Aboubakr Elnashar

1. ABOUBAKR
ELNASHAR
UPDATE
ON
POLYCYSTIC
OVARY
SYNDROME
Prof.
Aboubakr
Elnashar
Benha
university
Hospital,
Egypt
CONTENTS
❑
INTRODUCTION
I.
DIAGNOSIS
II.
RISK
ASSESSMENT
III.TREATMENT
ABOUBAKR
ELNASHAR

2. PCOS
▪
Prevalence
▪
Most
common
disorder
in
women
of
reproductive
age
▪
8%
(NIH
criteria,1990)
▪
18%
(Roterdam
criteria,
2003)
▪
12%
(AE,
PCOS,
2009)
▪
Primary
cause
of
anovulatory
infertility.
▪Aetiology:
Unknown
▪±associated
with
▪
overproduction
of
androgens
by
the
ovaries
▪in
the
majority
genetic
in
origin.
ABOUBAKR
ELNASHAR
ABOUBAKR
ELNASHAR
ABOUBAKR
ELNASHAR

3. ABOUBAKR
ELNASHAR
ABOUBAKR
ELNASHAR
Manifestations
of
PCOS
across
the
lifespan.

4. I.
DIAGNOSIS
ABOUBAKR
ELNASHAR
DIAGNOSTIC
CRITERIA
1.
Irregular
menstrual
cycles
▪
Post
menach:
▪
<
1y:
Irregular
cycles
are
normal
{pubertal
transition}.
▪
>
1
y:
90
days
for
any
one
cycle
▪
>
1
to
<
3
y:
<
21
or
>
45
days.
▪
>
3
years:
<
21
or
>
35
days
or
<
8
cycles
per
year.
▪
Primary
amenorrhea
by
age
15
or
>
3
years
post
thelarche
(breast
development).
ABOUBAKR
ELNASHAR

5. ▪With
irregular
cycles:
▪PCOS
should
be
considered
▪assessed
according
to
the
guidelines.
▪Ovulatory
dysfunction:
can
still
occur
with
regular
cycles.
▪If
anovulation
suspected:
test
progesterone
levels.
ABOUBAKR
ELNASHAR
2.
Clinical
hyperandrogenism
▪Comprehensive
history
and
▪Physical
examination
for
clinical
hyperandrogenism.
▪Adults:
▪Acne
▪Alopecia
▪Hirsutism
▪Adolescents:
▪Severe
acne
▪Severe
or
progressive
hirsutism.
ABOUBAKR
ELNASHAR

6. ABOUBAKR
ELNASHAR
ABOUBAKR
ELNASHAR
▪Assessing
hirsutism:
Modified
Ferriman
Gallway
score
(mFG).
▪The
gold
standard
for
evaluating
hirsutism
help
assess
response
to
treatment.
▪Only
terminal
hairs
relevant
in
pathological
hirsutism
▪untreated
>
5
mm
long,
variable
shape&
pigmented
▪
9
body
areas
most
sensitive
to
androgen
are
assigned
a
score
from
0
(no
hair)
to
4
(frankly
virile),
and
these
separate
scores
are
summed
to
provide
a
hormonal
hirsutism
score
▪
A
cut-off
score
of
hirsutism,
depend
on
ethnicity.
▪
Mild
hirsutism:
8-15
▪
Moderate:
16
-
25
▪
Severe
>25
(II-2).
ABOUBAKR
ELNASHAR
Country
Total
score
USA,
UK
8
Mediterranean,
Hispanic,
and
Middle
Eastern
9-10
South
American
6

7. ABOUBAKR
ELNASHAR
▪Assessing
alopecia.
▪The
Ludwig
visual
score
ABOUBAKR
ELNASHAR

8. 3.
Biochemical
hyperandrogenism
▪Most
useful
when
cl
hyperandrogenism
is
unclear.
▪Assay:
▪High
quality
assays
needed
for
most
accurate
assessment:
chromatography–mass
spectrometry(LCMS)/mass
spectrometry&
extraction/chromatography
immunoassays
▪Direct
free
testosterone
assays
▪Radiometric
or
enzyme-linked
assays
▪Not
preferred,
should
not
be
used
▪{poor
sensitivity,
accuracy
and
precision}.
ABOUBAKR
ELNASHAR
▪Use
▪
Free
androgen
index=
TX
100
/
SHBG
if
>
4.5:
PCOS
Not
done
routinely
in
presence
of
hirsutism
▪calculated
bioavailable
testosterone.
▪Calculated
Free
testosterone
▪Androstenedione
&
DHEAS
▪
could
be
considered
if
total
or
FT
are
not
elevated
▪
However,
have
limited
role
in
PCOS
diagnosis.
ABOUBAKR
ELNASHAR

9. 4.
US
&
polycystic
ovarian
morphology
(PCOM)
▪US
should
not
be
used
▪<
8
years
after
menarche
{high
incidence
of
multi-follicular
ovaries
in
this
life
stage}
▪
Irregular
menstrual
cycles
&
hyperandrogenism
▪
US
is
not
necessary
for
PCOS
diagnosis
▪
however
US
will
identify
PCOS
phenotype.
ABOUBAKR
ELNASHAR
Criteria
of
polycystic
ovarian
morphology
▪
12
or
more
follicles,
2
-
9
mm
in
diameter
and/or
▪
Ovarian
volume
>10
cm
3
.
ABOUBAKR
ELNASHAR

10. ▪TVS
▪Preferred
if
sexually
active
▪With
frequency
8MHz,
the
threshold
for
PCOM
▪Follicle
number
per
ovary
(FNPO)
≥
20
&/or
▪Ovarian
volume
≥
10ml
on
either
ovary
▪ensuring
no
▪corpora
lutea
▪cysts
or
▪dominant
follicles
▪With
frequency
8
MHz:
threshold
for
PCOM
▪
FNPO:
12
▪
an
ovarian
volume
≥
10ml
on
either
ovary.
ABOUBAKR
ELNASHAR
Diagnostic
criteria
of
the
polycystic
ovaries
morphology
(PCOM)
depending
on
examination
technique
0
20
20
ABOUBAKR
ELNASHAR

11. 4
different
phenotypes
of
PCOS
based
on
Rotterdam
Criteria
Phenotypes
Anovulation
Hyperandrogenism
PCO
Severe
=Frank
+
+
+
Classic
+
+
-
Ovulatory
-
+
+
Non
hyperandrogenic
=Mild
+
-
+
ABOUBAKR
ELNASHAR
❑Anti-müllerian
hormone
(AMH)
should
not
yet
be
used
as
an
alternative
for
the
detection
of
PCOM
or
to
diagnose
PCOS.
ABOUBAKR
ELNASHAR

12. ▪
DIAGNOSIS
of
adolescent
PCOS
▪
Criteria
for
the
diagnosis
differ
from
those
used
for
adult
▪
Irregular
menstruation
plus
Moderate
to
severe
hyperandrogenism
and/or
hyperandrgemia
▪
Exclusion
of
other
causes
of
hyperandrogenism
with
menstrual
irregularity
ABOUBAKR
ELNASHAR
ABOUBAKR
ELNASHAR

13. II.
RISK
ASSESSMENT
1.
Cardiovascular
disease
risk
▪All
with
PCOS
should
be
offered
▪Regular
monitoring
for
wt
change&
excess
wt
▪Monitoring
could
be
▪At
each
visit
or
at
a
minimum
6-12
monthly
▪Weight,
Height
▪waist
circumference
▪BMI
ABOUBAKR
ELNASHAR
❑All
with
PCOS
should
be
assessed
for
▪Individual
CVD
risk
factors
and
▪Global
CVD
risk.
▪
PCOS
at
increased
risk
of
CVD.
▪obesity
▪cigarette
smoking
▪dyslipidemia
▪hypertension
▪impaired
glucose
tolerance
and
▪Lack
of
physical
activity
ABOUBAKR
ELNASHAR

14. ▪
All
women
with
PCOS
should
have
blood
pressure
measured
annually.
▪
Overweight&
obese
PCOS,
regardless
of
age
▪should
have
a
fasting
lipid
profile
▪total
cholesterol
▪low
density
lipoprotein
cholesterol
▪high
density
lipoprotein
cholesterol
and
▪triglyceride
level
at
diagnosis
▪Thereafter,
measurement
should
be
guided
by
▪the
results
and
▪global
CVD
risk.
ABOUBAKR
ELNASHAR
2.
Gestational
diabetes,
impaired
glucose
tolerance
&
type
2
diabetes
▪5
fold
in
Asia
▪4
fold
in
the
Americas
▪3
fold
in
Europe
are
increased
in
PCOS,
with
risk
independent
of,
yet
exacerbated
by
obesity.
▪In
all
with
PCOS
▪Glycaemic
status
▪should
be
assessed
at
baseline
▪thereafter,
every
one
to
three
years,
based
on
presence
of
other
diabetes
risk
factors.
ABOUBAKR
ELNASHAR

15. ❑In
high
risk
women
with
PCOS
▪Including
▪BMI
>
25kg/m
2
or
in
Asians
>
23kg/m
2
▪history
of
abnormal
glucose
tolerance
or
▪family
history
of
diabetes,
▪hypertension
or
▪high
risk
ethnicity
▪OGTT
is
recommended.
▪Otherwise
▪fasting
glucose
or
▪HbA1c
should
be
performed.
ABOUBAKR
ELNASHAR
▪OGTT
should
be
offered
in
all
with
PCOS
▪when
planning
pregnancy
or
▪seeking
fertility
treatment
{increased
hyperglycaemia&
comorbidities
in
pregnancy}.
▪If
not
performed
preconception,
an
OGTT
should
be
offered
▪at
<
20
weeks
gestation
▪all
women
with
PCOS
should
be
offered
the
test
at
24-28
weeks
gestation
ABOUBAKR
ELNASHAR

16. 3.
Obstructive
sleep
apnea
(OSA)
▪Screening
should
only
be
considered
▪to
identify
and
alleviate
related
symptoms,
▪Snoring
▪Waking
unrefreshed
from
sleep
▪Daytime
sleepiness
▪the
potential
for
fatigue
to
contribute
to
mood
disorders.
ABOUBAKR
ELNASHAR
▪A
simple
screening
questionnaire
(Berlin
tool)
▪if
positive
▪referral.
▪raises
the
likelihood
of
OSA
▪does
not
quantify
symptom
burden
▪alone
does
not
justify
treatment.
▪If
women
with
PCOS
have
OSA
symptoms
and
a
positive
screen
▪should
be
referred
to
a
specialist
centre
for
further
evaluation.
ABOUBAKR
ELNASHAR

17. 4.
Endometrial
cancer
▪Two
to
six
fold
increased
risk
of
endometrial
cancer,
▪often
presents
before
menopause
▪however
absolute
risk
remains
relatively
low.
▪low
threshold
for
investigation
of
end
cancer
in
PCOS,
with
▪TVS
and/or
▪Endometrial
biopsy
▪recommended
with
▪Persistent
thickened
endometrium
and/or
▪Risk
factors
▪prolonged
amenorrhea
▪abnormal
vaginal
bleeding
or
▪excess
weight.
ABOUBAKR
ELNASHAR
▪Routine
ultrasound
screening
of
endometrial
thickness
in
PCOS
is
not
recommended.
▪Optimal
prevention
for
endometrial
hyperplasia
and
endometrial
cancer
▪not
known.
▪A
pragmatic
approach
could
include
▪COCP
or
▪Progestin
therapy
in
those
with
cycles
longer
than
90
days.
ABOUBAKR
ELNASHAR

18. III.
TREATMENT
1.
LIFE
STYLE
1.
Diet
2.
Exercise
3.
Behavioral
2.
INFERTILITY
3.
NON
INFERTILITY
ABOUBAKR
ELNASHAR
I.
LIFESTYLE
INTERVENTIONS
▪In
all
women
with
PCOS:
▪Healthy
eating
▪Regular
physical
activity
▪Healthy
lifestyle
behaviours
▪In
over
wt
&
obese:
Wt
reduction
▪5%
to
10%
▪significant
clinical
improvements
▪considered
successful
wt
reduction
within
6
months
ABOUBAKR
ELNASHAR

19. 1.
Dietary
intervention
▪Healthy
eating
principles
should
be
followed
for
all
women
with
PCOS
across
the
life
course
▪No
one
dietary
type
recommended
in
PCOS
▪To
achieve
weight
loss
▪An
energy
deficit
of
▪30%
or
▪500
-
750
kcal/d
▪1,200-1,500
kcal/d
could
be
prescribed
considering
individual
▪energy
requirements
▪body
weight
▪food
preferences
and
▪physical
activity
levels
ABOUBAKR
ELNASHAR
2.
Exercise
❑Eencourage
&
advise
the
following
for
prevention
of
weight
gain
&
maintenance
of
health:
▪
In
adults
from
18-64
years
A
minimum
of
▪
150
min/w
of
moderate
intensity
physical
activity
or
▪75
min/w
of
vigorous
intensities
or
▪An
equivalent
combination
of
both
including
muscle
strengthening
activities
on
2
non-
consecutive
days/w
ABOUBAKR
ELNASHAR

20. ▪
In
adolescents
at
least
▪
60
mins
of
moderate
to
vigorous
intensity
physical
activity/day
▪
including
those
that
strengthen
muscle&
bone
at
least
3
times
weekly.
▪
Activity
be
performed
in
at
least
10
minute
bouts
or
around
1000
steps,
aiming
to
achieve
at
least
30
min
daily
on
most
days.
ABOUBAKR
ELNASHAR
Physical
activity
intensity
and
examples.
•Predicted
maximal
heart
rate
(HRmax)
=
208
–
(0.7
X
AGE[years]);†
metabolic
equivalent
(MET)
where
1
MET
is
the
O2/kg
body
weight/min
required
to
sustain
ones
resting
metabolic
rate
[3.5
mL/kg/min])
ABOUBAKR
ELNASHAR

21. 3.
BEHAVIOURAL
STRATEGIES
▪
Cognitive
behavioural
interventions
▪goal-setting
▪Self-monitoring
▪stimulus
control
▪Problem
solving
▪assertiveness
training
▪Slower
eating
▪reinforcing
changes
and
relapse
prevention
▪To
optimise
▪weight
management
▪healthy
lifestyle
and
▪emotional
wellbeing
in
women
with
PCOS.
ABOUBAKR
ELNASHAR
ABOUBAKR
ELNASHAR
▪
Weight
reduction
in
over
wt
and
obese
PCOS
A.
Life
style
B.
Medication
C.
Bariatric
surgery

22. b.
Anti-obesity
medications
▪
Failure
to
lose
10%
of
wt
despite
life
style
changes
and
diet
control
(Mathys,
2005)
▪
Can
be
considered
with
lifestyle,
considering
▪
cost
▪
contraindications
▪
side
effects
▪
availability
▪
regulatory
status
▪
avoiding
pregnancy
when
on
therapy.
ABOUBAKR
ELNASHAR
▪
Orlistat
(Rx:
Orly):
First
drug
approved
by
FDA
▪
Type
of
drug/actions:
▪
Peripherally
acting
pancreatic
lipase
inhibitor:
▪
reduces
absorption
of
ingested
fat.
▪
Dosing:
▪
120
mg
3
times
daily
with
meals
(or
over
the
counter
alli®
at
half
dose,
60
mg)
ABOUBAKR
ELNASHAR

23. ▪
Adverse
effects:
GIT:
diarrhea,
flatulence,
if
large
amounts
fat
are
ingested.
▪
Precautions:
▪Binds
fat
soluble
vits.
▪Patient
should
▪Take
multivitamin.
▪Reduce
fat
and
calorie
diet.
▪
Contraindications:
▪Pregnancy
▪Cholestasis,
chronic
malabsorption
syndromes,
▪Co
administration
with
cyclosporine.
▪Can
increase
urinary
oxalate
ABOUBAKR
ELNASHAR
c.
Bariatric
Surgery
▪
3
rd
-line
treatment
option
▪
Indications:
(NICE,
2013)
1.
Morbid
obese:
failed
to
lose
wt
by
other
means
2.
Moderate
obesity:
with
significant
co-morbid
condition
that
could
be
improved
by
wt
loss
▪
Should
be
considered
an
experimental
therapy
in
women
with
PCOS,
for
the
purpose
of
having
healthy
baby,
with
risk
to
benefit
ratios
currently
too
uncertain
to
advocate
this
as
fertility
therapy.
ABOUBAKR
ELNASHAR

24. ▪
Most
suitable
technique:
laparoscopic
adjustable
gastric
band
{tightness
of
the
band
can
be
adjusted
to
accommodate
for
increased
demands
of
pregnancy}
▪
Pregnancy
avoidance
▪During
periods
of
rapid
weight
loss
▪For
at
least
12
months
after
bariatric
surgery
with
appropriate
contraception
ABOUBAKR
ELNASHAR
ABOUBAKR
ELNASHAR
2.
TREATMENT
OF
INFERTILITY

25. 1
ST
LINE
PHARMACOLOGICAL
TT
❑
Assessment
of
factors
that
may
affect
fertility,
TT
response
or
pregnancy
outcomes
1.
General
Factors
▪Blood
glucose,
weight,
blood
pressure
▪Smoking,
alcohol,
diet,
▪Exercise,
sleep
and
▪Mental,
emotional
&
sexual
health
▪should
be
optimised
▪To
improve
reproductive&obstetric
outcomes
ABOUBAKR
ELNASHAR
2.
Tubal
patency
testing
▪Risks,
benefits,
costs
&
timing
should
be
individualized
▪Should
be
considered
prior
to
ovulation
induction
for
women
with
PCOS
where
there
is
suspected
tubal
infertility.
ABOUBAKR
ELNASHAR

26. ❑
Ovulation
induction
principles
▪
Pregnancy
should
be
excluded
prior
to
ovulation
induction.
▪
Unsuccessful,
prolonged
use
of
ovulation
induction
agents
should
be
avoided,
due
to
poor
success
rates.
ABOUBAKR
ELNASHAR
Weight
reduction
letrozole
Obese
&overweight
Normal
weight
&No
weight
loss
&
No
ovulation
LOD
GnT
No
ovulation
after
3
cycles.
No
pregnancy
after
6
cycles.
No
pregnancy
after
6
cycles.
No
pregnancy
after
spontaneous,
CC,
FSH
ovulation
IVF
Other
surgical
indication
Difficult
follow
up
Less
aggressive
No
desire
for
surgery
Add
metformin
IGT
&IR
ABOUBAKR
ELNASHAR

27. 1.
Letrozole
❑Should
be
considered
first
line
pharmacological
TT
for
ovulation
induction
❑Other
ovulation
induction
agents
can
be
used
if
▪Letrozole
is
not
available
▪Use
is
not
permitted
▪Cost
is
prohibitive.
ABOUBAKR
ELNASHAR
▪
Advantages
of
letrozole
over
CC
[Casper
&
Metwally,
2006]:
▪
A
high
rate
of
monofollicular
development:
reduce
the
risk
of
multiple
pregnancies.
▪
A
shorter
half-life
(48
hours
versus
two
weeks
for
CC):
lower
risk
of
teratogenicity.
▪
No
direct
antiestrogenic
adverse
effects
on
the
endometrium
{absence
of
peripheral
estrogen
receptor
blockade
and
the
shorter
half-life}.
▪
Lower
serum
estradiol
levels
–
This
is
a
particular
advantage
for
women
with
breast
cancer
undergoing
ovarian
stimulation
prior
to
gonadotoxic
therapy
and
possibly
for
women
with
endometriosis
undergoing
in
IVF
ABOUBAKR
ELNASHAR

28. ▪
ACOG
2018
▪
While
they
previously
suggested
letrozole
as
first-line
therapy
(over
CC)
only
for
women
with
a
BMI
>30
kg/m
[20],
they
now
recommend
it
for
all
women
with
PCOS,
regardless
of
BMI.
▪
They
recommend
lifestyle
changes
&
weight
loss
for
all
obese
women
with
PCOS
to
try
to
restore
ovulatory
cycles
without
the
use
of
ovulation
induction
agents.
ABOUBAKR
ELNASHAR
2.
Clomiphene
citrate
&
Metformin
▪
CC
could
be
used
alone
▪
Metformin
could
be
used
alone:
women
should
be
informed
that
there
are
more
effective
ovulation
induction
agents.
▪
Indications:
▪
obese
(BMI
≥
30kg/m
2
)
▪
CC-resistant
PCOS
ABOUBAKR
ELNASHAR

29. 2
nd
line
pharmacological
TT
1.
Gonadotrophins
▪
Used
as
second
line
agents
▪
in
women
with
PCOS
who
have
failed
first
line
oral
ovulation
induction
therapy
▪
Could
be
considered
as
first
line
treatment
▪
in
the
presence
of
ultrasound
monitoring
▪
following
counseling
on
▪
cost
▪
potential
risk
of
multiple
pregnancy
ABOUBAKR
ELNASHAR
▪
GnT,
where
available
&
affordable
▪
Should
be
used
in
preference
to
CC
combined
with
metformin
in
CC-resistance
PCOS
▪
GnT
with
the
addition
of
metformin
▪
could
be
used
rather
than
GnT
alone,
in
▪
CC-resistance
PCOS
▪
Either
GnT
or
LOD
▪
could
be
used
in,
CC-resistance
PCOS,
following
counseling
on
benefits
and
risks
of
each
therapy.
ABOUBAKR
ELNASHAR

30. ❑Where
GnT
are
prescribed,
the
following
should
be
considered:
▪
Cost
&
availability
▪
Expertise
required
for
use
in
ovulation
induction
▪
Degree
of
intensive
US
monitoring
required
▪
No
difference
in
clinical
efficacy
of
GnT
preparations
▪
low
dose
GnT
protocols
optimise
monofollicular
development
▪
Risk
&
implications
of
potential
multiple
pregnancy
ABOUBAKR
ELNASHAR
▪
GnT
induced
ovulation
▪Should
only
be
triggered
when
there
are
fewer
than
3
mature
follicles
▪should
be
cancelled
if
▪there
are
more
than
2
mature
follicles
▪the
patient
advised
to
avoid
unprotected
intercourse.
ABOUBAKR
ELNASHAR

31. ▪
GnT
regimens:
50-75
IU
14
days
7
days
Chronic
low
dose
step-up:
▪
Start
with
50
–
75
IU/day
for
14
days.
▪
Increase
by
25–37.5
every
7
days
until
follicular
development
is
observed.
▪
Maintained
until
follicular
selection
is
achieved.
▪
Recommended
in
PCOS
(low
OHSS).
ABOUBAKR
ELNASHAR
2.
Laparoscopic
ovarian
surgery
▪
Could
be
second
line
therapy
for
CC
resistant
PCOS
,
▪
Could
potentially
be
offered
as
first
line
treatment
if
laparoscopy
is
indicated
for
another
reason
▪
Risks
▪
should
be
explained
to
all
women
ABOUBAKR
ELNASHAR

32. ❑Where
LOD
is
to
be
recommended,
the
following
should
be
considered:
▪
Comparative
cost
▪
Expertise
required
for
use
in
ovulation
induction
▪
Risks:
▪
Intra-operative
and
post-operative
risks
are
higher
in
overweight&
obese
▪
±a
small
risk
of
lower
ovarian
reserve
or
loss
of
ovarian
function
▪
Periadnexal
adhesion
ABOUBAKR
ELNASHAR
❑Restricted
Indications
of
LOD
1.
Failure
of
ovulation
of
1st
line
pharmacological
TT.
in
▪
Absence
of
other
causes
of
infertility
▪
Normal
BMI
▪
{often
unsuccessful
in
obese
women}
(Amer
et
al,
2004).
2.
±Prophylaxis
against
re-development
of
OHSS:
Rare
(Eftehar
et
al,
2016;
Seyam,
Hefzy,
2018)
ABOUBAKR
ELNASHAR

33. ❑
LOD
▪
Not
treatment
of
▪
Hirsuitism.
▪
No
clear
evidence
that
LOD
improves
menstrual
regularity
or
the
androgenic
symptoms
of
PCOS,
compared
to
most
of
the
medical
treatments
used
in
the
included
studies
(Cochrane
SR,
2017)
▪
Failure
to
get
pregnant
▪
Not
repeated
ABOUBAKR
ELNASHAR
3
RD
LINE
TT
▪
IVF
third
line
▪
Where
other
ovulation
induction
therapies
have
failed.
▪
IVF
is
effective
▪
when
elective
single
embryo
transfer
is
used,
multiple
pregnancies
can
be
minimised.
▪
Counseling
prior
to
starting
TT,
including
on:
▪
availability,
cost
and
convenience
▪
increased
risk
of
OHSS
▪
options
to
reduce
the
risk
of
OHSS
ABOUBAKR
ELNASHAR

34. ▪
Urinary
or
recombinant
follicle
stimulation
▪
Can
be
used
▪
Insufficient
evidence
to
recommend
specific
FSH
preparations.
▪
Exogenous
recombinant
LH
▪
Should
not
be
routinely
used
in
combination
with
FSH
▪
GnRH
antagonist
protocol
▪
preferred
over
GnRH
agonist
long
protocol
▪
Reduce
▪
duration
of
stimulation
▪
total
gonadotrophin
dose
▪
incidence
of
OHSS
ABOUBAKR
ELNASHAR
▪
HCG
▪
should
be
used
at
the
lowest
doses
to
trigger
final
oocyte
maturation
▪To
reduce
the
incidence
of
OHSS.
▪Triggering
with
a
GnRHa
and
freezing
all
suitable
embryos
▪
could
be
considered
▪
With
a
GnRH
antagonist
protocol
▪
At
an
increased
risk
of
developing
OHSS
or
▪
Where
fresh
embryo
transfer
is
not
planned.
ABOUBAKR
ELNASHAR

35. ❑Adjunct
metformin
▪In
Agonist
Protocol:
▪
No
effect
on
CPR
or
LBR
▪
Reduces
the
risk
of
OHSS
(Cochrane
SR,
2014,
ESHRE,2018)
▪
Improves
the
rates
of
miscarriage
and
implantation
(Palomba
et
al,
2013).
▪In
antagonist
protocol:
not
recommended
▪No
decrease
in
OHSS
▪Decrease
in
CPR
(Jacob
et
al,
2016;
RCT)
▪Metformin
before
and/or
during
OS
is
not
recommended
with
the
GnRH
antagonist
protocol
for
women
with
PCOS
(ESHRE,
2019)
ABOUBAKR
ELNASHAR
❑In
agonist
protocol
with
adjunct
metformin
therapy
▪Dose:
1000-2550mg
daily
850mg
twice
daily
for
16
d
(short
term)
▪Start:
at
the
start
of
GnRha
treatment
▪Cessation
at
the
time
of
the
pregnancy
test
or
menses
(unless
the
metformin
therapy
is
otherwise
indicated)
▪Side-effects
ABOUBAKR
ELNASHAR

36. 3.
TREATMENT
OF
NON-FERTILITY
•
Hyperandrogenism
•
Irregular
cycles
ABOUBAKR
ELNASHAR
LINES
OF
TREATMENT
❑Life
style:
1.
Diet
2.
Exercise
3.
Behavioral
I.
1
st
line
therapy:
COCP
alone
II.
2
nd
line
therapy
1.
COCP
plus
Metformin
2.
COCP
plus
Antiandrogen
3.
Metformin
ABOUBAKR
ELNASHAR

37. I.
FIRST
LINE
THERAPY
COCP
alone
❑
Indications:
1.
Adult
women
with
PCOS
for
management
of
hyperandrogenism
and/or
irregular
menstrual
cycles.
2.
Should
be
considered
in
adolescents
1.
with
a
clear
diagnosis
of
PCOS
for
management
of
clinical
hyperandrogenism
and/or
irregular
menstrual
cycles.
2.
who
are
deemed
“at
risk”
but
not
yet
diagnosed
with
PCOS,
for
management
of
cl
hyperandrogenism&irregular
menstrual
cycles.
ABOUBAKR
ELNASHAR
▪
Absolute
contraindications
for
COCP
1.
history
of
migraine
with
aura
2.
DVT/pulmonary
emboli
(PE)
3.
Known
thrombogenic
mutation
4.
Multiple
risk
factors
for
arterial
CVD
5.
History
of
ischemic
heart
disease
or
stroke
6.
Complicated
valvular
heart
disease,
7.
Breast
cancer
8.
Neuropathy
9.
Severe
cirrhosis
ABOUBAKR
ELNASHAR

38. ▪
Other
risk
factors
for
DVT
need
consideration
1.
Smoking.
2.
BMI
>
30
kg/m
2
▪
Consider
additional
PCOS
related
risk
factors
1.
high
BMI
2.
hyperlipidemia
3.
Hypertension
▪
For
Hirsutism
▪COCP
and
▪additional
cosmetic
therapy
for
at
least
6
months
ABOUBAKR
ELNASHAR
❑BMI:
▪≤35
kg/m
2
with
no
specific
metabolic
and/
or
CV
abnormalities
▪Any
type
▪Choice
acc
to:
▪
preferences
of
the
physician
and
patient
▪
specific
clinical
characteristics
of
the
patient
(Italian
society
of
endocrinology,
2015)
▪≥35
kg/m
2
:
▪COC
should
be
prescribed
with
caution
▪≥40
kg/m
2
:
▪Not
used(RCOG,
2011).
▪If
contraception
is
needed:
alternative
measures,
such
as
progestin-only
methods
(Italian
society
of
endocrinology,
2015)
ABOUBAKR
ELNASHAR

39. ▪
Type:
▪
Androgenic
activity:
▪
Anti-androgenic:
Drospirenone,
CPA,
Dienogest
▪
Minimal
androgenic:
norgestimate
and
desogestrel
▪
Most
androgenic:
Levonorgestrel,
norethisterone
▪
Lowest
risk
of
DVT:
Levonorgestrel,
Norethisterone
Norgestimate
ABOUBAKR
ELNASHAR
▪
No
COCP
preparation
is
superior
▪
Use
▪
lowest
effective
estrogen
dose:
20-30
ug
EE
or
equivalent
▪
Antiandrogenic
or
minimally
androgenic
▪
35
ug
EE
plus
cyproterone
acetate
▪
Not
first
line
in
PCOS
(higher
DVT
risk)
▪
Should
only
be
used
when
treating
▪
Moderate
to
severe
hirsutism
or
▪
Acne
ABOUBAKR
ELNASHAR

40. ▪
Other
lower
risk
preparations
▪
recommended
first
line
▪
Contraception
▪
irregular
menstrual
cycles
▪
mild
to
moderate
hirsutism
ABOUBAKR
ELNASHAR
II.
Second
line
pharmacological
therapies
1.
COCP
+
Metformin
▪Should
be
considered
in
women
with
PCOS
for
▪management
of
metabolic
features,
▪where
COCP
+
lifestyle
does
not
achieve
goals.
▪Could
be
considered
in
▪Adolescent
PCOS
▪BMI
≥
25kg/m
2
▪
Most
beneficial
in
high
metabolic
risk
groups
▪those
with
diabetes
risk
factors
▪impaired
glucose
tolerance
▪high-risk
ethnic
groups.
ABOUBAKR
ELNASHAR

41. 2.
COCP
+
Anti-androgens
▪Evidence
in
PCOS
▪relatively
limited.
▪Anti-androgens
must
be
used
with
contraception
{prevent
male
fetal
virilisation}.
▪Can
be
considered
▪after
6/12
cosmetic
treatment
+
COCP
▪if
they
fail
to
reach
hirsutism
goals.
▪with
androgenic
alopecia.
ABOUBAKR
ELNASHAR
Spironolactone
(Aldactone)
❑Dose:
100-200
mg/d
remission:
decrease
dose
to
25-50
mg
100-200
mg/d
from
D1-D21
❑Mechanism
:
on
receptor
ovary
&
adrenals
Liver
kidney
ABOUBAKR
ELNASHAR

42. 3.
Metformin
▪should
be
considered
in
▪Adults
for
▪weight,
hormonal
and
metabolic
outcomes
▪Adolescents.
with
a
▪clear
diagnosis
of
PCOS
or
▪symptoms
of
PCOS
before
diagnosis
is
made.
▪Most
useful
with
▪BMI
≥
25kg/m
2
▪High
risk
ethnic
groups.
ABOUBAKR
ELNASHAR
▪
Metformin
appears
safe
long-term.
▪Side-effects
▪GI
effects
▪dose
related
▪self-limiting.
▪low
vitamin
B12.
▪How
to
avoid
▪starting
low
dose
▪500mg
increments
1-2
weekly.
▪extended
release
preparations
▪administration
with
food
▪Ongoing
monitoring
ABOUBAKR
ELNASHAR

43. ❑Inositol
▪(in
any
form)
should
currently
be
considered
experimental
in
PCOS
▪with
emerging
evidence
of
efficacy
highlighting
the
need
for
further
research.
ABOUBAKR
ELNASHAR
PROGESTINS
Irregular
cycles
❑
If
amenorrhea
for
3
months
or
more
▪
induce
withdrawal
bleed
▪
with
progesterone
(after
negative
pregnancy
test)
▪
Hormonal
therapy
·
COCP
·
Progesterone
PRN
to
induce
withdrawal
bleeding
▪
Medroxyprogesterone
acetate
10
mg
daily
for
10-14
days
▪
Micronized
progesterone
400
mg
daily
for
10-14
day
▪
Dydrogesrerone
ABOUBAKR
ELNASHAR

44. ▪
TREATMENT
of
adolescent
PCOS
▪
Should
be
individualized
depending
on:
age,
symptoms,
risk
factors
&
choices
▪
1st
line:
lifestyle
modifications
▪
1st
line
pharmacological:
COCP
▪
2nd
line
pharmacological:
▪
COCP+
Metformin
▪
COCP+
Antiandrogen
▪
Metformin
ABOUBAKR
ELNASHAR
ABOUBAKR
ELNASHAR
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can
get
this
lecture
and
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lectures
from:
1.
My
scientific
page
on
Face
book:
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Elnashar
Lectures.
https://www.facebook.com/groups/227744884091351/
2.
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share
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3.
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4.
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