction in miscarriage rate with reduction in miscarriage rate with

polypectomypolypectomy

Hysteroscopic tubal Hysteroscopic tubal occlusion for hydrosalpinxocclusion for hydrosalpinx

Rosenfield R et al F&S 2005Rosenfield R et al F&S 2005–– One obese patient, one pregnancyOne obese patient, one pregnancy

Hitkari et al F&S 2007Hitkari et al F&S 20075 ti t ith h d l i d i5 ti t ith h d l i d i–– 5 patients with hydrosalpinx and prior surg.5 patients with hydrosalpinx and prior surg. Successful placement in 2/5Successful placement in 2/5 0 pregnancies0 pregnancies

Kerin J et al F&S 2007Kerin J et al F&S 2007–– 2 patients, 2 pregnancies2 patients, 2 pregnancies–– Tissue encapsulation of proximal insert between 4Tissue encapsulation of proximal insert between 4--

43 mos in 545 women 43 mos in 545 women

Uterine septum repairUterine septum repair

119 patients (32%, 14% IVF failure, 119 patients (32%, 14% IVF failure, SAB) with septum age matched to 116 SAB) with septum age matched to 116 controls ( 20%, 6% IVF fail, SAB) controls ( 20%, 6% IVF fail, SAB) ( , , )( , , )

After repair After repair -- Both groups equalBoth groups equal Miscarriage rate drops from 91% to Miscarriage rate drops from 91% to

17% (Sanders J Repro Med 51 2006)17% (Sanders J Repro Med 51 2006)

Ozgur, k et al Reproductive Biomedicine Online 14:335 2007

1.6 mm (5 F) in diameter1.6 mm (5 F) in diameter Two poles separated 2 mm at distal shaft Two poles separated 2 mm at distal shaft

by ceramic insulatorby ceramic insulator

VERSAPOINT System for VERSAPOINT System for Bipolar Hysteroscopic SurgeryBipolar Hysteroscopic Surgery

VERSAPOINT System for VERSAPOINT System for Bipolar Hysteroscopic SurgeryBipolar Hysteroscopic Surgery

yy

Electrodes designed for variable Electrodes designed for variable tissue effectstissue effects–– Ball tip Ball tip –– precise vaporizationprecise vaporization

and desiccationand desiccation Spring tip Spring tip –– rapid tissue vaporization and desiccationrapid tissue vaporization and desiccation

–– Twizzle tip Twizzle tip –– vaporization and needlevaporization and needle--like cuttinglike cutting Given small size and focused tissue effects, best forGiven small size and focused tissue effects, best for

–– polypectomy, adhesiolysis, vaporization of smallerpolypectomy, adhesiolysis, vaporization of smallersubmucous myomatasubmucous myomata

55

Uterine VascularityUterine VascularityCompostionCompostion11 of Gases Found byof Gases Found byHysteroscopic Electrosurgical Vaporization*Hysteroscopic Electrosurgical Vaporization*

BipolarBipolar UnipolarUnipolar AirAir(normal saline)(normal saline) (glycine)(glycine)

HydrogenHydrogen 51.051.0 49.049.0 0.000050.00005

COCO 25.725.7 26.126.1 0.000010.00001

COCO22 6.56.5 7.57.5 0.03140.031422

OO22 2.92.9 3.03.0 20.947620.9476

NN 1.41.4 2.32.3 78.08478.084

CC22HH22 3.63.6 4.14.1

CHCH44 2.82.8 2.52.5 0.00020.0002

MiscMisc22 6.06.0 5.6 5.6

** Munro et al. JAAGL Nov 2001Munro et al. JAAGL Nov 2001

1 1 -- Measured in mole percentMeasured in mole percent2 2 -- Acetylene, Propane, C3 Olefin, Isobutane, nAcetylene, Propane, C3 Olefin, Isobutane, n--Butane, C4 Alkene, C5 HydrocarbonButane, C4 Alkene, C5 Hydrocarbon

----

----

Monitoring Venous Air Monitoring Venous Air EmbolismEmbolism Doppler, TE echoDoppler, TE echo 0.1 0.1 -- 0.250.25 End title CO2 or End title CO2 or .025 .025 -- 0.50.5

Nitrogen tensionNitrogen tensionCVP and PulmonaryCVP and Pulmonary 0505 0 750 75

Sensitivity

mL/Kg/min air entrapment

CVP and Pulmonary CVP and Pulmonary .05 .05 -- 0.750.75artery P increaseartery P increase

Mean Art P decrease Mean Art P decrease 0.75 0.75 -- 1.251.25 Ventricular dysrhythmiasVentricular dysrhythmias 1.251.25 MillMill--wheel murmurwheel murmur 1.51.5 Cardiovascular collapseCardiovascular collapse 2.02.0

Cervical StenosisCervical Stenosis

Pabuccu R et al JMIG 2005Pabuccu R et al JMIG 2005–– Hysteroscopic shaving for cervical Hysteroscopic shaving for cervical

stenosisstenosis 3 patients, 3 pregnancies3 patients, 3 pregnancies

Operative Office Operative Office HysteroscopyHysteroscopy Standard ApproachStandard Approach

–– Speculum Speculum –– preferable side openingpreferable side opening–– TenaculumTenaculum

Vaginoscopic approachVaginoscopic approach Vaginoscopic approachVaginoscopic approach–– No speculum or tenaculumNo speculum or tenaculum–– Bettocchi S, Selvaggi L. A vaginoscopic approach Bettocchi S, Selvaggi L. A vaginoscopic approach

to reduce the pain of office hysteroscopy. J Am to reduce the pain of office hysteroscopy. J Am Assoc Gynecol Laparosc 1997;4:255Assoc Gynecol Laparosc 1997;4:255--8.8.

–– Cicinelli E, Parisi C, Galantino P, Pinto V, Barba Cicinelli E, Parisi C, Galantino P, Pinto V, Barba B, Schonauer S. Reliability, feasibility, and safety B, Schonauer S. Reliability, feasibility, and safety of minihysteroscopy with a vaginoscopic of minihysteroscopy with a vaginoscopic approach: experience with 6,000 cases. Fertil approach: experience with 6,000 cases. Fertil Steril 2003;80:199Steril 2003;80:199--202202

Standard HysteroscopyStandard Hysteroscopy

56

Vaginoscopie : TechniqueVaginoscopie : Technique

1 2

Office Hysteroscopic Office Hysteroscopic proceduresprocedures Diagnostic HysteroscopyDiagnostic Hysteroscopy Visually directed endometrial biopsyVisually directed endometrial biopsy PolypectomyPolypectomy PolypectomyPolypectomy MyomectomyMyomectomy AdhesiolysisAdhesiolysis MetroplastyMetroplasty Proximal tubal recanalizationProximal tubal recanalization

Test questionsTest questions

11 Congenital anomalies that affect Congenital anomalies that affect fertility includefertility includea)a) Uterine SeptumUterine Septuma)a) Uterine SeptumUterine Septumb)b) Uterine DidelphysUterine Didelphysc)c) Vaginal septumVaginal septumd)d) Uterine fibroidsUterine fibroids

Test QuestionTest Question

22 HysterscopicHysterscopic adhesiolysisadhesiolysis must be must be performed under laparoscopic performed under laparoscopic guidance to avoid uterine perforationguidance to avoid uterine perforationg pg p

a)a) TrueTrueb)b) FalseFalse

Test questionTest question

HysteroscopicHysteroscopic myomectomymyomectomy increases increases the risk of uterine rupture during the risk of uterine rupture during pregnancypregnancyp g yp g y–– True True –– FalseFalse

Test questionTest question

Methods proven to prevent recurrence Methods proven to prevent recurrence of intrauterine adhesions includeof intrauterine adhesions includea)a) Estrogen therapyEstrogen therapya)a) Estrogen therapyEstrogen therapyb)b) Foley catheter in the uterine cavityFoley catheter in the uterine cavityc)c) Post op Post op adhesiolysisadhesiolysisd)d) Soy productsSoy productse)e) IUDIUD

57

AAGL 41st Global CongressNovember 6, 2012

Does Treating Endometriosis Improve Fertility?

David Adamson, MDDirector, Fertility Physicians of Northern CaliforniaAdjunct Clinical Professor, Stanford University

Associate Clinical Professor, UCSF

Disclosures

Grants/Research Support: Auxogyn, Bayer‐Sherring, EMD‐SeronoConsultant: LabCorpOther: CEO and Founder ‐ Advanced Reproductive Care

Learning Objectives

• Describe the role of observation, ovarian stimulation, ovarian suppression, surgery and combined treatments.

• List the clinical indications for performing ART• List the clinical indications for performing ART.

• Explain confounding variables affecting management of endometriomas.

Treatment Options• Observation/Symptomatic

• Surgery

• Medical Treatments

– Ovarian SuppressionOvarian Suppression

– Combined suppression and surgery

– Intrauterine insemination (IUI)

– Controlled Ovarian Stimulation (COS)

• Assisted Reproductive Technologies (ART)

Adamson, Frison & Lamb. The effect of pelvic endometriosis on fertility.Presented: Pacific Coast Fertility Society Annual Meeting. Oct 1979.

Published: Fertil Steril. 1982 Dec;38(6):659-66.

SURGERYSURGERY

58

Appearance Changes With AgeAppearance Mean Age Age Range

Clear only 21.5 17-26

Red only 26.3 16-38y

White only 29.5 20-39

Black only 31.9 20-52

Disease Progression in Infertility

• Laparoscopy for unexplained infertility

– Patients with normal pelvis

• Those negative not preg repeat L/S 2 years

– 20% macroscopic endometriosis% p

Pepperell and McBain, Br J OG 1985: 92; 569‐580

Sutton, Fertil Steril. 1997;68(6): 1070–1074.

Infertility Outcomes: Surgery

• Minimal/Mild Disease

– Controversial for many years

– Summary non‐randomized studies

surgery vs. no treatment 58% vs. 45%

– Fecundity not different 6‐7%

– Endocan RCT(NNT 7.7) 37.5% vs. 22.5% ( )

– Gruppo Italiano RCT 19.6% vs. 22.2%

– Combined Endocan/Italy OR 1.66 (1.09‐2.51)

– Cochrane: laparoscopy may improve PR (1)

– ESHRE, RCOG (A level 1a):ablation/lysis effective (2,3)(1) Jacobson. Cochrane Database Syst Rev. 2002;(4):CD001398.

(2) ESHRE guidelines. Hum Reprod 2005;20:2698‐704.

(3) RCOG. Guideline No XX. 2005.

Surgical Treatment of Minimal Endo

• 341 women

• Stage I‐II

• 36 week follow‐up

• Pregnancy rates

– 31% vs. 18%

– Italian 29 vs 24%

– OR 1.7

Vercellini, Hum Reprod 2009;24(2): 254-69.

Infertility Outcomes: Surgery• Moderate/Severe Disease

– Severe anatomic distortion– Very low background pregnancy rate– Numerous uncontrolled trials show benefit– L/S > laparotomy: RR 1.87; p=0.031 (1)

Surgery indicated for invasive adhesive cystic– Surgery indicated for invasive, adhesive, cystic endometriosis (Evidence level 3) (2,3)

– Conservative surgical therapy with laparoscopyand possible laparotomy are indicated. (4)

(1) Adamson. Fertil Steril 1993;59(1):35‐44.(2) RCOG Guideline No XX. 2005.(3) ESHRE guidelines. Hum Reprod 2005;20:2698‐704.(4) ASRM Practice Committee. Fertil Steril 2006;86(Suppl4):S156‐60.

Pregnancy Rates Following Surgical Excision: Negative Correlation With Stage

CPR Ref Stage of Endometriosis P‐value

Min Mild Mod Sev

1 year Guzick 39% 31% 30% 25% NS1 year Guzick 39% 31% 30% 25% NS

1 year Adamson 45%‐‐ ‐‐32%‐‐ NS

1.5 years Osuga ‐‐45%‐‐ ‐‐28%‐‐ <0.05D’Hooge. Sem Reprod Med 2003;21:243‐53.

59

Endometrioma Treatment Endometriomas• Cyst >5 cm (? Endometrioma)

– According to protocol• Endometriomas Size to treat

– Unknown– ? > 3‐4 cm

• Technique– Stripping preferred where possible (1 2)– Stripping preferred where possible (1,2)

• Lower recurrence rate– Drainage and coagulation (3)

• Avoid damage to normal ovarian tissue– Potentially greater with stripping

(1) Hart. Cochrane Syst. Rev. 2008 Apr 16;(2):CD004992.

(2) Pellicano. Fertil Steril 2008;89:796‐9.

(3) Vercellini. Am J Obstet Gynecol. 2003 Mar;188(3):606‐10.

Complete Posterior Cul‐de‐sac Obliteration and DIE

Estimated Life Table Pregnancy Rates (1)

% Pregnant Laparoscopy Laparotomy

1 Year

2 Years

29.6 ± 14.4

29.6 ± 14.4

0 ± 0.0

23.7 ± 12.2BRESLOW p=0.084

(1) Adamson. Lasers Surg Med Suppl. 1992;4:1-85.(2) Vercellini . Am J Obstet Gynecol 2006 Nov;195(5):1303-10. (3) Vercellini. Hum Reprod 2009 Oct;24(10):2504-14.

• No clarity as to best surgical approach (2,3)• Complication rates 0-13% (3)

ESHRE Guidelines

• Insufficient evidence whether surgical excision of moderate‐severe disease enhances pregnancy rates (1‐3)

• Probable negative correlation between stage of endometriosis and pregnancy rate after surgical removal (4)(1) Adamson et al. Fertil Steril1993;59:35‐44.

(2) Guzick et al. Fertil Steril 1997;67;822‐9.(3) Osuga et al. Gynecol Obstet Invest 2002;53(Suppl 1), 33‐9.(4) Kennedy (ESHRE). Hum Reprod 2005;20:2698‐704.

Surgical Techniques• Minimize number of surgeries (1)

• Use least invasive approach: laparoscopy (1)

• Minimize tissue trauma (1)

• Remove all disease (no RCT proof)

• Consider adhesion barrier(1)• Consider adhesion barrier(1)

– No evidence on any benefit of improving pregnancy outcomes (2,3)(1) Robertson. J Obstet Gynaecol Can. 2010 Jun;32(6):598‐608.

(2) Metwally. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD001298.

(3) Ahmad. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD000475.

Fecundity (f) FollowingTreatment of Endometriosis

2 0

3.0

4.0

5.0

Month 1-3

Month 4-6

Month 7 9Monthly

0.0

1.0

2.0

Year 1 Year 2 Year 3

Month 7-9

Month 10-12

Adamson et al. Fertil Steril. 1993;59(1):35-44.

f1=4.4%

f2=2.9% f3=0.6%

yf (%)

60

Adamson. Fertil Steril2010;94(5):1609-15.

Conclusion• Endometriosis Fertility Index (EFI)

– Simple, robust and validated clinical tool

– Predicts pregnancy rates for patients following surgical staging of endometriosis

– Very useful in developing treatment plans for infertile endometriosis patients

• Prospective validation by other clinicians should encourage widespread application of the EFI to benefit patients

MEDICAL TREATMENTS

OVARIAN SUPPRESSION

IUI

COS

Ovarian Suppression For Fertility• No evidence of fertility benefit from ovarian suppression: 25 RCTs (1)

– Costs and delay time to pregnancy

• GnRHa treatment before IUI is not d drecommended

– 1 RCT suggesting benefit IVF and IUI– Insufficient evidence to determine benefit in IUI alone (2)(1) Hughes. Cochrane Syst Rev 2007 Jul 18;(3):CD000155.

(2) Rickes. Fertil Steril 2002;78(4):757‐62.

Meta-analysis: Surgery Better AND Suppression Not Helpful

Adamson et al. Am J Obstet Gynecol. 1994;171(6):1488-505.

Infertility Outcomes: Ovarian Suppression and Surgery

• Adjunct to Surgery (16 RCTs)– Preoperative

• No data conclusively show benefit (1)– Postoperative

• No data show benefit (1)D i f ili• Does not improve fertility(A. Level 1b)(2,3)

• Delay in attempting pregnancy, costs, side effects render ovarian suppression not appropriate(1) Yap. Cochrane Database Syst Rev. 2004;(3):CD003678.

(2) ESHRE guidelines. Hum Reprod 2005;20:2698‐704.(3) RCOG. Guideline No XX. 2005.

61

Endometriosis TreatmentStage I and II

COS + IUI Appropriate BEFORE LaparoscopyCOS + IUI Appropriate BEFORE Laparoscopy

COS + IUI AppropriateBEFORE Laparoscopy

IUI +/‐ COS

• IUI with COS effective in improving fertility in minimal/mild endometriosis (1,2)

• Role of unstimulated IUI is uncertain (2)Role of unstimulated IUI is uncertain (2)

• Double insemination should be considered (3)

(1) Tummon. Fertil Steril 1997;68(1):8‐12.(2) Costello. Aust NZ J Obstet Gynaecol 2004;44(2):93‐102.(3) Subit. Am J Reprod Immunol 2011 Aug;66(2):100‐7.

Laparoscopy Prior to IUI/COS

• Insufficient data to recommend laparoscopic surgery prior to IUI/COS

• Unless

– Historyy

– Evidence of anatomic disease

– Sufficient to justify the physical, emotional, financial and time costs

(1) Tanahatoe. Fertil Steril 2003;79(2):361‐6.

(2) Tanahatoe. Hum Reprod 2005;20(11):3225‐30.

When To Do Laparoscopy?• Younger women (?<37 years of age)• Short duration of infertility (<4 years)• Normal male factor• Normal or treatable uterus• Normal ovulation, or• Easily treatable ovulation disorder• Limited prior treatmentLimited prior treatment• Appropriate candidate for laparoscopy

– “Treatable” disease reasonably suspected (NNT)– OR= 1.66 (1)– No contraindications to laparoscopy– Patient accepts 9‐15 months attempting before IVF(1) Jacobson. IVF Cochrane Database Syst Rev. 2010 Jan 20;(1):CD001398.(2) ASRM Practice Committee. Fertil Steril. 2006;86(Suppl 4):S156‐60.

ENDOMETRIOSIS

AND IVF

Impact of Endometriosis Stageon IVF Outcomes

• Only observational studies for ART (e.g. Rosenwaks 2002; Barnhart 2002)

• With laparoscopic retrieval, probably yes• With transvaginal retrieval, probably nog p y• No studies have had sufficient power toevaluate the impact of extensive disease (AFS Score >71) (1)

• IVF PR lower in endometriosis (Level 1a) (2)(1) Guzick et al. Fertil Steril 1997;67:822‐9.


62

Role of IVF in Endometriosis

• Although IVF may be less effective for IVF than for other causes of infertility, it should be considered for use to improve the success rate above expectant management.

(1) Barnhart. Fertil Steril 2002;77:1148‐55.

(2) Benschop. Cochrane Syst. Rev. 2010;11:CD008571.(3) Soliman.1993 Jun;59(6):1239‐44.(4) De Hondt. Curr Opin Obstet Gynecol 2006 Aug;18(4):374‐9

IVF and Endometriosis

• For women with stage III/IV endometriosis who fail to conceive following conservative surgery or because of advancing reproductive age, IVF is an effective alternative (1)

• IVF is appropriate treatment especially if tubal pp p p yfunction is compromised, if there is also male factor infertility, and /or other treatments have failed (Level IIb) (2,3)

(1) ASRM Practice Committee. Fertil Steril 2006;86(Suppl 4):S156‐60.

(2) RCOG. Guideline No XX. 2005.


Endometriomas and Endometriosis Before IVF

• Laparoscopy for >4 cm endometriomas (GPP) (1‐3)– Confirm histologic diagnosis– Reduce risk of infection– Improve access to follicles– Possibly improve ovarian responseE l i i k f i t• Explain risk of poor ovarian response post‐op

• Reconsider decision if previous ovarian surgery• No evidence of benefit of surgery for endometriosis

before IVF (4)(1) RCOG. Guideline No XX. 2005.(2) Kennedy (ESHRE). Hum Reprod 2005;10:2698‐704.(3) Hart (Cochrane). Hum Reprod 2005;20:3000‐7.(4) Benschop. Cochrane Syst. Rev. 2010 Nov 10;(11):CD008571.

Role of Ovarian Suppression Before IVF

• No RCT’s with adequate controls– Generally not helpful for infertility– Does not improve endometriomas

• Some data suggesting improved pregnancy rates when suppression precedes IVF (1‐3)

– GnRHa for 3‐6 months increases PR 4X (A. Level 1a) (3,4)– Prolonged treatment with GnRHa in mod/severe should be

considered because improved pregnancy rates have beenconsidered because improved pregnancy rates have been reported (A. Level 1b)(5)

– Optimal duration of treatment unknown (range 2‐26 weeks)– Our practice treats additional 4‐12 weeks for moderate/severe

endometriosis• No data on oral contraceptives

(1) Rickes. Fertil Steril 2002;78:757‐62.(2) Surrey. Fertil Steril 2002;78:699‐704.(3) Sallam. Cochrane Database Syst.Rev. 2006 Jan

25;(1):CD004635.(4) RCOG. Guideline No XX. 2005(5)ESHRE guidelines. Hum Reprod 2005;20:2698‐704.

Endometrioma TreatmentBefore ART

• 4 Trials; n=312

• GnRHa vs. GnRH antagonist• CPR: No difference• NMOR and Ovarian Response: GnRHa > Antagonist

• Surgery (Aspiration or Cystectomy) vs. Expectant Managementg y ( p y y) p g• CPR: No difference• NMOR and Ovarian Response: Aspiration > Expectant

• Cystectomy vs. Expectant• COS response less with cystectomy

• Aspiration versus cystectomy• CPR and NMOR: No difference

Benschop. http://summaries.cochrane.org/CD008571. Accessed Sep 23, 2012.

Failed IVF Treatment Endo

63

SUMMARYSUMMARY

Management Summary (1)

• Pelvic Pain– Initially analgesics, NSAID’s, OC’s

• Infertility with other factors normal– CC 100mg CD 3‐7 + IUI for 3‐6 cycles, d didepending on age

– Other ovarian stimulation regimen

• Persistence of pain and/or infertilitywithout other significant infertility factors– Laparoscopy, diagnostic & operative

Management Summary (2)• Surgery well performed is effective treatment

– All stages endometriosis & endometriomas– Infertility and Pain

• Ovarian suppression generally effective for pain• Repeat surgery

– Limited benefit for fertility, some for pain• Pre‐IVF treatment ONLY

S i bl t i di– Suppression: reasonable extensive disease– Surgery: ? large > 3‐4 cm endometriomas

• Endometriosis NO effect on IVF LBR except– Extensive disease +/or endometriomas

(1) Adamson et al. Am J Obstet Gynecol. 1994;171(6):1488‐505.

(2) Adamson. Fertil Steril 2005;84(6):1582‐4.(3) Adamson GD. Modern Management Endometriosis 2006:289‐305. (4) ASRM Practice Committee. Fertil Steril. 2006;86(Suppl 4):S156‐60.

THANK

YOU!

ReferencesAdamson. Am J Obstet Gynecol. 1994;171(6):1488‐505. Adamson. Fertil Steril 1982 Dec; 38(6):659‐66. Adamson. Fertil Steril 1993; 59(1):35‐44. Adamson. Fertil Steril 2005; 84(6):1582‐4. Adamson. Fertil Steril 2010; 94(5):1609‐15. Adamson. Lasers Surg Med Suppl. 1992; 4:1‐85. Adamson. Modern Management Endometriosis 2006:289‐305. Ahmad. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD000475. ASRM Practice Committee. Fertil Steril 2006; 86(Suppl4):S156‐60. ASRM Practice Committee. Fertil Steril. 2006;86(Suppl 4):S156‐60. Barnhart. Fertil Steril 2002;77:1148‐55. Benschop. Cochrane Syst. Rev. 2010;11:CD008571. Costello. Aust NZ J Obstet Gynaecol 2004; 44(2):93‐102. D’Hooge. Sem Reprod Med 2003; 21: 243‐53. De Hondt. Curr Opin Obstet Gynecol 2006 Aug;18(4):374‐9. ESHRE guidelines. Hum Reprod 2005; 20:2698‐704. Guzick et al. Fertil Steril 1997; 67;822‐9. Hart. Cochrane Syst Rev. Hum Reprod 2005;20:3000‐7. Hart. Cochrane Syst. Rev. 2008 Apr 16; (2):CD004992. Hughes. Cochrane Syst Rev 2007 Jul 18;(3):CD000155. Jacobson. Cochrane Database Syst Rev. 2002; (4):CD001398. Jacobson. IVF Cochrane Database Syst Rev. 2010 Jan 20; (1):CD001398. Kennedy (ESHRE). Hum Reprod 2005; 20: 2698‐704. Littman. Fertil Steril 2005. Metwally. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD001298. Osuga et al. Gynecol Obstet Invest 2002; 53(Suppl 1), 33‐9.

References

Pellicano. Fertil Steril 2008; 89:796‐9.Pepperell and McBain, Br J OG 1985: 92; 569‐80. RCOG Guideline No XX. 2005. Rickes. Fertil Steril 2002;78(4):757‐62. Robertson. J Obstet Gynaecol Can. 2010 Jun;32(6):598‐608. Sallam. Cochrane Database Syst.Rev. 2006 Jan 25;(1):CD004635. Soliman.1993 Jun;59(6):1239‐44. Subit. Am J Reprod Immunol 2011 Aug; 66(2):100‐7. Surrey. Fertil Steril 2002; 78:699‐704.Sutton, Fertil Steril. 1997; 68(6): 1070–4. Tanahatoe. Fertil Steril 2003; 79(2):361‐6. Tanahatoe. Hum Reprod 2005; 20(11):3225‐30. Tummon. Fertil Steril 1997; 68(1):8‐12. Vercellini. Am J Obstet Gynecol 2003 Mar; 188(3):606‐10. Vercellini. Am J Obstet Gynecol 2006 Nov; 195(5):1303‐10. Vercellini. Hum Reprod 2009; 24(10):2504‐14. Vercellini. Hum Reprod 2009; 24(2): 254‐69. Yap. Cochrane Database Syst Rev. 2004; (3):CD003678.

64

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

OtherAsianIndo-Euro

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

65

http://www.imq.org/

http://www.usdoj.gov/crt/cor/pubs.htm

http://www.usdoj.gov/crt/cor/13166.htm

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2078538

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