EVIDENCE BASED MANAGEMENT OF OVARIAN DRILLING IN WOMAN WITH PCOS

2. INDEX
• DEFINITION
• HISTORY
• INDICATION
• METHODS
• MOA
• PREDICTORS
• OUTCOMES
• COMPLICATIONS
• OTHER METHODS
• TAKE HOME MESSAGE

3. PCOS

4. HISTORY
 Stein and Leventhal in 1935 - wedgeresection(1/3of
ovary)
 Series of 108 patients undergoing bilateral ovarian
wedge resection
 Regular menstrual cyclicity - restored in 95%
 Pregnancy ratewas 85% (Stein IF et al West J Surg Obstet
Gynecol 1964)
 The procedure was often associated with development
of periadnexal adhesions, negating the beneficial
effects of surgery (Toaff R et al; Am J Obstet Gynecol1976).

5. • Ovarian drilling was first used in the treatment of PCOS in 1984
and has evolved as a safe and effective surgery by HALVARD
GJÖNNAESS

6. INDICATION OF LOD
• MAIN INDICATION FOR LOD IS CC-RESISTANT PCOS - AS A SECOND-
LINE THERAPY FOR ANOVULATORY INFERTILE PCOS CASES;
SPECIFICALLY, AS AN ALTERNATIVE TO GONADOTROPINS
• PARTICULARLY IN THOSE WITH HYPERSECRETION OF LUTEINIZING
HORMONE (LH)
• NORMAL BODY MASS INDEX
• THOSE NEEDING LAPAROSCOPIC ASSESSMENT OF THE PELVIS
• WHO LIVE TOO FAR AWAY FROM THE HOSPITAL FOR THE INTENSIVE
MONITORING REQUIRED DURING GONADOTROPIN THERAPY
Royal College of Obstetricians and Gynaecologists 2007
ACOG Practice Bulletin No 108: Obstet Gynecol. 2009

7. METHOD

8. SURGICAL TECHNIQUE:

9. SURGICAL TECHNIQUE:
• RULE OF FOUR : Four punctures per ovary, each for 4 s at 40 W (rule of 4) -
640 J of energy per ovary
• Depth – 2-5mm
• Diameter – 3mm
• Energy – 30 - 40W of cutting current
• Site – antimesentric border, avoid hilum
• Irrigation fluid should be used immediately after each treatment to cool the
ovary.
TulandiTetal,IntJFertilWomensMed1997;42(6):436–44

10. NUMBER OF PUNCTURES
• The least effective thermal
dose was 600 J per ovary
• 60 J/cm3 of ovarian tissue
• Menstrual cycle resumption &
ovulation & conception rate in
the thermal dose adjusted
based on ovarian volume (60
J/cm3) was higher than in cc-
resistant PCOS patients with
fixed dose 4 puncutre (600 J
per ovary).
Zakherah S,et al.,Fertil Steril. 2011;95(3):1115–8.
Np = 60 J/cm3 of ovarian tissue divied by 40 W X 4 s

11. A PROSPECTIVE DOSE FINDING STUDY OF THE AMOUNT OF THERMAL
ENERGY REQUIRED FOR LAPAROSCOPIC OVARIAN DIATHERMY
30-40 W wasapplied
foraduration of 3-5s per
puncture, giving a total thermal
energy of 150 J perpuncture.
S.a.k.amer et al; Human Reproduction 2003

12. LASER VS
ELECTROCOAGULATION
Saleh AM et al, Obst Gynecol Scand2004
Electrocoagula
tion group
LASER group OR (95% CI)
Spontaneous
ovulation
82.7 77.5 1.4
0.9-2.1
Pregnancy rate 64.8 54.5 1.5
1.1-2.1

13. UNILATERAL V/S BILATERAL??
Farquhar et al Cochrene review 2012

14.  Live birth was reported in 36% of women having
undergone unilateral drilling and 40% in thosewho
had undergone bilateral drilling.
 The difference was not significant (OR 0.83;
95%CI 0.24 to 2.78; P = 0.76)
UNILATERAL V/S BILATERAL??
Roy et al. Archives of Gynecology and Obstetrics 2009

15. MOA
 Removal of a mechanical barrier i.e. Disruption ofovarian
sclerotic capsule believed to help in escape of ovulated oocyte
 Destroying the androgen-producing ovarian stroma
 Reducing the size of the ovary was thought to allow
gonadotrophins to act more effectively
 Surgery may increased blood flow to the ovaries,resulting in
increased delivery of gns
 Growth factors those are vasoactive and angiogenetic in nature
contribute to local change in blood supply.
 Increased insulin-like growth factor-i (igf-i) production
 Reduced inhibin levels - increased FSH levels
katz et al., 1978; ben shlomoet al., 1998; Rossmanith WG et al clin endocrinol1991
cohen, 1996; takeucht et al., 2002; al ojaimi, 2004

16. HORMONAL CHANGES
 Serum LH concentration increases immediately after surgery and then
decreases
 LH pulse frequencies do not change; LH pulse amplitudes - reduced
 Pituitary responsiveness to GnRH stimulation also decreases
concomitantly with a decline in serum testosterone concentration,
suggesting that destruction of ovarian stroma has an indirect
modulating effect on the pituitary–ovarian axis
 Effect of LOD on FSH is variable and less pronounced
 The FSH concentration generally increases rapidly and thereafter
demonstrates a cyclical rise, in keeping with restoration of ovulatory
function.
 Normal inhibin pulsatility is restored, indicating the resumption of
normal intraovarian paracrine signaling.
 This will restore FSH: LH ratio, helps in recruitment of new cohort of follicle
and resumption ofovulation.
katz et al., 1978; ben shlomoet al., 1998; Rossmanith WG et al clin endocrinol1991
cohen, 1996; takeucht et al., 2002; al ojaimi, 2004

17. LOD AS A FIRST LINE RX IN PCOS???

18. CC should therefore remain the standard first-
line OI in anovulatory womenwith PCOS.
However, LOD could be recommended as a first
line if laparoscopy is indicated for other reasons
in these women

19. LOD V/S Gonadotrophin in CC Resistant??
Farquhar et al Cochrene review 2012

20. LOD V/S Gonadotrophin in CC Resistant??
Farquhar et al Cochrene review 2012

21.  There was no evidence of a significant difference in
rates of clinical pregnancy, live birth or miscarriagein
women with clomiphene resistant PCOS undergoing
LOD compared to other medicaltreatments.
 The reduction in multiplepregnancy rates in women
undergoing LOD makes this option attractive.
 There areongoing concernsabout the long- term
effects of LOD on ovarianfunction.
LOD V/S Gonadotrophin in CC Resistant??
Farquhar et al Cochrene review 2012

22. PROGNOSTIC FACTORS

23. PROGNOSTIC FACTORS

24. FAVORABLE
• YOUNG AGE
• BMI<25
• INFERTILITY <3.5YRS
• LH>10
UNFAVORABLE
• HIGHER BMI ≥ 35
• AMH ≥ 7.7
• LASER
• TEST. ≥ 4.5 nmol/ltr
• FAI ≥ 15
PROGNOSTIC FACTORS

25. OUTCOME

27. Within 1-year of the procedure
Spontaneous ovulation - 30-90%
Pregnancy rates - 13-88%
LOD alone is usually effective in <50% of women
In such cases, addition of CC and recombinant FSH (rFSH) may be considered after
3 and 6 months respectively
LOD also improves the sensitivity of the ovaries towards subsequent CC and FSH,
especially in those who are less hyperandrogenic and less insulin-resistant
Thessaloniki Fertil Steril. 2008;89:505–22
Bayram N et al,.BMJ. 2004;328:192
Mitra s et al., J Nat Sci Biol Med. 2015

28. LOD and IVF
Retroseptive study
Group I (n=150) : including PCOS women who had history of LOD at least 6
months to 3 years before IVF/ICSI
Group II (n=150) : including PCOS patients without history of drilling
Antagonist Protocol in all
Eftekhar M et al.,Int J Fertil Steril. 2016

29. LONG TERM EFFECT
• S.Amer et al., studied 116 anovulatory women with polycystic ovary syndrome
(PCOS) who underwent LOD between 1991 and 1999
• The LH:FSH ratio, LH, testosterone, free androgen index decreased significantly
after LOD and remained low during the medium- and long-term follow-up periods.
• Mean ovarian volume decreased significantly (P < 0.05) from 11 ml before LOD to
8.5 ml at medium-term and remained low (8.4 ml) at long-term follow-up
• The beneficial endocrinological and morphological effects of LOD
appear to be sustained for up to 9 years in most patients with PCOS
Human Reproduction Vol.17, No.11 pp. 2851–2857, 2002

30. LAPAROSCOPIC OVARIAN DRILLING
FAILURE
Laparoscopic ovarian drilling failure is defined as failure to ovulate within 6-8
weeks, recurrence of anovulatory status after an initial response or failure to
conceive despite regular ovulation for 12 months
LOD improves responsiveness of the polycystic ovaries to subsequent OI
agents, reintroduction of drug treatments (first CC and then gonadotrophins) and
possibly IVF can be considered in those do not spontaneously become pregnant
within 6 months after LOD once ovulation has been re-established or after 3
months when ovulation has not been detected
Amer SA. Recent Advances in Obstetrics and Gynaecology. 24th ed. London: Royal
Society of Medicine Press Ltd; 2009
Mitra et al.,Journal of Natural Science, Biology, and Medicine 2015

31. REPEATED LOD??..

32. overall (20) LOD sensitive (12) LOD resistant (8)
Ovulation rate 12 10 2
Pregnancy rate 10 8 1
Repeat LOD is highly effective in women who previously responded to the first
procedure, But not recommended.

33. COMPLICATIONS OF LOD
 Complications related toanaesthesia.
 Complications related toentry.
 Complications related to drillingitself.

34.  Bleeding from drillingsite
 Laceration of utero-ovarian ligament
 Useof excessiveamountof energywill destroy large
number of follicles resulting in decreased ovarian
reserve.
 Use of energy with electrode may cause desication of
hilarvessels, resulting in prematureovarian failuredue
to necrosis of ovary.
COMPLICATIONS RELATED TO DRILLING

35. ADHESION FORMATION
 Reported incidence of adhesion is from 0-70%
 Great diversity of rate of adhesion may be due to
variation in techniques & partlyon interpretation of
findings on secondlook
 Adhesion formation is more with LASERthan
electrocoagulation

36. • Post-operative adhesion rates - 0-100% (mean 35.5%, 95%ci: 30.8-40.4)
• Pregnancy rates -35-87% (mean 64.3% 95%ci: 58.2-70.7)
• No correlation between the adhesion rates and pregnancy rates (spearman's
rho=0.055, p=0.858)
• None of the preventive measures during or after the procedure were found to
be effective in reducing the rate of post-operative adhesions, thereby
increasing the pregnancy rates.
• The incidence of peri-adnexial adhesions after lod might not be associated
with adverse reproductive outcomes.

37. PREVENTION OF ADHESIONS
• Restriction in the number of punctures
• Use of an insulated needle
• Activation the coagulating current only after the needle is
inside the ovarian stroma
• Irrigation of the peritoneal cavity at the end of the procedure(↓
temperature)
• Creation of pseudo ascites
• Unilateral application of the procedure

38. OVARIAN DRILLING & POF
• Potential risk is POF
- The ovarian blood supply is damaged inadvertently
- Large number of punctures are made, leading to excessive destruction of
ovarian follicular pool
- Production of anti-ovarian antibodies
• A prospective comparative study found that the extent of ovarian tissue
damage was limited, ranging from 0.4% after four to 1% after eight
coagulation punctures, each of 40 W for 5 s
• Changes in ovarian reserve markers can be interpreted as normalization
of ovarian function rather than a reduction of ovarian reserve
• Preventive Methods : Coagulation should not be done within 8-10 mm of the
ovarian hilum, Unilateral drilling, Use of the harmonic scalpel, Use of bipolar
energy, <5 perforations with monopolar
Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus, Fertil Steril. 2008
Farquhar CM et al., Fertil Steril. 2002
El-Sheikhah A et al., J Obstet Gynaecol. 2004

40. TRANSVAGINAL
HYDROLAPAROSCOPY
 Advantage of the vaginal approach - the direct access to
the tubo-ovarian organs and the ovarian fossa without
use of any additionalmanipulation.
 Access to the pouch of Douglas is obtained through a
needle puncture technique of the posterior fornix.

41. TRANSVAGINAL
HYDROLAPAROSCOPY
ADVANTAGE DISADVANTAGE
• Rectal puncturing
• Adjusting to the viewing angle
of THL may be
disadvantageous for the initial
operations
• The orientation of the
structures is reversed from
laparoscopy
• Visual field is limited
 Safety of the transvaginal
access
 Scar less procedure
 Advantage in obesepatients
 Reduced risk of postoperative
adhesion.
 Very low morbidity
 Office setting procedure

42.  A specially designed laparoscopic instrument (Kayalaparoscopic
drilling device) was inserted through the 5-mm ancillaryport.
 This instrument is 37 cm long with a distal grasper-like tip
containing two prongs
 Each prong is 25 x 4 mm in area and consists of 10 needle-like
teeth, which are 2 mm in length and 0.4 mm in diameter.
 The maximum opening distance achieved between the two rows of
teeth is 30 mm
 Ovarian tissue was placed between the jaws of theinstrument
and squeezed by applying someforce
 The instrument was slipped over to the neighboring untreated
ovarian tissue, its jaws closed again, and consequently the entire
ovarian surface was subjected to this procedure
LAPAROSCOPIC OVARIAN
MULTINEEDLE INTERVENTION (LOMNI)

43. Hakan Kaya et al. Journal of Minimally Invasive Gynecology (2005)

44. LAPAROSCOPIC OVARIAN
MULTINEEDLE INTERVENTION
(LOMNI)
ADVANTAGES
 Need for electrosurgery or
laser is eliminated, decreasing
the cost and possibly
preventing adhesion
formation.
 Although squeezing of ovarian
tissue during our technique
might destroy some ovarian
tissue, the extent of destruction
might be expected to be lower
than the other techniques, which
might yield relatively
uncontrolled energy forms.
LIMITATIONS
• A limitationof the instrument is
the 2-mm needle length
indicating superficial
penetration of the ovarian
tissue. Abnormal follicles
below that level might not be
drained

45.  The idea of needle drilling came through the
observation of improved ovarian performance in
patients with PCOS after previous follicular aspiration for
IVF trials.
 Transvaginal ultrasound-guided follicular aspiration in
the midluteal phase for all persistent follicles.
ULTRASOUND-GUIDED
TRANSVAGINAL NEEDLE OVARIAN
DRILLING(UTND)
Mio Y et al. FS1991

46.  Procedure - under generalanesthesia with Propofol ,
using a 16-gauge, 35-cm long sharp needle connected
to a continuous manual vacuum pressure.
 Number - Different angles with between 3-6 punctures
 All the small follicles visible by ultrasound were aspirated.
ULTRASOUND-GUIDED TRANSVAGINAL
NEEDLE OVARIAN DRILLING(UTND)

48. PCOS : FERTILITY RX
• FIRST-LINE TREATMENT :
• LETROZOLE
• ANTI-ESTROGEN CLOMIPHENE CITRATE (CC)
• SECOND-LINE INTERVENTION:
• LETROZOLE + METFORMIN
• EXOGENOUS GONADOTROPHINS
• LAPAROSCOPIC OVARIAN SURGERY (LOS)
• CC + METFORMIN (IF NOT USED)
• THIRD-LINE TREATMENT : IVF

49. Yiping Yu et al., NATURE SCIENTIFIC REPORTS: JUNE 2017

50. Yiping Yu et al., NATURE SCIENTIFIC REPORTS: JUNE 2017

51. • The network meta-analysis demonstrates that hMG therapy result in
higher pregnancy rates than BLOD, ULOD and CC therapies.
• Pregnancy, live birth and ovulation rates are significantly higher in
metformin+letrozole and FSH groups than CC group.
• The abortion rate in the metformin+letrozole group is significantly lower
than that in the metformin+CC group.
• Ranking probabilities show that, apart from gonadotropin (FSH and
hMG), metformin+letrozole is also potentially more effective in improving
reproductive outcomes than other therapies.
• In conclusion, owing to the low quality of evidence and the wide
confidence intervals, no recommendation could be made for the
treatment of ovulation-induction in patients with CCR PCOS.
Yiping Yu et al., NATURE SCIENTIFIC REPORTS: JUNE 2017

52. TAKE HOME MESSAGE….
 The MAIN INDICATION for LOS is CC resistance in women with
anovulatory PCOS
o young age
o raised LH levels
o exaggerated response to gonadotropins
o noncompliance or nonfeasibility with frequent, intensive monitoring
o needing laparoscopic assessment of the pelvis
 Monopolar diathermy is the most widely used technique, although no
technique is superior
 LOS can achieve unifollicular ovulation with no risk of OHSS or high-
ordermultiple pregnancy
 Despite all its advantages it should be kept in mind that after all it’s a
surgical procedure which has its own risks.
 Proper & meticulous surgical technique will help in avoiding damage
to normal ovarian tissue and interm avoid premature ovarian failure
and long term adhesion formation
 LOS should not be offered for non-fertility indications