Adhesions are an important yet often neglected cause of impaired fertility The use of adhesion prevention agents should be considered in laparoscopic surgeries as well as Open Surgeries, where adhesion formation is expected

1. Adhesion & Infertility :PreventiveAdhesion & Infertility :Preventive
Techniques & TechnologyTechniques & Technology

2. Dr. Niranjan Chavan
MD, FCPS, DGO, DFP, MICOG, DICOG, FICOG
Professor and Unit Chief, L.T.M.M.C & L.T.M.G.H
Chairperson, FOGSI Oncology and TT Committee (2012-2014)
Treasurer, MOGS (2017- 2018)
Chair and Convener, FOGSI Cell- Violence against Doctors (2015-2016)
Chief Editor, AFG Times (2015-2017)
Editorial Board, European Journal of Gynecologic Oncology
Editor of FOGSI FOCUS, MOGS, AFG & IAGE Newsletters
Member, Managing Committee, IAGE (2013-2017)
Member , Oncology Committee, AOFOG (2013 -2015)
Recipient of 6 National & International Awards
Author of 15 Research Papers and 19 Scientific Chapters
Course Co-Ordinator, of 11 batches, of MUHS recognized Certificate Course of
Basic Infertility Management Including Endoscopy (BIMIE) at LTMGH

3. INFERTILITY
• Infertility is “a disease of the reproductive system
defined by the failure to achieve a clinical pregnancy
after 12 months or more of regular unprotected sexual
intercourse.”… (WHO-ICMART glossary).
• Primary infertility; couple have failed to conceive before.
• Secondary infertility; woman has previously been
pregnant regardless of the outcome of the pregnancy
and now unable to conceive.

4. CHANCES OF CONCEPTION
• People who are concerned about their fertility should
be informed that over 80% of couples in the general
population will conceive within 1 year if:
- the woman is aged under 40 years
- they do not use contraception and have regular
sexual intercourse.
• Half of those who do not conceive in the first year
will do so in the second year
(cumulative pregnancy rate over 90%)(cumulative pregnancy rate over 90%)

5. CAUSES OF INFERTILITY
• Male factor
• Ovarian factor
• Tubal factor
• Uterine and cervical factor
• Peritoneal factor
• Unexplained

7. PERITONEAL FACTORS
• Endometriosis
• Pelvic adhesions
• Pelvic inflammatory disease

8. PERITONEAL ADHESIONS
• Peritoneal adhesions are pathological bonds usually between
omentum, intraoperative organs and the abdominal wall.
• These bonds may be a thin film of connective tissue, a thick
fibrous bridge containing blood vessels and nerve tissue, or a
direct contact between two organ surface
• Peritoneal adhesions are a consequence of peritoneal
irritation by infection or surgical trauma.
• Their prevalence after major abdominal procedures has been
evaluated at 63%-97%

9. TYPES OF POST OPERATIVE
ADHESONS
• Type 1 : de novo adhesion formation :adhesions formed at
sites that did not have previous adhesions.
Type 1A : no previous operative procedure at the site of
adhesions
Type 1B : previous operative procedures at the site of
adhesions
• Type 2 : Adhesion Reformation
Type 2A : no operative procedure at the site of
adhesions besides adhesiolys
Type 2B : other operative procedures at the site of
adhesions besides adhesiolysis

10. PATHOGENESIS
PERITONEAL TRAUMA
• Mechanical trauma
• Thermal, electrical or
chemical trauma
• Foreign bodies
• Infection
• Inflammation
• Ischemia

11. PATHOGENESIS
ADHESION FORMATION
• Fibroblast proliferation
• Mesothelial over-growth
• Neovascularization

12. PATHOGENESIS
FORMATION OF FIBRIN BANDS
• Inflammatory exudate
• Fibrin deposition
• Fibrin band formation

13. PATHOGENESIS
FULLY HEALED PERITONEUM
• Fibrinolytic activity
• Tissue plasminogen
activator
• 5-7 days normal surface
healing

14. Why Do Adhesions Form?Why Do Adhesions Form?
Surface 1
Surface 2
Surface 1
Surface 2
Surface 2
Surface 1 Surface 1
Surface 2
Fibrin
EE

15. DE NOVO /REFORMED/SURGICAL SITE
• De novo adhesions occur as a result of the
surgical procedure
• Reformed adhesions occur at the same
location as previous adhesions that were lysed
or resected
• Surgical site adhesions form at the anatomical
location of the primary surgical procedure
(i.e.: cystectomy: ovary)

16. Why Do Adhesions Form?
Laparoscopy = Less AdhesionsLaparoscopy = Less Adhesions
• Less tissue handlingLess tissue handling
• Better magnificationBetter magnification
• Precise haemostasisPrecise haemostasis
• Less drying of surfacesLess drying of surfaces
Surgical & Clinical Adhesion ResearchSurgical & Clinical Adhesion Research
Study (SCAR & SCAR-2) , 1999Study (SCAR & SCAR-2) , 1999
Adhesion formation dependsAdhesion formation depends
uponupon TYPE of surgeryTYPE of surgery performedperformed
• High RiskHigh Risk :: Lap Adhesiolysis,Lap Adhesiolysis,
Endometrioma drainageEndometrioma drainage
• Low Risk : Lap tubal sterilizationLow Risk : Lap tubal sterilization
• Medium risk: All othersMedium risk: All others

17. Why Do Adhesions Form?
Surgical & Clinical Adhesion ResearchSurgical & Clinical Adhesion Research
Study (SCAR & SCAR-2) , 1999Study (SCAR & SCAR-2) , 1999
ForFor High RiskHigh Risk
Laparoscopic procedures,Laparoscopic procedures,
the risk of adhesionthe risk of adhesion
formation & re-admissionformation & re-admission
is almostis almost EQUALEQUAL toto
Laparotomy! (60 to 90%)Laparotomy! (60 to 90%)

18. Impact of Post-Op Adhesions afterImpact of Post-Op Adhesions after
LaparoscopyLaparoscopy
• PelvicPelvic PainPain
• IntestinalIntestinal ObstructionObstruction : Major cause, 31-40%: Major cause, 31-40%
• Important cause of hospitalImportant cause of hospital readmissionsreadmissions &&
subsequent repeat surgerysubsequent repeat surgery
• InfertilityInfertility : 15-20% of secondary infertility is solely: 15-20% of secondary infertility is solely
adhesion- related*adhesion- related*
• Even after adhesiolysis, 85% adhesions willEven after adhesiolysis, 85% adhesions will re-re-
formform****
**Consensus In Adhesion Reduction management, TOG 2004;6(2), RCOG PressConsensus In Adhesion Reduction management, TOG 2004;6(2), RCOG Press
** Diamond MP (2000): Incidence of Post surgical adhesions- Peritoneal Surgery,** Diamond MP (2000): Incidence of Post surgical adhesions- Peritoneal Surgery,
Springer Verlag, New YorkSpringer Verlag, New York

19. Good Surgical TechniqueGood Surgical Technique
• Minimizing tissue traumaMinimizing tissue trauma
• Meticulous haemostasisMeticulous haemostasis
• Irrigation to prevent dryingIrrigation to prevent drying
of surfacesof surfaces
• Non- reactive suture materialNon- reactive suture material
• Use of sub-serosal suturesUse of sub-serosal sutures
LAPAROSCOPIC
SURGERY
AVERAGE
ADHESION
FORMATION
RATE [1,2]
1. Myomectomy 40%
2. Ovarian
Drilling
30-40%
3. Endometriosis
surgery
70-80%
4. Adhesiolysis 70-80%
1. Consensus In Adhesion Reduction management, TOG 2004;6(2), RCOG Press1. Consensus In Adhesion Reduction management, TOG 2004;6(2), RCOG Press
2. Diamond MP (2000): Incidence of Post surgical adhesions- Peritoneal Surgery,2. Diamond MP (2000): Incidence of Post surgical adhesions- Peritoneal Surgery,
Springer Verlag, New YorkSpringer Verlag, New York

21. ADHESION - REDUCTION ADJUVANTS &ADHESION - REDUCTION ADJUVANTS &
PROPOSED MECHANISMS OF ACTION-1.PROPOSED MECHANISMS OF ACTION-1.
Class of adjuvant Mechanism of action
Fibrinolytic agents
-
Fibrinolysin;Streptokinase;Urokinase;Hyal
uronidase;Chymotrypsin;Plasminogen
Activators
Fibrinolysis
Plasminogen Activators
Anticoagulants-
Heparin;Citrates;Oxalates;
Prevention of fibrin & clot formation
Antiinflamatory Agents
Corticosteroids,NSAIDS,Antihistaminics,
calcium channel blockers,Progesterone
Reduce vascular permeability
Reduce histamine release
Stabilises lysosomes
Antibiotics-
Tetracyclines, cephalosporins
Prevent infections

22. ADHESION - REDUCTION ADJUVANTS &ADHESION - REDUCTION ADJUVANTS &
PROPOSED MECHANISMS OF ACTION-2PROPOSED MECHANISMS OF ACTION-2
Adhesion reduction Adjuvants Mechanism of
Action
Mechanical separation
Intra-abdominal instilates
Crystalloids solutions, Dextrans
Mineral oils,silicone, vasseline,hyaluronic
Acid,carboxy methyl cellulose
Surface separation
Hydroflotation
Barriers
Endogenous tissues,omental grafts,
peritoneal grafts,Bladder strips, foetal
membranes.
Exogenous materials
Fibringlue, polytetrafluroethelene,
Oxidised regenerated cellulose,geletin rubber
sheets,poloxamer 407,Repel

23. ADHESION PREVENTION
• Postoperative Instillates (Hydroflotation)
• Crystalloid solutions
– Lactated ringer’s solution
– Saline
- Dextran 40/70
LIQUID HYDROFLOTATION

24. RINGER LACTATE DEXTRAN 40,70RINGER LACTATE DEXTRAN 40,70
•PH 5.5 - 6.5 4.5 - 5.7
•Electrolyte Na + 147 Na + 154
Content Cl - 155.5 Cl - 154
mmol/L K+ 4 Or 5% Dextrose
Ca++ 2.3
•Oncotic Non Oncotic Hyper Oncotic
Pressure
•Intra Compartment Tissue Odema Tissue Dehydration
Fluid Balance
•Cardiovascular Unlikely Potential Risk
Overload
•Plasma Half 20minutes 6-12hours
Life
•Effect on Haemostasis Dilution Only Impaired+Dilution Effects
•Content Crystalloids Poly Saccharide
Dextran 40,60,70
•Function Removes Small Peritoneal Tratransiudate
Blood Clots Siliconizing

25. No. of
Author Patients Results
Rosenberg S.M. et al., 1984 21 Non-efficacious
Adhesion Study Group, 1983 47 Non-efficacious
Larsson B. et al., 1985 54 Non-efficacious
Jansen R.P.S., 1985 82 Non-efficacious
Wiseman D. et al., 1998 Meta-analysis of 23
studies
ADHESION PREVENTION
CRYSTALLOID CLINICAL STUDIES

26. 0
50
100
150
200
250
300
350
0 1 2 3 4 5 6 7 8 9
Crystalloid(ml)
Hours
CRYSTALLOID SOLUTIONS
ADHESION PREVENTION
• As a post-op instillate, not
effective in preventing
adhesions
– rate of absorption is 35-62
ml/hour
– 300 ml are absorbed in about
7 hours
– the process of peritoneal
healing and adhesion
formation takes place during
the first 5-7 days

27. Adhesion Barriers ofAdhesion Barriers of
Doubtful EfficacyDoubtful Efficacy
• Anti- inflammatory agents (e.g. NSAIDS)
• Fibrinolytics (e.g. Streptokinase)
• Anticoagulants (e.g. Heparin)
• Antibiotics (Intra peritoneal instillation)
• Progesterone
• GnRH agonists
• Normal Saline : too rapidly absorbedNormal Saline : too rapidly absorbed
““Insufficient usefulness in clinical practice”Insufficient usefulness in clinical practice”

28. Methods of Adhesion Prevention in
Laparoscopic Surgery
• Preventing Gas-Induced dryingPreventing Gas-Induced drying
of peritoneal surfaces by usingof peritoneal surfaces by using
pre-warmed, humidifiedpre-warmed, humidified COCO22
(Thermoflator, Karl Storz)(Thermoflator, Karl Storz)
• Adhesion barrier substancesAdhesion barrier substances

29. Adhesion Barriers PreviouslyAdhesion Barriers Previously
Used in PracticeUsed in Practice
Product Name Description Drawback
1. Hyskon High mol. Wt.
solution
Anaphylaxis
2. Sepracoat Sterile cellulose
membrane
Poor efficacy
3. Intergel Hyaluronic acid
lubricant
Post operative pain

30. Currently Used Adhesion Barriers :Currently Used Adhesion Barriers :
None PerfectNone Perfect
Site- Specific
Agents
Description Drawback
1. Preclude ePTFE membrane Needs to be sutured in place, 2nd
surgery to remove
2. Interceed Oxidised regenerated
cellulose
1. Bloodless field required
2. Migrates
3. Seprafilm Carboxymethyl cellulose
membrane
Difficult to handle laparoscopically
4. SurgiWrap Polylactide film Needs to be sutured in place, but
dissolves in 1 year
5. SprayGel/
SprayShield
Hydrogel Expensive
Broad Agent Description Drawback
1. Adept Icodextrin solution Studies ongoing

31. INTERCEED
• Oxidized Regenerated Cellulose
• Absorbable Adhesion Barrier
• Apply end of procedure
• Remove all irrigating fluid and instillates from
peritoneal cavity
• Cut to size
• Apply interceed (if it twin’s black, then blood is
present, remove interceed and achieve
hemostasis
• No sutures needed
• Moisten with 5ml of irrigant/3x4 inch piece

32. ADHESION PREVENTION
INTERCEED BARRIER
SIX HOURS AFTER ADDITION OF IRRIGATION SOLUTION

33. ADHESION PREVENTION
WRAPPING OVARY WITH
INTERCEED BARRIER

34. ADHESION PREVENTION
WRAPPING OVARY WITH
INTERCEED BARRIER

35. ADHESION PREVENTION
WRAPPING OVARY WITH
INTERCEED BARRIER

36. %AdhesionFree
 Adhesion Free Outcomes - GYNECARE INTERCEED Barrier was 1.6 to 2.5
times more effective than good surgical technique alone in achieving an adhesion
free outcome.
 Studies include adhesiolysis, endometriosis, ovarian, tubal, and fimbria
procedures.
Effectiveness: Adhesion Free Outcomes
Wiseman DM et al. J. Repro Med 1999;44:325
ADHESION PREVENTION
0
10
20
30
40
50
60
70
Azziz Nordic Sekiba Franklin van Geldorp Li and Cooke
GYNECARE INTERCEED
Barrier
Control

37. REDUCTION OF OVARIAN ADHESIONS
WITH INTERCEED BARRIER
ADHESION PREVENTION
%AdhesionFreeOvaries
 GYNECARE INTERCEED BARRIER Control
 100
 80
 60
 40
 20
 0
Keckstein J. et al. Hum Reprod 1996;11:579.
P< 0.05

38. INTERCEED BARRIER TURNS BLACK WITH
BLOOD
ADHESION PREVENTION

39. PRVENTION OF DENOVO ADHESION FORMATION
AFTER LAPAROSCOPIC MYOMECTOMY-Randomized
trial to evaluate the effectiveness of an oxidized
regenerated cellulose absorbable barrier
Fertil Steril 1995 Mar;63(3):491-3
Department of Obstetrics & Gynaecology of the University of
Cagliari,Italy.
“50 premenopausal patients submitted to laparoscopic
myomectomy (control group n = 25) & surgery + interceed group
(treatment group n=25)
A second look laparoscopy performed 12-14 weeks after
myomectomy.
Number of adhesion free patients were 3 out of 25(12%) in control
group & 15 out of 25(60%) in treatment group(P<0.05)
Cellulose absorbable barrier significantly reduce adhesion
formation”.

40. Comparative StudyComparative Study
NormalNormal
SalineSaline
SolutionSolution 4% Icodextrin4% Icodextrin
Solution (Adept®)Solution (Adept®)
Sprayable HydrogelSprayable Hydrogel
(SprayShield®)(SprayShield®)

42. SURGERIES INCLUDED :
Lap AdhesiolysisLap Adhesiolysis
Lap MyomectomyLap Myomectomy
Lap Endometriosis SurgeryLap Endometriosis Surgery

43. Icodextrin 4% (AdeptIcodextrin 4% (Adept®)®)
• Clear, colourless fluidClear, colourless fluid
that contains glucosethat contains glucose
polymer Icodextrinpolymer Icodextrin
• 1.5 Litres left in1.5 Litres left in
peritoneal cavityperitoneal cavity
• Hydroflotation &Hydroflotation &
Colloidal osmosisColloidal osmosis
• Delayed absorptionDelayed absorption
(about 4 days)(about 4 days)

44. Sprayable Hydrogel (SprayShieldSprayable Hydrogel (SprayShield®)®)
• Composed ofComposed of Water (90%)Water (90%) , Polythene glycol &, Polythene glycol &
LysineLysine
• 2 streams of liquid combine to form a bright2 streams of liquid combine to form a bright
blue solid polymerblue solid polymer
• Adherent gel sticks instantly to tissuesAdherent gel sticks instantly to tissues
• Remains for 7 daysRemains for 7 days

45. Study ProtocolStudy Protocol
 All patients between 20-40 yrs, no medicalAll patients between 20-40 yrs, no medical
illness & no prior surgeryillness & no prior surgery
 All patients underwentAll patients underwent
Second-look laparoscopy afterSecond-look laparoscopy after 3 months3 months
 Adhesions were graded by:Adhesions were graded by:
• Site of Adhesion- At Surgical Site/ RemoteSite of Adhesion- At Surgical Site/ Remote
• Type of Adhesion- Thin/Filmy or DenseType of Adhesion- Thin/Filmy or Dense

47. Adhesions at Second Look ScopyAdhesions at Second Look Scopy
Thin/
Filmy
Adhe-
sions
Dense
Adhe-
sions
Total %
NORMAL
SALINE
N = 11N = 11
3 8 100%
ADEPT®
N = 11N = 11
7 2 82%
SPRAY
SHIELD®
N = 13N = 13
3 0 23%
At
Surgical
Site
Remote
Adhe-
sions
10 9
6 3
1 2
NATURE OF ADHESION SITE OF ADHESION

49. Metroplasty + Adept®

50. Adept®, 3 Months Later

51. Adept®, 6 Months Later

53. Myomectomy + SprayShield®

54. SprayShield®, 3 Months LaterProcedure Barrier Patients (N) Reference Year
LAPAROTOMY
Ovarian Surgery
Cystectomy Interceed 66 Larsson B. et al.. 1995
Interceed 52 Franklin et al.. 1995
. Pelvic Sidewall
Adhesiolysis
Interceed 134 Azziz R. et al. 1993
Interceed 28 Li &.cooke 1994
Tubal Surgery
Adhesiolysis Interceed 66 Larrson B. et al. 1995
Salpingostomy Interceed 21 Curto J.M. et al. 1992.
Myomectomy
Perclude 16 Tulandi T. et al. 1995
Interceed 50 Mais V. et al. 1995
Seprafilm 54 Diamond et al 1995
LAPAROSCOPY
Ovarian cystectomy Interceed 17 Keckstein et al 1996
Ovarian drilling Interceed 20 Giannacodimos 1996
Endometriosis Interceed 32 Mais et al 1995
Clinical Studies With Barriers
Confirm Efficacy

55. COSTCOST
RsRs
15,00015,000
toto
23,00023,000
RsRs
33003300

56. Cost Effective??Cost Effective??
• Adhesion BarrierAdhesion Barrier
Rs 4000 – Rs 16,000Rs 4000 – Rs 16,000
• Quality of lifeQuality of life:: AdhesionAdhesion
sequelae – Infertility,sequelae – Infertility,
Intestinal Obstruction,Intestinal Obstruction,
PainPain
• Cost of a secondCost of a second
MAJOR surgeryMAJOR surgery
• ComplicationsComplications of aof a
second surgerysecond surgery
(adhesiolysis – bowel(adhesiolysis – bowel
trauma)trauma)

57. Side Effects??Side Effects??
Adept
(Icodextrin)
SprayGel
(Sprayable
Hydrogel)
SprayShield
(Sprayable
Hydrogel)
1. Paralytic Ileus (1.9%) Still under study, some
instances of chemical
peritonitis reported
Slightly less than Spraygel
2. Peritonitis (1.5%)
3. Haematological
problems (1.1%)
““Mostly Safe, Low Incidence of Side EffectsMostly Safe, Low Incidence of Side Effects

58. • High–Risk Surgeries (More risk of Adhesions)High–Risk Surgeries (More risk of Adhesions)
• Ovarian surgeryOvarian surgery
• Endometriosis surgeryEndometriosis surgery
• MyomectomyMyomectomy
• AdhesiolysisAdhesiolysis
 Adhesion BarriersAdhesion Barriers
Recommended,Recommended,
Benefits OutweighBenefits Outweigh
CostsCosts
• Post operative AdhesionsPost operative Adhesions definitely impairdefinitely impair
fertilityfertility and impair quality of lifeand impair quality of life

59. To Conclude…To Conclude…
• Adhesions are an important yetAdhesions are an important yet oftenoften
neglectedneglected cause of impaired fertilitycause of impaired fertility
• The use ofThe use of adhesion prevention agentsadhesion prevention agents shouldshould
be consideredbe considered inin laparoscopiclaparoscopic surgeries as wellsurgeries as well
asas Open SurgeriesOpen Surgeries , where adhesion formation, where adhesion formation
isis expectedexpected
• PREVENTING ADHESIONS ISPREVENTING ADHESIONS IS MUCHMUCH MOREMORE
EFFECTIVE THAN TREATING THEM!EFFECTIVE THAN TREATING THEM!