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OBSTETRICS

The vascular anastomoses in monochorionic twin pregnancies

and their clinical consequencesLiesbeth Lewi, MD, PhD; Jan Deprest, MD, PhD; Kurt Hecher, MD, PhD

A ll twin pregnancies are at increasedrisk of death dueto miscarriage andpreterm birth. However, monochori-onic twins, which constitute 20% of alltwins, face the highest risks. For a mono-chorionic twin, the risk of death betweenthe first trimester and 24 weeks is about12%,which is 6 times higher thanthe 2%risk of a dichorionic twin pregnancy.1

Although most deaths occur24 weeks,even after viability monochorionic twinsremain at significantly increased risk.2

Complications of the shared circulationaccount for this excess mortality.1,3,4

During intrauterine life, dichorionictwins have completely separate circula-tion systems, whereas about 95% ofmonochorionic twins have vascularanastomoses on the placental surfacethat connect the 2 circulations.5,6

The nearly ever-present blood ex-change is responsible for some uniquecomplications in monochorionic twins,such as the twin-to-twin transfusionsyndrome (TTTS), the twin anemiapolycythemia sequence (TAPS), the twinreversed arterial perfusion (TRAP) se-quence, and monoamniotic twinning.7

Another consequence of the shared cir-culation is that the well-being of one

twin critically depends on that of theother. After the diagnosis of spontane-ous demise of one of a monochorionicpair, the survivor has a 15% risk of deathand a 25% risk of neurodevelopmentalimpairment8 because of acute exsangui-

nation along the anastomoses into its de-mised cotwin. The fact that their well-being is interrelated also poses somespecific problems in the management ofpoor growth and imminent demise ofthe growth-restricted twin or if 1 twinhasa severeanomaly andselective reduc-tion is considered. In this review, we willdescribe the technique of placental injec-tion. Further, we will discuss the role ofthe vascular anastomoses in each of thecomplications described above and pro-

vide an update on their management.

Injection studies of the

monochorionic placenta

Placental injection from complicatedmonochorionic twin gestations oftenprovides exceptionally useful informa-tion that would otherwise be lost on rou-tine pathological examination. Never-theless, placentas from pregnanciescomplicated with single death and de-layed delivery can no longer be evaluated

because of postmortem involution of theplacental part of the demised twin.

Although placental injection is time-

consuming, it is basically a simple tech-

nique that can be performed by anyone

with minimal surgical skills. After deliv-

ery, it is important to mark the cords of

the first- and/or second-born twin with 1

and/or 2 clamps, respectively. The pla-

centa should be stored in the refrigerator

(at 4C) until examination. The soonerthe placenta is examined the better, but

an interval of up to 10 days is feasible. It

takes about 1 hour to inject a placenta.

Before catheterization, it is best to cut

both cords at about 5 cm from their pla-

cental insertion, because the arteries are

less coiled in their distal segment, which

makes it easier for catheter insertion

(Figure 1). Of each cord, we catheterize

both arteries and the vein and use a 22G

(blue) catheter for the artery and a 16G

(gray) for the vein (Insyte-W; Vialon,

Becton Dickinson, Franklin Lakes, NJ).

For placentas from pregnancies deliv-

ered26 weeks, pediatric 26G and 24G

catheters (BD Neoflon; Becton Dickin-

son) can be used for arterial and venous

catheterization, respectively. Once in-

side the vessel, we fix each catheter to the

cordwithVicryl3/0(Ethicon,Johnson&

Johnson, NewBrunswick, NJ)to prevent

subsequent dislodgement. In 90%,

there is an anastomosis that connects the2 umbilical arteries at the base of thecord

From the University Hospitals Leuven, Leuven,

Belgium (Drs Lewi and Deprest), and University

Medical Center Hamburg-Eppendorf,

Hamburg, Germany (Dr Hecher).

Received July 12, 2012; revised Sept. 10,

2012; accepted Sept. 21, 2012.

J.D. is the recipient of a grant of Fonds voor

Wetenschappelijk Onderzoek Vlaanderen

(FWO; 1.8.012.07.N.02).

The authors report no conflict of interest.

Reprints not available from the authors.

0002-9378/free

2013 Mosby, Inc. All rights reserved.

http://dx.doi.org/10.1016/j.ajog.2012.09.025

For Editors Commentary, see

Contents

Monochorionic twin pregnancies are at increased risk of adverse outcome because of the

vascular anastomoses that connect the 2 fetal circulation systems. The shared circulation

is responsible for some unique complications in monochorionic twins, such as the twin-

to-twin transfusion syndrome, the twin anemia polycythemia sequence, the twin reversed

arterial perfusion sequence, and monoamniotic twinning. Another consequence of the

shared circulation is that the well-being of one twin critically depends on that of the other.

In this review, we will describe the technique of placental injection. Further, we will discuss

the role of the vascular anastomoses in each of the complications described above and

provide an update on their management.

Key words: anemia polycythemia, anomaly, complication, growth, monoamniotic,monochorionic twin pregnancy, placenta, reversed arterial perfusion, review, transfusion

Expert Reviews www.AJOG.org

JANUARY 2013 American Journal of Obstetrics &Gynecology 19
http://dx.doi.org/10.1016/j.ajog.2012.09.025http://dx.doi.org/10.1016/j.ajog.2012.09.025

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(Hyrtlanastomosis). To save time, only 1artery may be catheterized, but we preferto catheterize both from the start as it ismore difficult to catheterize the otheronce injection is started.

For color injection, we always use un-diluted barium sulphate (Micropaque;Guerbet, Villepinte, France), which isavailable in every radiology department.To have a better macroscopic view of theanastomoses, we add water-solublecoloragents for each set of arteries and veins:

blue (methylene blue), red (eosin), andpurple (mixture of methylene blue andeosin). We inject the arteries and vein ofeach twin successively with a 20-mL sy-ringe until all peripheral branches arefilled and backpressure prevents furtherinjection. We then clamp the cords againto prevent further leakage with 1 and 2clamps to identify the first- and second-born twin, respectively. Finally, for opti-mal visualization, we remove the amnioticmembranes from the chorionic surface

and rinse the placenta under cold tap wa-ter. Afterinjection, thenumberand type of

anastomoses arerecorded.We take a high-resolution digitalphotograph perpendicu-lar to the chorionic surface to documentthe angioarchitecture.

Anastomoses can be of 3 types: arte-rioarterial, arteriovenous, and veno-venous. Arterioarterial and venovenousanastomoses are superficial and bidirec-tional anastomoses. Superficial refersto the fact that they are visible on the sur-face of the chorionic plate, forming di-rect communications between the arter-

ies and veins. Bidirectional means thatthey allow flow in both directions de-pending on the relative intertwin vascu-lar pressure gradients. An arterioarterialanastomosis functions as a flexible arte-riovenous connection and thus compen-sates for any imbalance that occurs overthe unidirectional arteriovenous anasto-moses (Figure 2). Most monochorionicplacentas typically have only 1 arterioar-terial anastomosis. Venovenous anasto-moses are more rare and seen in only

about 25% of monochorionic placen-tas.5,6 The function of venovenous anas-

tomoses is less well established. Veno-venous anastomoses may be associatedwith decreased perinatal survival5 andcause demise because of sudden changesin venous return. However, this associa-tion has not been confirmed by other se-

ries. Nevertheless, in the absence of avenovenous anastomoses, each twin hasits own placental territory defined by thevenous vessels that drain oxygen-richblood back to its owner. In contrast, inthe presence of a venovenous anastomo-sis, there is no longer an individual butrather a common and most probablyflexible venous drainage area (Figure 3).

On the other hand, arteriovenousanastomoses are usually referred to asdeep and unidirectional anastomoses.

Deep refers to the fact that the anasto-mosis itself occurs at the capillary levelwithin a shared placental lobule. Unidi-rectional means that they allow flow in1 direction only. It receives its arterialsupply from one twin and gives its ve-nous (well-oxygenated) drainage to theother. The supplying artery and drainingvein of the arteriovenous anastomosisare visible on the chorionic surface as anunpaired artery and vein that pierce thechorionic plate at close proximity of one

other to supply the underlying, sharedplacental lobule. Because of the arterio-venous anastomoses, the monochori-onic placenta actually consists of 3 parts:2 that belong to each twin individually,and a third part that is shared and sup-plied by arteriovenous anastomoses.

Because of their unidirectional nature,arteriovenous anastomoses can create atransfusion imbalance, unless an oppo-sitely directed transfusion by other su-perficial or deep anastomoses provides

adequate compensation. About 90% ofmonochorionic placentas have severalarteriovenous and venoarterial anasto-moses in combination with an arterioar-terial and/or venovenous anastomosis.In about 5% of monochorionic placen-tas, there are only arteriovenous anasto-moses and in another 5% there are noanastomoses.5,6

TTTS

TTTS is an antenatal sonographic diag-nosis based on the presence of polyhy-

FIGURE 1

Technique of placental injection

A B

C D

A, Insertion of catheters after cord is cut 5 cm from its placental insertion. B, Three catheters fixed to

cord. C, Before injection with purple, blue, white, and red barium-sulphate mixtures. D, Injection of

one of the arteries.

Lewi.Vascularanastomoses in monochorionic twinpregnancies and theirclinical consequences. Am J Obstet Gynecol 2013.

Expert Reviews Obstetrics www.AJOG.org

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dramnios (deepest vertical pocket 8cm) with a distended bladder in the re-cipient and oligohydramnios (deepestvertical pocket 2 cm) with a small orempty bladder in the donor. Becauseamniotic fluid increases with gestation,

most Europeans adhere to the gesta-tional age-dependent cutoff of a deepestpocket10 cm after 20 weeks to definethe degree of polyhydramnios. Twin-to-twin transfusion syndrome is some-what a misnomer, as in the overallmajority there is no difference in hemo-globin concentration between donorand recipient twin.9 As such, the nametwin oligopolyhydramnios sequencemay be better suited.10

About 1 in 10 monochorionic twins

develop TTTS, usually between 16-26weeks.3 Why certain monochorionictwins are affected and others are not re-mains elusive because of the lack of ani-mal models and ethical constraints toroutinely perform fetal blood sampling.Both postnatal injection studies5 and invivo fetoscopic observations11,12 indi-cate the presence of at least 1 unidirec-tional arteriovenous anastomosis as ananatomical prerequisite for the develop-mentofTTTS(Figure4). Although there

is no unique pattern of anastomoses, thepresence of an arterioarterial anastomo-sis seems to be protective. As such, anarterioarterial anastomosis is present inonly 1 of 5 TTTS placentas in contrast to4 of 5 placentas not complicated byTTTS.5 Also, a mathematical computermodel simulating TTTS demonstratedthat an arterioarterial anastomosis in-deed compensates more efficiently forany flow imbalance than oppositely di-rected venoarterial anastomoses.13 This

isduetoamuchlowerresistanceoverthedirect arterioarterial anastomosis thanover arteriovenous anastomoses, whichoccur at a capillary level.

Although the vascular anastomosesare an anatomical prerequisite, thepathogenesis of TTTS must be morecomplex than a simple net transfer of redblood cells, because both twins usuallyhave similar hemoglobin values.9 Asmentioned above, TTTS is a problem ofamniotic fluid discordance with a vol-

ume-overloaded recipient and a vol-ume-depleted donor and not a problem

of hemoglobin discordance with a poly-cythemic recipient and anemic donor.Therefore, endocrine factors related tofluid and pressure homeostasis are likelyto be involved as well. Due to the inter-twin blood exchange, one twin is ex-

posed to the endocrine environment ofthe other. As such, transfer of renin-an-giotensin-aldosterone effectors from thedonor may partly explain the recipientshypertensive cardiomyopathy and vol-ume overload.14

TTTS is the most important cause ofdeath and handicap in a monochorionictwin pregnancy.15 Because TTTS occursprior to viability, the prognosis is dismalwithout treatment. Polyhydramnios-re-lated miscarriage or the preterm birth of

2 sick neonates is common, as is the in-trauterine demise of one or both twins.

Fetoscopic laser coagulation of all anas-tomoses along the equator is currentlythe best treatment option regardless ofdisease severity.16 For early detectionand because TTTS is often difficult topredict, it is generallyrecommended that

all monochorionic twins are scanned ev-ery fortnight, especially between 16-26weeks. Laser aims to cure the disease bydisconnecting the 2 fetal circulations.Successful interruption leads to a nor-malization of urine output, of amnioticfluid volumes, and of cardiac function inthe recipient twin. After laser, there is a50-60% survival of both twins and an80% survival of survival of at least 1twin.17 Donor twins seem to have some-what lower survival rates (60%) than

recipient twins (70%).18

Of surviving in-fants, 11% have some form of develop-

FIGURE 2

Typical monochorionic diamniotic placenta from an uncomplicatedpregnancy

A

B

A, Typical monochorionic diamniotic placenta from uncomplicated pregnancy. Delivery was at 35

weeks of 2 healthy neonates of 2534 g and 2440 g. Placenta is equally shared. Each twin has its own

individual placental territory (veins colored bluefor twin 1 and veins colored brownfor twin 2) defined

by venous chorionic plate vessels of each twin (dotted line). There is 1 artery-to-artery anastomosis

(star); 5 arteriovenous anastomoses (from twin 1 to 2) (open circles); and 6 oppositely directed

venoarterial anastomoses (dotted circles). B, Magnification of artery-to-artery anastomosis. Each

artery-to-artery anastomosis functions as flexible arteriovenous anastomosis. Depending on directionof flow, it can act as arteriovenous anastomosis from twin 1 to 2 (solid arrow), or as venoarterial

anastomosis from twin 2 to 1 (dotted arrows).

Lewi.Vascularanastomosesin monochorionictwin pregnancies and their clinicalconsequences. Am J Obstet Gynecol 2013.

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mental impairment. Cerebral palsy is themost common impairment, affecting5%. Both donor and recipient are atequal risk of long-term impairment.Also, in single survivors, the risk ofhandicap is not increased,19 supportingthe concept that laser protects the survi-vor in case of intrauterine demise of its

cotwin. The single most important pre-dictor of adverse long-term outcome isan early gestational age at birth.20

It is clear that outcome after laser sur-gery is far from perfect, because at bestonly 50-60% of parents will take home 2healthy babies. Missed anastomoses arecommon and, depending on the thor-oughness of the injection technique, arefound in about 5-30% of cases.21,22 Thetype and size of missed anastomoses cor-relate with the outcome.23 As such,

missed large arteriovenous anastomosesmay lead to recurrent TTTS or double

demise, unless a compensating arterioar-terial anastomosis is missed as well. Onthe other hand, missed small arterio-venous anastomoses can result inTAPS.23 The latter develops usually sev-eral weeks after the procedure with

mostly a recipient that becomes anemicand the former donor becoming polycy-themic. TAPS is associated with missedsmall-caliber anastomoses (1 mm)(Figure 5) that, owing to the polyhy-dramnios and increased intrauterinepressure, may not bevisible atthe time ofsurgery. However, a chronic net transfu-sion via these hairlike anastomoses maylead to severe hemoglobin discordancesseveral weeks later in ongoing twin preg-nancies. TAPS is usually not associated

with severe amniotic fluid discordanceand is only picked up by serial measure-ment of the middle cerebral artery(MCA)-peak systolic velocities (PSV).Connecting the dots of coagulated anas-tomoses with laser may decrease thechance of missing these tiny anastomo-ses and thereby improve outcome. Thebenefit of drawing a line along the entireequator from one edge of the placenta tothe other is currently the subject of amulticenter randomized trial24 (Figure 6).

Fetal complications because of incom-plete coagulation commonly occur. Wetherefore recommend placental injec-tion of all placentas that underwent lasertreatment,except thosewith single intra-uterine demise and delayed delivery asthe anastomoses can no longer be docu-mented. Placental injection is also ameans of quality control and may im-prove the surgical technique. As such,most missed anastomoses are locatednear the placental edge.22 Finally, pla-

cental examination provides a goodlearning experience for any fetal medi-cine specialist who seeks to embark onendoscopic laser surgery.

TAPSIn contrast to TTTS, which is essentiallyan amniotic fluid discordance, TAPS ischaracterized by a severe hemoglobindiscordance caused by a chronic nettransfusion over minuscule and usually

unidirectional anastomoses. TAPS canbe diagnosed antenatally based on dis-

cordant MCA-PSV measurements. Onetwin typically has an elevated MCA-PSV(1.5 multiples of the median) and inthe other twin the MCA-PSV is de-creased (1 multiples of the median).25

The anemic twin often has decreasedamniotic fluidwhereas the recipient twinmay have increased fluid, but the discor-dance is not as severe as is required forthe diagnosis of TTTS.26 TAPS can alsobe definedby postnatalcriteria. Here, thehemoglobin discordance should be at

least 8 g/dL. Also, to differentiate chronicTAPS from an acute intrapartum trans-fusion, there should be an increased re-ticulocytecountintheanemictwinandadecreased count in the polycythemictwin with a ratio of1.7 or placental in-jection should demonstrate only tiny(1 mm) anastomoses.25

Spontaneous TAPS occurs in about5% of previously uncomplicated mono-chorionic twin pregnancies,3 whereasiatrogenic TAPS after incomplete laser

treatment for TTTS occurs in up to 13%of ongoing twin pregnancies.27 In con-

FIGURE 3

Another monochorionicdiamniotic placenta fromuncomplicated pregnancydelivered at 37 weeks andbirthweights of 2180 g and

2380 g

This placenta has artery-to-artery (solid starand

purple colored artery) and large vein-to-vein

(open starand pinkcolored vein) anastomoses.

In contrast to placenta in Figure1, it is impossible

here to delineate individual venous territories ac-

curately and to determine which twin has larger

territory. Dotted lines reflect some possible pla-

cental distributions depending on where one as-

sumes venous return is located for each twin.

Lewi.Vascularanastomoses in monochorionic twin

pregnancies and their clinical consequences. Am J ObstetGynecol 2013.

FIGURE 4

Monochorionic diamnioticplacenta from patient whodeveloped twin-to-twintransfusion syndrome withdouble intrauterine demise

at 24 weeks

Placenta is equally shared. There is 1 tiny artery-

to-artery anastomosis (star) that could insuffi-

ciently compensate flow over 7 arteriovenous

anastomoses (open circles) from donor (twin 1,

540 g) to recipient (twin 2, 750 g).

Lewi. Vascular anastomoses in monochorionic twinpregnancies and their clinical consequences. Am J ObstetGynecol 2013.



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trast to TTTS that typically presents inthe previable period between 16-26weeks, spontaneous TAPSusually occurs26 weeks and thus in the viable pe-riod.3 On the other hand, iatrogenicTAPS usually develops within 1-5 weeksafter the procedure.27

The placentas of spontaneous and iat-rogenic TAPS show some striking simi-larities23,28 (Figure 7). In contrast toTTTS, the anastomoses in TAPS aresmaller and fewerin number, supporting

the hypothesis that TAPS is a purechronic net transfusion of red bloodcells, whereas in TTTS with its largeranastomoses there is a more elaborateplasma exchange so endocrine factorsmay play a role as well. Similar to TTTS,an arterial anastomosis seems to protectagainst the development of TAPS. Assuch, an arterioarterial anastomosis ispresent in only 1 of 5 TAPS placentas incontrast to 4 of 5 placentas not compli-cated by TAPS. If present, the diameter

of the arterioarterial anastomoses is alsosmaller in TAPS andalways1mm,soit

can inadequately compensate for anyflow imbalance.28,29

As compared to TTTS, spontaneousTAPS usually presents in the viable pe-riod, so its mortality and morbidity ismuch lower. TAPS is in fact the TTTS ofthe neonatologist. As prenatal medicinespecialists, we stole this term to denote acondition that occurs in the previableperiod when no neonatologist is in-volved yet. In our series of 202 mono-chorionic pairs, only 1 intrauterine

death was attributable to TAPS.3

Neona-tal complications are mainly hematolog-ical and include the need for transfusionand partial exchange transfusion of theanemic and polycythemic twin,30 respec-tively. Nevertheless, the need for a severepreterm birth to manage the problemmay complicate the outcome. Also,rarely, antenatal cerebral lesions may oc-cur due to severe anemia-polycythemia,such as cerebellar hemorrhage or cere-bral infarction. Because iatrogenic TAPS

is a common complication if both twinssurvive, a weekly to fortnightly measure-

ment of the MCA-PSV is an essentialpart of the postlaser follow-up. Further,because in previously uncomplicatedtwins, TAPS may cause late intrauterinedemise, we measure the MCA-PSV rou-tinely every fortnight from 20 weeks un-

til birth. Especially in pairs with worsen-ing growth discordance24 weeks, oneshould be suspicious of TAPS.31

The management will mainly dependon gestational age and accessibility of theequator. However, due to its rarity andthe lack of comparative studies, there isnofirmguidanceonwhatisbest.IfTAPSis suspected, we always reevaluate theMCA-PSV in 2-3days.If thediscordancepersists prior to 30 weeks or if there ishydrops in the anemic twin, then our

next step would be a cordocentesis andintrauterine transfusion (IUT). A secondIUT may be considered to prolong ges-tation. However, if there is rapid recur-rence of the anemia after 2 IUTs and de-pending on the gestational age, thecondition of the twins, and the accessi-bility of the equator, the options are anelective delivery, a selective reduction, ora (re)laser of the vascular anastomoses.In rapid recurring anemia, there is a sig-nificant risk of hyperviscosity-related

complications in the receiving twin, sousually only up to 2 IUTs are attempted.

FIGURE 5

Monochorionic diamniotic placenta from patient who developed twinanemia polycythemia sequence 3 weeks after laser treatment

Patient was delivered at 29 weeks because of nonreassuring heart rate tracing. Twin 1 (ex-donor) and

twin 2 (ex-recipient) had hemoglobin of 19 and 8.8 g/dL, respectively. Placenta is shared equally.

There is a tiny missed venoarterial anastomosis from twin 2 to 1 at edge of placenta.

Lewi.Vascularanastomoses in monochorionic twinpregnancies and theirclinical consequences. Am J Obstet Gynecol 2013.

FIGURE 6

Monochorionic diamnioticplacenta after laser coagulationof placenta at 20 weeks whereline was drawn with laseron placental surface

Coagulation line is clearly visible connecting one

edge of placenta with other (dotted line). Patient

delivered 2 healthy newborns of 2310 g and2100 g, respectively.




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A fetoscopic laser procedure for TAPS is

more difficult than for TTTS, because of

the lack of polyhydramnios, the minus-

cule anastomoses, and the more ad-

vanced gestational age. After 30 weeks

and administration of steroids, an elec-

tive delivery seems a reasonable option.

TRAP sequence

In TRAP sequence, blood flows from an

umbilical artery of the pump twin in a

reversed direction into the umbilical ar-

tery of the perfused twin, via an arterio-

arterial anastomosis and usually returns

via a venovenous anastomosis back to

the pump twin. Theperfusedtwin is thus

a true parasite. The perfused twins

blood supply is by definition deoxygen-

ated andresults in variable degrees of de-

ficient development of the head, heart,

and upper limb structures. Usually, theperfused twin does not have any func-

tional cardiac activity, hence also the

name acardiac twin.Two criteria seem to be necessary forthe development of a TRAP sequence.The first is the presence of an arterioar-terial anastomosis and the second a dis-cordant development32 or an intrauter-ine demise of one of the monochorionictwins,33 allowing for reversal of bloodflow (Figure 8). In dichorionic twinpregnancies, intrauterine demise of 1twin in the first trimester invariably leadsto a vanishing twin, whereas in mono-

chorionic twins, existing anastomosesmay actually prevent vanishing and sus-tain further cell growth and some degreeof differentiation of the demised twin.Whenever a single intrauterine demise isdiagnosed in a monochorionic twinpregnancy in the first trimester, the pos-sibility of TRAP sequence should be keptin mind, which can be easily diagnosedby demonstrating the reversed bloodflow in the umbilical artery with colorDoppler flow.

TRAP is a rare condition and compli-cates probably only about 1% of mono-

chorionic twin pregnancies. The condi-

tion is associated with a high risk ofperinatal death caused by a combinationof high-output cardiac failure and poly-hydramnios-related preterm birth.34

The outcome may be improved by an in-tervention to arrest the circulation of theacardiac twin. The type of technique willdepend on the clinical presentation andmay consist of a coagulation of theumbilical cord and/or placental anasto-moses or of intrafetal laser or radiofre-quency ablation (RFA).35,36 With the

widespread introduction of the first-tri-mester scan, TRAP is increasingly beingdiagnosed in the first trimester. How-ever, intrauterine intervention can onlysafely be performed16 weeks, after fu-sion of amnion and chorion. We offer allour patients a prophylactic interventionat 16 weeks, because pump twin demiseis difficult to predict in the early secondtrimester and it precludes the difficultyof achieving arrest of flow in the largerandoftenhydropicmass later on in preg-

nancy. However, in a series of 24 TRAPcases diagnosed in the first trimester, 1 of

FIGURE 8

Placenta of monochorionic monoamniotic triplet complicated by twinreversed arterial perfusion sequence and miscarriage at 15 weeks

triplet 1

triplet 2

acardiac

triplet1

triplet 2

acardiac

Cords were entangled. Placenta shows 1 arterioarterial anastomosis (solid star) from cord of smaller

triplet 1 (open arrow) and venovenous anastomosis (open star) to larger triplet 2 (open arrow). Triplet

1 was therefore pump triplet, whereas triplet 2 was draining triplet.

Lewi.Vascularanastomosesin monochorionictwin pregnancies and their clinicalconsequences. Am J Obstet Gynecol 2013.

FIGURE 7

Monochorionic diamnioticplacenta complicatedby spontaneous twin anemiapolycythemia sequencedelivered at 35 weeks

Growth had been concordant throughout preg-

nancy. At birth, there was growth discordance of

30%. Twin 2 weighed 2445 g with hemoglobin of

22 g/dL requiring partial exchange transfusion.

Twin 1 weighed 1720 g with hemoglobin of 12

g/dL. Placenta is equally shared. There was 1

tiny arterioarterial anastomosis (star), 4 tiny ar-

teriovenous anastomoses from twin 1 to 2 (open

circles), and 1 tiny oppositely directed venoarte-

rial connection (dotted circle).

Lewi.Vascularanastomoses in monochorionic twinpregnancies and their clinical consequences. Am J Obstet

Gynecol 2013.



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3 had an intrauterine demise of thepump twin at the time of the plannedintervention at 16-18 weeks.37 Of thoseundergoing prophylactic surgery, 90%survived. Because of the high mortalityof TRAP in the first trimester, small case

series have been reported on the out-come ofintrafetal coagulation in first tri-mester.38,39 Although these show prom-ising results, larger series arenecessary todemonstrate that a first-trimester inter-vention is safe and will improve the sur-vival rate in TRAP sequence.

Monoamniotic twinpregnancies

Monoamniotic twins not only share asingle placenta but also the amniotic sac.Diagnosis is made reliably in the first tri-

mester by the presence of a single amni-otic sac surrounding the 2 twins and thelack of an intertwin septum. Transvagi-nal ultrasound scan can help to demon-strate the lack of intertwin septum. Asboth twins are in the same amniotic sac,cord entanglement is usually already de-monstrable in the first trimester by thesimultaneous recording of 2 differentheart rates within the same pulsed-wavesampling gate. Contrary to previous be-lief, several recent case reports indicate

that the number of yolk sacs does not ac-curately predict amnionicity. As such, aminority of monoamniotic twins has 2yolk sacs, whereas a minority of diamni-otic twins has only a single yolk sac.40,41

Monoamniotic twins are rare andabout 1 in 20 monochorionic twins aremonoamniotic. They are thought toarise from a late cleavage of the inner cellmass. The cords typically insert close toone another on the chorionic plate withlarge-caliber anastomoses connecting

the stem vessels of both twins (Figure 9).Nearly all monoamniotic placentas havean arterioarterial anastomosis as com-pared to 80%of monochorionic diamni-otic placentas.42 TRAP sequence is notuncommon and also all conjoined twinsare by definition monoamniotic. Bothare readily detectable in the first trimes-ter, but prognosis is determined primar-ily by these complicating features ratherthan by the monoamnionicity itself.Nevertheless, even in the absence of

TRAP and conjoined twinning, mono-amniotic twins are at increased risk of

adverse outcome as compared to their

diamniotic counterparts. First, discor-

dant structuralanomalies are morecom-

mon, affecting up to 20% of monoamni-

otic twin pregnancies43 as compared to

6% of diamniotic twin pregnancies.3

Late embryonic cleavage and imbalancesacross the large-caliber anastomoses

possibly account for this increased prev-

alence. Second, monoamniotic twins are

at increased risk of unexpected and

mostly double intrauterine demise. In

the largest series on monoamniotic

twins, 15% and 4% of ongoing preg-

nancies were complicated by intrauter-

ine demise 20 and 32 weeks, res-

pectively.44 In comparison, in a large

prospective series of monochorionic di-

amniotic twins, 6% and 1.2% were com-plicated by intrauterine demise20 and

32 weeks, respectively. In monochori-

onic diamniotic twins, TTTS is the most

importantcause of death.3 In contrast, in

monoamniotic twins, because of the

nearly ever-present arterioarterial anas-

tomoses, TTTS is a rarer occurrence. The

main cause of death in a monoamnio-

tic pair is probably an acute fetofetal

hemorrhage across the large-caliber

anastomoses that is triggered by cord

compression.Although death is usually unexpected,

careful surveillance and planned pre-

term birth seem to improve survival

rates to 80%.45 If a severe anomaly is de-

tected in 1 twin, selective feticide can be

performed by ultrasound-guided bipo-

lar cord coagulation and subsequent fe-

toscopic laser transection of the cord.

Release of the entanglement is important

to prevent demise of the healthy twin

later on in pregnancy. Cord transection

is technically challenging, therefore al-

though the survival rates seem compara-

ble to those of cord coagulation in diam-

niotic twins, the preterm premature

rupture of membrane rates are some-

what higher and gestational age at birth

lower in monoamniotic than in diamni-

otic twin pregnancies.46 There is no firm

evidence to guide management, but as

would most fetalmedicine specialists, we

would recommend inpatient monitor-

ing from

28 weeks, and an elective pre-term birth at 32-33 weeks after the ad-

ministration of antenatal corticosteroidsfor lung maturation.47

Single intrauterine death

Unequal placental sharing, placental in-sufficiency, or hemodynamic imbal-ances such as in TTTS or TAPS maycause intrauterine death of 1 twin. Fur-thermore, because of the shared circula-tion single death may lead to double de-mise or antenatal brain damage, becauseof acute exsanguination of the survivingcotwin into its demised twins circula-tion. A recent systematic review demon-strated that in monochorionic twins,single demise will result in a double

death in about 15%, and neurodevelop-mental impairment in another 25% dueto acute perimortem exsanguination, inaddition to a 68% risk of preterm birth.8

Antenatal brain damage is often de-tectable on prenatal ultrasound exami-nation, but does not become apparentuntil several weeks after the insult. Mag-netic resonance imaging may detectbrain lesions earlier and with better def-inition.48,49 Initially, thromboembolicphenomena with passage of thrombo-

plastin from the demised to thesurvivingtwin were thought to be responsible for

FIGURE 9

Monoamniotic placentawith short distance between2 marginal cord insertions

Delivery was elective at 32 weeks with birth of 2

healthy neonates of 1510 g and 1570 g, respec-

tively. Placenta is unequally shared. There is 1

large arterioarterial anastomosis from twin 1 to 2(star). There is no individual placental part for

twin 1 that is entirely supplied through at least 8

arteriovenous anastomoses from twin 2.




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these lesions.50 A variety of studies havefailed to provide such evidence. On theother hand, perimortem exsanguinationis well documented.51 Fetal blood sam-pling within 24 hours of the demise has

consistently revealed a decreased hemat-ocrit in surviving twins whereas coagula-tion profiles were normal.52

The outcome of the surviving cotwinmay depend on the type and direction ofvascular anastomoses and the fetopla-cental mass of the demised twin. Thepresence of arterioarterial anastomosesmay be associated with higher rates ofdeath and neurologic damage.53 How-ever, significant anemia and cotwindeath may occur, even in the absence of

arterioarterial anastomoses as the survi-vor may also exsanguinate across artery-

to-vein or vein-to-vein anastomoses.54

Treatment of TTTS by laser coagulationmore frequently results in single demiseas compared to amniodrainage, but itconsistently less often leads to doublede-mise.55 Also, anemia in the survivor is

rare in the event of single demise afterlaser,56 and the neurological morbidityappears less than after amniodrain-age.57,58 These findings provide furtherevidence that the anastomoses are re-sponsible for most of the adverse out-comes associated with single demise inmonochorionic twins.

From10-14 weeks,single demise oc-curs in about 4% of monochorionic twinpregnancies, whereas double demise oc-curs in at least 6%.1 Perimortem exsan-

guination of the survivor occurs duringor soon after the demise of its cotwin.Therefore, a preemptive preterm deliv-ery seems inappropriate, as it will onlyworsen the outcome of the survivingtwin by adding the complications of pre-term birth. MCA-PSV measurementsare an effective means to predict fetalanemia.56 If fetal anemia is excluded,then a major exsanguination is unlikelyand the prognosis is most likely favor-able.54,56 However, if anemia is present,

there is currently insufficient evidencethat a rescue IUT improves outcome.Whereas it may prevent cotwin death, itmay come too late to prevent brain in-jury58 and careful follow-up of these fe-tuses with detailed brain scans and pre-natal magnetic resonance imaging isindicated. Placental injection may stillreveal useful information provided thedelivery occurred within 2 weeks afterthe event. If only a few small unidirec-tional anastomoses are detected, thenthe

outcome for the surviving twin is likelyto be favorable, since this precludes amajor exsanguination. On the otherhand, the presence of large bidirectionalanastomoses explains the occurrence ofbrain damage or later demise of the sur-viving cotwin (Figure 10).

Discordant growth

Discordant growth (discordance25%)without TTTS is not more common inmonochorionic than in dichorionic

twins and occurs in about 10-15%.1,3,4

The degree of discordance, expressed in

percentage, is determined as (A B) *100/A,whereA is the estimated weightofthe heavier and B is the weight of thelighter twin. Monochorionic twins areby definitionmonozygotic andthus havethe same genetic growth potential.

Growth in monochorionic twins is de-termined by the division of the singleplacenta between the twins6,59 as well asby the vascular anastomoses.5,6 These 2factors determine the venous returnupon which the fetus depends for its ox-ygen and nutritional supply.

Unequal placental sharing appears tobe the most important determinant ofdiscordant growth in monochorionictwins.6,59 Although it remains impossi-ble to assess the functional placental ter-

ritory for each individual twin antena-tally, the umbilical cord insertion sitesmay provide a good estimate. As such,the combination of a velamentous andcentral cord insertion is more commonin monochorionic twins. Additionally,nearly a quarter of these twins have abirthweight discordance of20%.59Thesite of cord insertion can be reliably de-tected on a prenatal ultrasound exami-nation in the second60 and even in thefirst61 trimester. Although we cannot as-

sess the degree of sharing with prenatalultrasound, we maywell usea discordantcord insertion as a substitute for unequalplacental sharing and thus identify agroup of monochorionic twins at highrisk for discordant growth.

Vascular anastomoses also influencegrowth in monochorionic twins. Assuch, an unbalanced net arteriovenoustransfusionas in TTTS and TAPSmayrestrict and improve the growth of the do-nor and recipient twin, respectively.4,28

Successful laser coagulation has beenshown to reduce any existing growth dis-cordance, probably by improving thegrowth of the donor62 and/or restrictingthe recipients growth.63,64 On the otherhand, growth discordance may reverse af-ter laser, in cases with unequal placentalsharingwhere the recipient has the smallerplacental share (Figure 11).

Unequallysharedplacentashavelargerar-terioarterial anastomoses, a larger netflow over arteriovenous anastomoses,

and a larger diameter of all anastomosestaken together than equally shared pla-

FIGURE 10

Monochorionic diamnioticplacenta at 28 weeksfrom pregnancy that wascomplicated by early-onset typeIII discordant growth

There was intrauterine demise of smaller twin at

25 weeks. Survivor was anemic (hemoglobin of

7.6 g/dL) and was given intrauterine transfusion.Three weeks later, surviving twin was noted to

have infarction of entire brain, except for cere-

bellum and brain stem. Patient went into preterm

labor and twin 2 died intrapartum. Twin 1 was

polycythemic. Placenta is unequally shared.

Smaller twin 1 has velamentous cord insertion

and no individual placental part. There were 2

large arterioarterial (solid stars), 1 venovenous

(open star), several arteriovenous (open circles),

and several venoarterial (dotted circles) anasto-

moses. Large artery-to-artery anastomoses ex-

plain anemia in larger twin, because of exsan-guination into body of demised twin.

Lewi.Vascularanastomoses in monochorionic twinpregnancies and their clinical consequences. Am J ObstetGynecol 2013.



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centas, which may reduce the impact oftheir placental territory discordance andresult in reduced birthweight discor-dance. This elaborate intertwin bloodexchange fulfills a beneficial and oftenlifesaving role by increasing the avail-ability of oxygen and nutrients to thetwin on the smaller placental share.6 As aconsequence, inappropriate use of laser

coagulation of the vascular anastomosesas a treatment for severe discordantgrowth will cause the demise of the twinwith the smaller share, where both twinsmay have survived, had they remainedunseparated. On theother hand, a tightlylinked interfetal circulation, and espe-cially the large arterioarterial anastomo-sis, may result in sudden and unpredict-able intertwin transfusion imbalancesand intrauterine demise, of which inabout 50% are a demise of both twins.65

Monochorionic pairs with discordantgrowth from early on in pregnancy (20

weeks) have different placental charac-teristics and different clinical outcomesthan those where discordant growtharises later on. Twin pregnancies withearly-onset discordant growth typicallyhave an unequally shared placenta with

large anastomoses. Intrauterine demiseoccurs in about 20% of cases and mosthave an abnormal umbilical arteryDoppler evaluation from 16 weeks(Figure 12). On the other hand, preg-nancies with progressively increasinggrowth discordance 26 weeks havemore equally shared placentas withsmaller anastomoses. Doppler examina-tion in the umbilical artery of the smallertwin is always normal and the survivalrate is nearly 100%. Nevertheless, about

1 in 3 pregnancies with late-onset discor-dantgrowth havesevere hemoglobin dif-ferences at the time of birth and these pla-centas typically have few small and mostlyunidirectional arteriovenous anastomosesas seen in TAPS placentas. Late-onset dis-cordant growth in a monochorionic twinpair should therefore raise the suspicion ofTAPS and is an indication for MCA-PSVmeasurements.31

Next to a classification based on gesta-tional age at first presentation, growth-

discordant monochorionic pairs canalso be classified according to the Dopp-ler characteristics of the umbilical arteryof the smaller twin.66 If a large arterioar-terial anastomosis is present, as in caseswith early-onset discordant growth, thenthis may result in a cyclical variation inthe diastolic flowcomponent andthus inan intermittent absent or reversed end-diastolic flowpattern in the umbilical ar-tery of the smaller twin. The smaller twinof a growth-discordant monochorionic

pair maythus have a normalflow pattern(type I), a persistent absent or reversedend-diastolic flow (type II), or an inter-mittent absent or reversed end-diastolicflow (type III). Each of these types hasdistinct placental features and differentclinical outcomes. Large arterioarterialanastomoses (2 mm) are present in70%,18%, and 98% of typeI, type II, andtype III, respectively. Pregnancies withnormal umbilical artery Doppler mea-surements in the smaller twin (type I)

have the most favorable outcome with alow risk of deterioration or unexpected

demise and a survival rate of nearly100%. On the other hand, a persistentabsent end-diastolic flow(typeII) carriesthe worst prognosis as 90% eventuallyshow signs of deterioration and immi-

nent death and survival rates are only60%.67 Pregnancies with an intermittentabsent end-diastolic flow pattern (typeIII) have an intermediate prognosis withan 85% survival, but are the most unpre-dictable. Because of the large arterioarte-rial anastomoses, unexpected death ofthe smaller twin without any signs of de-terioration occurs in about 15% of preg-nancies. In about half of these cases,there is also a cotwin demise of the largertwin. In type III, especially the larger

twin seems to be at increased risk ofantenatally acquired brain injury. Prob-

FIGURE 11

Placenta of monochorionicdiamniotic twin pregnancyafter successful laser treatmentfor twin-to-twin transfusionsyndrome

At 23 weeks before laser surgery, recipient (twin

2) waslarger with estimatedfetalweightof 578g

vs donor 442 g. At 31 weeks at time of birth,

recipient was much smaller with birthweight of

810 g as compared to donor 1560 g. Recipient

has smaller part of placenta, reflecting lower

birthweight (dotted line). There were no missed

anastomoses.

Lewi.Vascularanastomoses in monochorionic twinpregnancies and their clinical consequences. Am J ObstetGynecol 2013.

FIGURE 12

Placenta of monochorionicdiamniotic twin pregnancywith early-onset type IIIdiscordant growth (36%)

Birth was by emergency caesarean section be-

cause of abnormal heart rate tracing in smaller

twin. Birthweights were 1075 g (twin 1) and

670 g (twin 2). Smaller twin was diagnosed with

coarctation, which was treated by stent place-

ment on day 26 and coarctectomyat 9 months of

age. Largertwin had peripheral pulmonary artery

stenosis requiring no treatment. Placenta is un-

equally shared. There is little individual territory

for smaller twin (dotted line). There is large

arterioarterial (star) and several arteriovenous

(open circles) and venoarterial (dotted circles)anastomoses.




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ably because of the large arterioarterial

anastomosis, short episodes of bradycar-

dia and hypotension in the smaller twin

may lead to large volume shifts from the

larger to the smaller twin, increasing the

risk of ischemic brain lesions.

Clearly, the natural history and out-come of discordant growth is much bet-

ter than that of untreated TTTS. Out-

come will be primarily determined by

the onset andseverity of the discordance,

the degree of growth restriction, by the

interval growth, and by the amniotic

fluid of the smaller twin. As such, a dis-

cordancy of40% that is present from

16 weeks with a smaller twin that is well

below the5th centile andthat shows little

growth and oligohydramnios (2 cm

deepest pocket) at 19 weeks is likely tohave a poor outcome. Nevertheless, pro-

spective series of unselected monochori-

onic pairs are needed to document the

pregnancy and especially the long-term

neurodevelopmental outcome accord-

ing to the different Doppler patterns and

to refine the current classification sys-

tem, as better criteria are necessary to

distinguish the discordant growth cases

with favorable outcome from those with

a high risk of death and handicap.

The optimal management of discor-dant growth in monochorionic twin

pairs is not well established. In our insti-

tutions, we follow up pregnancies with

early-onset discordant growth and an

abnormal umbilical artery Doppler eval-

uation (type II and III) on a weekly basis.

In the previable period, we may offer a

selective reduction by umbilical cord co-

agulation to pregnancies with signs of

imminent fetal death of the smaller twin,

such as growth stop and anuria with an-

hydramnios.68 From 28 weeks, these

patients are usually hospitalized for in-

patient monitoring, and are candidates

for elective preterm birth at 32-33 weeks

after the administration of antenatalcor-

ticosteroids for lung maturation. Pairs

with late-onset discordant growth and a

normal umbilical artery Doppler evalua-

tion in the smaller twin are also moni-

tored on a weekly basis with measure-

ment of the MCA-PSV to exclude

evolution of TAPS and are usually deliv-ered around 34-35 weeks.

We do not routinely offer laser coagu-lation of the vascular anastomoses as atreatment for discordant growth with anabnormal umbilical artery Doppler eval-uation, because most do well withouttreatment. Also, due to unequal placen-

tal sharing, demise of the smaller twinoccurs in 50-70% of cases. As such, laserimproves neither the survival rates, northe neurologic outcome.65,69 Further-more, the procedure is technically morechallenging due to the absence of poly-hydramnios andentry is alwaysin the sacof the appropriately grown twin with thebest chances of survival. Also, in type IIIcases, the procedure will be hampered bythe multiple and large anastomoses.

Discordant anomaliesMajor congenital anomalies are morecommon in monochorionic twin preg-nancies and occur in about 6% ofpairs.3,70 Concordance (both twins sim-ilarlyaffected) for a structural anomaly israre (20%). Several hypotheses exist toexplain this increased incidence. Pos-sibly the zygotic splitting itself isteratogenic, resulting in abnormalities,such as midline defects.71 Furthermore, inmonochorionic twin gestations, transfu-

sion imbalances through the anastomo-ses during embryogenesis or during laterfetal life may account for at least part ofthe cardiac or brain anomalies observedin these pregnancies. As such, the preva-lence of congenital cardiac anomalies inmonochorionic twins has been reportedto be 2.3% in those without TTTS and7% in those with TTTS, compared to0.6% in the general population. Pulmo-nary valve stenosis in recipients ac-counted for all the additional congenital

heart defects detected in TTTS cases,suggesting a causative role for the hemo-dynamic imbalance of TTTS in its devel-opment.72 Furthermore, severe ischemicbrain lesions because of exsanguinationof the surviving twin into the fetal-pla-cental unit of the demised twin are awell-known phenomenon in monocho-rionic pairs.

The vascular anastomoses are not onlyimplied in the etiology of major congen-ital anomalies in monochorionic gesta-

tions, they also influence their manage-ment. Because of the anastomoses, the

conventional technique of potassiumchloride injection as a means of selectivefeticide cannot be used. Double intra-uterine demise may occur because oftransfusion of the potassium chloride tothe nonaffected twin or because of acute

exsanguination of the healthy twin in thefetoplacental unit of the dead twin.As such, minimal invasive techniques

have been proposed to produce com-plete circulatory confinement of the af-fected twin. At present, ultrasound-guided bipolar cord coagulation andintrafetal RFA are the preferred ap-proaches. RFA is especially indicated incases with oligohydramnios or anhydr-amnios, with a short umbilical cord inthe target twin, and at an earlier gesta-

tional age or smaller fetal tissue volume.Ideally, fetal therapy centers have accessto both cord and intrafetal coagulationtechniques, so that the choice of tech-nique can be tailored to the specific de-mands of each case. Fetal loss rates arehigher as compared to selective feticideby potassium chloride in multichorionicpregnancies. The overall survival rate isabout 70-80% with normal develop-mental outcome in 90% of survivinginfants. About half of the losses are at-

tributable to intrauterine demise of thehealthy cotwin usually within the first 2postoperative weeks and about half topostnatal losses due to very pretermbirth.73-75 Neurodevelopmental impair-ment is largely due to an early gestationat birth.

CONCLUSIONIn summary, the vascular anastomosesare responsible for some unique compli-

cations in monochorionic twin pregnan-cies. They also account for the increasedmortality and morbidity as compared todichorionic twins, which have separatecirculations. As long as thetwinsare con-nected to this shared circulation, inter-twin transfusion imbalances may occurand each twin is exposed to the hor-monal environment of its cotwin. Theshared circulation is also responsible forthe fact that the well-being of each twincritically depends on the well-being of

the other one. Placental injection studiesare vital for our understanding of these



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complications and also for the choice ofthe best management. f

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