Surgical Treatment Of PCOS Prof.Dr.Timur Gьrgan Hacettepe University,Faculty of Medicine Dept. Of Ob&Gyn,Ankara,Turkey

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Surgical Treatment Of PCOSProf.Dr.Timur
GürganHacettepe University,Faculty of
MedicineDept. Of ObGyn,Ankara,Turkey
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The Goals of ART
To minimize the risk of complications To
optimize pregnancy rates To produce healthy,
genetically normal,singleton full-term deliveries
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A step-by-step approach to ovulation induction in
PCOS
Step Approach 1 Weight loss if BMI ie
elevated 2 Clomiphene citrate
glucocorticoids 3 Insulin sensitizer as a single
agent 4 Insulin sensitizer clomiphene
citrate 5(3) Gonadotropin treatment 6 Insulin
sensitizer gonadotropin treat. 7(4) Ovarian
surgery 8 IVF/ICSI IVM
Kim LH, Taylor AE, Barbieri RL. Fertil Steril
73 1097-8, 2000, ASRM/ESHRE 2007
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The potential problems of gonadotropin therapy

• Difficult to titrate the dose to achieve
  monofollicular ovulation.
• Multiple gestations (gt30 percent)
• Risk of OHSS
• Need of careful monitoring
• High cost
• High spontaneous abortion rate

Wang, CF et al. Fertil Steril 1980 33479.
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NICE Guidelines

• Ovarian diathermy
• Women with PCOS who have not responded to CC
  should be offered laparoscopic ovarian drilling
  because it is effective

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Laparoscopic Ovarian Drilling

• Technique
• Endocrine Changes
• Clinical Changes
• Acne and Hirsutism
• Ovulation
• Pregnancy Rates and Outcomes
• In vitro Fertilization
• Selection Criteria
• Complications
• Future Applications

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Traditional Wedge resection

• Side effects
• POF rate 20-80
• Pelvic adhesion rate 40-75
• Lead to irreversible infertility

• Side effects
• Pelvic adhesion rate1982
• Ovulation dysfunction due to cicatricle on the
  surface of ovary
• Difficulty in control quality and depth of
  drillings

Laparoscopic ovarian drilling
Iatrogenic exhaustion of ovarian reserve- POF?
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OVARIAN DIATHERMY
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Technique

• Two or three incision L/S approach
• 40 w per puncture for 2-3 seconds
• Avoid hilum avoid bleeding
• Continuous irrigation
• Various energy sources
• 5 to 6 punctures seems optimal
• One or both ovary
• Tulandi T et al.,1998 Amer SA et al.,2003
  Malkawi HY et al.,2005 Roy K et al.2008

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Conception rates after LOD Sheffield Prospective
Study
puncture
1
2
3
4
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PCOS - SURGICAL TREATMENT
Technical options
Wedge resection Ovarian biopsy Capsule
resection Electrodesiccation Laser
vaporization Endocoagulation
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1. Is there still a role for surgical treatment ?

• 2. How should surgery be performed ?

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PCOS - OVARIAN DRILLING
Mechanisms of action
Central Intraovarian
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PCOS - OVARIAN DRILLING
Endocrine changes
Decline in serum androgen and estrogen
levels Decrease in both serum immuno- and
bioactive LH levels Unchanged, decreased or
increased serum FSH levels Unchanged or decreased
DHEAS levels
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PCOS - OVARIAN DRILLING
Intraovarian mechanisms
Destruction of the androgen producing
stroma Drainage of follicles with high androgen
and inhibin content Alterations in the levels of
various intraovarian growth factors
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PCOS - OVARIAN DRILLING
Central mechanisms
Markedly reduced LH amplitudes with no change in
pulse frequency Markedly attenuated response to
GnRH challenge test
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Why does ovarian surgery in PCOS help? Endocrine
implications
Ovarian surgery
Continuation of follicle growth in subsequent
cycles after ovarian surgery occurs in an
Environment with less androgens and lower LH
and FSH levels compared with pretreatment
levels.
Rapid reduction in all ovarian hormones With
increased pituitary hormones
Initiation of folliculogenesis Increase ovarain
hormone production
Systematic review. Hendriks, ML et al. Hum
Reprod 2007
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CLINICAL RESULTS

• Acne and Hirsutism different results
• 40 of 25 patients with acne and 23 of 43
  patients with hirsutism were improved 4 to 9
  years after LOD
• Amer SA et al.,2002
• 62.2 of patients had moderate to severe
  acne or mild to severe hirsutism and reduced by
  half at 3 to 5 years following LOD
• Neather et al., 1994
• LOD significantly reduced the percentage of
  patients with a Ferriman-Gallwey score of gt8 from
  57.7 preoperatively to 51.1 at 2 months
  following LOD
• Api M et al., 2005
• In a randomized trial of 50 patients
  comparing LOD with gonadotropin treatment,
  Farquhar et al found no difference in acne or
  hirsutism at 6-month follow-up
• Farquhar et al.,2002

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Laparos. ovarian surgery-Cumulative preg. rates

Cumulative preg. rate
() Author
12 m 18 m
24m Heylen et al-1999 68 73 73 Li et
al-1998 54 62 68 Felemban et al-2000 54 68 82
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Felemban et al. Fertil Steril 2000 73266-9
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Ovulation and pregnancy rates
Gomel V et al. RBM Online 2004935-42
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Reproductive outcome
Unlu C et al. Curr Opin Obstet Gynecol
200618286292.
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Pregnancy Rates and Outcomes

• variable rates of pregnancy following LOD 50 -
  80 within 1 year of the procedure
• due to heterogeneous samples, with the inclusion
  of patients that are not CC resistant or that do
  not meet classic criteria for PCOS

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Lapar. ovarian drillingCrude ovulation and preg.
rates

• Ovulation rates
• Electrocoagulation - 64-92
• Laser - 55-70
• Pregnancy rates
• Electrocoagulation - 52-80
• Laser - 0-56

Al-Took S et al. J Soc Obstet Gynaecol Can 1997
19 721-9
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Late endocrine effects of ovarian electrocautery
in women with PCOS Ovarian electrocautery
normalizes ovarian function, including androgen
production and the results seem to be stable for
18-20 years percent ovulation rate
Observation period normal overweight
all p value weight 3
mo 78(21/27) 65(13/20) 72(34/47)
NS 1 y 89(24/27) 65(11/17) 80(35/44)
NS 3 y 79(19/24) 50(10/20) 66(29/44)
lt.05 10 y 68(12/15) 71(12/17) 69(29/42)
NS gt10 y 80(12/15) 69(11/16)
74(23/31) NS
Long term observational study 165 infertile PCOS
women(Gjonnaess H. - FS 1998 April 694 697-701
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Lapar. ovarian cautery-Late effects

• 165 infertile women with PCOS (ages 23-25)
• ?10 year of follow-up available in 51 patients
• 24 were gt40 y (mean 44 y)
• Only 1 (49 y) had FSH19, 19 y after lapar.
  ovarian drilling
• gt18 year of follow-up in 15 patients
• 34 / 51 (67) conceived and had 63 infants (1-6)

Gjonnaess H. Fertil Steril 69 697-701, 1998
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The Evidence

• Is it better than gonadotrophins?

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LOD versus FSH randomised controlled trial

• 29 Dutch hospitals
• 168 subjects with CC resistant PCO
• 83 LOD
• 85 rFSH
• Bayram et al, BMJ 2004

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LOD versus FSH

• Bayram et al, 2004

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Conclusions of study

• An electrocautery strategy and ovulation
  induction with recombinant follicle stimulating
  hormone are similarly effective in inducing
  ovulation
• Multiple pregnancies can largely be avoided by
  electrocautery and clomifene citrate before
  rFSH

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Ovarian drilling Med ovulation vs
gonadotropin Ovulation rate
Laparos. Drilling-Cochrane Library 2005, Issue 3
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Ovarian drilling Med ovulation vs
gonadotropin Live birth rate
Laparos. Drilling-Cochrane Library 2005, Issue 3
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LOD v METFORMINPalomba et al, 2004 JCEM
p0.1
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Pregnancy Rates and Outcomes- Abortion

• Women with PCOS have a higher than average
  frequency of spontaneous abortions (SAB), 40 to
  53.
• The SAB rates following LOD range from 8 to 21
  (similar to normal population)
• Felemban A et al., 2000 Colacurci N, et
  al.,1997)
• LOD may therefore reduce the SAB rates in PCOS
  patients by normalizing high LH levels ?
• AND reduction in androgen levels and insulin
  resistance may also contribute to lower SAB rates
  by improving oocyte quality or endometrial
  receptivity

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Ovarian drilling Med ovulation vs
gonadotropin Miscarriage rate
Laparos. Drilling-Cochrane Library 2005, Issue 3
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Multiple Pregnancy

• Meta-analysis of 5 RCTs
• Multiple pregnancy with LOD is significantly
  lower (OR 0.13, CI 0.17-0.98) than
  godadotrophin therapy

Consensus on infertility treatment related to
polycystic ovary syndrome. Human Reprod 2008,
23462
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Ovarian drilling Med ovulation vs
gonadotropin Multiple pregnancy rate
Laparos. Drilling-Cochrane Library 2005, Issue 3
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Unilateral vs bilateral drilling Ovulation rate
Laparos. Drilling-Cochrane Library 2005, Issue 3
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Repeat LOD Ovulation rates
Amer et al, Fertil Steril (2003)
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Repeat LOD Conception rates
Amer et al, Fertil Steril (2003)
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Laparoscopic Ovarian Drilling and in Vitro
Fertilization

• LOD improves the effectiveness of gonadotropin
  treatment
• PCOS patients have a higher rate of cycle
  cancellation due to an exaggerated response to
  gonadotropin therapy with an associated increased
  risk of OHSS.
• Ovaries pretreated with LOD tend to respond to
  stimulation with parenteral gonadotropins in a
  more controlled fashion, similar to non-PCOS
  ovaries

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Ovarian Drilling IVF

• 1. Improves effectiveness to gonadotropin
  treatment /Decreases the number of ampulles used
• 2.Decreases OHHS rate
• 3.Decreases cancellation rate
• 4.Decreases Abortion rate
• 5.Decreases multiple pregnancy rate
• 6. Increase pregnancy rate
• Tozer AJ et al.,2001

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PCOS - OVARIAN DRILLING
Advantages
Avoids the need for intensive cycle
monitoring Produces a normal hormonal
environment Induces resumption of spontaneous
ovulation Enables more favourable response with
subsequent gonadotropin stimulation Avoids
OHSS Avoids multiple gestation
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NICE Guidelines

• Ovarian drilling
• Women with PCOS who have not responded to CC
  should be offered laparoscopic ovarian drilling
  because it is as effective as gonadotrophin
  treatment and is not associated with an increased
  risk of multiple pregnancy

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Social Factors

• Cost effectiveness
• Patient preference for treatment with LOD
• Minimally invasive procedure that eliminates the
  inconvenient daily injections and frequent office
  visits required for gonadotropin treatment

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LOD vs GONADOTROPHINECONOMIC CONSIDERATIONS

Cost of term pregnancy LOD 22-33 lower
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Ovarian drilling Med ovulation vs
gonadotropin Cost analysis
Laparos. Drilling-Cochrane Library 2005, Issue 3
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PCOS - OVARIAN DRILLING
Complications
Related to lapsc. and energy use Avulsion of the
uteroovarian ligament Bleeding from the drilled
holes Ovarian atrophy Adhesion formation Premature
ovarian failure ? Ovarian cancer ?
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PCOS - OVARIAN DRILLINGAdhesion formation
Gomel V et al. RBM Online 2004935-42
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PATIENT SELECTION

• Everything in medicine is
• patient selection the chief determinant of
  results

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LH and Pregnancy rates in LOD
Pregnancy rate

60
40
20
LH (iu/l)
lt10
gt10
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Free Androgen Index and the outcome of LOD

P lt 0.05 P lt 0.01 P lt 0.001


FAI
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BMI and the outcome of LOD

P lt 0.05 P lt 0.01 P lt 0.001


BMI (kg/m2)
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With proper patient selection, the pregnancy rate
after laparoscopic ovarian diathermy is up to 80
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Whats new?
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• The value of measuring AMH in women with
  anovulatory
• polycystic ovary syndrome undergoing
• laparoscopic ovarian diathermy
• Human Reproduction 2009
• Amer, Li, and Ledger

High AMH (gt7.7ng/ml) predicts poor response
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Future Applications

• LOD as first line treatment / same results
• Cleemann L et al.,2004Amer SA et al.,2009
• Patients going diagnostic or operative
  laparoscopy
• who have completed six ovulaatory cycles without
  pregnancy / Not eligible for gonadotropin therapy
• PCOS patients with dysfunctional uterine
  bleeding and /or endometrial hyperplasia

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Randomized controlled trial comparinglaparoscopic
ovarian diathermy withclomiphene citrate as a
first-linemethod of ovulation induction inwomen
with polycystic ovary syndrome Amer, Li,
Metwally, Emarh LedgerHuman Reproduction 2009
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Disadvantages of LOD is the requiste of
laparoscopy ?

• Transvaginal hydrolaparoscopy
• Gordts et al., 2009
• Transvagianl ultrasound guided interstitial
  Nd-YAG laser or unipolar needle
• Kaajik et al.,1997Api et al.,2009
• Simple aspiration of follicles under ultrasound
  guidance
• Badaway et al., 2009

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Ovarian interstitial YAG-laser An effective new
method

• Transvaginal ultrasound guided ovarian
  interstitial laser-coagulation treatment in
  anovulatory women with PCOS.
• Spontaneous ovulation rate of 84.2, during the
  6-month postoperative period.
• Decrease in serum LH and testosterone
• No significant operative complications were
  encountered.
• The ultrasound-guided transvaginal ovarian
  interstitial laser treatment may be an effective
  new method to manage anovulation in PCOS
  patients.

Zhu W, et al. American Journal of Obstetrics and
Gynecology (2006) 195, 45863
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L/S treatment of PCOS with insulated needle
cautery 112 CC resistant infertile women. L/S
ovarian drilling Outcome measure No
() Menstrual pattern regular
90(80.4) irregular
22(19.6) Ovulatory status spontaneous
ovulation 82(73.2) ovulation
with CC 27(24.1) ovulation with
Gd 2(1.8) enrolled in in-vitro
maturation program 1(0.9)
Fertility and Sterility, ( Felemban A. Et al)Feb
2000,732266-269
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Ultrasound-guided immature follicle aspiration (
IMFA) to treat severe PCOS
A Ovary before puncture B Reinspection two
weeks after puncture
Schematic diagram for ultrasound microinvasive
surgery
a
b
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Minilaparoscopic ovarian drilling under local
anesthesia in patients with PCOS prospective
randomised study, 62 PCOS Group A 32........
Study group Group B 30........ Control group(
traditional ovarian ovarian drilling by L/S under
general anesthesia ) RESULT(S) Group A showed
a good intraoperative pain score The hormonal
profile after surgery did not differ between
groups. Operative times were also similar for
both groups. Post-op discharge within 2 hours
Significantly higher in group A. Pregnancy and
ovulation rates were not significantly different
between the groups.
Fulvio Z,FS 2000 Aug,742,376
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SUMMARY 1

• Laparoscopic ovarian diathermy, a very simple
  form of surgery, has a high success rate and has
  a definite, useful role in the management of
  anovulatory infertility in women with PCOS.

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SUMMARY 2

• Laparoscopic ovarian diathermy is an excellent
  example to illustrate that the key to success of
  endoscopic surgery depends very much on
• 1. careful patient selection
• 2. the use of proper techniques

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Approach to ovulation induction in women with PCOS
Guzick DS, Clin Obs Gyn 20071255-267
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THANK YOU