Ohss updated

OVARIAN
HYPERSTIMULATION
SYNDROME (OHSS)
Osama M Warda , MD
Professor of Obstetrics & Gynecology
Mansoura University- EGYPT

Background
n  Ovarian hyperstimulation syndrome (OHSS) is
an exaggerated response to ovulation therapy.
n  The OHSS is typically associated with
exogenous gonadotropin stimulation & is rarely
observed with other agents ( e.g. CC, GnRH).
n  Clinicians who prescribe ovulation-inducing
agents must be prepared to recognize & manage
OHSS .

2WARDA

Background (contd.,)
n  OHSS is a self-limiting disorder that usually
resolves spontaneously within several days, but
may persist for longer periods, particularly in
conception cycles.
n  The syndrome is a broad spectrum of clinical
manifestations from mild illness needing only
observation to severe disease requiting
hospitalization & intensive care.
3WARDA

Background (contd.,)
n  The syndrome is characterized by ovarian
enlargement due to multiple ovarian cysts and an
acute fluid shift into the extravascular space.
n  Complications of OHSS include ascites, hemo-
concentration, hypovolemia, and electrolyte
imbalances.
n  Because the prevalence of therapy employing ART
is increasing, all physicians dealing with females in
the reproductive age should be familiar with OHSS
as it causes multi-organ dysfunction & may be
fatal. 4WARDA

Epidemiology “Brinsden
et
al
(1995)”
n  Rates
of
occurrence
have
been
es0mated
as
follows:

Ø  Mild
;
8-‐23%

Ø  Moderate;
1-‐7%

Ø  Severe;
0.25%

n  The
frequency
of
OHSS
may
increase
if:

a.  Ovary
overs+mulated
(high
E2
from
mul+ple
follicles)

b.  Protocols
combine
GnRH
agonists
and
gonadotropins,
as

compared
with
gonadotropin
alone
to
induce
ovula+on.

n  Only
women
in
childbearing
age
are
aﬀected
by
OHSS

5WARDA

Pathophysiology

n  The
hallmark
of
OHSS
is
increase
in
capillary

permeability
resul+ng
in
fluid

shiG
from
the

intravascular
space
to
3rd
space
compartments
.
This

occurs
due
to
hCG
s+mula+on.

n  Factors implicated in the process include:
1.  Increased
secre+on
or
exuda+on
of
protein-‐rich
fluid
from

enlarged
ovaries
or
peritoneal
surfaces.

2.  Increased
follicular
fluid
levels
of
pro-‐renin
&
renin

3.  Angiotensin-‐mediated
changes
in
the
capillary
permeability

6WARDA

Pathophysiology
n  Vascular
endothelial
growth
factor
(VEGF)
is
the
major
mediator

due
to
the
following
evidences
:

Ø  VEGF

serum
levels
increase
with
hCG
&
correlate
with
the

severity
of
OHSS.

Ø  The
expression
of
VEGF
&
VEGF
receptor
2
(VEGFR-‐2)
mRNA

increases
significantly
in
response
to
hCG,
and
peak
levels

coincide
with
maximum
vascular
permeability

Ø  Recombinant
VEGF
produces
effects
similar
to
OHSS
that
can
be

reversed
with
specific
an+serum.

n  Prostaglandins, inhibin, the renin-angiotensin-aldosterone system &
inflammatory mediators have all been implicated in the etiology of
OHSS. 7WARDA

Pathogenesis of OHSS
adopted from Soares et al (2008)
8WARDA

Pathogenesis of OHSS
adopted from Humaidan P et al (2010)
WARDA 9

RISK FACTORS

[Adopted from Humaidan P et al (feritl. steril 2010)*]; “modified”
Risk factor Threshold of risk
(A). Primary risk factors (patient-related):
1.  High basal AMH
2.  Young age
3.  Previous OHSS
4.  PCO-like ovaries
(B). Secondary risk factors ( ovarian response
related); On day of h C G trigger:
1.  High number of medium/large follicles
-  >3.36 ng/ml (independent predictor).
-  < 33 years
-  Moderate & severe cases /
hospitalization
-  > 24 antral follicles in both
ovaries combined.
-  ≥13follicles ≥ 11mm in diameter or
> 11 follicles≥10 mm diameter
According
to
MarAn
et
al
(1994)**,
if
the
pre-‐hCG
treatment
E2
is
>6000mcg
and
/or
if

>30
follicles
are
present,
the
rate
of
severe
OHSS
approaches
80%

10WARDA

RISK FACTORS
[Adopted from Humaidan P et al (feritl. steril 2010)]” modified”
Risk factor Threshold of risk
2. High or rapidly rising E2 levels & high
number of follicles
3. Number of oocyte retrieved
4. VEGF levels
5. Elevated inhibin- B levels
6. hCG administration for luteal phase supp.
7. Pregnancy (increase in endogenous hCG)
•  E2 5,000 pg/ml and/or≥18 follicles
predictive of severe OHSS
•  > 11predicts OHSS
•  Not applicable
•  Elevated levels on day 5 of
gonadotropin stimulation, at oocyte
retrieval and 3 days before
11WARDA

CLINICAL PRESENTATION
& CLASSIFICATION
According
to
Ame
of
onset,
2
main
clinical
forms

of
OHSS
early
&
late;

1-‐
Early
OHSS:
It
occurs
within
9
days
aUer
oocyte

retrieval
.
It
is
correlated
to
ovarian
response
to

exogenous
hCG
s0mula0on.

2-‐
Late
OHSS:
It
occurs
aUer
10
days
of
ovum

pickup,
and
correlated
to
endogenous
hCG

produced
by
implan0ng
embryo.

WARDA 12

CLASSIFICATION OF OHSS
Adopted from Navot et al fertil steril (1992)* with modification
OHSS stage Clinical features Lab. features
Mild : 1.  Abdominal distension/discomfort
2.  Mild nausea/vomiting
3.  Diarrhea
4.  Ovarian enlargement 5-12cm
No important
alterations
Moderate : 1.  Mild features +
2.  Ultrasound evidence of ascites
1.  Hematocrit>41%
2.  WBC >15,000
3.  Hypoalbuminemia
Severe 1.  Moderate features+
2.  Clinical ascites, and/ or
3.  hydrothorax, Severe dyspnea,
4.  Oliguria/anuria
To be continued
1.  Hct >55%
2.  WBC>25,000
3.  Cr Cl<50ml/min
4.  Cr >1.6mg/dl
To be continued
13WARDA

CLASSIFICATION OF OHSS
Adopted from Navot et al fertil steril (1992)
OHSS stage Clinical features Lab. features
Severe
OHSS
(continued)

5.  Intractable vomiting
6.  Tense ascites
7.  Low blood/central venous pressure
8.  Rapid weight gain(>1kg/24hrs)
9.  Syncope severe abdominal pain
10. Venous thrombosis
5.  Na+ <135mEq/L
6.  K+ > 5mEq/L
7.  Elevated liver
enzymes
Critical
OHSS
1- Anuria/ acute renal failure
2- Arrhythmia 3- Thromboembolism
4-Pericardial effusion
5- Massive hydrothorax
6-Arterial embolism
7- Adult RDS 8- Sepsis
Worsening of the
previous finding
14WARDA

Prognosis (Lucidi,2013)
n  Mild
and
moderate
cases
=
excellent
prognosis

n  Severe
cases
=
morbidity
is
clinically
signiﬁcant,
and
fatali+es

do
occur.
However,
the
prognosis
is
op+mis+c
if
adequate

treatment
is
given.

n  Death
from
OHSS
is
largely
due
to:

1. 
hypovolemic
shock

2.  Electrolyte
imbalance

3.  Hemorrhage

4.  Thromboembolism

n  Es+mated
fatality
rates
are
1per
400,000
–
500,000
s+mulated

cycles
15WARDA

PREVENTION OF OHSS
Introduction
16WARDA
•  Complete
preven+on
of
OHSS
is
s+ll
not
possible.

• 
Preven+on
strategies
can
be
divided
into
two
types—primary

and
secondary.

•  Primary
preven+on
methods
;
the
s+mula+on
protocol
is

individualized
(iCOS)
aGer

assessment
of
primary
risk
factors
to

classify
pa+ents
as
poor,
normal,
or
high
responders.

•  Secondary
preven+on
methods:
are
used
in
the
presence
of
risk

factors
arising
from
an
excessive
response
to
ovarian
s+mula+on

PREVENTION OF OHSS
Primary Prevention
1- Reducing exposure to gonadotropins
2-Using combined oral contraceptives
3- GnRH antagonists protocols
4- Avoidance of hCG in LPS
5- In vitro oocyte maturation (IVM)
6- Insulin- Sensitizing agents
WARDA 17

PREVENTION OF OHSS
Primary Prevention
18WARDA
1. Reducing Exposure to Gonadotrpins:
(a)
Reducing
the
dose
–
IUI
cycles:
e.g.
PCOS
pa+ents;
use

chronic
*
low-‐dose
step-‐up
protocols
are
associated
with
lower
OHSS
&

mul+ple
pregnancy.

(b)
Reducing
Dura+on
of
FSH
Exposure-‐
IVF/ICSI
cycles:

-‐
Use
of
“mild
s+mula+on
protocols**”
.

-‐
Once
E2

reach
250-‐300pg/ml
+
several
follicles
11-‐12mm,
we
begin
to

reduce
gonadotropin
dose
in
step-‐down
fashion
(more
physiologic)

PREVENTION OF OHSS
Primary Prevention
19WARDA
2- Using combined oral contraceptives:(
OCP-‐GnRH

agonist-‐
dual
suppression
protocol)
:
in
high
risk
pa+ents;

-‐OCP
for
28
days!
leuprolide
acetate
(Lupron)
1mg
started
on
day

21,
overlapping
OCP
for
7days.
On
D3
of
withdrawal
bleeding
low-‐
dose
(150
IU)
hMG
or
rFSH
is
started
&
leuprolide
dose
reduced
to

0.5mg/day.
Step-‐down
gonadotropin
adjustment
is
usually
made.

-‐In
some
pa+ents
start
gonadotropin
at
very
low
dose
(37.5
IU/d)

increased
in
a
step-‐up
fashion
un+l
follicles
=
12
mm
then
step
down.

PREVENTION OF OHSS
Primary Prevention
3. GnRH Antagonist Protocols:
-‐  The
differen+al
ac+on
of
GnRH
antagonists
at
both

pituitary
&
ovarian
receptors
suggests
that
antagonist-‐

suppressed
cycles
might
result
in
a
lower
incidence
of

OHSS.

-‐  Other
advantages
of
GnRH
antagonists:
lack
of
flare
effect,
no

accompanying
menopausal-‐
like
symptoms,
no
refractory

period,
reduced
risk
of
ovarian
cyst
forma+on,
shorter

treatment
cycle,
reduced
FSH
consump+on.

-‐  However,

clinical
pregnancy
rate
may
be
less
than
with
agonists

WARDA 20

PREVENTION OF OHSS
Primary Prevention
4. Avoidance of hCG for LPS:
-‐  Luteal
phase
defect
is
the
result
of
lowered
endogenous
LH

release
as
a
nega0ve
feedback
from
the
supra-‐physiological

levels
of
E2
&
P
of
ovarian
hyper-‐s0mula0on.

-‐  Based
on
the
currently
available
evidence,
it
is
recommended

that
LPS
in
GnRH
analog-‐suppressed
cycles
be
provided
in
the

form
of
P
with
or
without
supplemental
E2,
rather
than
in
the

form
of
hCG.

-‐  As
an
alterna0ve
to
P,
it
has
been
suggested
that
repeated

intranasal
administra0on
of
GnRHa
could
be
used
for
LPS.
(Pirard

C
et
al
2005)
WARDA 21

PREVENTION OF OHSS
Primary Prevention
5. In Vitro Oocyte Maturation (IVM):
-‐  In
PCOS,
and
OHSS-‐
high
risk
pa0ent.

-‐  It
is
an
aZrac0ve
yet
underu0lized
strategy
to
prevent

OHSS.

-‐  IVM
can
be
applied
in
pa0ents
undergoing
COS
for
ICSI,

where
hCG
was
given
when
the
leading
follicle
=12-‐14mm.

-‐  The
use
of
IVM
and
natural
cycle
IVF
combined
has

resulted
in
clinical
pregnancy
rates
comparable
to
those

obtained
with
conven0onal
IVF.
(Buckel
et
al
2005)

WARDA 22

PREVENTION OF OHSS
Primary Prevention
6. Insulin-Sensitizing Agents: ’metformin’
-‐  Women
with
PCOS
are
at
greater
risk
of
developing
OHSS.

-‐ 
Menormin
suppresses
insulin
levels
&
decreases
ovarian
theca
cell

androgen
produc+on,
resul+ng
in
improved
ovulatory
and
pregnancy

rates
(
Barbieri
(2000),
Aoa
et
al
2001)

-‐ 
Menormin
is
effec+ve
insulin
sensi+zing
agent
with
a
good
safety

profile
used
as
mono-‐therapy
or
in
combina+on
with
other
in
IO
drugs

and
as
a
pretreatment
before
IUI
or
IVF/ICSI.

-‐  A
2006
meta-‐analysis
of
8
RCT
of
menormin
co-‐administra+on
during

gonadotropin-‐s+mulated
IO
or
IVF
in
women
with
PCO
found
a

significant
posi+ve
effect
on
the
incidence
of
OHSS
(
Costello
et
al

2006)

WARDA 23

PREVENTION OF OHSS
Secondary Prevention
1.  Coasting
2.  Reduced dose of hCG
3.  Cryopreservation of all embryos
4.  Cycle cancellation
5.  Alternative agents for triggering ovulation
6.  GnRH antagonist salvage
7.  Intravenous albumin and hydroxyethyl starch
8.  Dopamine agonists
9.  Glucocorticoids
10.  Calcium gluconate infusion
11.  Non-recommended strategiesWARDA 24

PREVENTION OF OHSS
1- Coasting :
- It means withholding further gonadotropin stimulation
& delaying hCG administration until E2 levels plateau
or decrease significantly (Sher et al 1993).
- Despite its wide and popular use as the 1st line
intervention of choice to reduce severity of OHSS, yet
the scientific evidence base supporting the use of
coasting to prevent OHSS is NOT strog ( Humaidan et al
2010)
WARDA 25

PREVENTION OF OHSS
2- Reduced Dose of hCG:
n  Compared
to
the
standard
10,000
IU,
doses
of
5,000
IU
have
been

used
successfully
to
trigger
ovula+on
without
impairing
clinical

outcome
(Kolibianakis
et
al
2007).

n 
Cornell
low
dose
protocol,
which
determines
hCG
dosage

according
to
serum
E2
levels
on
the
day
of
hCG
administra+on.
A

sliding
scale
is
used,
with
between
5,000
and
3,300
IU
of
hCG

administered
to
women
with
E2
levels
of
2,000–3,000
pg/mL
.

Women
with
E2
levels
>3,000
pg/mL
undergo
coasAng
un+l
E2

falls
below
3,000
pg/mL.
(
Chen
et
al
2003)

n  Cycle
cancella+on
is
a
possible
drawback
of
low
dose
hCG

WARDA 26

PREVENTION OF OHSS
3- Cryopreservation of All Embryos:
n  Entails
normal
progression
of
IVF/ICSI
un+l
OPU,
followed
by

cryopreserva+on
of
embryos
to
be
thawed
&
implanted
at
a
later

date
when
pa+ent’s
hormones
are
not
elevated.

n 
Such
pa+ents
get
much
benefits
in
reversing
the
pathology
when

we
give
antagonist
(
e.g.
Citro+de
0.25
sc
daily
for4
days
star+ng

from
day
5.

n  No
significant
difference

in
clinical
pregnancy
between
cycle
with

fresh
ET,
and
those
with
thawed
embryos

(CDC
2005
Report)

WARDA 27

PREVENTION OF OHSS
4- Cycle Cancellation:
n  Cycle
cancella+on
&
withholding
of
hCG
is
the

only
guaranteed
method
for
preven+on
of
early

OHSS
(Schenker
&
Weinstein
1978).

n  Despite
the
eﬃcacy
of
this
method,
most

physicians
are
reluctant
to
use
it
in
IVF
cycles

because
of
the
ﬁnancial
burden
&
psychological

distress
to
the
pa+ent.

WARDA 28

PREVENTION OF OHSS
5- Alternative Agents for Triggering Ovulation:
A- GnRH agonist: Used
in
gonadotropin-‐only
or
antagonist-‐

s+mulated
cycles
(i.e.
No
receptor
down-‐regula+on).

n  Administra+on
of
a
bolus
dose
of
GnRHa
results
in
a
surge
(ﬂare)

of
gonadotropins
(LH&FSH)
mimicking
the
natural
surge
(Itskovitz

et
al
1991).

n  Luteal
phase
defect
is
the
main
drawback
of
this
method
resul+ng

in
extremely
high
early
pregnancy
loss
(Kolibianakis
et
al
2005,
)
,

hence
more
LPS
needed
(
Arslan
et
al
2005).

n  Luteal
phase
can
be
rescued
with
a
small
bolus
(1,500
IU
hCG

given
35
hrs
aGer
GnRHa
triggering
dose,
aGer
OPU
(
Humaidan
et

al
2009)
WARDA 29

PREVENTION OF OHSS
5- Alternative Agents for Triggering Ovulation:
B- Recombinant LH (rLH)
n 
Triggering
ovula+on
via
administra+on
of
rLH
would

more
closely
mimic
the
natural
LH
surge
than
is

achieved
with
hCG
administra+on
(Emperaire
et
al
2004)

n  Despite
the
safety
advantages
of
r
LH
in
terms
of
OHSS

reduc+on,
however,
reduced
pregnancy
rates
and
a

poor
cost/beneﬁt
ra+o
reduce
its
applicability
in
the

clinical
situa+on
(
Humaidan
et
al
2010)

WARDA 30

PREVENTION OF OHSS
6- GnRH Antagonist salvage:
-‐  Administra+on

of
an
antagonist
to
pa+ents
with
elevated

serum
E2
at
risk
of
developing
OHSS
may
provide
a
means

of
interrup+ng
the
development
or
progression
of
the

condi+on
while
salvaging
the
current
treatment
cycle.

(Shapiro
et
al
2005).

-‐ 
However,
the
endometrial
recep+vity
and
oocyte
quality

may
be
jeopardized.

WARDA 31

PREVENTION OF OHSS
7- Intravenous Albumin and Hydroxyethyl Starch:
-‐  Albumin
may
reduce
the
incidence
of
OHSS
by
binding
to
the

vasoac0ve
agents
responsible
for
its
development
removing
them

from
circula0on
&/or
it
increases
the
plasma
osmo0c
pressure.

(Shoham
et
al
1994).

-‐  The
evidence
suppor/ng
its
use
is
not
strong,
moreover
it
may

cause
pulmonary
edema
in
pa/ents
with
diminished
cardiac
reserve

(McClelland
,1990
).

-‐  Hydroxyethyl
starch
(HES)
is
a
cheaper,
poten+ally
safer

alterna+ve
to
albumin
and
should
be
the
1st
line
treatment

WARDA 32

PREVENTION OF OHSS
8- Dopamine Agonists:
-  principle: In
PCOS; Cabergoline
(Cb2)pretreatment
before
OI,

reduces
ovarian
response
to
FSH
by
controlling
LH
levels
à

poten0al
primary
preven/on
of
OHSS
in
such
cases
(Papaleo
et
al

2001).
Moreover,
Cb2
act
on
the
VEGF
receptors
implicated
in

vascular
hyperpermeability
during
OHSS
!
poten+al
2ry

preven+on
of
OHSS
(Gomez
et
al
2002).

-‐  Cabergoline
reduces
the
occurrence
of
moderate-‐severe
OHSS.
It

is
unlikely
to
have
a
clinically
relevant
nega0ve
impact
on
clinical

pregnancy
or
on
the
number
of
retrieved
oocytes
(Leitao
et
al

2014).

WARDA 33

PREVENTION OF OHSS
9- Calcium gluconate infusion:
-‐
Infusion
with
10
ml
of
10%
calcium
gluconate
solu+on
in

200
ml
physiologic
saline
within
30
min
of
ovum
pick
up

and
con+nued
thereaGer
on
day
1,
day
2
and
day
3
proved

to
be
as
eﬀec+ve
as
cabergolin
in
preven+ng
severe
OHSS

and
decreases
OHSS
occurrence
rates
when
used
for
high-‐
risk
pa+ents.
(Naredi
&
Karunkaran
2013)

WARDA 34

PREVENTION OF OHSS
10- Glucocorticoids.
n  Glucocor0coids
and
their
deriva0ves
have
an
inhibitory

effect
on
the
VEGF
gene
expression
in
vascular
smooth

muscle
cells
(Nauck
et
al
1998).

n 
An
addi0onal
effect
is
the
non
specific
preven0on
of

the
inflammatory
response
and
edema
forma0on

(
Perrec
2000).

n  The
op+mal
protocol
&
the
drawback
of
the
an+angiogenic

effect
on
the
endometrium
needs
more
inves+ga+on

WARDA 35

PREVENTION OF OHSS
SUMMARY
WARDA 36

PREVENTION OF OHSS
Non recommended strategies
1.  Follicular Aspiration:
-‐  Therapeu+c
principle:
Aspira+on
of
granulosa
cells
from
one

ovary
(before
IO)
has
been
proposed
as
a
means
of
inducing

intra-‐ovarian
bleeding
and
limi+ng
the
produc+on
of
OHSS

mediators
while
allowing
con+nued
contralateral
ovarian

development
(Gonen
et
al
1991).

-‐ 
Drawbacks:
include
cost,
pa+ent
discomfort,
and

increased
requirement
for
invasive
procedures
under

anesthesia.

WARDA 37

PREVENTION OF OHSS
Non recommended strategies
2. Aromatase Inhibitors.
-  Therapeutic principle: The aromatase enzyme catalyzes
the rate-limiting step in the production of E2 , therefore
aromatase inhibitors may help to reduce excessive E2
synthesis during ovarian stimulation and thereby reduce the
risk of OHSS.

-‐
Drawbacks:
aromatase inhibitors cannot yet be recommended
in a clinical setting because of lack of large trials to evaluate
the impact of aromatase inhibitors on OHSS in women with
an-ovulatory infertility associated with PCOS (Humaidan et al
2010)
WARDA 38

TREATMENT OF OHSS

Patient Assessment:
History
Taking
;
Careful assessment of the patient is
needed to classify disease severity.
-This should include a review of stimulation and a prediction
of underlying risk based on age, onset of presentation, follicle
number and size during stimulation, number of eggs
retrieved, peak E2 level, and E2 level at trigger.
- The history should include an estimation of urine output and
weight gain, and should seek to identify symptoms such as
abdominal pain, bloating, shortness of breath, and the ability to
maintain oral hydration.
WARDA 39

TREATMENT OF OHSS
Patient Assessment (contd.,):
Physical
examina+on
:

-‐
Should include measurement of vital signs, body weight,
abdominal girth at the umbilicus, presence of ascites, pleural
effusion, and signs of venous thromboembolic disease, such
as unilateral increase in calf diameter.
- Caution should be taken with pelvic examinations to minimize
the risk of trauma to enlarged ovaries.
- Initial laboratory investigations should screen for hemo-
concentration with a hematocrit and/or hemoglobin
measurement and urine specific gravity.
WARDA 40

TREATMENT OF OHSS
Outpatient or Inpatient
-  Outpatient management is usually possible in women with
mild & moderate OHSS. Women with severe disease may be
considered for outpatient management if they are able to
adhere to treatment and follow clinical instructions (Navot et al
1992).
-  Inpatient management : Women with OHSS who are unable
to maintain adequate oral hydration to minimize hemo-
concentration and/or unable to overcome the discomfort of
abdominal distension with oral analgesia need to be admitted
to hospital for IV hydration and possibly paracentesis
(Shmorgun 2011).
WARDA 41

TREATMENT OF OHSS
1- Paracentesis
- patient with tense ascites .
- It will relieve pain, respiratory discomfort & improve oliguria
- Insertion of an indwelling pigtail catheter under ultrasound
guidance circumvents the need for multiple attempts at drainage
and limits potential infectious complication (Whelan 2000).
- Clinical resolution is achieved when paracentesis output starts
to decrease as urine output increases. When ascites output is <
50 mL/ day the catheter can be removed (Rahami et al 1997).
WARDA 42

TREATMENT OF OHSS
2- Culdocentesis
- Paracentesis by trans-vaginal ultrasound guidance can
be done through the outpatient clinic (Abramov etal 1999).
- Culdocentesis can be offered in an attempt to prevent
disease progression from moderate to severe OHSS and
keep the woman out of hospital (Fluker et al 2000).
- In addition to alleviating discomfort, culdocentesis may
precipitate diuresis in women who are oliguric, and it helps
resolution of severe OHSS. ( Borenstein et al 1989)
-
WARDA 43

TREATMENT OF OHSS
3- Pleuracentesis:
Ø  Drainage of ascites usually resolves a
pleural effusion.
Ø  Symptomatic pleural effusions that persist
despite paracentesis can also be drained.
WARDA 44

TREATMENT OF OHSS
4- Fluids and electrolytes:
- Women should drink according to their thirst.
-  In addition, IV hydration with a crystalloid solution (100 to
150 mL/hr) should be instituted until diuresis occurs.
-  If clinical and laboratory findings indicate persistent intra-
vascular volume depletion despite aggressive IV fluid
hydration, IV albumin (15 to20 mL/hr of 25% albumin over 4
hours) should be initiated and repeated until hydration
status improves ( Fluker et al 2000)
-  Diuretics should not be used as they can further deplete
intravascular volume.
WARDA 45

TREATMENT OF OHSS
5- Pain relief:
-  Symptomatic relief of abdominal pain can be
achieved with acetaminophen and if necessary oral
or parenteral opiates.
- Non-steroidal anti-inflammatory agents with
antiplatelet properties should not be used because
they may interfere with implantation and may also
compromise renal function in women with severe
OHSS (Navot et al 1992).
WARDA 46

TREATMENT OF OHSS
6- Nausea and/or vomiting
Antiemetic agents considered to be safe in
early pregnancy should be used to
alleviate nausea and/or vomiting.
WARDA 47

TREATMENT OF OHSS
7- Thromboprophylaxis:
- Hospitalized patients should be considered at risk of
thrombosis secondary to hemo-concentration and
immobilization.
- Daily prophylactic doses of low-molecular weight heparin
(e.g., dalteparin sodium 5000 IU/day) and use of
thromboembolic deterrent stockings should be considered on
admission and continued until discharge.
- However, there have been several reports of thrombo-
embolism in women with OHSS treated with
thromboprophylaxis ( Hignett et al 1995, Hortskamp et al1994,
Cil et al 2000)
WARDA 48

TREATMENT OF OHSS
Monitoring the patient (Whelan et al 2000)
-  Admitted patients should be assessed by a physician at least once
daily, with more frequent assessment in cases of critical OHSS.
-  Weight and urine specific gravity should be recorded daily.
-  Vital signs, urine output, and fluid balance should also be recorded.
Urine output should be maintained at a minimum of 30 mL/hour.
-  Physical examination should assess hydration, cardiorespiratory
status, degree of ascites, and signs of thromboembolism.
-  Daily monitoring of hemoglobin, hematocrit, creatinine, electrolytes,
and albumin is useful to document disease progress.
-  A weekly measurement of liver enzymes may also be useful.
49WARDA

TREATMENT OF OHSS
Management of Complications
- Renal failure, thromboembolism, pericardial
effusion, and adult respiratory distress syndrome
are potential life-threatening complications of
OHSS.
- These conditions should be diagnosed early and
managed by a
multidisciplinary team possibly in an ICU setting.
WARDA 50

WARDA 51
SUMMARY &
CONCLUSIONS

Clinicians must remain alert to the
possibility of OHSS in all women
undergoing fertility treatment and
women should be counselled
accordingly.
WARDA 52
SUMMARY &
CONCLUSIONS

Diagnosis of OHSS:
n  Clinicians need to be aware of the symptoms &
signs of OHSS , as the diagnosis is based on
clinical criteria.
n  In women presenting with severe abdominal
pain or pyrexia, extra care should be taken to
rule out other causes of the patient’s
symptoms. The input of clinicians experienced
in the management of OHSS should be
obtained in such cases. [New 2016]
WARDA 53
SUMMARY &
CONCLUSIONS

n  The severity of OHSS should be graded
according to a standardised classification
scheme.
n  Units that treat women with OHSS should
inform the licensed center where the fertility
treatment was carried out to promote clinical
continuity and to allow the licensed centre to
meet its legal obligations.
WARDA 54
SUMMARY &
CONCLUSIONS

n  Fertility clinics should provide
verbal and written information
concerning OHSS to all women
undergoing fertility treatment,
including a 24-hour contact
telephone number.
WARDA 55
SUMMARY &
CONCLUSIONS

All acute units where women with
suspected OHSS are likely to present
should establish agreed local protocols
for the assessment and management of
these women and ensure they have
access to appropriately skilled clinicians
with experience in the management of
this condition.
WARDA 56
SUMMARY &
CONCLUSIONS

n  Licensed centres that provide fertility
treatment should ensure close liaison and
coordination with acute units where patients
may present [new 2016]
n  Women presenting with symptoms suggestive
of OHSS should be assessed face-to-face by a
clinician if there is any doubt about the
diagnosis or if the severity is likely to be
greater than mild. [New 2016]
WARDA 57
SUMMARY &
CONCLUSIONS

n  Outpatient management is appropriate for
women with mild or moderate OHSS and in
selected cases with severe OHSS.
n  Women undergoing outpatient management of
OHSS should be appropriately counselled and
provided with information regarding fluid intake
and output monitoring. In addition, they should
be provided with contact details to access advice.
n  Nonsteroidal anti-inflammatory agents should be
avoided, as they may compromise renal function.
WARDA 58
SUMMARY &
CONCLUSIONS

Women with severe OHSS being
managed on an outpatient basis
should receive thromboprophylaxis
with low molecular weight heparin
(LMWH). The duration of treatment
should be individualised, taking into
account risk factors and whether or
not conception occurs.
WARDA 59
SUMMARY &
CONCLUSIONS

n  Paracentesis of ascitic fluid may be
carried out on an outpatient basis by
the abdominal or transvaginal route
under ultrasound guidance.
n  There is insufficient evidence to support
the use of gonadotrophin-releasing
hormone antagonists or dopamine
agonists in treating established OHSS.
[New 2016]
WARDA 60
SUMMARY &
CONCLUSIONS

Women with OHSS being managed
on an outpatient basis should be
reviewed urgently if they develop
symptoms or signs of worsening
OHSS . In the absence of these,
review every2–3 days is likely to be
adequate. [New 2016]
WARDA 61
SUMMARY &
CONCLUSIONS

Baseline laboratory investigations
should be repeated if the severity of
OHSS is thought to be worsening.
Hematocrit is a useful guide to the
degree of intravascular volume
depletion.[New 2016]
WARDA 62
SUMMARY &
CONCLUSIONS

Hospital admission should be considered for
women who:
n  are unable to achieve satisfactory pain control
n  are unable to maintain adequate fluid intake
due to nausea
n  show signs of worsening OHSS despite
outpatient intervention G are unable to attend
for regular outpatient follow-up
n  have critical OHSS. [New 2016]
WARDA 63
SUMMARY &
CONCLUSIONS

n  Multidisciplinary assistance should be sought for
the care of women with critical OHSS and severe
OHSS who have persistent hemoconcentration and
dehydration.
n  Features of critical OHSS should prompt
consideration of the need for intensive care.
n  A clinician experienced in the management of OHSS
should remain in overall charge of the woman’s
care.
WARDA 64
SUMMARY &
CONCLUSIONS

n  Women admitted with OHSS should be
assessed at least once daily. More frequent
assessment is appropriate for women with
critical OHSS and those with complications.
n  Analgesia and anti-emetics may be used in
women with OHSS, avoiding non-steroidal
agents and medicines contraindicated in
pregnancy.
WARDA 65
SUMMARY &
CONCLUSIONS

n  Fluid replacement by the oral route, guided
by thirst, is the most physiological approach
to correcting intravascular dehydration.
n  Women with persistent hemoconcentration
despite volume replacement with
intravenous colloids may need invasive
monitoring and this should be managed with
anesthetic input.
WARDA 66
SUMMARY &
CONCLUSIONS

Diuretics should be avoided as they
further deplete intravascular volume,
but they may have a role in a
multidisciplinary setting if oliguria
persists despite adequate fluid
replacement and drainage of ascites.
WARDA 67
SUMMARY &
CONCLUSIONS

Indications for paracentesis include the following:
1.  severe abdominal distension and abdominal pain
secondary to ascites
2.  shortness of breath and respiratory compromise
secondary to ascites and increased intra-
abdominal pressure
3.  oliguria despite adequate volume replacement,
secondary to increased abdominal pressure
causing reduced renal perfusion.
WARDA 68
SUMMARY &
CONCLUSIONS

n  Paracentesis should be carried out under
ultrasound guidance and can be performed
abdominally or vaginally.
n  Intravenous colloid therapy should be
considered for women who have large
volumes of fluid removed by paracentesis.
n  Women with severe or critical OHSS and
those admitted with OHSS should receive
LMWH prophylaxis.
WARDA 69
SUMMARY &
CONCLUSIONS

n  The duration of LMWH prophylaxis should be
individualised according to patient risk
factors and outcome of treatment. [New
2016]
n  Women with moderate OHSS should be
evaluated for predisposing risk factors for
thrombosis and prescribed either
antiembolism stockings or LMWH if
indicated.
WARDA 70
SUMMARY &
CONCLUSIONS

n  In addition to the usual symptoms and
signs of venous thromboembolism (VTE),
thromboembolism should be suspected in
women with OHSS who present with
unusual neurological symptoms, even if
they present several weeks after apparent
improvement in OHSS.
WARDA 71
SUMMARY &
CONCLUSIONS

n  Surgery is only indicated in patients with
OHSS if there is a coincident problem such as
adnexal torsion, ovarian rupture or ectopic
pregnancy and should be performed by an
experienced surgeon.
n  Clinicians should be aware, and women
informed, that pregnancies complicated by
OHSS may be at increased risk of pre-
eclampsia and preterm delivery. [New 2016]
WARDA 72
SUMMARY &
CONCLUSIONS

WARDA 73
THANK YOU FOR
YOUR
ATTENSION
& PATIENCE

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