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13 Com
p
lications of
A
ssisted Re
p
roductio
n
Kee J.
O
ng
.
C
. L
i
E
nlan
X
ia
Yu
h
ua Li
u
The practice of assisted reproduction has evolved signifi
cantly since the birth
of Louise Brown, the world’s fi
rst baby born as a result of in vitro fertilization
IVF
)
, in 1978. Since then, more than 1 million babies have been born as a
result of assisted reproduction around the world. The chan
g
es in practice are
man
y
; amon
g
them: dail
y
blood tests and abdominal ultrasound have been
replaced b
y
infrequent transva
g
inal scans; laparoscopic ooc
y
te retrieval under
g
eneral anesthetic has been replaced b
y
transva
g
inal ultrasound–controlled
ooc
y
te collection with sedation anal
g
esia. In addition, advances include elec-
tive transfer of 1 to 2 embr
y
os and introduction of new laborator
y
techniques
s
uch as intrac
y
stoplasmic sperm in
j
ection (ICSI), in vitro maturation (IVM),
preimplantation
g
enetic dia
g
nosis, and new techniques in cr
y
opreservation.
While these chan
g
es have led to an increase in pre
g
nanc
y
rates, the
y
have also
been accompanied b
y
well-known complications such as multiple pre
g
nancies,
ovarian h
y
perstimulation s
y
ndrome, and possible adverse neonatal outcome.
Other complications associated with assisted reproduction ma
y
arise durin
g
different phases of treatment, from ovarian stimulation, from sur
g
ical proce-
dures such as ooc
y
te and sperm retrieval, and from embr
y
o transfer, and ma
y
affect lon
g
-term outcome amon
g
the offsprin
g
. This chapter does not include
complications related to laborator
y
practice.
C
ompl
i
cat
i
ons Assoc
i
ated w
i
th Ovar
i
an St
i
mulat
i
o
n
Ovarian Hyperstimulation Syndrom
e
O
varian stimu
l
ation is an integra
l
part o
f
assiste
d
repro
d
uction, an
d
ovarian
h
yperstimu
l
ation syn
d
rome (OHSS) is a
k
nown iatrogenic comp
l
ica-
tion resu
l
ting pre
d
ominant
l
y
f
rom ovarian stimu
l
ation. It can
b
e a
l
i
f
e
-
threatening condition and is characterized by fl
ui
d
s
h
i
f
t
f
rom t
h
e intravascu
l
ar
compartment to t
h
e t
h
ir
d
space
d
ue to increase
d
capi
ll
ary permea
b
i
l
ity an
d
https://t.me/med1917
28 K.J. On
g
et al.
o
varian neoan
g
io
g
enesis. T
h
is s
y
n
d
rome is invaria
bly
tri
gg
ere
d
a
f
ter a
d
min-
i
stration o
f
h
uman c
h
orionic
g
ona
d
otropins (
h
CG), a
l
t
h
ou
gh
on rare occasion
i
t can occur in t
h
e a
b
sence o
f
hCG
.
Th
e true inci
d
ence o
f
OHSS is un
k
nown; severe
f
orms o
f
OHSS are re
p
orte
d
i
n approximate
ly
0.5% o
f
stimu
l
ate
d
c
y
c
l
es, mo
d
erate
f
orms in 1%–7%, an
d
m
ild OHSS in 8%–23% [1]. Althou
g
h it can present earl
y
after the administra
-
t
ion o
f
h
CG or
l
ater
d
ue to secretion o
f
p
l
acenta
l
h
CG i
f
t
h
e patient is pre
g
nant,
the early-onset OHSS is more common. Several classifi
cations o
f
O
H
SS
h
ave
been suggested over the years, and Golan classifi
cation is the most frequently
u
se
d
[
2
]
.
Wh
i
l
e t
h
e exact mec
h
anism res
p
onsi
bl
e
f
or OHSS is un
k
nown, t
h
e
p
at
h
o
-
ph
ysio
l
ogica
l
casca
d
e o
f
OHSS consists o
f
neoangiogenesis an
d
increase
d
cap-
illary permeability of the enlarged ovarian and other endothelial surfaces, fl
ui
d
sh
i
f
t
f
rom t
h
e intravascu
l
ar s
p
ace to extravascu
l
ar s
p
ace,
h
emoconcentration,
decreased renal clearance, oliguria, hyperviscosity of blood, modifi
catio
n
i
n
c
oa
g
u
l
ation
f
actors, an
d
t
h
rom
b
oem
b
o
l
ic ris
k
s. Man
y
me
d
iators
h
ave
b
een
p
ropose
d
to
b
e invo
l
ve
d
in OHSS, an
d
vascu
l
ar en
d
ot
h
e
l
ia
l
g
rowt
h
f
actor
VEGF), a proan
g
io
g
enic
f
actor, is t
h
e most
l
i
k
e
ly
me
d
iator. VEGF is present
in high concentrations in the serum, follicular, and ascites fl
ui
d
o
f
p
atients
w
it
h
OHSS.
Th
e main ris
k
f
actors
f
or t
h
e
d
eve
l
opment o
f
OHSS inc
l
u
d
e young age,
l
ow
b
o
dy
wei
gh
t, po
ly
c
y
stic ovaries,
h
i
gh
serum estra
d
io
l
concentration (
>
3000–
4
000 pg/mL),
l
arge num
b
er o
f
oocytes retrieve
d
, an
d
past
h
istory o
f
OHSS
.
Patients c
l
assica
ll
y present wit
h
a
bd
omina
l
d
istension an
d
pain, nausea,
v
omitin
g
, wei
gh
t
g
ain, an
d
s
h
ortness o
f
b
reat
h
. C
l
inica
l
si
g
ns inc
l
u
d
e o
l
i
g
uria,
h
emoconcentration,
l
eu
k
oc
y
tosis, e
l
ectro
ly
te im
b
a
l
ance,
hy
percoa
g
u
l
a
b
i
l
it
y
,
a
scites, p
l
eura
l
e
ff
usion, an
d
a
d
u
l
t respirator
y
d
istress s
y
n
d
rome
.
T
h
rom
b
oem
b
o
l
ic event is increase
d
in OHSS an
d
can
b
e exp
l
aine
d
b
y
h
emoconcentration an
d
immo
b
i
l
ity resu
l
ting
f
rom t
h
is con
d
ition. Ot
h
er
factors include mechanical compression of venous blood fl
ow in the pelvic
b
rim an
d
t
h
e
l
ower
l
im
b
an
d
h
ig
h
estra
d
io
l
l
eve
l
. In a stu
d
y
b
y De
l
vigne an
d
R
ozen
b
erg [3], t
h
e aut
h
ors reporte
d
t
h
at t
h
e most
l
i
k
e
l
y t
h
rom
b
osis event is
v
enous in origin an
d
t
h
e majority occur in t
h
e nec
k
or arm veins
.
Ovarian torsion is more common in t
h
e presence o
f
OHSS. T
h
e c
h
aracter-
i
stic s
y
mptoms inc
l
u
d
e su
dd
en, extreme a
bd
omina
l
pain accompanie
d
by
n
ausea. Ovarian torsion occurs in 1 o
f
5000 stimu
l
ate
d
c
y
c
l
es [4], an
d
ear
ly
d
iagnosis an
d
untwisting o
f
t
h
e ovary at
l
aparoscopy or
l
aparotomy is essentia
l
a
n
d
may resu
l
t in surviva
l
o
f
t
h
e ovary
.
Primar
y
prevention is t
h
e most e
ff
ective wa
y
to avoi
d
t
h
is iatro
g
enic con
d
i
-
t
ion. Ovarian stimu
l
ation s
h
ou
ld
b
e contemp
l
ate
d
on
l
y w
h
en a
l
ternative treat-
m
ent suc
h
as
l
i
f
esty
l
e c
h
anges (
d
iet an
d
exercise)
h
as
f
ai
l
e
d
, especia
ll
y in
o
verweig
h
t patients wit
h
po
l
ycystic ovary syn
d
rome. Stimu
l
ation protoco
l
sh
ou
ld
b
e “so
f
t,”
f
or examp
l
e, t
h
e use o
f
l
ow-
d
ose step-up regimens.
A num
b
er o
f
secon
d
ary preventative measures
f
or OHSS inc
l
u
d
e cyc
l
e
c
ance
ll
ation
b
y wit
hh
o
ld
ing
h
CG, an
d
coasting, w
h
en gona
d
otropin a
d
minis-
t
ration can
b
e
d
ecrease
d
or stoppe
d
w
h
i
l
e continuing gona
d
otropin-re
l
easing
h
ormone agonist a
d
ministration. A
l
t
h
oug
h
coasting
h
as
b
een s
h
own to
b
e
eff
ective in compare
d
o
b
servationa
l
stu
d
ies, t
h
e on
ly
ran
d
omize
d
contro
ll
e
d
https://t.me/med1917
13. Com
p
lications of Assisted Re
p
roduction 12
9
tria
l
on coastin
g
, w
h
ic
h
compare
d
coastin
g
to uni
l
atera
l
f
o
ll
icu
l
ar aspiration,
showed no benefi
t [5].
El
ective cr
y
opreservation o
f
a
ll
em
b
r
y
os an
d
t
h
e use o
f
pro
g
esterone as
l
utea
l
-p
h
ase support
h
ave
b
een a
d
vocate
d
. Cr
y
opreservation o
f
a
ll
em
b
r
y
os
h
as not
b
een s
h
own to
b
e e
ff
ective in preventin
g
OHSS in s
y
stematic review
[6], but the use of pro
g
esterone can decrease the risk of OHSS, compared to
t
h
e use o
f
h
CG
l
utea
l
su
pp
ort.
I
t
h
as
b
een su
gg
este
d
t
h
at a
d
ministration o
f
a
lb
umin
d
urin
g
ooc
y
te
retrieva
l
in
h
i
gh
-ris
k
patients can interrupt t
h
e
d
eve
l
opment o
f
OHSS. S
y
stem
-
atic review by Aboulghar et al. [7] showed that it is benefi
c
i
al
but
also
assoc
i-
ate
d
wit
h
si
d
e e
ff
ects suc
h
as vira
l
transmission, nausea, vomitin
g
, an
d
f
e
b
ri
l
e
an
d
a
ll
ergic reactions. It is a
l
so expensive. Treatment o
f
OHSS is main
l
y sup-
portive. T
h
e con
d
ition is se
lf
-
l
imiting, an
d
reso
l
ution para
ll
e
l
s wit
h
d
ec
l
ine in
h
CG. W
h
i
l
e a mi
ld
d
e
g
ree o
f
OHSS can
b
e mana
g
e
d
as outpatient, severe cases
require
h
ospita
l
a
d
mission. Ear
ly
-onset OHSS usua
lly
ta
k
es a wee
k
to reso
l
ve,
w
h
ereas
l
ate-onset OHSS requires
l
on
g
er, approximate
ly
10–20
d
a
y
s. For
s
evere cases, t
h
e princip
l
es o
f
mana
g
ement inc
l
u
d
e circu
l
ator
y
support usin
g
intravenous fl
uids, maintenance of renal function, thromboprophylaxis, and
drainage of third-space accumulation of fl
u
i
d.
M
ult
i
ple Pregnanc
i
es
T
he incidence of multiple pre
g
nancies has increased substantiall
y
over the
past 20
y
ears and is attributed to the use of assisted reproductive technolo
g
ies.
Ovarian stimulation with the aim of inducin
g
multiple follicular developments
and the practice of multiple-embr
y
o transfer are responsible for the increased
risk of multiple pre
g
nancies. The risk of twin pre
g
nanc
y
resultin
g
from clo
-
miphene treatment is approximatel
y
10%; with IVF and 2 embr
y
os replaced,
the risk is 20%-30%
;
and with ovarian stimulation and intrauterine insemina-
tion, the risk is 10%-20%. Perinatal and maternal morbidit
y
and mortalit
y
are
increased in multiple pre
g
nancies compared to sin
g
leton pre
g
nancies [8].
Maternal risks include hi
g
her incidence of preeclampsia and
g
estational dia
-
betes. Assisted va
g
inal deliveries and cesarean section rates are considerabl
y
hi
g
her in multiple pre
g
nancies. The hi
g
her incidence of perinatal morbidit
y
and mortalit
y
is related to prematurit
y
and low birth wei
g
hts in multiple
g
esta-
tions. There is an increased risk of cerebral pals
y
in multiple pre
g
nancies, and
the risk also becomes hi
g
her as the number of babies increases
.
T
o reduce multiple pre
g
nancies, a “soft” stimulation protocol should be
used, and close monitorin
g
is required durin
g
treatment. All assisted-
conce
p
tion units should have set criteria for cancellation or conversion to
IVF. Patients must be counseled and made aware that multiple pre
g
nancies
are com
p
lications rather than “bonuses” from assisted re
p
roduction. Elective
s
in
gl
e em
b
r
y
o trans
f
er (eSET) is an e
ff
ective wa
y
o
f
re
d
ucin
g
mu
l
tip
l
e pre
g-
nancies. Ex
p
erience in Scan
d
inavian countries s
h
owe
d
t
h
at in se
l
ecte
d
p
atients
wit
h
goo
d
prognosis, pregnancy rates a
f
ter eSET are compara
bl
e to t
h
ose seen
f
o
ll
owing
d
ou
bl
e em
b
ryo trans
f
er [9,10].
https://t.me/med1917
30 K.J. On
g
et al.
C
a
ncer R
i
sks
O
ver t
h
e
y
ears, ovu
l
ation-in
d
uction a
g
ents
h
ave
b
een
l
in
k
e
d
to increase
d
r
is
k
o
f
ovarian or
b
reast cancer,
b
ut
d
irect causa
l
re
l
ations
h
i
p
is
h
ar
d
to
e
stablish because of the limitations of the studies, includin
g
small number of
s
u
bj
ects, s
h
ort
f
o
ll
ow-up, an
d
imprecise in
f
ormation on
d
ru
g
exposures or
i
n
d
ication o
f
use. Stu
d
ies
h
ave a
l
so
b
een
l
imite
d
by
reca
ll
b
ias in t
h
e case o
f
r
etrospective stu
d
ies an
d
t
h
e presence o
f
con
f
oun
d
in
g
f
actors. W
h
i
l
e ear
l
ier
s
tu
d
ies
by
W
h
ittemore et a
l
. [11] an
d
Rossin
g
et a
l
. [12] su
gg
este
d
an increase
d
r
isk, more recent studies have been reassurin
g
, and there does not appear to
b
e an
y
causal relationship between ovulation-inducin
g
dru
g
s and ovarian and
b
reast cancer
[
13,14
].
B
ased on current evidence
,
there is no conclusive link between ovulation
i
nduction and cancer risks. The limitations of current studies re
q
uire that
a
dditional studies be performed to monitor the lon
g
-term effects of ovulation
i
n
duct
i
o
n
.
C
ompl
i
cat
i
ons Assoc
i
ated w
i
th
Sur
g
ical Procedure
s
Oocyte Retr
i
eval
T
he use of transva
g
inal ultrasound–
g
uided ooc
y
te retrieval instead of
l
aparoscopic ooc
y
te collection has made the procedure safer. Despite its lo
w
c
om
p
lication rates,
p
atients still need to be counseled about the
p
ossible com
-
p
lications involved. There are limited data on this sub
j
ect, so complications
m
a
y
be underestimated. Ooc
y
te retrieval can inadvertentl
y
lead to dama
g
e to
p
elvic or
g
ans, bleedin
g
from va
g
inal wall, or intraabdominal bleedin
g
and
i
nfection, which ma
y
lead to serious morbidit
y
and mortalit
y
.
T
he most common complication associated with ooc
y
te retrieval is minor
v
a
g
inal bleedin
g
. Two prospective studies have been conducted; one reported
a
n incidence of 2.8%, whereas the other re
p
orted an incidence of 8.6% [15,16].
H
owever, Bennett et al. [16], who reported va
g
inal bleedin
g
in 8.6%, did not
p
rovide information on how assessment of va
g
inal bleedin
g
was made. Retro
-
s
pective studies have reported the incidence of intraabdominal bleedin
g
to be
b
etween 0.08% and 0.2% [17]. Pelvic infections leadin
g
to tubo-ovarian abscess
f
ortunatel
y
are rare and occur in
1% of procedures [15]. The pathoph
y
siolo-
g
ies of pelvic infections are possibl
y
due to inoculation of va
g
inal microor
g
an
-
isms into the ovary, reactivation of latent pelvic infl
ammatory disease, or
direct colonic injury [18]. Coliforms were the most commonly identifi
ed
organisms in pelvic infection, and patients with a history of pelvic infl
a
mm
a-
t
or
y
disease have a hi
g
her likelihood of tubo-ovarian and pelvic abscess [19].
P
roph
y
laxis antibiotics to date do not seem to be helpful in preventin
g
pelvic
i
nf
ect
i
o
n
.
https://t.me/med1917
13. Com
p
lications of Assisted Re
p
roduction 13
1
Th
e aspiration nee
dl
e ma
y
ina
d
vertent
ly
traumatize proxima
l
pe
l
vic struc-
tures. A
l
t
h
ou
gh
l
ar
g
e prospective stu
d
ies
h
ave not reporte
d
an
y
inci
d
ence o
f
b
owe
l
in
j
ur
y
, t
h
ere
h
ave
b
een 2 case reports o
f
per
f
orate
d
appen
d
ix
b
ut none
on ot
h
er parts o
f
t
h
e
b
owe
l
. It is a
l
so possi
bl
e t
h
at
b
owe
l
injuries occurre
d
wit
h
out
b
ein
g
d
ia
g
nose
d
an
d
reso
l
ve
d
spontaneous
ly
. In
j
uries to t
h
e ureter
h
ave
b
een reporte
d
in prospective stu
dy
an
d
case reports [15]. C
l
inicians
invo
l
ve
d
in oocyte-retrieva
l
proce
d
ures must
h
ave a
h
ig
h
in
d
ex o
f
suspicion;
to minimize t
h
is comp
l
ication, care s
h
ou
ld
b
e ta
k
en
d
uring t
h
e proce
d
ure, an
d
re
l
ia
bl
e transva
g
ina
l
u
l
trasoun
d
scan s
h
ou
ld
b
e avai
l
a
bl
e.
S
perm Retr
i
eval: Nonsurg
i
cal and Surg
i
ca
l
F
or men w
h
o pro
d
uce no sperm in t
h
e ejacu
l
ate, t
h
ere are a variety o
f
nonsurgica
l
an
d
surgica
l
retrieva
l
tec
h
niques to retrieve sperm
f
rom eit
h
er t
h
e
epi
d
i
dy
mis or t
h
e testic
l
e itse
lf
. T
h
e met
h
o
d
use
d
d
epen
d
s on t
h
e cause o
f
azoospermia. In patients w
h
o are anejacu
l
atory
d
ue to spina
l
cor
d
injuries or
d
ia
b
etes, nonsurgica
l
met
h
o
d
s, suc
h
as peni
l
e vi
b
ratory stimu
l
ation or e
l
ec-
troejacu
l
ation, can
b
e use
d
. A
l
t
h
oug
h
comp
l
ications are rare, c
l
inicians s
h
ou
ld
look out for autonomic dysfl
exia, which can result in acute hypertension. In
cases o
f
h
i
gh
bl
oo
d
pressure, su
bl
in
g
ua
l
ni
f
e
d
ipine 10–20 m
g
can
b
e a
d
minis-
tere
d
, an
d
patients s
h
ou
ld
b
e monitore
d
c
l
ose
l
y. Ot
h
er comp
l
ications inc
l
u
d
e
l
oca
l
s
k
in
b
ruising, an
d
t
h
ere is a 1 in 1000 c
h
ance o
f
recta
l
injury in t
h
e use
o
f
e
l
ectroe
j
acu
l
ation
.
S
urgica
l
sperm retrieva
l
appears to
b
e a sa
f
e proce
d
ure, especia
ll
y w
h
en
per
f
orme
d
un
d
er
l
oca
l
anest
h
esia. T
h
e
f
requencies o
f
comp
l
ications are
l
ow.
Specifi
c complications include wound infection, hematoma, and pain. In the
absence of hematoma, wound infection is rare. Signifi
cant hematoma may
resu
l
t
f
rom unrecognize
d
h
emorr
h
age o
f
t
h
e testicu
l
ar artery on t
h
e sur
f
ace
o
f
t
h
e tunica a
lb
uginea. Ina
d
vertent
b
iopsy o
f
epi
d
i
d
ymis can resu
l
t in epi
-
didymal obstruction and signifi
cantly complicate subsequent reconstructive
s
u
r
ge
r
y.
P
ermanent testicu
l
ar
d
evascu
l
arization resu
l
tin
g
in testicu
l
ar atrop
hy
h
as
b
een reporte
d
a
f
ter attempte
d
sperm retrieva
l
f
rom mu
l
tip
l
e testicu
l
ar sites.
For repeat sperm retrieva
l
proce
d
ures, up to 6 mont
h
s may
b
e necessary to
a
ll
ow comp
l
ete
h
ea
l
ing an
d
restoration o
f
optima
l
spermatogenesis a
f
ter
testicu
l
ar epi
d
i
d
yma
l
sperm retrieva
l
[20].
C
ompl
i
cat
i
ons Assoc
i
ated w
i
th
mbr
y
o Transfer Techn
i
qu
e
T
here is increasin
g
evidence to su
gg
est that poor embr
y
o transfer tech
-
nique is associated with hi
g
her incidence of ectopic pre
g
nancies. Nazari et al.
[21] reported an increased incidence of ectopic pre
g
nancies with hi
g
h-fundal
https://t.me/med1917
32 K.J. On
g
et al.
e
m
b
r
y
o trans
f
er compare
d
to mi
d
-
f
un
d
a
l
em
b
r
y
o trans
f
er, w
h
ereas Bennett
e
t a
l
. [22] s
h
owe
d
h
i
gh
er inci
d
ence o
f
cervica
l
ectopic pre
g
nanc
y
wit
h
l
ow
t
rans
f
er o
f
em
b
r
y
os
.
Safety of Assisted Reproduction
Th
e a
b
i
l
ity o
f
assiste
d
repro
d
uction to circumvent nature to ac
h
ieve preg
-
n
ancy
h
as
l
e
d
to concerns a
b
out its sa
f
ety. A
l
t
h
oug
h
Hansen et a
l
. [23] reporte
d
h
ig
h
er ris
k
s o
f
b
irt
h
d
e
f
ects in in
f
ants a
f
ter IVF/ICSI compare
d
to spontane
-
o
us
l
y conceive
d
in
f
ants, it is yet to
b
e esta
bl
is
h
e
d
i
f
t
h
e increase in ma
lf
orma
-
t
ions is re
l
ate
d
to assiste
d
repro
d
uctive tec
h
no
l
ogy or t
h
e
b
ac
k
groun
d
h
istor
y
of infertility. To date, there are no studies of suffi
cient power to assess t
h
e
effi
cacy and safety of assisted reproduction, and studies are hampered by lack
of control, sample size, lack of agreed defi
nition o
f
ma
lf
ormations, an
d
pres
-
e
nce o
f
con
f
oun
d
ing
f
actors
.
M
a
l
e o
ff
spring o
f
in
f
erti
l
e ma
l
es wit
h
c
h
romosome a
b
norma
l
ities suc
h
as
Y
-c
h
romosome micro
d
e
l
etions an
d
autosoma
l
a
b
errations are
l
i
k
e
l
y to in
h
erit
th
e same a
b
norma
l
ity [24]. Imprinting
d
isor
d
ers suc
h
as Bec
k
wit
h
-Wie
d
e-
m
ann syn
d
rome an
d
Ange
l
man syn
d
rome
h
ave
b
een reporte
d
to
b
e more
c
ommon in assiste
d
repro
d
uction,
b
ut again, stu
d
ies are
l
imite
d
b
y samp
l
e
s
ize. While singleton IVF and ICSI children were more likely to need health-
c
are resources t
h
an c
h
i
ld
ren
f
rom spontaneous conception, t
h
ere were no
d
i
ff
erences in cognitive
d
eve
l
opment
b
etween t
h
em [25]
.
D
ue to the constraints of the available studies, no conclusion can be drawn
a
t t
h
is stage. C
l
inicians must
b
e a
bl
e to provi
d
e proper counse
l
ing to coup
l
es
u
n
d
ergoing assiste
d
repro
d
uction an
d
must exp
l
ain t
h
at t
h
e possi
b
i
l
ity o
f
an
i
ncrease in
b
irt
h
d
e
f
ects exists
b
ut t
h
at a
b
so
l
ute ris
k
o
f
major anoma
l
ies is
s
ma
ll
[26].
C
onclus
i
on
A
ssisted re
p
roduction will continue to evolve, and the risk of com
p
lica
-
t
ions associated with sur
g
ical procedures such as ooc
y
te collection and sperm
r
etrieval will continue to diminish. There is a need for s
y
stematic reportin
g
of
a
ll cases of OHSS
,
and to decrease the risk of OHSS
,
ovarian stimulation should
b
e indicated onl
y
as a last option. If ovarian stimulation is required, a “soft”
s
timulation protocol should be used and should include adequate monitorin
g
.
A
lthou
g
h different secondar
y
preventative measures for OHSS are available,
p
rimar
y
prevention is effective in decreasin
g
the risk of developin
g
this iatro-
g
enic condition
.
U
r
g
ent attention is required to minimize the risk of multiple pre
g
nancies,
g
iven that elective sin
g
le-embr
y
o transfer is an effective method in properl
y
s
elected
p
atients. Based on the current literature, there is no conclusive link
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