MULTIFETAL

GESTATION (MFG)

Multifetal Gestation (MFG)

Multifetal pregnancies may result from
two or more fertilization events,
a single fertilization followed by an erroneous
splitting of the zygote, or
a combination of both.

NB. Either or both processes may be involved in the

formation of higher numbers.
Quadruplets, for example, may arise from as few as
one to as many as four ova

Types OF MFG
Monozygotic or Identical twins
Dizygotic or Fraternal twins Higher Order MG

MFG-Incidence
Dramatic increase in the past 30 years
ART
Old maternal age at birth

b/n 1980 and 2009

Twinning rate rose from 18.9 to 32.1 per 1000 live
births in i.e. 76 % rise (Martin, 2012). During the same
time,

The number higher-order multifetal births

increased more than 400% to a peak in 1998 and
decreased since then and it is 138 per 100,000
births in 2010.

Will OB 24th Ed.

Superfetation Vs Superfecundation
In superfetation, an interval as long as or longer

than a menstrual cycle intervenes between

fertilizations
Common in mares, as yet unproven in humans

Superfecundation refers to fertilization of two

ova within the same menstrual cycle but not at

the same coitus, nor necessarily by sperm from

the same male.

Monozygotic (Identical) Twining

MZ twins Arise from a single fertilized ovum

that divides
Relatively constant incidence world wide
(~ 1set in 250 births)
No identifiable Risk Factor independent of
race, heredity, age, and parity
However incidence of MZ T es in ART may be
due to minor trauma to the blastocyst during
manipulation

Among natural conceptions, MZ twins;

Consist of 30% of all twin pregnancies
Occur in 1 in 250 pregnancies

MZ Twinning
Despite virtually the same genetic heritage,
MZ twins Usually are not identical bs/e of
Unequal sharing of protoplasm
Discordant mutations
Postzygotic mutation
Inherited mutations with varying expression
Eg. differential expression of sex linked traits and
diseases in female fetuses due to skewed lyonization
(Glinianaia, 2008).
Post zygotic loss of Y chrs X0 (Turners) with female phenotype
and Normal 46XY male sibling

Teratogenic effect of MZ twining process

discordant malformation
Eg one with congenital heart disease the other Normar.

MZ Twining
MZT may vary by amniocity and chorionicity
depending on division time after fertilization.
1. Dichorionic, Diamniotic
cleavage at 0-4days (at morula stage)
single fused or two separate placenta
The lowest risk among monozygotic

2. Monochorionic+diamniotic
cleavage at 4-8days( Blastula)
I.e.one placenta two AF.

Risk of TTT

3. Monochorionic+monoamniotic
8-12 days( embryonic disc cleavage)
The highest risk ( mainly cord entanglement)

4. Conjoined( MC+MA) >13days

5/14/2016

SAMUEL BEZABIH

11

Dizygotic(Fraternal) Twining- DZT

DZTs result from fertilization of two separate ova
More common than MZ
Have identifiable risk factors ;affected by
race, age, parity,heredity,fertility rx

Among natural conceptions DZ twins

Consist 70% of all Twin pregnancies
Occur in ~ 1% to1.5% of pregnancies

Dizygotic(Fraternal) Twining- DZ
Risk factors
Race ( Yorube tribe of Nigeria ,1/ 20 birth ,
high level of FSH- High rate of DZ twins, the reverse is true
for Japanese women) (Knox and Morley (1960)

Age
peak at the age of 37:,
Maximal FSH stimulation - multiple follicles (Beemsterboer, 2006)
Increased ART use- more likely older women Ananth 2012 )
DZT frequency 4x increase b/n 15 and 37 (painter 2010)

Heredity
the family history of the mother is more important than
that of the father

Risk factors---DZT
Parity
Increasing parity has been shown to
independently increase the incidence of twinning
in all populations studied.

Infertility Treatment
Ovulation induction (FSH +CGTH /Ccitrate) and ART
(IVF-Transfer of multiple embryos- lkelihood of MG)

Maternal Nutritional status/ size

increased twining with good Nutritional status
Taller and heavier mom well nourished 25-30%
greater twining than smaller/ malnourished mom.
WWII- malnutrition- marked fall in DZT rate.

Dizygotic (Fraternal) Twining- DZ

Pituitary FSH secretion
The common factor linking race, age, weight,
and fertility to Multifetal gestation may be FSH
levels (Benirschke, 1973).
This theory is supported by the fact that
increased fecundity and a higher rate of
dizygotic twinning have been reported in
women who conceive within 1 month after
stopping oral contraceptives, but not during
subsequent months (Rothman, 1977).

DZT.RFs
This may be due to the sudden release of
pituitary gonadotropin in amounts greater
than usual during the 1st spontaneous cycle
after stopping hormonal contraception.
Indeed, the paradox of declining fertility but
increasing twinning with advancing maternal
age can be explained by an exaggerated
pituitary release of FSH in response to
decreased negative feedback from impending
ovarian failure (Beemsterboer, 2006).

Sex Vs Zygosity

Twins of opposite sex are almost always dizygotic.

Rarely , the karyotype or phenotype of a MZ twins can be
different.
This can be due to somatic mutations or chromosome
aberrations.
Most reported cases are related to postzygotic loss of the Y
chromosome in one 46,XY twin.
This results in a phenotypically female twin due to Turner
syndrome (45,X).
Zech and colleagues (2008) reported a rare case of a 47,XXY
zygote that underwent postzygotic loss of the X
chromosome in some cells and loss of the Y chromosome in
other cells.
The phenotype of the resultant twins was one male and
one female.
Karyotype analyses revealed both to be 46,XX/46,XY genetic
mosaics.

Chorionicity Vs Zigosity
Monochorionic twins are always MZ,
Approximately 70% of MZ twins are
monochorionic and 30% will have a
dichorionic placentation
Rarely, however, MC twins may in fact be dizygotic
(Hack, 2009).
Mechanisms for this are not yet clear but all
reported cases were concieved by ART
procedures. Ekelund and coworkers (2008)

All DZ twins will be dichorionic

Diagnosis Of MFG
Clinical
Ultrasound is used to determine Fetal number,
Chorionicity and Amniocity

Chorionicity
DC-lambda/ Twin Peak sign

MC- inverted T sign

Twin Peak sign

T sign

Maternal Physiology in MFG

In general, the degree of maternal physiological
change is greater with multiple fetuses than
with a single fetus.
Higher serum -hCG level early in 1st trim
Excessive N & V
Blood volume expansion- 50-60% in excess of
~500ml compared with singleton (40-50% increase)
RBC mass expansion---proportionately less than
that of singleton P
Both the remarkable increase in maternal BV and the increased iron and
folate requirements predispose to a greater prevalence of maternal
anemia.

average blood loss at delivery- 2x that of singleton

~ 1000ml

Maternal Physiology in MFG

Typical BP pattern in twin pregnancies

Lower DBP than in singletones as early as 8wk, but

generally higher at term

Vascular resistance- significantly lower than in

singletons through out pregnancy
CO 20% more than singleton P
Mainly due to greater SV and to a lesser degree to increased
heart rate

Pulmonary functions same as that of singleton preg.

If hydramnios develops, maternal renal function can
become seriously impaired, most likely as the
consequence of obstructive uropathy (Quigley, 1977).
Therapeutic Amniocentesis for symptomatic relief and avoidance
of preterm labor

Vanishing Twin
Loss /death of one fetus before 2nd trimester
The other develop to term and delivered as
singleton
The incidence of twins in the first trimester is
much greater than the incidence of twins at
birth.
one twin is lost or vanishes before the
second trimester in up to 10 to 40 percent of
all twin pregnancies (Brady, 2013).
The incidence is higher in the setting of ART.

Pregnancy Complication in MG
Fetal and infant complications
Abortions/Miscarriages
Preterm delivery
Low birthweight
FGR
Cerebral Palsy
PNM
Fetus acardiacus
Fetus papyraceous
Congenital anomalies

Pregnancy Complication in MG
The incidence of congenital malformations is appreciably increased
in multifetal gestations compared with singletons.
Glinianaia and associates (2008) reported that the rate of
congenital malformations was 406 per 10,000 twins versus 238
per10,000 singletons.
MC 2X more risk than DC

incidence in MG than singletons manly due to

structural defects in MZ twins- 03 categories
I.
II.

III.

20 to Teratogenic event in twining- Conjoined Twins, cardiac

anomallies, NTD , Sirenomelia
20 to vacsular anastomosis- TRAP, DIC and embolization from
dead fetus, BP fluctuations resulting in microcephally
hydranencephaly intestinal atresia aplasia cutis, or limb
amputation.
20 to fetal crowding EG. talipes equinovarus (clubfoot)
congenital hip dislocation. ( DZ Ts are also affected)

 Proportion of DZ Twins with congenital

malformation has been increasing in the past
30 yrs ( by 30%) while that of MZ remained
stable Possible consequence of ART

Pregnancy Complication in MG

PTB complicate up to 50 percent of twin, 75 percent of

triplet, and 90 percent of quadruplet pregnancies
(Elliott, 2007).
Preterm Birth
The duration of gestation decreases with increasing
fetal number .
According to Martin and colleagues (2012), more than
five of every 10 twins and nine of 10 triplets born in
the US in 2010 were delivered preterm.
Prematurity is increased six-fold and tenfold in twins
and triplets, respectively (Giuffre, 2012)
Preterm Birth GA?
60 percent of twins,
90 percent of triplets, and
virtually all of quadruplets

Pregnancy Complications
Low Birth Weight
LBW more in MG than singletones due to FGR and
PT birth
Weight parallels that of singleton till 28 -30wk, then
lags with clear divergence beginning 35-36 weeks
Incidence of overt FGR at 38 wk- 4x & half of twins
are affected
Based on growth curve of singletons

MZ more likely to have FGR than DZ bcse of

Unequal allocation of blastomeres,
vascular anastomosis unequal O2 and nutrient
ditribution, the twining event MZT eg in quintiplets of
3 DZ (all >1400gm) and 2 MZ twins (860and 990 gm )

Pregnancy Complication in MG
Maternal Complications
Increased medical complications than in
singleton pregnancies
HEG, GDM, HTN, Anemia

Hemorrhage
Polyhydramnios + 20 obstructive uropathy
Cesarean Delivery
Post partum Depression

Cumulative percent of singleton, twin, and triplet or higher-order multifetal

births according to gestational age at delivery in the US during 1990. (From Luke,
1994, withpermission.)

Pregnancy Complications
Prolonged Pregnancy
Bennett and Dunn (1969) suggested that a twin
pregnancy of > 40 weeks should be considered
postterm.
Twin stillborn neonates delivered at > 40 weeks
commonly had features similar to those of
postmature singletons

From an analysis of almost 300,000 twin births,

Kahn and coworkers (2003) calculated that > 39 weeks, the
risk of subsequent stillbirth was greater than the
risk of neonatal mortality.
Parkland- emprical 40weeks or more- Postterm

Incidence of Twin Pregnancy Zygosity and Corresponding TwinSpecific Complications Will 24th

Monoamniotic Twins

1% of MZ / 1 in 20 MC twins
High fetal death rate -10% resulting from

Cord entanglement (>50%),

Cong anomally,
preterm birth,
TTT

No M'gt to ascertain good outcome

unpredictability of cord entanglement and lack of
effective method to monitor it
Morbid cord entanglement appears to occur
early, and MA pregnancies that have successfully
reached 30- 32 weeks are at reduced risk.
Rupture of separating membrane in DA Ts
convert to MA with the same risk of MM

MA Twins
Color flow Doppler Sonography can be used to
diagnose entanglement
women with Monoamniotic twins are
recommended to undergo 1 hour of daily fetal
heart rate monitoring, beginning at 26- 28 weeks.
With initial testing, a course of betamethasone is
given to promote pulmonary maturation.
If fetal testing remains reassuring, cesarean
delivery is performed at 34 weeks and after a
second course of betamethasone.

MC Twins- Vascular Anastomosis

Placental vascular anastomosis is unique to
MC twins.
Superficial AA (commonest), VV, AV,
Deep AV at the capillary bed of a villus

Deep AV anastomosis
Common villous compartment/3rd circulation
Shunt depending on pressure and gradient
ConsequencesTwin Twin Transfusion syndrome (TTTS) ,
TRAP Sequence, Acardiac Twinning

TTTS
The prevalence TTTS is app 1- 3 /10,000 births (Simpson, 2013).
Unidirectional Blood flow through AV anastomosis
(Donor Recipient)an imbalance in blood volumes
Deoxygenated O blood in the Donors (D) Umbilical Artery is pumped
into shared Cotyledon Oxygenation in the chorionic villus Blood
leaves Villus through the Recipients (R) placental Vein
Donor
anemic, growth restricted, oligohydramnios- Stuck, Pale
contractures, and pulmonary hypoplasia
Recipient
polycythemic, Plethoric appearance
Circulatory overload/ Hypervolemia-Heart Failure-Hydrops,
Hydramnios
Hyperviscosity~~ Occlusive thrombosis,
Hyperbilirubinemiakernicterus

TTTS
Clinically important TTTS chronic with significant
vascular volume difference
Typical presentation ( mid pregnancy )
Hypovolemic Donor- reduced RBF Oliguria,
Oligohydramnios stuck (No AF, No motion)
Recipient- too much urine- Severe Hydramnios
polyhydramnios-oligohydramniossyndromepolyoli.

TTTS- Brain Damage

Cerebral abnormalities in ~8% of affected live

births.
Common in TTTS are;
Cerebral Palsy,
Microcephaly,
Proencephaly, Multisystem encephalomalecia

Mechanism - not well understood

Ischemic necrosis Cavitary brain lesions
D- Hypotension, Anemia
R- Hypotension sec to BP unstablity

Death of one Twin

Acute Hypotension in the living twin: Embolization of thromboplastic matter from dead
(less likely)

TTTS- Dx and Staging

Diagnosis
Previously- Wt Discordance and HGB
differences in MC twins late onset findings
Society of Feto-maternal Medicine criteria (2013)
Mc, DA twins
Hydramnios (SDP > 8cm) in one sac and
Oligohydramnios (SDP < 2cm) in the other

Staging
Quintero staging system(1999)

TTTS-Dx and staging

propose the following sonographic

findings as being suggestive of this diagnosis:
1. monochorionicity,
2. same-sex gender,
3. Hydramniosis defined if the largest vertical pocket is >
8 cm in one twin and oligohydramnios defined if the
largest vertical pocket is < 2 cm in the other twin,
4. umbilical cord size discrepancy,
5. cardiac dysfunction in the recipient twin with
Hydramniosis,
6. abnormal umbilical vessel or ductus venosus Doppler
velocimetry, and
7. significant growth discordance
Harkness and Crombleholme (2005)

TTTS- Staging

Once identified, TTTS is typically staged by the Quintero staging

system (Quintero and colleagues, 1999). These are defined as follows:
Stage I
MC- DA Gestation with discordant amnionic fluid volumes
(R SDP>8cm, Donor SDP<2cm), but urine still visible
sonographically within the donor twin's bladder.

Stage II
criteria of stage I, but urine is not visible within the donor's
bladder.

Stage III
criteria of stage II and abnormal Doppler studies of the umbilical
artery, ductus venosus, or umbilical vein
Umbilical Artery- Abscent/Reverse EDF,
Ductus Venosus- abscent/ REDF,
Umbilical Vein-Pulsatile flow

Stage IV
ascites or frank hydrops in either twin; and

Stage V
demise of either fetus.

TTTS- Prognosis and Management

Prognosis depends on stage and GA
Stage I- >3/4th remain stable/ regress without
intervention
Stage III or more- worse prognosis, 70-100%
perinatal loss if no intervention

Treatment Options
Serial amnioreduction
Laser ablation of anastomosis
Septostomy
Selective feticide

TTTS-Selective Fetal Reduction

Selective reduction has generally been considered if

severe AF and growth disturbances develop before 20
weeks
In such cases, both fetuses typically will die without
intervention
Which Twin to be selected for reduction? depending on evidecce of damage and comparison of
prognosis

Methods
UV/Umbilcal cord occlusion of the selected T using;
radiofrequency ablation,
fetoscopic ligation, or
coagulation with laser, monopolar, or bipolar cauterization
(Challis, 1999; Chang, 2009; Donner, 1997)

Injection of lethal substances is inappropriate;both can

be affected through the shared circulation

Growth Discordance
Affects ~15% of Twin pregnancies
More common in MC than DC (b/se of
unequal sharing of the common placenta,
aside from TTTS)
Typically occurs late 2nd or 3rd T
Poor prognosis if seen before 20week
Diagnosis
AC difference of > 20mm
Wt difference of > 20% ( >25-30%- most accurately
predict adverse perinatal outcome)

Growth Discordance Causes

MZ

DZ

Vascular anastomosis
Unequal sharing of
placenta (probably the

Difference in genetic
growth potential Esp.
in opposite sexes
Placental implantation
site difference- sub optimal

most important
determinant)

Discordance for
structural anomalies

implantation site- GR

Placental pathology
Iux crowding

Growth Discordance-Management

Growth assessment and calculation of wt

discordance- mainstay

MC more frequent assessment than DC- b/se of

increased risk of death and neurologic damage
Eg Q2wk for MC and Q 4week for DC

Fetal surveillance if GR in one or both fetuses

NST, BPP, Umb A Doppler recommended, but no
prospective trial evaluation

Delivery
no sufficient data about optimal time
Size discordance alone doesnt prompt delivery,
except occasionally at advanced GA
RCOG (2008)- 37wk for MC and 38wk for DC

Delivery Timing in MFG

Risk of PNM start to increase after 38
wks of GA
> 40wk- post-term for twins
Delivery recommendations for
uncomplicated twin pregnancies are
DC- DA- 38 weeks
MC-DA- b/n 34 and 37 weeks
MC-MA- 32-34 week
( ACOG 2014)

Delivery Route in MFG

The optimal Route of delivery depends on
type of twins, presntation and GA.
MA twins
C/D, to avoid cord complications
DA Twins
Twin-A Vertex, GA> 32wk- Vaginal delivery
Twin A Breech- Most prefer CD b/se of fear of ChinChin locking in vaginal delivery

Optimal delivery route for high order MFGs is

unknown

The

End
!!!