Ohss updated

detailed information on ovarian hyper stimulation syndrome

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

2. Background

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

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

(contd.,)
! The syndrome is characterized by ovarian
enlargement due to multiple ovarian cysts and an
acute fluid shift into the extravascular space.
!  Complications of OHSS include ascites, hemo-
concentration, hypovolemia, and electrolyte
imbalances.
! 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.
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5. Epidemiology “Brinsden(et(al((1995)”
! Rates&of&occurrence&have&been&es0mated&as&follows:&
" Mild&;&8:23%&
" Moderate;&1:7%&
" Severe;&0.25%&
! 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."
! Only&women&in&childbearing&age&are&affected&by&OHSS&
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6. Pathophysiology""
! The"hallmark"of"OHSS"is"increase"in"capillary"
permeability"resul+ng"in"fluid""shiG"from"the"
intravascular"space"to"3
rd
"space"compartments"."This"
occurs"due"to"hCG"s+mula+on."
! Factors implicated in the process include:
1. Increased"secre+on"or"exuda+on"of"protein4rich(fluid(from"
enlarged"ovaries"or"peritoneal"surfaces."
2. Increased"follicular"fluid(levels(of(pro4renin(&(renin(
3. Angiotensin4mediated"changes"in"the"capillary"permeability"
"
6 WARDA

7. Pathophysiology
! Vascular"endothelial"growth"factor"(VEGF)"is"the"major"mediator"""
due"to"the"following"evidences":"
" VEGF""serum"levels"increase"with"hCG"&"correlate"with"the"
severity"of"OHSS."
" The"expression"of"VEGF"&"VEGF"receptor"2"(VEGFRR2)"mRNA"
increases"significantly"in"response"to"hCG,"and"peak"levels"
coincide"with"maximum"vascular"permeability""
" Recombinant"VEGF"produces"effects"similar"to"OHSS"that"can"be"
reversed"with"specific"an+serum."
! Prostaglandins, inhibin, the renin-angiotensin-aldosterone system &
inflammatory mediators have all been implicated in the etiology of
OHSS.
"
&
&
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8. Pathogenesis of OHSS
adopted from Soares et al (2008)
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9. Pathogenesis of OHSS
adopted from Humaidan P et al (2010)
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10. 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(pre4hCG(treatment(E2(is(>6000mcg(and(/or(if(
>30(follicles(are(present,(the(rate(of(severe(OHSS(approaches(80%(
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11. 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
• Not applicable
• Not applicable

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12. 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.&&&
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13. 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

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14. 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
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15. Prognosis (Lucidi,2013)
! Mild"and"moderate"cases"="excellent"prognosis"
! Severe"cases"="morbidity"is"clinically"significant,"and"fatali+es"
do"occur."However,"the"prognosis"is"op+mis+c"if"adequate"
treatment"is"given."
! D
1. "hypovolemic"shock"
2. Electrolyte"imbalance"
3. Hemorrhage""
4. Thromboembolism"
! Es+mated"fatality"rates"are"1per"400,000"–"500,000"s+mulated"
cycles"
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16. PREVENTION OF OHSS
Introduction
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• 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""

17. 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





&
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18. PREVENTION OF OHSS
Primary Prevention
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1. Reducing Exposure to Gonadotrpins:
(a)"Reducing"the"dose"–"IUI"cycles:"e.g."PCOS"pa+ents;"use""
chronic"*"lowRdose"stepRup"protocols"are"associated"with"lower"OHSS"&"
mul+ple"pregnancy."
"(b)"Reducing"Dura+on"of"FSH"ExposureR"IVF/ICSI"cycles:"
""R"Use"of"“mild"s+mula+on"protocols**”"."
""R"Once"E2""reach"250R300pg/ml"+"several"follicles"11R12mm,"we"begin"to"
reduce"gonadotropin"dose"in"stepRdown"fashion"(more"physiologic)""

19. PREVENTION OF OHSS
Primary Prevention
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2- Using combined oral contraceptives:("OCPRGnRH"
agonistR"dual"suppression"protocol)":"in"high"risk"pa+ents;"
ROCP"for"28"days!"leuprolide"acetate"(Lupron)"1mg"started"on"day"
21,"overlapping"OCP"for"7days."On"D3"of"withdrawal"bleeding"lowR
dose"(150"IU)"hMG"or"rFSH"is"started"&"leuprolide"dose"reduced"to"
0.5mg/day."StepRdown"gonadotropin"adjustment"is"usually"made."
RIn"some"pa+ents"start"gonadotropin"at"very"low"dose"(37.5"IU/d)"
increased"in"a"stepRup"fashion"un+l"follicles"="12"mm"then"step"down.""
"

20. PREVENTION OF OHSS
Primary Prevention
3. GnRH Antagonist Protocols:
: The"differen+al"ac+on"of"GnRH"antagonists"at"both"
pituitary"&"ovarian"receptors"suggests"that"antagonistR"
suppressed"cycles"might"result"in"a"lower"incidence"of"
OHSS."
: Other"advantages"of"GnRH"antagonists:"lack"of"flare"effect,"no"
accompanying"menopausalR"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"
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21. 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)&
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22. 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&=12R14mm.&&
: 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)&
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23. 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"monoRtherapy"or"in"combina+on"with"other"in"IO"drugs"
and"as"a"pretreatment"before"IUI"or"IVF/ICSI."
: A"2006"metaRanalysis"of"8"RCT"of"menormin"coRadministra+on"during"
gonadotropinRs+mulated"IO"or"IVF"in"women"with"PCO"found"a"
significant"posi+ve"effect"on"the"incidence"of"OHSS"("Costello"et"al"
2006)"
&
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24. 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 strategies
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25. PREVENTION OF OHSS
Secondary Prevention
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 1
st
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)
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26. PREVENTION OF OHSS
Secondary Prevention
2- Reduced Dose of hCG:
! 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)."
! "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)"
! Cycle"cancella+on"is"a"possible"drawback"of"low"dose"hCG"
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27. PREVENTION OF OHSS
Secondary Prevention
3- Cryopreservation of All Embryos:
! 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."
! "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.""
! No"significant"difference""in"clinical"pregnancy"between"cycle"with""
fresh"ET,"and"those"with"thawed"embryos""(CDC"2005"Report)"
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28. PREVENTION OF OHSS
Secondary Prevention
4- Cycle Cancellation:
! Cycle"cancella+on"&"withholding"of"hCG"is"the"
only"guaranteed"method"for"preven+on"of"early"
OHSS"(Schenker"&"Weinstein"1978)."
! D
physicians"are"reluctant"to"use"it"in"IVF"cycles"
because"of"the"financial"burden"&"psychological"
distress"to"the"pa+ent."
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29. PREVENTION OF OHSS
Secondary Prevention
5- Alternative Agents for Triggering Ovulation:
A- GnRH agonist: Used"in"gonadotropinRonly"or"antagonistR"
s+mulated"cycles"(i.e."No"receptor"downRregula+on)."
! 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)."
! 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)."
! 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)"

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30. PREVENTION OF OHSS
Secondary Prevention
5- Alternative Agents for Triggering Ovulation:
B- Recombinant LH (rLH)
! "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)"
! D
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)"

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31. PREVENTION OF OHSS
Secondary Prevention
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."
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32. PREVENTION OF OHSS
Secondary Prevention
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"1
st
"line"treatment"
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33. PREVENTION OF OHSS
Secondary Prevention
8- Dopamine Agonists:
- principle: In&PCOS; Cabergoline&(Cb2)pretreatment&before&OI,&
reduces&ovarian&response&to&FSH&by&controlling&LH&levels&#&
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).""""
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34. PREVENTION OF OHSS
Secondary Prevention
9- Calcium gluconate infusion:
R"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"highR
risk"pa+ents."(Naredi"&"Karunkaran"2013)
&"
"
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35. PREVENTION OF OHSS
Secondary Prevention
10- Glucocorticoids.
! Glucocor0coids&and&their&deriva0ves&have&an&inhibitory&
effect&on&the&VEGF&gene&expression&in&vascular&smooth&
muscle&cells&(Nauck&et&al&1998).&
! &An&addi0onal&effect&is&the&non&specific&preven0on&of&
the&inflammatory&response&and&edema&forma0on&&
(&Perrec&2000).&
! The"op+mal"protocol"&"the"drawback"of"the"an+angiogenic"
effect"on"the"endometrium"needs"more"inves+ga+on"
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36. PREVENTION OF OHSS
SUMMARY
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37. 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"
intraRovarian"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.""
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38. 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)


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39. 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.
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40. TREATMENT OF OHSS
Patient Assessment (contd.,):
Physical"examina+on":"
R"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.

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41. 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).
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42. 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).
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43. 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)
-

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44. TREATMENT OF OHSS
3- Pleuracentesis:

" Drainage of ascites usually resolves a
pleural effusion.
"  Symptomatic pleural effusions that persist
despite paracentesis can also be drained.

WARDA 44

45. 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

46. 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

47. 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

48. 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

49. 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.
49 WARDA

50. 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

51. WARDA 51
SUMMARY &
CONCLUSIONS

52. 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

53. Diagnosis of OHSS:
! Clinicians need to be aware of the symptoms &
signs of OHSS , as the diagnosis is based on
clinical criteria.
!  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

54. ! The severity of OHSS should be graded
according to a standardised classification
scheme.

! 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

55. ! 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

56. 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

57. ! Licensed centres that provide fertility
treatment should ensure close liaison and
coordination with acute units where patients
may present [new 2016]
! 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

58. ! Outpatient management is appropriate for
women with mild or moderate OHSS and in
selected cases with severe OHSS.
!  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.
! Nonsteroidal anti-inflammatory agents should be
avoided, as they may compromise renal function.
WARDA 58
SUMMARY &
CONCLUSIONS

59. 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

60. ! Paracentesis of ascitic fluid may be
carried out on an outpatient basis by
the abdominal or transvaginal route
under ultrasound guidance.
! 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

61. 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

62. 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

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

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

65. ! 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.
! Analgesia and anti-emetics may be used in
women with OHSS, avoiding non-steroidal
agents and medicines contraindicated in
pregnancy.
WARDA 65
SUMMARY &
CONCLUSIONS

66. ! Fluid replacement by the oral route, guided
by thirst, is the most physiological approach
to correcting intravascular dehydration.
! 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

67. 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

68. 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

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

70. ! The duration of LMWH prophylaxis should be
individualised according to patient risk
factors and outcome of treatment. [New
2016]
! 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

71. ! 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

72. ! 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.
! 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

73. WARDA 73
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