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Chapter 35: Multiple pregnancy
Table 35.1. Gestational age according to multiplicity in 961 IVF babies
(1978–1987)
Deliveries
Gestational age
(weeks)
Preterm
(< 37)
Term 86 (427) 42 (53) 5 (1) 75 (481)
Total 100 (494) 100 (125) 100 (20) 100 (639)
Mean 38.7 36.0 33.5 38.0
(± SE) (0.12) (0.24) (0.57) (0.12)
Reproduced with permission from Rizk B, et al. [6].
Table 35.2. Birth weight categories according to multiplicity in 961 IVF babies
(1978–1987)
Birth
weight (g)
<1000 2 (8) 3 (9) 4 (3) 2 (20)
1000–1499 2 (8) 5 (12) 18 (14) 4 (34)
1500–2499 10 (52) 45 (119) 70 (53) 26 (224)
2500–3499 58 (304) 45 (118) 8 (6) 50 (428)
3500 29 (155) 2 (4) - (0) 18(159)
Total 100 (527) 100 (262) 100 (76) 100 (865)
Mean 3124 2389 1895 2793
(± SE) (29.2) (36.3) (53.9) (26.1)
Singleton
%(n)
14 (67) 58 (72) 95 (19) 25 (158)
Singleton
%(n)
Twin %
(n)
Twin %
(n)
Triplet %
(n)
Triplet %
(n)
Total %
(n)
Total babies
%(n)
Table 35.4. Observed and expected deaths
Singleton babies Twin and triplet babies
Observed
deaths
Stillbirths 3 3.2 8 5.6
Deaths 0–7 days 5 2.4 6 6.8
Deaths 8–27 days 2 0.6 2 1.3
Deaths 28 days to
1 year
Reproduced with permission from Rizk B, et al. [6].
Table 35.5. Stillbirth and death rates for IVF babies
1 1.9 4 2.9
Expected
deaths
Observed
deaths
Expected
deaths
Rate Singleton Twin Triplet Total
Stillbirth rate per 1000 births 5.07 20.8 24.7 11.4
Perinatal death rate per 1000 births 13.5 38.2 37.0 22.9
Neonatal death rate per 1000 live
births (0–27 days)
Infant death rate per 1000 live
births (<1 year)
Reproduced with permission from Rizk B, et al. [6]
11.9 21.3 25.3 15.8
13.7 28.4 50.6 21.1
Reproduced with permission from Rizk B, et al. [6].
Table 35.3. Stillbirth and perinatal death rate per 1000 total births and infant
mortality rate per 1000 live births in IVF babies compared with mortality rates in
England and Wales
Bourn-Hallam
Outcome
Stillbirth 11.4 5.5
Perinatal mortality rate 22.9 9.8
Neonatal deaths 15.8 5.3
Early 11.6 4.3
Late 4.2 1.0
Postneonatal mortality 5.3 3.9
Infant mortality 21.1 9.4
Reproduced with permission from Rizk B, et al. [6].
IVF babies
England
and Wales
there is further increase in aneuploid risk for dizygotic (or
greater) gestations as well as the known increase associated
Figure 35.7. Monochorionic twins, “T” sign.
with advancing maternal age, this assumes even greater importance in assisted reproduction and multiple gestations.
Nuchal translucency (NT) measurement has become an
integral part of singleton pregnancy evaluation. In addition to
aneuploidy, abnormal NT measurements have been shown to
be associated with fetal congenital heart disease and other
293
Section 4: Early pregnancy after infertility treatment
Figure 35.8. Nuchal translucency, twin A.
anatomic abnormalities. Studies evaluating the quality of NT
measurements in multiple gestations have shown that there is
no significant difference between image quality in singleton
versus multiple gestations (Figures 35.8, 35.9).
However, as would not be unexpected, the fetuses that are
located farthest from the uterine wall in multiple gestations are
more difficult to evaluate and have poorer image scores [11].
Importantly, NT distributions and cut-off values do not differ
between singleton and multiple gestations and can therefore be
used for evaluation with the same sensitivity [12]. Abnormal
NT evaluation in twin gestations has been shown to be associated with future development of twin–twin transfusion and
discordance for anomalies.
Maternal serum analyte (marker) interpretation in conjunction with NT measurement is commonly used in singleton
gestations, with free beta human chorionic gonadotropin
(β-hCG) and pregnancy-associated plasma protein A (PAPPA) and NT having a 90% detection rate with a 5% false-positive
rate. However, the Fetal Medicine Foundation found a decrease
to 75% in dizygotic pregnancies discordant for trisomy 21 [13].
Second-trimester serum analyte (most commonly maternal
serum alpha-fetoprotein, β-hCG, serum estriol, and inhibin)
has also been shown to have a decreased detection rate in
multiple gestation as compared with singletons [14]. In conclusion, serum screening tests in multiple pregnancy hav e not
been found to be as sensitive in singletons. Nuchal translucency
alone offers a better detection rate and can be followed up with
early diagnostic testing [15].
Invasive procedures
As in singleton pregnancies, when there are maternal agerelated risks, abnormal first- or second-trimester screening, or
the finding of congenital anomalies, definitive fetal karyotype
assessment is often requested in multiple gestations. Both
amniocentesis and chorionic villus sampling can be safely
accomplished in multiple gestations.
Figure 35.9. Nuchal translucency, twin B.
Amniocentesis is generally performed after 15 weeks.
Ultrasound evaluation should always be performed with care
to accurately determine the location of each fetus and sac in
order to be able to distinguish which specimen was from which
fetus in case the results return discordance for aneuploidy.
Unless there is discordance for an anomaly, in general both
twins need to be sampled. There is some question whether both
need to be sampled in a monozygotic gestation. As there have
been reports of postzygotic mutations and discordance for
abnormalities, however, most authorities recommend that
both be sampled. Continuous ultrasound guidance is used
during the procedure and single- and double-needle techniques
can be utilized. Indigo carmine dye is injected into the sac of the
tested fetus so that when the next sac is sampled clear fluid
confirms that the same sac is not being inadvertently resampled. When high-order gestations are sampled, each successively tested sac is injected with dye. Methylene blue is not to
be used because of significant associated fetal risks. There are
limited data on the risks of procedure-associated loss rates in
multiple gestations, with a reported range from 2.3% to 8.1%.
As the background loss rate for twins prior to 24 weeks is 6%, it
is unclear whether the loss rate is attributable to the procedure
or to the twin pregnancy [16]. Amniocentesis is also used
frequently in multiple gestations for assessment of fetal lung
maturity or intra-amniotic infection. Continuous ultrasound
guidance during the procedure is again used to improve the
success rate and safety.
Chorionic villus sampling (CVS) can also be performed in
multiple gestations, and is usually performed at 10–12 weeks’
gestation using either a transabdominal or transcervical
approach. Each placenta can usually be biopsied using the
transabdominal technique due to a variety of procedural “windows.” However, because of placental/cervical orientation, only
one placenta in a multifetal gestation is typically able to be
sampled transcervically. Continuous ultrasound guidance is
used for these procedures. As with amniocentesis, care is
needed to determine the location of each placenta in relation
294
to each sac and fetus. Also as with amniocentesis, there are
limited data on the procedural loss rate for CVS in multiple
gestations. The reported studies show acceptable loss rates
(0.6–4.2%) in relation to the background loss rate [16]. In
both multifetal amniocentesis and CVS, operator experience
is of paramount importance in determining loss rates.
Multifetal reduction
Because of the significant increase in risk associated with multi-
ple gestations, especially high-order ones, reduction of the number of fetuses has been used in an attempt to decrease overall
morbidity and mortality. Multifetal pregnancy reduction (MPR)
and selective termination (ST) are techniques developed in an
attempt to decrease specific risks from multiple gestation.
Ultrasound is essential in the performance of MPR and ST for
use in identifying chorionicity, in diagnosis of anomalies, and for
guidance during the procedure itself. The most commonly used
technique for MPR and ST involves injection of potassium
chloride into the fetus(es) to be reduced. This can be done safely
in multichorionic gestations as there are no interfetal vascular
anastamoses. However, virtually all monochorionic gestations
have some degree of vascular communication and this allows
passage of the toxin used between gestations. Further, adverse
hemodynamic changes can occur in the survivor due to blood
loss into the dead fetus. As discussed previously,early assessment
of chorionicity can generally be established by ultrasound assessment of membrane status.
MPR is usually done at 10–13 weeks. This is beyond the time
when most spontaneous losses will have occurred, and allows
for ease in technical performance of the reduction procedure
and use of CVS (if desired) prior to reduction. The fetus(es)
reduced are usually those that are most easily accessible (usually
those closest to the anterior uterine wall). If possible, the fetus
nearest the cervix is avoided for the reason of theoretical concerns about infection and uterine irritability. The unintended
loss rate (loss of the entire pregnancy before 24 weeks) from the
procedure was 9.6% in the largest reported series [17].
However, this is weighed against the reported benefits, with
one study of triplet gestations reduced to twins compared with
expectant management showing a decrease in the rate of preterm delivery (less than 31 weeks) from 26.7% to 10.4% [18].
Most reductions are to twins, although some now advocate
consideration of reduction to singleton.
Selective termination has been shown to be feasible and to
help improve perinatal outcomes. It involves early diagnosis of
abnormalities to allow selective reduction of the affected fetus.
This can be accomplished as early as 11–14 weeks. A large series
involving triplet gestations found that ST resulted in significantly longer gestations than with expectant management (35.6
versus 31.1 weeks), higher mean birth weight, and more liveborn fetuses (97.4% versus 85.6%) [19 ]. A common situation
for ST would be one fetus of a multiple gestation with anencephaly. The anomaly can result in polyhydramnios of the
affected fetus due to impaired swallowing, with increased risk
for preterm labor and delivery (Figure 35.10). The technique for
Chapter 35: Multiple pregnancy
Figure 35.10. Anencephaly, twin B.
ST usually involves the injection of potassium chloride into the
thorax or heart of the a ff ected fetus under ultrasound guidance.
Monochorionic fetal reduction involves specific procedures
to avoid the risks due to interfetal placental vascular communications. It is most commonly done by cord occlusion via ultrasound guidance followed by fetoscopywith cord ligation, bipolar
coagulation, or laser occlusion. Because of technical limitations,
it is generally only performed in the second trimester and is
reserved for reductions indicated for reasons of discordance for
anomalies, twin–twin transfusion, and monochorionicity.
Pregnancy surveillance
Ultrasound plays an integral role in the surveillance of multiple
gestations and improvements in the outcomes of these pregnancies and would not be possible without advances in the
technology. The use of ultrasound in pregnancy can be divided
into four main categories:
1. Growth evaluation
2. Doppler velocimetry
3. Cervical length evaluation
4. Antenatal testing
Growth evaluation
Multiple gestations have a significantly increased risk of fetal
growth abnormalities compared with singletons and also are at
risk for discordant growth between fetuses. Growth abnormalities in twin and triplet gestations have been shown to be related
to the increase in morbidity and mortality, second only to
prematurity [20]. The finding of intrauterine growth restriction
(IUGR) in a fetus from a twin or tripletgestation, or the development of significant birth weight discordance between fetuses,
results in higher perinatal mortality, most likely due to placental
dysfunction/insufficiency [21,22]. Most management protocols
for twins recommend growth evaluation every 4 weeks after
18–20 weeks when dichorionic and every 2–4 weeks when
295
Section 4: Early pregnancy after infertility treatment
monochorionic (due to the further increased risk for twin–twin
transfusion). In trichorionic triplet gestations, growth evaluation is generally recommended every 3–4 weeks, and every 2–3
weeks when the triplets are monochorionic. A special note
should be made when there is a finding of a velamentous cord
insertion of one or more of the fetuses. This has been reported
to occur in as many as 28.2% of triplet gestations and is significantly associated with small-for-gestational age fetuses [23].
Doppler velocimetry
Pulsed-wave Doppler assessment of velocity in the fetal umbilical and middle cerebral arteries is commonly performed during ultrasound evaluation of multiple gestations; however, the
available data do not support a benefit for the routine assessment of these in uncomplicated twin and triplet gestations. In
contrast, studies do show that Doppler evaluation can result in a
significant improvement in the accuracy of ultrasound in the
prediction of fetal growth restriction in both twins and triplets.
Cervical length evaluation
A relatively recent advance in the management of multiple
gestation has been the use of endovaginal assessment of cervical
length in the prediction of risk for preterm birth (generally
defined as prior to 35 weeks). The finding of a cervix that is
normal in length (25 mm or more) is very reassuring that the
risk of preterm delivery is not high. One study of twins found
that in women who were actively contracting, none of the 21
women with a cervical length of 25 mm or higher delivered
within the next 7 days. In contrast, in 66 women with contractions and a length less than 25 mm, 16 delivered within this
interval [24]. In a study of triplet gestations, a length of less than
or equal to 25 mm between 15 and 20 weeks had a specificity
and positive predictive value of 100% for delivery prior to 28
weeks. This length found at 21–24 weeks’ gestation had a sensitivity of 86% for prediction of delivery prior to 28 weeks [25].
Identification of risk for preterm delivery can allow for timely
administration of antenatal corticosteroids and consideration
of tocolysis.
Cervical length evaluation can also be used to assess for risk
of early second-trimester delivery due to cervical insufficiency.
The risk of early second-trimester delivery is known to be
increased in multiple gestations and this is felt to be due to
biochemical changes and mechanical forces on the cervix from
overdistension. The sonographic finding s of a shortened cervical length, dilatation of the internal os, and/or funneling of
the membranes into the endocervical canal are the earliest
identifiable manifestations of cervical insufficiency [26].
Findings that are concerning for cervical insufficiency may
allow for identification of women who need more intense
follow-up or possible placement of a cervical cerclage
(Figures 35.11, 35.12, 35.13).
Antenatal testing
Because of the increased rates of perinatal mortality in multiple
gestations, antenatal assessment of fetal well-being is used in
essentially all of these pregnancies. However, regarding the
Figure 35.11. Quadruplet gestation, normal cervix.
296
Figure 35.12. Twin gestation cervix with funneling and shortening.
Figure 35.13. Twin gestation, cervix with cerclage.
Chapter 35: Multiple pregnancy
efficacy in uncomplicated multiple gestations, prospective data
are lacking. Assessment of well-beinghas been shown to decrease
mortality in higher-risk settings including IUGR, growth discordance, amniotic fluid volume abnormalities, monochorionic-
ity/monoamnionicity, and preeclampsia [27]. Initiation of
antenatal testing is recommended when any significant maternal
or fetal complication arises after viability. In uncomplicated twin
and triplet gestations, testing is usually started at 32 weeks and
continued weekly until delivery. Biophysical profile (BPP) and
nonstress test (NST)/amniotic fluid volume (AFV) assessment
have been shown to be equivalentpredictors of well-beingin twin
gestations. As continuous and identifiable NST monitoring of
each fetus in a triplet or higher gestation cannot be assured, BPP
is the testing method of choice.
Intrapartum assessment
At the time of labor and/or delivery, multiple gestations pose
multiple problems for the delivery team. Ultrasound assessment
is considered an essential component in the intrapartum management of these pregnancies. The management of premature
labor, abnormal fetal lie, abnormal placentation, cord presentation/accidents, and retained placental tissue are all improved by
the use of ultrasound. In twin gestations with planned vaginal
delivery, assessment of presentation is paramount both for initial
assessment and also after delivery of the first twin. If a nonvertex
second twin version is needed, ultrasound monitoring enhances
the safety of the procedure. If there is consideration of breech
extraction, estimation of fetal weight and head extension of the
second twin is necessary (Figure 35.14). When cesarean delivery
is needed, ultrasound evaluation of a transverse back-down presentation of the presenting fetus allows planning for a vertical
uterine incision to allow safe delivery of the fetus. If there is
persistent hemorrhage in the third stage of labor or placental
examination suggests incomplete removal, ultrasoundevaluation
can be used to assess for retained tissue and guide curettage, if
needed [28].
Figure 35.14. Breech presentation, twin A.
References
1. Benirschke K, Kim CK.
Multiple pregnancy. N Engl J
Med 1973; 288: 1276–84.
2. Benirschke K, Kim CK.
Multiple pregnancy. NEnglJ
Med 1973; 288:1329–36.
3. Brinsden PR. Controlling the
high order multiple birth rate:
the European perspective.
Reprod Biomed Onliine 2003;
6:339–44.
4. Dube J, Dodds L, Armson BA.
Does chorionicity or zygosity
predict adverse perinatal
outcome in twins?. Am J Obstet
Gynecol 2002; 186: 579–83.
5. Scholtz T, Bartholomaus S,
Grimmer I. Problems of
multiple births after ARTT:
medical, psychological, social
and financial aspects. Hum
Reprod 1999; 14: 2932–7.
6. Rizk B, Doyle P, Tan SL, et al.
Perinatal outcome and
congenital malformations in
in-vitro fertilization babies
from the Bourn-Hallam
group. Human Reprod 1991;
6(9): 1259–64.
7. Tan SL, Doyle P, Campbell S,
et al. Obstetric outcomeof invitro fertilization pregnancies
compared to naturally
conceived pregnancies. Am J
Obstet and Gynecol 1992;
167(3): 778–84.
8. Kinzler WL, Ananth CV,
Vintzileos AM. Medical and
economic effects of twin
gestations. J Soc Gynecol
Invest 2000; 7: 321–7.
9. Nowak E, Blickstein I,
Papiernik E. Iatrogenic
multiple pregnancies: do
they complicate perinatal
care?. J Reprod Med 2003; 48:
601–9.
10. Glazebrook C, Sheard C, Cox
S. Parenting stress in firsttime mothers of twins and
triplets conceived after
in vitro fertilization. Fertil
Steril 2004; 81:
11. Zohav E. Quality of nuchal
translucency measurements
in multifetal pregnancies.
505–11.
J Matern Fetal Neonatal Med
2006; 19(10): 663–6.
12. Maslovitz S. Feasibility of
nuchal translucency in triplet
pregnancies. J Ultrasound
Med 2004; 23(4): 501–4.
13. Avgidou K, Papgeorghious
A, Bindra R, et al.
Prospective first-trimester
screening for trisomy 21 in
30,564 pregnancies. Am J
Obstet Gynecol 2005; 192:
1761–7.
14. Wald NJ, Rish S. Prenatal
screening for Down
syndrome and neural tube
defects in twin pregnancies.
Prenat Diagn 2005; 25:740–5.
15. American College of
Obstetricians and
Gynecologists. Screening for
fetal chromosomal
abnormalities. ACOG
Practice Bulletin 77.
Washington, DC, American
College of Obstetricians and
Gynecologists, 2007.
16. Rochon M, Eddleman K,
Stone J. Invasive procedures
in multifetal pregnancies.
Clin Perinatol 2005; 32(2):
355–371.
17. Evans MI, Berkowitz RL,
Wapner RJ, et al.
Improvement in outcomes of
multifetal pregnancy
reduction with increased
experience. Am J Obstet
Gynecol 2001; 184:97–103.
18. Papgeorghiou AT, Avgidou
K, Bakoulas V, et al. Risks of
miscarriage and early
preterm birth in trichorionic
triplet pregnancies with
embryo reduction versus
expectant management: new
data and systematic review.
Hum Reprod 2006; 21:
1912–17.
19. Geipel A. Targeted firsttrimester penatal diagnosis
before fetal reduction in
triplet gestations and
subsequent outcome.
Ultrasound Obstet Gynecol
2004; 24
20. Garite TJ,
JP, et al. Twins and triplets:
(7): 724–9.
Clark RH, Elliot
297
Section 4: Early pregnancy after infertility treatment
The effect of plurality and
growth on neonatal outcome
compared to singleton
infants. Am J Obstet Gynecol
2004; 191: 700–7.
21. Hamilton EF, Platt RW,
Morin L, et al. How small is
too small in a twin
pregnancy?. Am J Obstet
Gynecol 1998; 179: 682–5.
22. Rodis JF, Arky L, Egan JF,
et al. Comprehensive fetal
ultrasonic growth
measurements in triplet
gestations. Am J Obstet
Gynecol 1999; 181: 1128–32.
23. Feldman DM, Borgida AF,
Trymbulak WP, et al.
Clinical complications of
velamentous cord insertion
in triplet gestations. Am J
Obstet Gynecol 2002; 186(4):
809–11.
24. Fuchs I, Tsoi E, Henrich W,
et al. Sonographic
measurement of cervical
length in pregnancies in
threatened preterm labor.
Ultrasound Obstet Gynecol
2004; 23:42–6.
25. Guzman ER, Walters C,
O’Reilly-Green C, et al. Use of
cervical ultrasonography in
prediction of spontaneous
preterm birth in triplet
gestations. Am J Obstet Gynecol
2000; 183(5): 1108–13.
26. Marder SJ, Jackson M.
Sonographic assessment of
incompetent cervix during
pregnancy. Semin Roentgenol
1999; 34:35–40.
27. American College of
Obstetricians and
Gynecologists. Special
problems of multiple
gestation. ACOG
Educational Bulletin 253.
Washington, DC, American
College of Obstetricians and
Gynecologists, 1998.
28. Egan JF, Borgida AF.
Multiple gestations: the
importance of ultrasound.
Obstet Gynecol Clin North
Am 2004; 31(1): 141–58.
298
Chapter
Ultrasonography in the prediction and management
36
of ovarian hyperstimulation syndrome
Botros Rizk, Christopher B. Rizk, Mary G. Nawar, Juan A. Garcia-Velasco and Hassan N. Sallam
Ovarian hyperstimulation syndrome
Ovaria n hype rstimulatio n syndrome (OHSS) is a serious iatrogenic compl ication of ovarian stimula tion. It is characte rized by
bilateral mu ltiple follicular and thecal lutein ovari an cyst s
( Figures 36.1 , 36. 2, 36.3 ) a nd in acute shift in bod y flui d distribution, resulting in ascites (Fi gure 36.4 ) and pleur al eff usio n
( Figure 36.5 )[1,2 ,3 ,4, 5,6 ,7, 8). OHSS may pres ent in its mild
form, w ith the patien t compl aining of discomf ort and distension. Howeve r, the sev ere form may be compl icated by hemoconcen tration, thromboem bolis m, renal failure , and adu lt
respirato ry distress syndro me [ 9,10 ].
Ov ar ian h yp er stim ulatio n c an b e ear ly or la te in onset
[Figure 36.6 ], spontaneous o r iatrogenic in e tiology [Figure 36.7 ],
moder ate or sever e in clinica l manifes tations. OHSS can
prese nt 3– 7 day s after the ovulatory dose of human chori onic
gonad otropin (hCG) (early ons et) or 12– 17 days after hCG
admin istratio n (late onset) ( Figure 36.6 ). Early-ons et OHSS
relates to excessive preovulato ry respon se to stimulatio n,
where as late-onset OHS S relates to the oc currence of pregnancy, particularly mu ltiple pregnan cy [ 11, 12]. Most cases of
OHSS are iatrog enic as a result of gonad otropin ovarian sti mulation . Rare ly, spontane ous cases of OHSS can occur du e to
the prese nce of FSH recepto r muta tions [13 ].
Classi fication of ovarian hyperstimulation
syndrome
The objec tives of OHS S classi fication accor ding to its severity
are threefold [ 14 ]. The fi rst objec tive is to co mpare the incidence of OHSS ; the second is to evalu ate the e fficacy of the
different approaches for the prevention of the syndrome; and
the final objective is to plan the management of OHSS depending on its severity and the presence or absence of complications.
Aboulghar and Mansour [14] reviewed the classifications of
OHSS over the last four decades (see Table 36.1). Rabau et al.
prese nted the first classi fication of OHSS ( 1), and this w as
reorganized by Schenker and Weinstein into mild, moderate,
and severe [2]. Golan et al. were the first to use ultrasonography
in the classification of OHSS [3]. Patients with ascitic fluid that
is detected by ultrasound but have no clinical manifestations of
ascites are classified as “moderate OHSS” to distinguish them
from “mild OHSS,” which is very common, and “severe OHSS,”
which could be associated with complications. Navot et al.
suggested making a distinction between severe and lifethreatening OHSS by dividing it into two subgroups [4].
The most recent classification with further modifications
was introduced by Rizk and Aboulghar [15]. They classified the
syndrome into moderate and severe [15]. The purpose of the
classification is to categorize patients with OHSS into more
defined clinical groups that correlate with the prognosis of the
syndrome. Treatment may be advised depending on the group
to which the patient belongs. The great majority of cases of
OHSS presenting with symptoms belong to the moderate
degrees of OHSS. In addition to the presence of ascites on
ultrasound, the patient’s complaints are usually limited, so
mild abdominal pain and distension and their hematological
and biochemical findings are normal. Severe OHSS is divided
into three grades according to the clinical manifestations.
Patients with severe OHSS of grade C have life-threatening
complications such as adult respiratory distress syndrome,
and would require intensive-care treatment.
*
Moderate OHSS
Discomfort, pain, nausea, abdominal distension, no clinical
evidence of ascites, but ultrasonic evidence of ascites and
enlarged ovaries; normal hematological and biological profiles;
can be treated on an outpatient basis with extreme vigilance.
*
Severe OHSS
*
Grade A: Dyspnea, oliguria, nausea, vomiting,
diarrhea, abdominal pain; clinical evidence of ascites
plus marked distension of abdomen or hydrothorax;
ultrasound scan showing large ovaries and marked
ascites. Normal biochemical profiles can be treated as
in patient or out patient depending on the physician’s
comfort, the patient’s compliance, and medical facilities.
*
Grade B: All symptoms of grade A, plus massive
tension ascites, markedly enlarged ovaries, severe
dyspnea, and marked oliguria; biochemical changes
in the form of increased hematocrit, elevated serum
creatinine, and liver dysfunction; would be treated in
an inpatient hospital setting with expert supervision.
Ultrasonography in Reproductive Medicine and Infertility, ed. Botros R. M. B. Rizk. Published by Cambridge University Press. © Cambridge
University Press 2010.
Section 4: Early pregnancy after infertility treatment
Figure 36.1. Hyperstimulated ovaries. Reproduced with permission from
reference [8].
Figure 36.3. Bilateral enlarged cystic ovaries.
follicular and theca lutein cysts. The second is acute body fluid
shifts resulting in ascites and pleural effusion. The fluid shifts
appear to be the end result of increased capillary permeability.
Rizk et al. [16] and Pellicer et al. [17] investigated the role of
vascular endothelial growth factor (VEGF) and interleukins in
the pathogenesis of OHSS. While many mediators have been
investigated, VEGF production by the granulosa cells and the
endothelial cells is responsible for the majority of the fluid
leakage (Figure 36.8). The VEGF family includes four different
dimeric forms (A–D) and placental growth factors, which all
bind differently to the three receptors (VEGF-R1 to R3) that are
expressed on endothelial cells. It appears that VEGF-A stimulating VEGF-R2 is responsible for the increased capillary permeability and fluid leakage (Figures 36.9, 36.10).
Figure 36.2. Hyperstimulated ovaries. Reproduced with permission from
reference [7].
*
Grade C: OHSS complicated by respiratory distress
syndrome, renal shut-down, or venous thrombosis, which
is critical; would be treated in an intensive-care setting.
Pathophysiology of OHSS
The pathophysiology of OHSS involves the explanation of two
phenomena. The first is the presence of multiple hemorrhagic
Factors predicting ovarian hyperstimulation syndrome
The cornerstone of successful prevention of OHSS is accurate
prediction (Table 36.2). Rizk and Smitz reviewedtheir experience
in the prediction of OHSS [18]. Prediction of OHSS depends on
identification of factors prior to ovarian stimulation, such as the
history of previous OHSS or polycystic ovary syndrome [18,19].
Other personal factors are age, body mass index, allergies, and
hyperinsulinism [19]. Rizk [13] investigated the role of folliclestimulating hormone (FSH)-receptor mutations and polymorphisms in the development of OHSS. Mutations in the
FSH-receptors could be activating, leading to predisposition to
OHSS, or conversely, inactivating, resulting in sterility.
Polymorphisms of FSH receptors have also been investigated
and, to date, 744 single-nucleotide polymorphisms have been
identified in the FSH receptor gene. Genetic studies of FSH-
receptor mutations have increased the expectations that OHSS
may be predicted in advanceon the basisof FSH-R genotype [13].
The potential association of the S
to ovarian stimulation for IVF [20,21] led to the hypothesis that
680
the N
allele could be associated with hyper-responders, i.e.,
patients at risk of iatrogenic OHSS. In an elegant study published
by Daelemans et al. [22], no statistically significant differences
680
allele with poor responders
300
Chapter 36: Prediction and management of OHSS
(a)
(c)
(b)
(d)
(e)
Figure 36.4a–f. Ascites in severe ovarian hyperstimulation syndrome.
between the IVF control population and the OHSS patients in
allelicor genotypic frequencieswere found. However, Daelemans
et al. observed a significant enrichment in allele 680 as the
severity of OHSS increased (P = 0.034). The authors suggested
that the genotype in position 680 of the FSH receptor cannot
predict which patients will develop OHSS, but could be a predictorof severity of OHSS symptoms amongOHSS patients [22].
(f)
During ovarian stimulation, a sharp rise in estradiol or high
levels in the presence of a large number of follicles is the best
predictor (Figure 36.11). Increased blood flow to the ovaries and
increased ovarian stromal blood flow are also useful predictors of
OHSS (Figures 36.12, 36.13, 36.14). The occurrence of pregnancy
(Figure 36.15), particularly multiple pregnancies, adds to the risk
of developing OHSS (Figure 36.16).
301
y
y
Section 4: Early pregnancy after infertility treatment
Figure 36.5. Right pleural effusion in ovarian hyperstimulation syndrome.
Iatrogenic OHSS
Third space fluid shift
Massive
recruitment
and growth
of follicles
Exogenic
FSH
hCG
symptoms
Early OHSS
Oversecretion of vasogenic molecules
Massive luteinization
hCG stimulates LH/CGr
hCG
EARLY
OHSS
Ovarian
response
hCG 3–9 days 10–17 days
Figure 36.6. Classification of ovarian hyperstimulation syndrome: early
and late.
LATE
OHSS
Pregnancy
−4 −3 −2 −1 0 1 2 3 4 5 6 7 8 9 101112131415161718
Deliver
Spontaneous OHSS
Third-space fluid shift
Oversecretion of vasogenic molecules
Implantation
Ovulation-Fertilization
Cycle Day 1
−4 −3 −2 −10123456
Figure 36.7. Chronological development of iatrogenic and spontaneous ovarian hyperstimulation syndrome. Reproduced with permission from reference [48].
Massive recruitment and
hCG stimulates (mutant) FSHr
Ultrasonography in prediction of OHSS
Massive luteinization
hCG stimulates LH/CGr
growth of follicles
7 8 9 101112131415161718
Weeks
Deliver
Baseline ovarian volume and the prediction of OHSS
Baseline necklace sign appearance
The diagnosis of polycystic ovaries at ultrasound examination
(the necklace sign) is crucial in the prediction of OHSS [18,19].
It improved the prediction of OHSS to 79% in a Belgian multicenter study [19].
Danninger et al. studied the baseline ovarian volume prior to
stimulation, to investigate whether it would be a suitable
predictor for the risk of OHSS [23]. They performed three-
dimensional volumetric ultrasound assessment of the ovaries
prior to ovarian stimulation and on the day of hCG injection.
302