Surgical induction of ovulation 2017

2. Prof. Mahmoud Zakherah
Prof of Obstetrics and Gynecology,
Women’s Health Hospital Assiut
mszakhera@gmail.com
2017

3. Definitions
Infertility
Subfertility
Sterility

4. Physiological backgrounds
Hypothalamus
Gonadotrophin-releasing
hormone (GnRH)
pulsatile secretion
Pituitary
FSH
LH
Prolactin
Ovary
Estradiol
Progesterone
AMH

5. Physiological backgrounds
Menstrual cycle Ovarian cycle

6. Ovarian cycle
Recruitment
Selection
Dominance
Ovulation
 Estradiol surge 36h
 LH surge- 36h -+ve feedback mechanism
 Ovulation------fertilization—implantation

7. Ovarian cycle
Unripe
follicle
Ripening
follicle
Ovulation Corpus
luteum
Regression of
Corpus luteum

8. Etiology of infertility

9. Ovulatory disorders
Ovulatory disorders are a common
cause of infertility 20% , which in most
cases is treatable with ovulation
induction agents.
 The goal of therapy in these women is
monofollicular development and
subsequent ovulation.

10. Ovulatory disorders
The method of ovulation
induction selected by the clinician
should be based upon the
underlying cause of anovulation
and the efficacy, costs, risks, and
potential complications associated
with each method as they apply to
the individual woman.

11. Diagnosis of Ovarian factor

12. Diagnosis of Ovarian factor
Investigations
Ovulation monitoring: (transvaginal
sonography (follicle 18mm) U/S:
folliculometry
Midluteal progesterone: (day 21) >3 ng/ml,
>10 ng/ml
Premenstrual biopsy : (PEB): Secretory
changes (not done)---???????
Endometrial scratching

13. Ovulation monitoring
Folliculometry Trilaminar endometrium

14. Anovulation

15. WHO Classification of Anovulation
WHO type 1 (hypogonadotropic hypogonadism),
can be caused by any lesion affecting the pituitary or
hypothalamus and affecting gonadotropin
production
WHO type 2 (normogonadotropic hypogonadism)
is by far the commonest cause of anovulation and is
most commonly caused by polycystic ovarian
syndrome.
WHO type 3 (hypergonadotropic hypogonadism)
is usually an indication of ovarian failure.

16. WHO Group II (hypothalamic
pituitary dysfunction (70 to 85%(
Hypothalamic pituitary dysfunction
Eugonadotrophic=Normogonadotrophic
This includes a heterogeneous group of patients who
can present either with regular cycle
oligomenorrhoea, or even amenorrhoea.
The midluteal serum progesterone is low, FSH levels
are in the normal range and prolactin is normal.
Most of these patients are likely to have PCOS.

17. WHO Group II (hypothalamic
pituitary dysfunction (70 to 85 %)
Treatment
I-Non pharmacologic
Weight loss and exercise life style modification
II–Pharmacologic
Antiestrogens as CC tamoxifen or combination
Human gonadotrophins
Insulin sensitizers
Dopamine agonists
Aromatase inhibitors
III - Surgical induction of ovulation
(LOD)

18. Surgical
Induction of
Ovulation

19. P C O
S
PCOS is a heterogenous
disorder.
Clinical verities.
Wedge resection 1935.
CC 1960.
LOD Gjönnaess 1984

21. Women with polycystic ovary syndrome who have
not responded to clomifene citrate 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 level (A) evidence

22. Normal ovary
A N
Normal Ovary measures an average of 6.5ml (5.4-7.6ml) in premenopausal
women

24. Laparoscopic Ovarian Drilling (LOD(

25. Mechanism of action of LOD
The mechanisms of action are not understood
 Placebo effect(Aono et al, 1976)
Destruction of androgen producing ovarian stroma
Correcting abnormal ovarian pituitary feedback (Balen and
Jacobs, 1994)
VEGF and IGF-1, which are typically increased in patients
with PCOS(Amin et al,2003)
Reduction of ovarian inhibin with a resultant rise in
FSH ????(Amer et al,2007 found no change)

26. Mechanism of action of LOD
Puncturing of follicles androgens .
 Crowding of follicles.
 LH FSH

27. Not HOW but WHY

28. Indications of LOD
CC resistant PCOS
Persistent high LH
Intolerable side effects of drugs as
CC and HMG.
Other indications of laparoscopy.
No available or feasible
monitoring .

29. Indications of LOD
Decrease OHSS in ART cycles.
(Amer et al,2007
Recurrent miscarriage ? High LH.
Prevention of long term
morbidity (metabolic and
cardiovascular risks found no
benefit ).

30. Advantages of LOD
Single action.
No intense monitoring.
Less expensive than gonadotropins
Monofollicular ovulation
No risk of multiple pregnancy.
Less OHSS
Less RPL due to effect on LH
Long lasting effect 12-18 mo. .

31. Evolution of Surgical management of PCOS
Initially , laparoscopic wedge resection
 Biopsy (celioscopic ovarian resection) multiple
small ("punch") biopsies of the ovarian surface
(Sumioki, 1988).
] Laparoscopic ovarian diathermy (Gjonnaess ,
1984). Needle point electrode (drilling), (4-10
points (92%-69%).
Laser vaporization or photo-coagulation
(Daniell, 1989)

32. Evolution of Surgical management of PCOS
Transvaginal ultrasound follicular
aspiration (Maio et al , 1991).
Cryocautery ( Ali ,1992 ).
Bipolar diathermy of PCO (Kovacs, 1993).
Endo coagulation (Amin,1994).

33. Evolution of Surgical management of PCOS
Unilateral ovarian drilling (Balen and Jacobs,1994).
Single Puncture Electrocoagulation of Ovarian Stroma
"SPECOS“ Shawki,1996
Transvaginal ultrasound-guided electrocautery
(Syritsa,1998)
Removing one ovary (Kaaijk, 1999).
Transvaginal hydrolaparoscopy (Gordts et al,2009,fertil
steril).
Single port laparoscopic surgery LOD (2010)

34. UNILATERAL VERSUS BILATERAL LAPAROSCOPIC OVARIAN DRILLING (LOD) IN WOMEN
WITH POLYCYSTIC OVARIAN SYNDROME (PCOS): A RANDOMIZED CLINICAL TRIAL
Alaaeldin A. Youssef (MD), Mahmoud S. Zakherah
(MD), Esam A. Khalifa (MD), Ahmed F Amin
(MD)and Mohamed MF Fathalla (MD)(2003)
Conclusions : Unilateral LOD is as effective as
bilateral LOD as regards resumption of regular men-
strual cycles, ovulation and pregnancy rate, and en-
docrinological changes. Unilateral LOD is superior to
bilateral LOD, it has the advantages of less ther-mal
damage to the ovaries, shorter operative time and less
CO2 consumption and fewer incidences of postoperative
adnexal adhesions.

35. Methodology of Ovarian Drilling
Preoperative requirements
Documented PCOS (clinical, hormonal and
sonographic). Rotterdam2004-AES 2009
Clomiphene resistance 150mg 3cycles
Normal prolactin or treated.
Inability or unwilling to undergo gonadotropin
therapy
Normal endometrial cavity with patent tubes(HSG).
Normal semen analysis

36. Documented PCOS

37. TVS LAPAROSCOPY
Documented PCOS

38. Methodology of Ovarian Drilling
Operative requirements
Extended lithotomy position
General endotracheal anesthesia - Spinal ??
 10mm or 5mm telescope Angle Zero
Video assisted triple puncture laparoscopy
High flow CO2 insufflator
Atraumatic grasper .
Monopolar needle

39. Methodology of Ovarian Drilling
Instillation of Ringer’s lactate (300
ml) into the pouch of Douglas to
enhance ovarian cooling after
drilling {hydrocortisone+Heparin}
Grasping of the ovarian ligament or
flipping over the ovary,
The ovary is lifted then rotated and
then puncture.

40. Methodology of Ovarian
Drilling
Unipolar current is advised in a cutting
mode to minimize thermal damage; the
power is activated just before touching the
ovary (Corson needle) (Bipolar-LASER
may be used ).
Antimesenteric border perpendicular
The number of cauterization points
depends on the ovarian volume (4-10
punctures).

41. Methodology of Ovarian Drilling
Avoid cauterization at
Mesovarium
Hilum
Corpus luteum
Ovarian ligament
Infudibulopelvic ligament

42. How many punctures?
How many punctures

43. How many punctures?
Too little is insufficient
Too much is harmful
The solution is : Adjust

44. How many punctures?
In earlier studies
(Gjonnaess,1989) there was an
assumption that the greater
the amount of energy, the
more effective the procedure.

45. How many punctures?
Later on, lower thermal doses through
use of a fixed number of puncture points
regardless of ovary size (Felemban et
al,2000) or unilateral ovary cauterization
had been reported, aiming to decrease the
potential risks of ovarian failure and
adnexal adhesions (Balen and

46. How many punctures?
Rule of Four
40 W-4 seconds-4 puncture points(rule 0f 4).
After diathermy, each ovary should be lowered into
the pool of saline.
No coagulation should be done within 1 cm from
the helium.
At the end of the procedure both ovaries should be
irrigated with Ringer's lactate.
 It was concluded that “the solution to pollution is
dilution“.

48. How many punctures?
Zakherah et al 2010, concluded
that adjusted diathermy dose based
on ovarian volume for laparoscopic
ovarian drilling of polycystic ovary
syndrome has a better reproductive
outcome compared with fixed
thermal dosage.

49. Adjusted LOD
New terminology
Means tailoring the number of punctures
according to Ovarian Volume (Zakherah et al ,2011)

51. Adjusted LOD
Because we were planning to use the least
effective dose, our suggested dose was 625
J/10.8 cm3
= 60 J/cm3
of ovarian tissue. The
required number of punctures then was
calculated by dividing total individual
ovarian dose with dose delivered in each
puncture point. ( e.g. 12 cm3
x60=720 j
÷150=4.8 punctures)

52. Adjusted LOD
LOD using a thermal dose of 60 J/cm3
(adjusted LOD) has a better reproductive
outcome compared with fixed thermal dosage
of 600 J per ovary in treatment of patients with
PCOS with CC resistance.
Adjusted ovarian drilling based on ovarian
volume has no detrimental effect on the
ovarian reserve

53. Predictors of the outcomeClinical predictors
Marked obesity(BMI≥35)
History of infertility >3 years .
Biochemical predictors
 High LH levels≥10IU)
Marked hyperandrogenemia.
Insulin resistance
(Amer et al,2004)

54. 2014

55. Outcomes of Ovarian Drilling
Clinical Outcome of Ovarian Drilling
Restoration of regular menstruation in approximately 80%.
The mean ovulation rate was 70% and the cumulative
pregnancy and live birth rate was 76% and 64% ,
respectively (Bayram et al,2004)
Miscarriage rate is similar to general population .
Reproductive performance seems to last for may years in
about one third of cases (Amer et al,2002).

56. Outcome of Ovarian Drilling
Hormonal Changes After Ovarian Drilling
 Decline in the LH levels
Decrease in androgens (testosterone and
androstenedione) (Armar etal,1990)
Increase in serum prolactin
 Rise in FSH levels ?(Api ,2008=no change )
Gjonnaess (1998) concluded that ovarian electrocautery
for PCOS normalizes ovarian function including
androgen production, and these results seem to be
stable for 18-20 years

58. Unilateral versus Bilateral
Unilateral as effective as bilateral
Contralateral ovary may ovulate first
(Al-Mizyen and Grudzinskas 2007)

59. Complications of ovarian drilling
A part from the need of surgery under general
anesthesia and the risk of any surgical procedure
1- Pelvic adhesions
Adhesion formation rates following laparoscopic ovarian
drilling ranged from zero (Daniell and Miller, 1988) to
100% (Greenblatt and Casper, 1987).
Lt more prone to adhesions
The mean adhesion score of the patient treated with
CO2 laser was significantly higher than that treated
with electrocautery (Cohen, 1995).

60. Complications of ovarian drilling
Factors influencing adhesion formation
Thermal dosage
(So the reduction in damage was produced by
unilateral ovarian drilling (Roy et al ,2009)may
reduce the postoperative adhesion formation).
Armor recommend 4p-40ws-4 sec
stromal not surface –perpendicular
Pelvic lavage and induction of artificial ascites
“the solution to pollution is dilution“
200 Hartmann’s-cooling

62. Complications of ovarian drilling
2- Ovarian atrophy and premature ovarian failure
Ovarian atrophy has been reported by Dabirashrafi
(1989) as a complication of excessive drilling of polycystic
ovaries.
It is therefore advised that no coagulation should be
done within 1 cm of the ovarian helium, the number of
cauterization points should be individualized according
to the ovarian size and the wattage chosen should
depend on the thickness of the ovarian capsule .

63. Is ovarian reserve diminished after laparoscopic
ovarian drilling?
The PCOS women both with and without LOD had
significantly greater ovarian reserve than the age-
matched controls having normal ovulatory menstruation
(Weerakiet et al ,2007).
 LOD, if applied properly, normalizes the exaggerated
ovarian morphologic and endocrinologic properties.
(normalization of ovarian function rather than a
reduction of ovarian reserve )(Api,2009)

64. .

65. The impact of laparoscopic ovarian drilling on
AMH & ovarian reserve: a meta-analysis April
2017Saad A Amer1, Tarek T El Shamy2, Cathryn James, Ali
H Yosef , Ahmed A. Mohamed,
LOD significantly lowers circulating AMH, but this
may not necessarily reflect a real damage to
ovarian reserve. Given its proven efficacy and its
long-term benefits, LOD should remain as an
option in the management of anovulatory PCOS
patients.

66. How to avoid DOR
Adjust
Cutting mode
Short time
Low wattage
Lavage
Unilateral
Never drill

67. Complications of ovarian drilling
3- Epithelial ovarian tumors
There is a theoretical concern that ovarian drilling may
increase the incidence of epithelial ovarian tumors
There is no long-term follow-up to evaluate this
association

68. LOD Vs Gonadotropin therapy
NO difference in the live birth rate and miscarriage rate
in women with Clomiphene-resistant PCOS undergoing
LOD compared to gonadotrophin treatment.
The reduction in multiple pregnancy rates in women
undergoing LOD makes this option attractive. However,
there are ongoing concerns about long-term effects of
LOD on ovarian function. Farquhar et al,2007. Cochrane
Database Syst Rev. 2007).

69. Failed LOD 20-30% of anovulatory women with PCOS
failed to respond to LOD (Farquhar,2004).
Insufficient thermal dosage
Inherent resistance ovary to the effects of
drilling.
post-operative adhesion
Hyper prolactaenaemia observed in some
patients after LOD

70. Adjuvants after ovarian drilling
CC or low dose gonadotropins
NAC is a novel adjuvant therapy after unilateral
LOD which might help improve overall reproductive
outcome (a pilot study ) (Nasr A,2010).
Metformin increases the ovulation and
pregnancy rates in infertile women, following
LOD(Kocak and Ustün ,2006).
Weight reduction.
IVF.
Repeat LOD ,we will add more complications

71. Repeated LOD in polycystic ovary
syndrome
Repeat LOD is highly effective in women
who previously responded to the first
procedure (Amer ,et al ,2003).
DO NOT Repeat
You will repeat failure
After 1 y follow up IVF
Antagonist Vs Long protocols

72. Current status in LOD
LOD may be preferred as 2nd
line
therapy (Amer,2008)
 LOD and gonadotropins have been
shown to be equally effective in
ovulation and pregnancy rates(Farquhar
et al,2005). (Moderately quality
evidence)

73. The Society of Obstetricians and
Gynecologists of Canada 2010
1-Weight loss, exercise, and lifestyle modifications
have been proven effective in restoring ovulatory cycles
and achieving pregnancy in overweight women with
PCOS and should be the first-line option for these
women. (II-3A).
2. Clomiphene citrate has been proven effective in
ovulation induction for women with PCOS and should
be considered the first-line therapy.. (I-A)

74. The Society of Obstetricians and
Gynecologists of Canada 2010
3-Metformin may be added to clomiphene citrate in women
with clomiphene resistance who are older and who have
visceral obesity (I-A).. Metformin combined with
clomiphene citrate may increase ovulation rates and
pregnancy rates but does not significantly improve the live
birth rate over that of clomiphene citrate alone (I-A) .
4. Gonadotropins should be considered second-line
therapy for fertility in anovulatory women with PCOS. The
treatment requires ultrasound and laboratory monitoring.
High costs and the risk of multiple pregnancy and ovarian
hyperstimulation syndrome are drawbacks of the treatment
(II-2A).

75. The Society of Obstetricians and
Gynecologists of Canada 2010
5. Laparoscopic ovarian drilling may be considered
in women with Clomiphene-resistant PCOS,
particularly when there are other indications for
laparoscopy. (I-A)
Surgical risks need to be considered in these patients.
(III-A).
6. In vitro fertilization should be reserved for women
with PCOS who fail gonadotropin therapy or who have
other indications for IVF treatment (II-2A).

76. is it time to relinquish the
procedure?
1. LOD is a safe and cost effective procedure.
2. A single treatment results in uni- follicular
ovulation.
3. No need of continuous monitoring as seen
with hormonal treatment.
4. No fear of multiple births and ovarian
hyper stimulation.
5. LOD increase the sensitivity to
gonadotrophins and it is as effective as
gonadtrophins in PCOS

77. 2016

78. Conclusion
Surgical treatment of PCOS
not recommended to be the
first line of treatment but are
advisable for clomiphene
resistant cases, as they are
not free of adverse effects.

80. Never DrillOvarian volume less than 10
cm3.
FSH more than 9 IU/L
Previous ovarian drilling
.except
AMH less than 5 ng/ml
Only used as a 3rd
line therapy