This is based on International guidelines on PCOS management. This was moderated by Dr Rajesh & Dr Rakhi Gajbhiye

1. Panel Discussion on Ovulation
Induction In PCOS
DR Rajesh Gajbhiye
Dr Rakhi Gajbhiye
Consultant Gynaecologists,Mauli Women’s Hospital
Nagpur

2. INTRODUCTION
✤ PCOS is the most common endocrinopathy among
the reproductive age group women.
✤ It affects about 12%-21%
✤ Commonest cause of normogonadotropic
anovulation
91% of WHO II cohort.

4. 1st line non pharmacological
Management
Lifestyle Interventions
✤ Weight reduction(5-10%),international guidelines.
✤ Exercise-50 min mod intensity
✤ diet

6. What investigations prior to OI?

7. ✤ TSH,OGCT,Fasting insulin
✤ AMH,Free testosterone
✤ USG for AFC and other pathologies.
✤ Day-2 -FSH, LH,Prolactin
✤ Tubal Patency
✤ HSA

10. Predictive markers for ovarian
response ?

11. Predictive marker for ovarian
response
✤ Pt AMH AFC
✤ PR 0.7-1.36 5-7
✤ NR 1.5-3.4 8-14
✤ HR >3.5 >15

13. First Line Management

17. ✤ LETROZOLE: Should be considered first line Tt for
OI in PCOS to improve ovulation, pregnancy and
live birth rates. (International Guidelines)
✤ Monofollicular growth
✤ No antiestrogen action on endometrium and cervical
mucus
✤ Live birth rate is increased
✤ Letrozole resistance is very less

18. Clomiphene citrate and metformin (Guidelines)
Clomiphene citrate could be used alone in women with PCOS to improve ovulation
and pregnancy rates.
Metformin could be used alone in women with PCOS, women should be informed that
there are more effective ovulation induction agents.
Clomiphene citrate could be used in preference, when considering clomiphene citrate or
metformin for ovulation induction in women with PCOS who are obese (BMI is ≥ 30
kg/m2) with anovulatory infertility and no other infertility factors.
If metformin is being used for ovulation induction in women with PCOS who are obese
(BMI ≥ 30kg/m2) with anovulatory infertility and no other infertility factors, clomiphene
citrate could be added to improve ovulation, pregnancy and live birth rates.
Clomiphene citrate could be combined with metformin, rather than persisting with
clomiphene citrate alone, in women with PCOS who are clomiphene citrate-resistant,
with anovulatory infertility and no other infertility factors, to improve ovulation and
pregnancy rates.
The risk of multiple pregnancy is increased with clomiphene citrate use and therefore
monitoring needs to be considered.

20. Metformin with Gonadotrophins
In patients with CCR-PCOS undergoing ovulation induction
with gonadotrophins, the addition of metformin increases
the rates of clinical pregnancy and live birth and reduces the
cancellation rate.
§ In patients with PCOS undergoing assisted reproduction
technniques, metformin co-treatment reduces the OHSS risk
and increases the pregnancy rate. No evidence exists of
reduced spontaneous abortion risk in women with PCOS who
have undergone pre-gestational metformin tretment.
§ No evidence exists of increased risk of major anomalies
in women with PCOS undergoing metformin treamtent during
the first trimester.
§ Adequately powered RCT are needed to evaluate the
efficacy of metformin treatment in different PCOS phenotypes.
RBM online 2016

21. Second line management

23. Individualised controlled ov
stimulation(ICOS)

24. The starting dose for gonadotropin is based on
• age
• body mass index (BMI)
• existence of PCOS,
• previous history of OHSS
or high response.

25. FSH-ur/recom
HMG/FSH

26. Choice of FSH
Urinary or recombinant follicle stimulation hormone can be
used in women with PCOS undergoing controlled ovarian
hyperstimulation , with insufficient evidence to recommend
specific follicle stimulating hormone (FSH) preparations.

27. Systematic reviews and meta-analysis have demonst

28. Gonadotrophins
Gonadotrophins could be used as second line pharmacological agents in women with PCOS
who have failed first line oral ovulation induction therapy and are anovulatory and infertile,
with no other infertility factors.
# Gonadotrophins could be considered as first line treatment, in the presence of ultrasound
monitoring, following counselling on cost and potential risk of multiple pregnancy, in
women with PCOS with anovulatory infertility and no other infertility factors.
Gonadotrophins, where available and affordable, should be used in preference to clomiphene
citrate combined with metformin therapy for ovulation induction, in women with PCOS with
anovulatory infertility, clomiphene citrate-resistance and no other infertility factors, to
improve ovulation, pregnancy and live birth rates.
Gonadotrophins with the addition of metformin, could be used rather than
gonadotrophins alone, in women with PCOS with anovulatory infertility, clomiphene
citrate-resistance and no other infertility factors, to improve ovulation, pregnancy and live
birth rates.
Either gonadotrophins or laparoscopic ovarian surgery could be used in women with PCOS
with anovulatory infertility, clomiphene citrate-resistance and no other infertility factors,
following counselling on benefits and risks of each therapy.

31. Second line -Laparoscopic Ovarian
Drilling

33. lap ov drilling ?
✤ CC Resistance
✤ LH hypersecretion
✤ PCOS pts require assessment of pelvis

34. . Laparoscopic ovarian surgery (Guidelines)
Laparoscopic ovarian surgery could be second line therapy for
women with PCOS, who are clomiphene citrate resistant, with
anovulatory infertility and no other infertility factors.
Laparoscopic ovarian surgery could potentially be offered as
first line treatment if laparoscopy is indicated for another
reason in women with PCOS with anovulatory infertility and
no other infertility factors.
Risks should be explained to all women with PCOS
considering laparoscopic ovarian surgery. Where laparoscopic
ovarian surgery is to be recommended, the following should be
considered:

35. ● comparative cost
● expertise required for use in ovulation induction
intra-operative and post-operative risks are higher
in women who are overweight and obese
● there may be a small associated risk of lower ovarian
reserve or loss of ovarian function
● periadnexal adhesion formation may be an associated
risk

36. No evidence of a significant difference in rates of
a) clinical pregnancy,
b) live birth
c) miscarriage in women with clomiphene-resistant
PCOS undergoing LOD compared to other medical
treatments.
The reduction in multiple pregnancy rates in women
undergoing LOD makes this option attractive.

37. How to monitor Ovulation Induction?

38. Monitoring starts..
• D7,D8,D9…any day could be a start in IUI cycle
if IVF D5
• Growth pattern to be followed..Day X 2mm
appro.,doppler flow
• Alternate day monitoring is advisable if required
changed according to the need
• Sustained growth…is must In healthy follicles, genes
direct cytodifferentiation, proliferation, and follicular fluid
formation.
Hormones-E2,Progesterone

39. Clinical classifications
✤ Group A : Mild variety, minimal clinical and
biochemical hyperandrogenicity and ovarian
changes
✤ Group B: Moderate
✤ Group C : Severe degree of clinical,Biochemical of
Hand PCOM

40. Elaborate gonadotrophin protocols in
second line.

41. Protocols for group A &B
✤ Step 1 Protocol
✤ CC 50mg twice daily or Letrozole (2.5mg twice
daily)
✤ day d3-d7
✤ HMG/FSH ( 75 IU) on day 3
✤ + Dydrogesterone 10mg BD/Natural progest.200 mg
BD

42. Step 2 protocol
✤ CC/Letroz 2.5mg BD from d3 to d7+
✤ HMG / FSH on d3 and d8
✤ Follicular study from day 10
✤ HCG trigger lead follicle 17-18mm
✤ IUI/TI

43. STEP 3 PROTOCOL
✤ Interrupted
✤ Gn alternate day 3,5,7,9 overlapping with CC,LZ
✤ Sequential
✤ Gn started after CC,LZ
✤ d4 or d5 and given continuously till lead follicle 17-
18mm

46. Step 4 protocol
✤ Group C PCOS
✤ Grossly androgenised with e/o hyperinsulinemia
✤ Pretreatment
✤ ISA,Lifestyle changes
✤ OC Pills
✤ OV drilling
✤ Downregulate LH,androgen make her fit for OI+ IUI,IVF

48. Third line management
In the absence of an absolute indication for IVF ± ICSI,
women with PCOS and anovulatory infertility could be
offered IVF as third line therapy where first or second line
ovulation induction therapies have failed.

49. For IVF which protocol in PCOS

50. . A gonadotrophin releasing hormone antagonist protocol
is preferred in women with PCOS undergoing an IVF ±
ICSI cycle, over a gonadotrophin releasing hormone
agonist long protocol, to reduce the duration of
stimulation, total gonadotrophin dose and incidence of
ovarian hyperstimulation syndrome (OHSS) .
(International PCOS guidelines)

53. Ovulation Trigger,which,dose?

54. Ovulation Trigger,When to give HCG..
•Triple line Endo >7mm,follicle >17mm
• Perifollicular and subendometrial Hallo…oedema
• Cumulus presence..30-40%
• Follicular volume..0.6 to 1.5ml
• Flow Indices…PSV: >10,RI:<0.5
• Perifollicular Vasularity..3/4th
• Sub Endo vasularity..minimum 5 spiral vessels
reaching to zone 4,ant & post,RI<0.6
• Endo peristalsis 3to5/ min

55. Triggering final oocyte maturation with a gonadotropin-
releasing hormone (GnRH) agonist and freezing all suitable
embryos could be considered in women with PCOS having
an IVF/ICSI cycle with a GnRH antagonist protocol and at an
increased risk of developing OHSS or where fresh embryo
transfer is not planned.
Human chorionic gonadotrophins is best used at the lowest
doses to trigger final oocyte maturation in women with
PCOS undergoing an IVF ± ICSI cycle to reduce the
incidence of OHSS.
In IVF ± ICSI cycles in women with PCOS, consideration
needs to be given to an elective freeze of all embryos.

56. ✤ AGONIST TRIGGER
✤ TRIPRORELIN 0.2Mg
✤ LEUPROLIDE 1-1.5Mg
✤ BUSERELIN 0.5Mg

57. Dual Trigger
✤ Described by Shapiro.Both GnRh A followed by
hCG (1000-2500 IU)
✤ OHSS risk is minimised by GnRh agonist
✤ luteal fn was rescued by added hCG

58. When to withhold Trigger

59. ✤ When more than Two mature follicles.
✤ E2 level of 3000 pg/ml

60. Strategies to prevent OHSS

61. ✤ Titration of COS
✤ Use of less aggressive stimulation protocol
✤ Monitor ovarian response carefully
✤ If >2 follicles abort cycle or convert IVF
✤ Use antagonist protocol
✤ agonist trigger
✤ Coasting
✤ Elective single embryo transfer

62. Components of OHSS free clinic

63. OHSS FREE CLINIC
With the advent of GnRH agonist triggering the concept of OHSS free clinic
has come. It is based on the three segment approach to prevent OHSS
• Segment A
It consists of optimization of the ovarian stimulation, including GnRH
agonist triggering in a GnRH antagonist cycle.
• Segment B
It consists of optimum cryopreservation methods for oocyte or embryo
vitrification.
• Segment C
Includes embryo replacement in a receptive, non-stimulated endometrium
in a natural cycle or with artificial endometrial preparation. (PAUL
DEVOERY hum reprod 2011)8

64. In-vitro Maturation

66. In-vitro maturation
In women with PCOS, is in-vitro maturation (IVM) effective for improving
fertility outcomes?
term in vitro maturation (IVM) treatment cycle is applied to “the maturation in
vitro of immature cumulus oocyte complexes collected from antral follicles”
(encompassing both stimulated and unstimulated cycles, but without the use of a
human gonadotrophin trigger).
In units with sufficient expertise, IVM could be offered to achieve pregnancy and
livebirth rates approaching those of standard IVF ± ICSI treatment without the risk
of OHSS for women with PCOS, where an embryo is generated, then vitrified and
thawed and transferred in a subsequent cycle.

67. Conclusion
✤ The rational of ovulation is to ensure an optimal number of
mature oocytes on one hand and to prevent OHSS on the
other hand.
✤ Lifestyle interventions and oral ovulation drugs form the first
line
✤ Gonadotropins and LOD -second line
✤ IVF-third line-antagonist protocol with agonist trigger and
Freeze all
✤ OHSS free clinic is the need of hour.

68. Thank you