Tremendous advances and extensive human studies have uncovered the complexity and management of PCOD Global prevalence -2.2% to 26% Roughly 1 in 15 women worldwide, (Lancet, 2007) 

1. How are they different ??
Difficulties & Solutions made Easy
Dr. Sharda Jain
Dr. Jyoti Agarwal

3. Tremendous advances and extensive
human studies have uncovered the
complexity and management of PCOD

4. Global prevalence -2.2% to 26%
Roughly 1 in 15 women worldwide, (Lancet, 2007)
36% of women in
India are suffering
from PCOS
Indian J Pediatr. 2012 Jan;79 Suppl 1:S69-73. J Pediatr Adolesc Gynecol. 2011 Aug;24(4):223-7
50 % presents with infertility
50 % presents with recurrent miscarriages

5. PCOD is a Metabolic Syndrome
with Huge Reproductive
Implications
Huge impact on the
reproductive , metabolic , and
cardiovascular health of affected
girls and women

6. THREE MAJOR CULPRITS
Central player : Insulin Resistance
• Hyperandrogenism
• Altered Gonadotropins
• Recently Target Genes
All interact with each other

7. Clinical manifestation of PCOD
Acne ObesityHirsutismAcantosis
Infertility
HAIR LOSS
IRREGULAR MENSES

8. Her primary concern is
- INFERTILITY
- Early pregnancy loss
- She wants
Baby
Baby
Baby …

9. Obesity
Pre-Diabetes
Hypertension
Fatty Liver
Diabetes type II Dyslipidemia
Insulin Resistance Hypo-Thyroidism
Metabolic Syndrome Vitamin-D deficiency
It is Good to rule out & counsel
problems of …… before start
infertility treatment

10. Obesity is seen in more than 50 % of
women with PCOS
Patients of BMI > 27.5 kg/m2
are likely to take longer to conceive
So it is good to lose weight by
structured weight loss programme
Over weight BMI > 22.5
Obese BMI > 27.5
Severe Obese BMI > 32.5
Morbid Obesity BMI >37.5

11. Methods of weight reduction
follow a pyramidal approach
• Diet and life style modification
• Anti obesity drugs _ banned world wide
•Bariatric surgery
(Definitely good option for severe and morbidly obese )

12. Diet management
Eat small meals at
regular intervals
Eat fruits, vegetables,
beans,whole grains,
fish, nuts and seeds in
plenty
Limit sugars and salt
intake
Avoid saturated fats &
carbohydrates
Early dinner
Nothing in the mouth
after 7 pm

13. Daily moderate exercise for 40 – 60 min
improves body's use of insulin and can help
relieve symptoms of PCOS
Running/Jogging
Chakki Chalanasana

14. Let zumba fitness
Be your stress reliever &
An effective way to reduce weight

15. As little as 5% of initial weight loss
over 6 months improves
fertility outcome

16. Sleeve Gastrectomy &
Gastric Bypass surgery
are done routinely
Pregnancy should be delayed in the first year
Bariatric Surgery
Significant and sustained
weight loss of 40-50 kg is expected

17. FIRST LINE
CLOMIPHENE CITRATE
SECOND LINE
LOD/GONADOTROPINS
THIRD LINE
IVF
R
E
S
I
S
T
A
N
C
E
R
E
S
I
S
T
A
N
C
E
F
A
I
L
U
R
E
The Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop
Group March 2–3, 2007, Thessaloniki, Greece.
Human Reproduction 2008
INFERTILITY GUIDELINE FOLLOWED WORLD OVER

18. AIM - Optimal Ovarian Stimulation for IVF
Be careful to :
• Avoid understimulation
• Avoid overstimulation
• Minimize cycle cancellation
• Avoid OHSS altogether
OI in PCOS is a big challenge
OPTIMAL STIMULATION
OVER STIMULATION
UNDER STIMULATION

19. Drugs used to stimulate ovaries
alone or in combination
• Clomiphene citrate
• LETOVAL/ANASTRIZOLE
(ADDOVA)
• Tamoxifen
Gonadotropins
Purified FSH
Highly Purified FSH
rFSH / RLH
hMG
• LOD
• IVF
Life style modification

20. Recommended First Line
treatment for OI
remains Clomiphene Citrate
• Simple to use
• Minimal side effects
• Cost effective

21. Clomiphene citrate
• Starting Dose 100mg
day 2 onwards for 5
days
• Max to 150 mg
• If ovulation confirmed ,
maintain same dose
• Side effects
• Hot flushes , bloating ,
dryness of vagina ,
headache , abdominal
distension , visual
symptoms ,and ovarian
hyperstimulation
In the presence of visual problems (scotomas) CC
should be discontinued promptly

22. Monitoring by serial sonography is a must

23. Are we happy with
clomiphene ????

24. • 70% to 90 % will
ovulate
• 40 % will become
pregnant
• 75 % of conceptions
occur during first
three cycles
Y
e
s

25. No
• Its antiestrogenic action causes poor / delayed
endometrial growth and hostile cervical mucus
• Its presence at the time of ovulation inhibits
progesterone formation by granulosa cells in luteal
phase
•
•Start early in cycle – Day 2 or Day 1
• Longer CC free peroid before ovulation
• Higher pregnancy rates

26. Clomiphene and ovarian malignancy
• When used only for 6 cycles , the risk of
ovarian cancer will not exceed that of other
women
But
• More than 12 cycles of use in a life time is
associated with three fold increase in
risk of ovarian cancer.
N Engl J Med 1994; 331(12):771-6

27. Options for women
not responding to CC include
• Extended use of clomiphene citrate
• Using letrazole , Anastrizole (ADDOVA) , Tamoxifen
• Pretreatment with oral contraceptives
• Adding dexamethasone in hirsutism hyperandrogenemia
• Concomitant use of insulin sensitizers
• Cabergoline in patients with hyperprolactenemia
• Gonadotropins
• Laparoscopic drilling

28. Off Label Drugs for OI
• Letrozole/Anasetrazole
non steroidal selective
estrogen enzyme modulator
• Brings about
monofollicular growth
• Prevents premature surge
Tamoxifen
• 20-40 mg/day x 5 days
max 60 mg/day
• No anti-estrogenic effect
on endometrium
• Ovulation rates 65 -75%
• Pregnancy rates 30 - 35%

29. Insulin sensitizers : Metformin
Cochrane review Jan 2008 : metanaylsis
• Metformin combined with CC is more
effective in OI as compared with CC alone
in obese & CC resistant cases
• Cheaper option than LOD
• Co administration prevents hyperstimulation

30. Metformin has an excellent safety
profile , categoy B drug in pregnancy
• 500 to 850 mgm three times a day
• S/E ….. diarrhoea, nausea, vomiting
• To avoid them metformin should be taken
with meals and the dose increased gradually
• Monitor renal function

31. Evidence Based Medicine
• Use of metformin in PCOS should be restricted to
those patients with glucose intolerance
ESHRE/ASRM-Sponsored PCOS Consensus
Workshop *,2007, Thessaloniki, Greece
• Metformin may be added to CC in women with
clomiphene resistance who are older and have
visceral obesity (I-A)
SOGC guidelines, 2010

32. Comparison in Asian women with
PCOS
OI - 23.7 % Met alone
- 59 % CC alone
- 68 % in combined grp
PR - 7.9 % ,
- 15.4 %
- & 21.1 % respectively
Fertil Steril
2008

33. OTHER DRUGS WHICH CAN BE USED
• Rosiglitazone
• Pioglitazone
• Myo inositol
• D chiro inositol
• N acetyl cysteine
• Combination with vitamin D3 and melatonin
• Combinations with other micronutrients
NEEDS BIG RANDOMISED TRIALS

34. Gonadotropins : second line of Rx
Today recent advances
and better technology
has given us safe and
effective gonadotropins
with higher pregnancy
rate , lower abortion
rate and lower risk of
hyperstimulation
• Effective daily dose
of gonadotropins
• Age
• Weight
• Day 2 FSH
• Antral follicle index
• AMH

35. Dosage Of Gonadotropins
Age PCOS-FSH
hyperresponder
Normal
responder
<30yrs 37.5/50/75 iu 150iu
30-35 yrs 75/100iu 150iu
>35yrs 150iu 225iu

36. Which gonadotropins in PCOS?
hMG OR recFSH
• Elevated LH is frequently encountered in PCOS
• Excessive LH secretion with detrimental effects
on reproductive function
• Use of FSH-only products rather than hMG
seems more logical
Balasch, Reproductive BioMedicine Online;February 2003

37. Days 7 14 21 28
hCG
150 IU 112.5 IU 75 IU hCG
Foll.  10 mm
75 IU112.5 IU 150 IU
6 12
75 IU hCG
Foll.  14 mm
½
Which Protocol should be used in PCOS ?
75 IU 112.5 IU 150 IU
Step
up
Step down
Sequential

38. LOD appears to be as effective as routine
gonadotropin therapy in the treatment of
clomiphene-insensitive PCOS
Drilling of follicles
releases androgen rich
follicular fluid and
decreases androgen
producing stroma
Indications
• CC Resistance
• Pts. who persistantly
hypersecrete LH
Complications
Haemorrhage, bowel
injury, adhesions,
premature menopause

39. Results of therapies for ovulation induction
and pregnancy rate in pcos patient
Therapeutic
option Ovulation % Pregnancy %
Multiple
Pregnancy %
Spont .
Abortion %
Clomiphene 80 40 8 – 10 20 – 25
Gonadotropin 80 -99 40 – 70 15 – 25 20 – 25
LOD 70 -90 44 – 66 2 20
Metformin
+ Clomiphene
27 – 96
(75)
30 – 60
(58)
_ _

40. 33 – 50 % of patients
will need IVF
Donot waste time
Early referral should be in mind

41. IVF STIMULATION PROTOCOLS IN
PCOS PATIENT
• Stimulation in PCOs is a
problem
• Response is not predictable
• Dose is not predictable
• Poor responders/ hyper-
responders
• Number of days of
stimulation is not
predictable.
• Decreased fertilization rate
• Control over the cycle is
difficult.

42. RESPONSE OF PCOS TO
STIMULATION
High order multiple pregnancy rate increased
OHSS is a Real
Problem

43. Mortality due to critical
OHSS in IVF
is totally Unacceptable
DEVROEY 2011

44. 44Dr Razia S
WE SHOULD ALL AIM FOR
OHSS FREE ART CLINICS

45. We have given up Agonist protocol in PCOD patients
Fragmentation of IVF
• All PCOD patients are taken for antagonist
protocol to minimise risk of OHSS
• Ovulation triggering with GnRH agonist instead
of HCG trigger
• Freeze all embryos & do ET in next cycle or do
blastocyst transfer
Zero % OHSS

46. During pregnancy
She is at high risk for
• Miscarriages
• Gestational
diabetes
• PIH
• Preterm
• IUGR / IUD

47. FIRST LINE
CLOMIPHENE CITRATE
SECOND LINE
LOD/GONADOTROPINS
THIRD LINE
IVF
R
E
S
I
S
T
A
N
C
E
R
E
S
I
S
T
A
N
C
E
F
A
I
L
U
R
E
In conclusion