1. הריונות מרובי עוברים MULTIPLE PREGNANCY
We shall refer to multiple pregnancy or multifetal preg as “twins preg” because it is the most frequent

2. When dealing with multifetal pregnancy you should be prepared for surprises

3. This amazing event atracted scientists for many years until now

4. multiple gestation General concerns:
Multiple gestations are HIGH RISK pregnancies.
The major problems are:
PRETERM BIRTH
LOW BIRTH WEIGHT

5. Frequency MULTIFETAL PREGNANCY Twins: 2% of all deliveries-
12% of NND.
Monozygotic 1/250 (1/3 of twins)
Tiplets: 1/802
Quadriplet: 1/803

6. Epidemiology: In 1970’s multiple gestations  1% of births
In 1990’s multiple gestations > 2% due to:
75% - Assisted Reproductive Technologies (ART)
25% - older age childbearing

7. Epidemiology: Up to 10% of natural conceptions begin as twins
Multiple gestation
Epidemiology:
Up to 10% of natural conceptions begin as twins
By early 1st trim. transvaginal sonography.
vanishing sac
5+5 wk (LMP)
Bateman,1990; Boklage,1990

8. Epidemiology: Multiple gestation "Natural" (1970’s) ART ( 1990's)
Twins :80 births : 55 to x 2
Triplets :6400 (1:802) : to x 6
Quadruplets 1:512,000 (1:803) x 10-20
balanced by fetal reduction
5+5 wk (LMP)

9. Definitions: Monozygotic Twins (Identical) Multiple gestation
Dizygotic Twins (Fraternal):
66% U.S. twins
fertilization of 2 ova by 2 sperm
Monozygotic Twins (Identical)
33% U.S twins
division of 1 ovum fertilized
by same sperm
unlike sex: 33% of twin pairs

10. Etiology MULTIFETAL PREGNANCY Causes of twining
(race, heredity, age, parity, fertility agents, IVF)
Genesis of monozygotic twins
Monoamniotic twins
When searching for etiological factors only fraternal twins should be considered

11. Risk factors for dizygotic twins:
Multiple gestation
Risk factors for dizygotic twins:
Age:
older mothers
Race:
1:20 in nigeria
1:80 whites
1:150 japanese
Parity:
higher
Family history

12. Risk factors for dizygotic twins:
Multiple gestation
Risk factors for dizygotic twins:
ART results:
35% of twins
77% of higher order multiples
Clomiphene citrate: 10-15%
Gonadotropins: 20-40%
IVF ~ number of embryos

13. Monozygotic twinning:
Multiple gestation
Monozygotic twinning:
random event ~ 1:250 pregnancies.
not influenced by age, race
increased with ovulation induction (?)
sex ratio in pairs: female>male

14. Definitions: Superfecundation - twins fertilized by different fathers
Multiple gestation
Definitions:
Superfecundation - twins fertilized by different fathers
Superfetation - 2nd ovum fertilized at different month (in animals)
Heterotopic Multiple Gestation - intrauterine
pregnancy coexisting with extauterine one (IVF)

15. Definitions: Dichorionic: separate chorions
Multiple gestation
Definitions:
Dichorionic: separate chorions
Diamniotic: separate amnions
Monochorionic: common chorion
Monoamniotic: common amnion
Dizygotic Twins: always Di-Di
Monozygotic Twins: Di-Di; Di-Mo; Mo-Mo

16. Chorionicity & amnionicity impact:
Multiple gestation
Chorionicity & amnionicity impact:
MZ Twins Frequency Mortality
Di-Di % %
Mo-Di % %
Mo-Mo % %

17. Embryology of membranes
Multiple gestation
Blastocyst implantation: day 6-7 (embryonic age)
amniotic
cavity
exocoelomic cavity
(primary yolk sac)

18. Embryology of membranes
Multiple gestation
Chorionic cavity: day 14 (embryonic age)
secondary yolk sac
chorionic cavity
(exraembryonic coelom)

19. Embryology of membranes
Multiple gestation
Folding & amniotic cavity: day (embryonic age)
cephalocaudal
folding
lateral folding

20. Embryology of membranes
Multiple gestation
Embryology of membranes
chorion
chorionic
cavity
embryo
Where is the amniotic membrane in this ultrasound image?
yolk sac
decidua capsularis
amnion - ?
6+2 wk (LMP)

21. Embryology of membranes
Multiple gestation
6 wk (LMP)
amnion
7 wk (LMP)
9 wk (LMP)
8 mm
21 mm

22. Zigosity Multifetal pregnancy DC/DA MC/DA MC/MA Con- -joined 3%
Conception chorion amnion embryonic disc
DC/DA
MC/DA
MC/MA
Con-
-joined
Fraternal
~1/3 identical
~2/3 identical 3%
1/50000
Chorionicity depends on the timetable of events after conception
Multifetal pregnancy

23. Monozygotic twinning:
Multiple gestation
Monozygotic twinning:
division <3 days: Di-Di
division 4-8 days: Mo-Di
division 9-13 days: Mo-Mo
division >13 days: Conjoined twins

24. Monozygotic twinning:
implantation
Monozygotic twinning:
Multiple gestation
Dichorionic – always diamniotic
Monoamniotic – always monochorionic

27. The dividing membrane is thin but doubled (diamniotic)

28. What is the corionicity in the lt sac? DA!

29. Unlike sexes : DC – male chasing his co-twin

30. Two males practicing monosexual relationship

31. Diagnosis MULTIFETAL PREGNANCY History Physical examination X rays
Ultrasound
Biochemical test

32. Diagnosis: Multiple gestation
Historically up to 2/3 not diagnosed until labor:
poor dates
late/poor prenatal care
absence of ultrasound screening

33. Diagnosis: Clinical Hints: Multiple gestation
family history, late childbearing, black race
ART: clomiphene citrate, gonadotropins, IVF
Large for dates uterus: fundal height >3 cm
Elevated MSAFP > 2 MOM
More than one audible FHR (late finding)

34. Definitive diagnosis:
Multiple gestation
Definitive diagnosis:
Ultrasound
Multiple gestations outcome is improved with
screening all pregnancies at weeks.

36. Differential Diagnosis:
Multiple gestation
Differential Diagnosis:
Misdated pregnancy
Polyhydramnios
Uterine myomas
Ovarian cyst
Hydatiform mole
What are the situations in the DD?

37. Di-Di Mo-Di Mo-Mo Determination of chorionicity & amnionicity:
Multiple gestation
Determination of chorionicity & amnionicity:
Early determination: 8-10 weeks is optimal
Di-Di
Mo-Di
Mo-Mo

39. Determination of chorionicity & amnionicity:
Dichorionic-Diamniotic: late determination
Unlike sex fetuses
"Lambda" or “Y” sign
Thick membrane (> 2mm) 3-4 layers
Two separate placentas
Multiple gestation
Placentas may fuse (40%), but
no vascular anastamosis occurs

40. Interplacental vascular anastamosis > 20%
Multiple gestation
Determination of chorionicity & amnionicity:
Monochorionic-Diamniotic: late determination
Same sex fetuses
"T" sign
Thin membrane: 2 layers
Fused placenta
Interplacental vascular anastamosis > 20%

41. Interplacental vascular anastamosis - almost always
Multiple gestation
Determination of chorionicity & amnionicity:
Monochorionic-Monoamnionic: late determination
Same sex fetuses
No membrane seen between fetuses
Adequate fluid with free movement of both fetuses
Single placenta
Interplacental vascular anastamosis - almost always

42. Maternal adaptation: Multiple gestation
Weight gain ~ 15 kg (twin gestation)
Plasma volume
Cardiac output
Systemic vascular resistance
Venous engorgement

43. Maternal adaptation: Multiple gestation Tidal volume Residual volume
Ventilation
Decreased GIT motility
Renal plasma flow
Uterine volume: 10 liters at term
(x2 as singleton)

44. General management: Multiple gestation Nutrition
2700 kcal/day – twins
2400 kcal/day – singleton
2100 kcal/day – non pregnant
Elementary Iron mg/day
Folate 1 mg/day
protein gr/day
Reduce activity and increase rest (after 20 weeks)

46. Fetal reduction-needle in chest

48. General management : Clinic visits every 2 wks after 24 wks:
Multiple gestation
General management :
Clinic visits every 2 wks after 24 wks:
Preterm labor Education
Fetal movement counts daily after 32 weeks

49. Obstetric ultrasound: every 2-4 weeks
Multiple gestation
Obstetric ultrasound: every 2-4 weeks
Fetal growth assessment
Biophysical profile
Presentations
Placental site
Cervix length
Doppler study
singletons
weight
twins
triplets
Flattening of growth curve after 30 wks in twins
(kg)

50. Non Stress Test: Multiple gestation Weekly after 34 weeks
More frequent and earlier if indicated
Assess fetal well-being

51. Complications Multiple gestation
Unfortunately we are not living in a perfect world… and the rate of complication for twins is quite high

52. Complications: Multiple gestation Fetal: Abortion / vanishing twin
Inevitable abortion X 2 as in singleton
50 % of early 1st trim. twin sacs are finally deliver as twins
80 % of early 1st trim. alive twins are finally deliver as twins
Congenital Anomalies: usual & unique

53. Complications: Fetal: Multiple gestation
Hydramnios / Oligohydramnios: TTTS
Discordant growth
Intrauterine growth retardation:
IUGR ~ 70% of multiple gestations
More than 50% of twins < 2500 gr at birth
Intrauterine fetal death of one or more fetuses

54. Complications: Multiple gestation Maternal: Hyperemesis gravidarum
Anemia (40%)
GDM
Pregnancy induced hypertension:
twins %
triplets - 60%

55. Complications: Maternal-fetal: Multiple gestation
Premature uterine contractions / labor
twins: 10% of all preterm deliveries
twins: 25% of prenatal deaths
worse < 32 weeks and birth weight < 1500gr
Premature rupture of membranes
Antepartum hemorrhage:
abruptio placenta
placenta previa

56. Intrapartum hemorrhage
Multiple gestation
Labor:
Intrapartum hemorrhage
abruptio placenta
placenta previa
uterine rupture
Postpartum hemorrhage
atonia uteri
placental residia
DIC
birth canal trauma

57. Labor: Multiple gestation Malpresentation
Cord accident: prolapse, entanglement
Prematurity associated morbidity and mortality
Birth trauma (interlocking, breech extraction)
Instrumental delivery
Cesarean delivery

58. Premature delivery: Average length of gestation to delivery :
Multiple gestation
Premature delivery:
Average length of gestation to delivery :
No. fetuses weeks(LMP)
~33
~29

59. Premature delivery: Twins: X 12 as singletons
Multiple gestation
Premature delivery:
Twins: X 12 as singletons
> 50% of twins deliver < 37 weeks
91% of triplets deliver < 37 weeks

60. Premature delivery: Multiple gestation
Liberal policy of tocolysis may be justified
The decision to administer tocolytics is influenced by:
gestational age
fetal well-being
subtle cervical changes
history of prior preterm delivery
Prophylactic tocolysis in multiple gestations is not indicated

61. Premature delivery: Multiple gestation
Contraindications for tocolytic use:
unexplained vaginal bleeding
fetal distress
chorioamnionitis
advanced cervical dilation.

62. Premature delivery: Multiple gestation
Special considerations for tocolysis in multiple gestations:
High intravascular volume and cardiac output.
Careful fluid balance using beta-mimetics:
increased risk for pulmonary edema
Fetal status may preclude use:
indomethacin with oligohydramnios

63. Vascular anastomoses between fetuses
Effects of anastomotic circulation
Twin to twin transfusion
Acardiac twin
Multifetal pregnancy

64. A-V, A-A, V-V shunting between placental vessels
Multiple gestation
Twin-to-twin transfusion syndrome (TTTS):
A-V, A-A, V-V shunting between placental vessels
of the monochorionic twins
10-20% of monochorionic: (Mo-Mo > Mo-Di)
80%-100% perinatal mortality if not treated
(lethal in early, acute form)

65. Twin-to-twin transfusion syndrome (TTTS):
Multiple gestation
Twin-to-twin transfusion syndrome (TTTS):
Ultrasound:
oligo/polyhydramnios - the first finding
stuck twin:
severe oligohydramnios
fetus stucked close to the uterine wall
discordancy:
>20-25% weight difference
>20mm abdominal circuference difference

66. Twin-to-twin transfusion syndrome (TTTS): Donor twin:
Multiple gestation
Twin-to-twin transfusion syndrome (TTTS):
Donor twin:
small & anemic
poor renal perfusion
small urinary bladder
oligohydramnios

67. Twin-to-twin transfusion syndrome (TTTS):
Multiple gestation
Twin-to-twin transfusion syndrome (TTTS):
Recipient twin:
large & polycythemic (>5 gm% Hb difference)
large urinary bladder
hypertrophic heart
polyhydramnios
CHF, hydrops & death from circulatory overload
polyhydramnious can cause early labor

68. Twin-twin transfusion syndrome
Prenatal
Donor : anemia, oligohydramnios, IUGR,
Recipient :polycytemia, polyhydramnios, macrosomia
Postnatal
Donor : swollen placenta, pale
Recipient : red, congested, hypertrophy of placenta, injection studies:anastomoses.
Multifetal pregnancy

69. Twin-to-twin transfusion: mechanism
Donor
Recipient
Chronic blood loss
Chronic blood gain
Hypovolemia Anemia Hypoxia IUGR Decreased renal flow  Oligohydramnios
Hypervolemia Polyhydramnios Polycytemia Embolization Hypertension Cardiac failure
Placental shunt

70. Twin transfusion with stuck twin
Donor twin with progressive oligohydramnios
Stuck twin
Recipient twin with progressive polyhydramnios

71. Twin transfusion with stuck twin
Donor twin with progressive oligohydramnios
Stuck twin
Recipient twin with progressive polyhydramnios

72. Twin transfusion with stuck twin
Donor twin with progressive oligohydramnios
Stuck twin
Recipient twin with progressive polyhydramnios

73. Twin transfusion with stuck twin
Donor twin with progressive oligohydramnios
Stuck twin
Recipient twin with progressive polyhydramnios

74. Twin transfusion with stuck twin
Donor twin with progressive oligohydramnios
Stuck twin
Recipient twin with progressive polyhydramnios

75. Twin transfusion with stuck twin
Donor twin with progressive oligohydramnios
Stuck twin
Recipient twin with progressive polyhydramnios

76. The “stuck twin”

77. The folding of the membrane
Early stages of the stuck twin phenomenon: folding of the membrane

80. Twin-to-twin transfusion syndrome (TTTS):
Multiple gestation
Twin-to-twin transfusion syndrome (TTTS):
Treatment:
Bed rest improves intrauterine blood flow
Laser coagulation of shunting vessels
Aggressive serial amniocentesis
Septostomy (?)
If treated - survival up to the 80%
To attain > 28 weeks seems to be critical

81. Discordant growth and IUGR:
Multiple gestation
Discordant growth and IUGR:
Discordance:
100% x ( weights / larger twin weight)
Discordance of 20-25%:
single IUGR fetus > 50%
Discordance > 25%:
X 6 risk of IUFD (compared to discordance < 25%)

82. Discordant growth and IUGR:
Multiple gestation
Discordant growth and IUGR:
At > 30% discordancy in weight:
fetal death (the smaller): %
congenital anomalies: %
low Apgars < 7 at 5 min.: %
periventricular leukomalacia: 17%

83. Discordant growth and IUGR:
Multiple gestation
Discordant growth and IUGR:
Ultrasound diagnostic criteria:
>20mm abdominal circumferences difference
>25% fetal weight difference

84. Discordant growth and IUGR:
Multiple gestation
Discordant growth and IUGR:
Management considerations:
chorionicity:
Di-Di virtually rules out TTTS
gestational age:
late IUGR suggests extrinsic causes
weight percentiles:
Both twins with normal percentiles - less concern

85. Discordant growth and IUGR:
Multiple gestation
Discordant growth and IUGR:
Management considerations:
pattern of growth important:
< 10th percentile or oligohidramnios or pathologic umbilical artery Doppler – close antepartum testing
isolated discordance at <32 weeks and <2000 gr, does not support intervention in the absence of other signs of fetal jeopardy.

86. Single IUFD in 2nd and 3rd trimester:
Multiple gestation
Single IUFD in 2nd and 3rd trimester:
Unlike the demise in early pregnancy, significant problems may occur depending upon the gestational age and chorionicity
Loss during the 2nd half of twin pregnancies: ~ 2-3%
X 3 as often in monochorionic as dichorionic
Fetus papyraceous - hylanized twin remnant

87. Single IUFD in 2nd and 3rd trimester:
Multiple gestation
Single IUFD in 2nd and 3rd trimester:
Overall morbidity and mortality approximates 45-50%
IUFD of one fetus is associated with preterm delivery in the surviving fetus
Associated with prematurity, fetal distress and PET
Maternal coagulopathy (DIC)

88. Single IUFD in 2nd and 3rd trimester:
Multiple gestation
Single IUFD in 2nd and 3rd trimester:
Monochorionic IUFD:
worst prognosis with placental anastomoses:
death of one fetus causes severe hypotension in the surviving twin
embolisation(?)/DIC and organ damage in the surviving twin:
CNS: porencephaly, hydrocephalus, microcephalus
limb reduction
renal cortical necrosis
intestinal atresia
aplasia cutis

89. Single IUFD in 2nd and 3rd trimester:
Multiple gestation
Single IUFD in 2nd and 3rd trimester:
Management depends upon:
chorionicity
cause of the demise
gestational age
Intensive fetal monitoring should be undertaken

90. Single IUFD in 2nd and 3rd trimester:
Multiple gestation
Single IUFD in 2nd and 3rd trimester:
Because of the potential for chronic damage, it is reasonable to deliver monochorionic gestations with lung maturity after 32 weeks
Timing of delivery for dizygotic twins with a single demise should be individualized

91. Presentations: Multiple gestation First twin presents vertex: 74%
Both twins vertex: %
First twin presents breech: 20%
Both twins breech: %
Other (transverse/oblique): 6%

92. Cesarean delivery: Multiple gestation Absolute indications:
monoamniotic twins
conjoined twins
first twin - not vertex
triplets and higher order
other Cesarian section indications:
non progressive labor
fetal distress
placenta previa
uterine scar: corporeal, >1 past CSLT’s
absolute CPD, etc.

93. Cesarean delivery: Multiple gestation Relative indications:
Second twin - not vertex:
Mother not willing to undergo breech delivery
Fetus <1.5 kg (? 2 kg)
one or both twins have non-reassuring fetal status
fetal discordancy: the first twin is the smaller member
single past low transverse cesarian delivery

94. Vaginal delivery: (ACOG, 1998)
Multiple gestation
Vaginal delivery: (ACOG, 1998)
During labour - continuous cardiotocogram
All patients should have a ready IV access
Double set-up delivery room
First twin - vertex vaginal delivery

95. Vaginal delivery: (ACOG, 1998)
Multiple gestation
Vaginal delivery: (ACOG, 1998)
Second twin - vertex presentation:
vertex vaginal delivery
Second twin - non vertex presentation:
internal podalic version and breech extraction
external cephalic version: less successful
expectant management

96. Vaginal delivery: (ACOG, 1998)
Multiple gestation
Vaginal delivery: (ACOG, 1998)
Second twin considerations:
Delay > 20 min. may increase morbidity of the 2nd twin.
Delays >15 min. are associated with a 6 fold increase in Cesarean section.
Morbidity and mortality are minimized with continuous CTG of twin B and the ability for immediate Cesarean section.

97. Vaginal delivery: (ACOG, 1998)
Multiple gestation
Vaginal delivery: (ACOG, 1998)
Second twin considerations:
~15% of vertex/nonvertex require a Caesarean section for the second twin:
Failure of second twin delivery
Second twin experiences fetal distress
prepare for double set-up delivery
placentas of multifetal pregnancies should be sent to pathology with each cord clearly labelled.

98. Diagnosis of multiple gestation Gestational age assessment
Prenatal diagnosis:
Diagnosis of multiple gestation
Gestational age assessment
Determination of Amnion/Chorion Status
Survey for anomalies: NTT, Triple screen, TIFFA
Invasive procedures: CVS, Amniocentesis
TIFFA: Targeted Imaging For Fetal Anomalies

100. Problems with prenatal diagnosis: Increase in multiple gestations and
aneuploidy with older maternal age
Increased background risk for anomalies
Correct determination of zygosity
Difficulties with interpretation of triple screen

101. Problems with prenatal diagnosis:
Multiple gestation
Problems with prenatal diagnosis:
Ability to sample all fetuses (CVS, AC)
Increased loss of pregnancies before 28 weeks
Increased loss rate with CVS and amniocentesis

102. Congenital anomalies: Incidence in twins: x2 as in singletons
Multiple gestation
Congenital anomalies:
Incidence in twins: x2 as in singletons
major malformations: 2.3% vs. 1%
Monozygotic: x2 as in dizygotic
chromosomal anomalies:
each twin ~ singleton
conjoined twins – higher incidence
risk of Down syndrome in twins:
1:370 for women aged 33
(35 in singeltons)

103. Congenital anomalies:
Unique to monozygotic twins:
conjoined twins
acardiac twin (TRAP syndrome)
fetus-in-fetu
Multiple gestation

104. Congenital anomalies:
Multiple gestation
Congenital anomalies:
Twinning process associated anomalies:
anencephaly
holoprosencephaly
sirenomelia
extrophy of cloaca
renal agenesis
anal atresia
tracheoesophageal fistula
situs inversus defects

105. NTD

106. Congenital anomalies:
Multiple gestation
Congenital anomalies:
Vascular disruption sequences
secondary to one twin demise:
porencephaly
hydranencephaly
hydrocephalus
multicystic encephalomalacia
microcephalus
limb reduction
renal cortical necrosis
intestinal atresia
aplasia cutis

107. Congenital anomalies:
Multiple gestation
Congenital anomalies:
Deformations due to crowding of fetuses:
congenital dislocation of hip
clubfoot

108. Twin to twin transfusion Mortality - up to 60%
Multiple gestation
Monoamniotic twins:
Cord entanglement
Twin to twin transfusion
Mortality - up to 60%
Ultrasound surveillance and delivery ~34 weeks

110. cord entanglement

111. 1st trim. spontaneous loss of one
Multiple gestation
Vanishing twin:
1st trim. spontaneous loss of one
or more with higher order multiples fetus
50 % - if only "sacs" are counted
20 % - if alive embryos counted
Higher loss rate with advancing maternal age
Excellent prognosis for remaining fetus(es)

112. Acardiac twin: Multiple gestation One of Mo-Mo twins grows despite of
the absence of cardiac activity / presence of heart.
Occurs at 1 : 30,000-40,000 pregnancies or slightly less than 1% of monozygous twins.
A normal ("pump") twin supplies perfusion
to acardiac twin.
"twin reverse arterial perfusion" (TRAP)
Oxygenated blood to the acardiac fetus in the artery

113. acardiac twin

114. Multiple gestation
Acardiac twin:
Hydramnios is a common finding (40%), with a strong association with PTD and CHF in the pump twin.
Better prognosis if acardiac twin
weight < 50% of the pump twin

115. Acardiac twin: Treatment: Multiple gestation
Conservative: digoxin and indomethacin
Fetal surgery: endoscopic laser prior to 24 weeks and umbilical cord ligation thereafter
Invasive techniques may be avoided if acardiac fetal mass very small or flow to acardiac decreasing or absent.

116. Conjoined twins: Multiple gestation Also called "Siamese" twins
Incomplete division of the embryonic
disk at day after conception
The incidence 1: ,000 births
High rate of congenital anomalies

117. Classification by the area of joining:
Multiple gestation
Conjoined twins:
Classification by the area of joining:
chest (thoracopagus)
head (craniopagus)
abdomen (omphalopagus)
coccyx and sacrum (ischiopagus)
body with two heads (dicephalus)
one head with two bodies (dipygus)

118. Conjoined twins Craniopagus Thoracopagus Ischiopagus
Multifetal pregnancy

120. presence of other anomalies
Multiple gestation
Conjoined twins:
Survival in conjoint twins depends upon:
extent of attachment
place of attachment
presence of other anomalies

121. In this old sonographic image this fetus is going to score using the head of his brother twin

122. In conclusion: twins pregnancy is quite a project but the lovely results justify the efforts..

123. Multiple gestation
Prof. S. Degani
June 2007