Management of Twin

8/12/2019 Management of Twin

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Management of twin-twin transfusion syndromeAuthorsKenneth J Moise Jr, MDAnthony Johnson, DOSection EditorsDeborah Levine, MDLouise Wilkins-Haug, MD, PhDDeputy EditorVanessa A Barss, MDDisclosures

All topics are updated as new evidence becomes available and ourpeer review processiscomplete.Literature review current through:Aug 2013. | This topic last updated:sep 6, 2013.

INTRODUCTIONInterventions for management of twin-twin transfusion syndrome (TTTS)

include:

Expectant management

Amnioreduction

Septostomy

Selective feticide

Fetoscopic laser ablation of vascular anastomoses

Fetoscopic laser ablation is generally considered the definitive treatment for severe (Quintero stage

II or above) TTTS between 16 and 26 weeks of gestation.

This topic will review interventions for management of TTTS and outcome. The pathogenesis,

clinical manifestations, and diagnosis of TTTS are discussed separately. (See"Pathogenesis and

diagnosis of twin-twin transfusion syndrome".)

EXPECTANT MANAGEMENT

STAGE 1Five studies that evaluated the frequency of progression from Quintero stage I disease

reported progression rates ranging from 10 to 46 percent with a collective average of 24 percent [1-

5]. However, in over half of the cases, either an amnioreduction (95 percent) or laser ablation (5

percent) was performed. In a small retrospective study, intervention was associated with an

improvement in long-term neurodevelopmental outcome (neurodevelopmental impairment with laser

therapy 0/16 versus 7/18 with conservative management), but not overall survival (survival with

laser therapy 30/40 [75 percent] versus 52/60 [87 percent] with conservative management) [5].

There are no good prospective data on the frequency of progression or outcome of well-defined

stage I disease in the absence of any intervention. A consensus conference was held by the North

American Fetal Therapy Network to evaluate the available information regarding management of

Quintero Stage I TTTS. The scientific panel, who were not actively involved in TTTS clinical care orresearch, concluded that there is normative equipoise to justify the performance of randomized

clinical trials to identify the optimal treatment strategy for mild TTTS [6].

Stage II or moreThe background incidence of loss in untreated pregnancies with severe

(Quintero stage II or above) TTTS is difficult to ascertain. A MEDLINE review identified 28 studies

involving a total of 68 pregnancies with untreated TTTS between 1966 and 1991 [7]. Overall

perinatal survival was 30 percent and survival by gestational age at diagnosis was:


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up were neurologically normal. These data, as well as data described below on the efficacy of

intervention, support intervention in severe or progressive disease.

INDICATIONS FOR INTERVENTIONAcute or chronic deterioration of one of the fetuses is the

major indication for intervention by preterm delivery. As an example, the recipient twin may develop

hydrops fetalis or the donor twin may exhibit progressive fetal growth restriction with nonreassuring

antepartum fetal testing.

In the absence of acute or chronic deterioration of one of the fetuses, the following interventions

have been used to treat severe or progressive TTTS.

FETOSCOPIC LASER ABLATIONFirst introduced by De Lia in 1990, laser ablation of placental

anastomoses has gained widespread acceptance as the definitive treatment for severe TTTS

between 16 and 26 weeks of gestation [8]. The value of this procedure was illustrated in a

randomized clinical trial that evaluated outcomes after laser ablation versus amnioreduction in 142

women with second trimester severe TTTS [9]. As compared with the amnioreduction group, the

laser group had a significantly higher likelihood of the survival of at least one twin to 28 days of age

(76 versus 56 percent) and at six months of age, a significantly lower incidence of cystic

periventricular leukomalacia (6 versus 14 percent), and survivors were significantly more likely to befree of neurologic complications at six months of age (52 versus 31 percent).

Subsequently, a meta-analysis of comparative studies found that compared with fetuses

undergoing serial amnioreduction, fetuses undergoing laser ablation were twice as likely to survive

and had an 80 percent reduction in neurologic morbidity (overall survival OR 2.04, 95% CI 1.52-

2.76; neonatal death: OR 0.24, 95% CI 0.15-0.40; neurologic morbidity OR 0.20, 95% CI 0.12-0.33)

[10]. In addition, a meta-analysis of three randomized trials reported laser coagulation of

anastomotic vessels resulted in fewer double deaths (RR 0.32-0.61, depending on Quintero stage,

three trials), fewer perinatal deaths (26 versus 44 percent, RR 0.59; 95% CI 0.40-0.87, one trial)

and fewer neonatal deaths (8 versus 26 percent, RR 0.29; 95% CI 0.14-0.61, one trial) than

pregnancies treated with amnioreduction [11].

Laser ablation in the United States is usually undertaken for Quintero stage II to IV TTTS between

16 and 26 weeks of gestation. This is in part due to the current FDA investigational device

exemption for fetoscopes that limits their use to treatment of TTTS between 16 and 26 weeks of

gestation. In addition, laser ablation in the late second trimester is subject to several technical

limitations: fetal vernix in the amniotic fluid reduces optimal visualization; placental vessels are

larger in caliber and more difficult to successfully coagulate; and greater in utero distances may not

be easily traversed by current fetoscopes.

A 2013 Society for Maternal-Fetal Medicine (SMFM) clinical guideline recommended the use of

laser ablation for the treatment of stage II to IV TTTS in continuing pregnancies


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Although laser therapy is not available at all tertiary obstetrical centers, 19 centers in the United

States offer this treatment (seewww.fetalhope.org).

ProcedurePreprocedural ultrasound should identify the placental umbilical cord insertion sites.

Proximate umbilical cord insertions (


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AMNIOREDUCTIONSerial amniocentesis to remove excess amniotic fluid in the recipient twin's

amniotic cavity results in higher survival rates than expectant management. Amnioreduction

reduces uterine overdistention, which is a risk factor for preterm labor and preterm premature

rupture of the membranes (PPROM). It also decreases pressure inside the amniotic cavity and thus

appears to improve uteroplacental perfusion [52].

The clinical threshold to begin serial amnioreductions is subjective. Potential indications includerelieving maternal symptoms of respiratory difficulty and possibly decreasing the risk of preterm

delivery in women with frequent contractions or decreased cervical length. It is probably most useful

for prolonging pregnancy in patients with mild TTTS who have already reached 26 weeks of

gestation since, in the United States, the Food and Drug Administration (FDA) has not approved

use of fetoscopes for treatment of TTTS in the third trimester.

However, weekly ultrasound surveillance is probably a safer alternative to amnioreduction in the

early stages of TTTS, as complications from the procedure may preclude subsequent successful,

definitive treatment by placental laser photocoagulation (see below). These complications include

unintentional perforation of the intervening membrane, amnion-chorion separation, intraamniotic

bleeding, and PPROM. Laser coagulation is contraindicated in the presence of PPROM. Amnion-

chorion separation is a major risk factor for development of PPROM [53,54].

Even without PPROM, iatrogenic membrane damage significantly increases the difficulty of

introducing the fetoscope for laser coagulation [55], while bloody amniotic fluid impedes

visualization; amnioexchange may be necessary in such cases.

ProcedureA variety of amnioreduction techniques have been described; there are no

randomized trials evaluating whether one is safer and more effective than another. There is no

consensus regarding how much fluid to remove, how rapidly to remove the fluid, use of tocolytic

medications, or use of antibiotics.

We begin by anesthetizing the skin with a long-acting local anesthetic (eg, bupivicaine). Under

ultrasound guidance, a long 18-gauge spinal needle is introduced into the amniotic cavity withpolyhydramnios, avoiding the placental edge, if possible. The placenta will be markedly thinned on

ultrasound imaging because of the excessive amniotic fluid.

Placing the needle as close to the midline of the uterus as possible with a slight angulation toward

the maternal xiphoid will reduce the risk of needle displacement as the uterine size diminishes with

drainage of amniotic fluid. The technique we prefer is to connect the needle to one end of the

specialized tubing included in a disposable thoracocentesis tray (male to male ends). The other end

of the tubing is connected to a short 18-gauge needle that is spiked into a disposable vacuum

bottle. This set-up maintains a closed system, avoids excessive needle manipulation, and allows

the rate of flow to be controlled with the rollerball valve in the line.

Some experts recommend removing no more than 5 liters of amniotic fluid over about an hour [56].

Decompression of the uterus with rapid removal of a large volume of fluid may cause placental

abruption or fetal bradycardia; therefore, we suggest removing smaller volumes of fluid in severe

TTTS.

OutcomeThe International Amnioreduction Registry reported outcomes from the largest series

of TTTS patients undergoing amnioreduction [57]. A total of 223 twin pregnancies from 20 fetal

medicine units were diagnosed with TTTS prior to 28 weeks of gestation and treated with 760

amnioreductions. The major findings from this series were:
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Complications of the procedure included PPROM within 48 hours of the procedure (6

percent), spontaneous delivery (3 percent), fetal distress (2 percent), fetal death (2

percent), placental abruption (1.3 percent), and chorioamnionitis (1 percent).

Both twins were live born in 55 percent of pregnancies, one twin was liveborn in 31 percent,

and both twins were stillborn in the remaining 14 percent. During the first four weeks of

neonatal life, an additional 30 percent of liveborn twins succumbed.

24 percent of recipient twins and 25 percent of donor twins that survived to four weeks of

age had evidence of intracranial abnormalities on neonatal cranial ultrasound.

SEPTOSTOMYThe goal of intentional perforation of the inter-twin membrane is to equilibrate

amniotic fluid volume and pressure between the two amniotic cavities [58]. However, computerized

models have not found that restoring amniotic fluid in the donor sac enhances donor swallowing

and intravascular volume, thereby reversing manifestations of TTTS [59]. As with amnioreduction,

septostomy is probably most useful for prolonging pregnancy in patients who have already reached

26 weeks of gestation.

ProcedureSeptostomy is usually performed alone, but may be performed in conjunction with

amnioreduction. When performed alone, under ultrasound guidance a long 22-gauge spinal needleis placed through the donor's sac and into the recipient's sac. A single puncture is all that is

required. Multiple punctures can lead to significant disruption of the inter-twin membrane and

entanglement of umbilical cords.

If both septostomy and amnioreduction are being performed, an 18-gauge spinal needle is

introduced into the recipient's sac to perform the amnioreduction. After the amnioreduction has

been completed, a long 22-gauge spinal needle is inserted through the 18-gauge needle and used

to puncture the inter-twin membrane.

A repeat ultrasound examination is performed 24 hours after septostomy to confirm that the

amniotic fluid volumes of the two sacs have equilibrated. The inter-twin membrane should be

visualized easily and noted to move freely.

OutcomeA randomized clinical trial in 73 women presenting with TTTS at less than 24 weeks of

gestation compared amnioreduction with septostomy [60]. There were no significant differences

between groups in the rate of survival of one twin or both twins. Long-term neurologic follow-up was

not reported. The major benefit of septostomy was that fewer patients required more than one

procedure (46 versus 69 percent, p = 0.04). Despite this potential benefit, many physicians choose

amnioreduction over septostomy as their first line of intervention because septostomy requires more

technical expertise than amnioreduction.

SELECTIVE FETICIDESelective feticide may be the best option when TTTS is complicated by a

life-threatening anomaly in one of the fetuses [61]or after failed laser ablation (eg, "stuck" donor

twin overlying the site of the placental anastomoses or significant intraamniotic bleeding during the

initial laser procedure that obscures fetoscopic visualization). Recurrent TTTS and twin anemia-

polycythemia sequence (TAPS; see below) after laser therapy have also been treated with selective

reduction. However, some experts have advocated this procedure in any pregnancy with advanced

stage TTTS (severe cardiac failure in the recipient fetus or severe intrauterine growth restriction in

the donor twin).

ProcedureUltrasound-directed cord coagulation is usually performed with a disposable 3 mm

bipolar cautery forceps. Laser can also be used to coagulate the cord under direct fetoscopic
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visualization; however, this procedure has failure rates as high as 5 percent compared with only

rare failures when bipolar forceps are used. A specialized needle that uses radiofrequency energy

to ablate the cord insertion (RFA) is another option. This ultrasound-directed thermal occlusion

technique offers the advantage of a smaller puncture (14- to 17-gauge needle) with the potential for

reduced maternal morbidity, but experience is too limited to determine success and complication

rates.

The fetus predicted to have the least chance for survival is usually selected for the reduction

procedure. The available data do not show a difference in survival according to whether the donor

or recipient twin was targeted [62]. If bipolar cautery is used, reduction of the recipient twin is

technically easier since its cord is easily visualized floating amid the excess amniotic fluid.

Oligohydramnios around the donor makes this twin a more difficult target, although the donor cord

can be grasped through the inter-twin membrane after entry into the recipient's amniotic cavity. This

results in a septostomy and the risk of subsequent cord entanglement. However, if the donor twin is

the primary target, amnioinfusion can be performed to improve access for the bipolar forceps.

Alternatively, RFA of the abdominal cord insertion can be undertaken, without the need for

amnioinfusion [63].

OutcomeExperience with selective feticide for TTTS is limited. One study including 15 cases of

TTTS treated with bipolar coagulation of the umbilical cord reported an overall survival of 87 percent

in the co-twin, but PPROM occurred in 20 percent of pregnancies within three weeks of the

procedure [64]. Another study including 22 cases of TTTS treated with bipolar cautery reported an

overall survival of 77 percent [65]. One infant had developmental delay at 16 months of age. In a

third series of 24 cases of TTTS, the overall survival was 92 percent (one fetal death and three

neonatal deaths) [62]. One infant exhibited mild motor delay at 18 months.

The acute cessation of blood flow through the umbilical cord prevents a hypotensive episode in the

surviving twin, which can lead to fetal anemia with subsequent death or neurologic insult.

CERCLAGE AND PROGESTERONE SUPPLEMENTATIONThe combination of

polyhydramnios and twins results in significant uterine overdistention, which is an established riskfactor for preterm birth that is possibly mediated, in part, by cervical shortening. (See"Pathogenesis

of spontaneous preterm birth".)

Fifteen to 25 percent of patients with TTTS have a short (25 mm) cervix. A multicenter

retrospective cohort study did not find a significant prolongation in duration of pregnancy among

TTTS patients with a short cervix who underwent cerclage before laser ablation, but the authors felt

a prospective randomized trial was warranted [66].

Progesterone supplementation has not been studied in TTTS. Routine progesterone

supplementation does not reduce the rate of preterm birth in multiple gestations, although there are

some data suggesting it may be useful in twin pregnancies with a short cervix. The use of

progesterone to reduce the risk of preterm birth is discussed separately. (See"Progesteronesupplementation to reduce the risk of spontaneous preterm birth", section on 'Twin pregnancy'.)

SUMMARY AND RECOMMENDATIONS

Expectant management of twin-twin transfusion syndrome (TTTS) results in an overall fetal

survival rate of only 30 percent. (See'Expectant management'above.)

The clinical threshold to begin serial amnioreductions is subjective. Serial amniocentesis to

remove excess amniotic fluid in the recipient twin's amniotic cavity results in higher survival
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rates than expectant management, but not as high as laser photocoagulation.

Disadvantages of amnioreduction are that multiple procedures are usually required and

complications from the procedure may preclude subsequent treatment by laser

photocoagulation of the vascular communications. No more than 5 liters of amniotic fluid

should be removed at the time of amnioreduction, and we suggest removing lesser

amounts in severe TTTS. (See'Amnioreduction'above.)

Selective feticide may be the best option when TTTS is complicated by a life-threatening

anomaly in one of the fetuses or after failed laser ablation. (See'Selective feticide'above.)

For women with severe (Quintero stage II-IV) TTTS under 26 weeks of gestation, we

suggest laser ablation of placental anastomoses rather than serial amnioreduction (Grade

2A). Laser ablation results in greater prolongation of gestational age, higher neonatal

survival, and improved long-term neurologic outcome. (See'Fetoscopic laser

ablation'above.)

For women with mild (Quintero stage I) TTTS under 26 weeks, we suggest expectant

management rather than invasive therapy (Grade 2C). We perform weekly ultrasound

examinations to detect progression to more severe disease. Amnioreduction in these cases

may decrease the chance for a later successful laser therapy. However, we consider laser

therapy for patients with stage I disease and excessive maternal symptoms due to extreme

polyhydramnios. (See'Amnioreduction'above.)

For women with TTTS after 26 weeks of gestation, we suggest serial amnioreduction or

septostomy rather than laser therapy (Grade 2C). The upper gestational age limit is due to

Food and Drug Administration restrictions on the use of current fetoscopes, as well as

technical issues that make laser therapy difficult in the third trimester. (See'Fetoscopic

laser ablation'above.)

For the first six weeks after laser therapy, we suggest intensive fetal surveillance with

weekly ultrasound examination to detect such complications as twin anemia-polycythemia

sequence or growth restriction. Thereafter, ultrasounds can be performed every two weeks.

We initiate antenatal testing by 30 weeks of gestation. Acute fetal compromise or poor

serial growth will often be detected and is an indication for early delivery. (See'Follow-upand delivery'above.)

We deliver all patients with TTTS by 37 weeks of gestation due to the risk of unexplained

fetal death late in pregnancy. (See'Follow-up and delivery'above.)

About 11 percent of survivors of laser therapy have some degree of long-term

neurodevelopment abnormality. Neurologic follow-up of apparently healthy neonates after

laser therapy is warranted. (See'Outcome'above.)

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Management of Twin

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