twin transfusion syndrome and survival following

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Mar 6, 2017 - K E Y W O R D S. Doppler ultrasonography; Fetoscopic laser surgery; Monochorionic pregnancy; Twin-to-twin ... of all monochorionic diamniotic twin pregnancies. It results from ..... onic triplet pregnancies. Fetal Diagn Ther.
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Received: 24 October 2016    Revised: 13 January 2017    Accepted: 6 March 2017 DOI: 10.1002/ijgo.12143

CLINICAL ARTICLE Obstetrics

Doppler assessment of patients with twin-­to-­twin transfusion syndrome and survival following fetoscopic laser surgery Enrique Gil Guevara1,2* | Andrea Pazos2 | Otilia Gonzalez2 | Pilar Carretero2 |  Francisca S. Molina2 1

The Center for Fetal, Cellular and Molecular Therapy, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA 2

Maternal-Fetal Medicine Unit, Department of Obstetrics and Gynaecology, University Hospital of Granada (CHUG), Granada, Spain *Correspondence Enrique Gil Guevara, The Center for Fetal, Cellular and Molecular Therapy, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA. Email: [email protected]

Abstract Objective: To investigate fetal-­survival rates following laser surgery for twin-­to-­twin transfusion syndrome (TTTS) and the impact of Doppler analysis. Methods: The present retrospective single-­center study included data from patients with pregnancies exhibiting TTTS treated with fetoscopic laser surgery between January 1, 2007, and December 31, 2016. Perinatal outcomes were examined and variables were compared between the donor and recipient fetuses that survived and died, respectively. Results: There were 86 pregnancies exhibiting TTTS treated with fetoscopic laser surgery included in the study. The median length of pregnancy at the time of surgery was 21.1 weeks. Both twin fetuses and at least one fetus survived in 61 (71%) and 73 (85%) pregnancies, respectively. Among recipient fetuses, ductus venosus a-­wave anomalies (P=0.026), shorter cervical length (P=0.044), and a greater than 25% discrepancy in the estimated weight of the twin fetuses (P=0.045) were associated with reduced survival. Conclusion: Among pregnancies exhibiting TTTS, laser surgery was associated with significant dual-­fetus survival. Preoperative ductus venosus anomalies were associated with lower survival among recipient fetuses, and 1-­week postsurgical ultrasonography data demonstrated lower survival among recipient fetuses with persistent anomalous ductus venosus compared with normalized ductus venosus. KEYWORDS

Doppler ultrasonography; Fetoscopic laser surgery; Monochorionic pregnancy; Twin-to-twin transfusion syndrome

1 |  INTRODUCTION

Differentiating between TTTS and selective fetal growth restriction (sFGR) is imperative; sFGR represents another adverse occurrence

Twin-­to-­twin transfusion syndrome (TTTS) affects approximately 10%

that is prevalent among monochorionic pregnancies but it presents a

of all monochorionic diamniotic twin pregnancies. It results from blood-­

different prognosis and postnatal outcomes.3,4

flow imbalances in placental anastomoses between two fetuses. These

Ultrasonography plays a critical role in the diagnosis of TTTS,

anastomoses cause one fetus, the recipient, to have a fluid overload

not only for the early diagnosis of chorionicity but also for estab-

and the other, the donor, to have fluid depletion; in lay terms, one

lishing differences in amniotic fluid between the two gestational

fetus bleeds into the other through a placental connection.1,2

sacs.

Int J Gynecol Obstet 2017; 1–5

wileyonlinelibrary.com/journal/ijgo

© 2017 International Federation of  |  1 Gynecology and Obstetrics

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Gil Guevara ET AL.

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Doppler assessment can be used to define different stages in TTTS

of TTTS (amniotic fluid discrepancy); Stage II, the bladder of the

and it has been demonstrated in studies that postnatal survival is as-

donor fetus was not visible; Stage III, anomalous blood flow of the

sociated with changes in fetal circulation.5,6 The most studied vessel

umbilical artery or ductus venosus identified in either twin during

in the recipient fetus is the ductus venosus because it is affected by

Doppler assessment; Stage IV, the recipient fetus displayed signs

fluid overload; in the donor fetus, the umbilical artery is the most

of hydrops.

studied vessel owing to the affects exerted by placental functionality.

Doppler measurements were taken without fetal breathing and

However, the assessment of recipient-­twin umbilical artery blood flow

movement, with an insonation angle below 30°; umbilical artery and

is not well understood.7

ductus venosus measurements were performed in the free loop of the

The recommended treatment in TTTS is laser coagulation of the

umbilical cord and in the fetal liver, respectively. Absent or reversed

8–10

end diastolic flow in the umbilical artery, and an absent or reversed

communicating vessels in the placenta by a fetoscopic approach.

In countries where laser fetoscopy is not available, amnioreduction is a

a-­wave in the ductus venosus were observed during a 6-­second ob-

treatment option; however, it has a lower survival rate in comparison

servation window in each of two measurements.

with laser therapy. High-­intensity focused ultrasound is a novel treatment option that is being tested in animal models.

11

Following antibiotic prophylaxis and local anesthesia, fetoscopic laser surgery was performed by equatorial photocoagulation of the

Fetoscopic laser surgery survival rates vary based on the severity

communicating vessels and the surrounding placental territory. A

of TTTS and Doppler examination plays an important role in assessing

600-­μm diameter diode laser fiber (VELAS; GIGAA Laser, Wuhan,

TTTS severity. The postoperative assessment of fetal vessels is very

China) with 30-­W power output was used for the photocoagulation

important because it helps in the evaluation of the development of

of the placental anastomoses. After surgery, all patients remained

both twins. The objective of the present study was to investigate fetal

under observation for 24 hours, including postoperative ultraso-

and neonatal survival in pregnancies with TTTS treated by fetoscopic

nography assessment. When possible, patients underwent a 1-­

laser surgery, and to assess the relationship between preoperative and

week follow-­up Doppler assessment with fortnightly assessments

postoperative Doppler findings.

in their local hospital thereafter. Pregnancy outcome data were collected at hospital discharge from patients or referring doctors,

2 |  MATERIALS AND METHODS

when available. Statistical analyses were performed using the Fisher exact test and χ2 test to compare categorical variables, when appropriate, and

The present retrospective study included data from all consecutive

the Mann-­Whitney U test was used for continuous data; a two-­

patients who underwent fetoscopic laser surgery for the treatment of

tailed P25% in estimated fetal weight of twins

4 (6)

4 (19)

0.095

4 (6)

4 (24)

0.045

Umbilical artery absent or reversed flow

9 (14)

5 (24)

0.315

12 (17)

2 (12)

0.726

Ductus venosus absent or reversed a-­wave

5 (8)

2 (10)

>0.99

7 (10)

0

0.336

4 (6)

1 (5)

>0.99

4 (6)

1 (6)

20 (31)

9 (43)

20 (29)

10 (59)

Donor fetus

Recipient fetus Umbilical artery absent or reversed flow Ductus venosus absent or reversed a-­wave

0.285

>0.99 0.026

a

Values are given as mean, median (range), or number (percentage), unless indicated otherwise.

Of the 30 recipient fetuses with preoperative ductus venosus Doppler anomalies, five did not survive to 1-­week postoperative

findings among donor twins were not associated with differences in survival.

Doppler follow-­up. Ductus venosus had normalized in 18 fetuses and

The fluid overload that occurs in the recipient fetus in TTTS can be

Doppler anomalies remained in seven fetuses; survival to final dis-

assessed using the a-­wave in the ductus venosus, and fluid depletion

charge was higher among fetuses who had normalized ductus venosus

in the donor fetus can be assessed through the umbilical artery flow.

Doppler evaluations (17 [94%] vs 3 [43%]; P=0.012).

Consequently, two situations can be observed during umbilical artery Doppler evaluation, hypovolemia or hypoxemia. In isolated TTTS,

4 |  DISCUSSION

donor-­fetus umbilical artery blood flow anomalies reflect the underlying hypovolemic status; in concurrent sFGR with TTTS, donor-­fetus umbilical artery Doppler anomalies reflect a chronic hypoxemic status

The present study included data from 86 patients who underwent fe-

due to impaired assigned placental territory. This concept can be fur-

toscopic laser surgery for TTTS and recorded survival rates of 71%

ther applied to multiple higher-­order pregnancies.14

and 85% for both twins and at least one twin, respectively; a low incidence of adverse events was observed.

The main objective of fetoscopic laser surgery in TTTS is survival of both fetuses. Higher dual survival has been reported with Quintero

Generally, TTTS is an acute event that can occur during mono-

stage I and II TTTS compared with Quintero stage III and IV TTTS.15,16

chorionic diamniotic twin pregnancies; consequently, it is critically

It is important to consider the prevalence of recipient-­fetus ductus ve-

important to establish the difference between isolated TTTS and

nosus anomalies for preoperative counselling of patients because it

concurrent TTTS with sFGR. This differentiation is important in pre-

affects survival in this group of twins substantially.

operative patient counselling because pregnancy outcomes differ

Umbilical artery flow anomalies in recipient fetuses are rare; a

between these entities.3,4 Outcomes of surgical management for

study by Patel et al.7 reported a prevalence of 4%. The present study

concurrent sFGR with TTTS are generally similar to those for isolated

found a prevalence of 6% among all recipient twins. Anomalies in

sFGR.3 For this reason, the present study did not include concur-

the umbilical artery of recipient fetuses could be due to poor cardiac

rent sFGR with TTTS because the aim was to describe preoperative

function because, in the context of hypervolemic status, fetuses are

findings and survival outcomes. This allowed the present study to be

not able to push blood forward into the umbilical arteries through-

compared with similar previous studies; a lower rate of donor twins

out diastole. The finding in the present study that all recipient twins

exhibiting anomalous umbilical artery Doppler results was observed

with umbilical artery flow anomalies also had ductus venosus Doppler

compared with previous studies.10–12 Conversely, 35% of recipient

anomalies supports the theory of cardiac impairment.

twins had anomalous ductus venosus Doppler findings. Preoperative

An important observation in the present study was that, higher

anomalous ductus venosus Doppler findings in recipient twins can be

survival was observed among recipient-­twin fetuses that had normal-

considered a negative prognostic finding, as evidenced by the lower

ized ductus venosus findings at 1-­week postsurgical Doppler evalua-

survival observed in the present study. Umbilical artery Doppler

tion compared with those with persistent ductus venosus anomalies.

Gil Guevara ET AL.

This difference could have been associated with a cessation in the hypervolemic state in the recipient twin and the stoppage of fluid overload following effective laser photocoagulation of the communicating vessels between the fetuses. A limitation of the present study was the number of patients included. Finally, in future studies of pregnancies with TTTS, it will be important that the potential of underlying sFGR complicating pregnancies be considered.

AUT HOR CONTRI B UTI O N S EGG and FSM contributed to the design and planning of the study, data analysis, and writing the manuscript. AP contributed to the conception of the study, data analysis, and the revision of the manuscript. OGV and PC contributed to data acquisition and the revision of the manuscript. All authors approved the final manuscript.

CO NFLI CTS OF I NTE RE ST The authors have no conflicts of interest.

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