Laser treatment in twin-to-twin transfusion syndrome

Seminars in Fetal & Neonatal Medicine (2007) 12, 450e457

available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/siny

Laser treatment in twin-to-twin transfusion syndrome Masami Yamamoto a,b, Yves Ville a,* a

Service de Gyne´cologie Obste´trique, CHI Poissy Saint Germain en Laye, Universite´ de Paris-Ouest, Versailles-St. Quentin en Yvelines, 10 Rue de Champ Gaillard, Poissy 78300, France b Unidad de Medicina Materno Fetal, Clı´nica Alemana, Hospital Padre Hurtado, Universidad del Desarrollo, Manquehue Norte 1410, Vitacura, Santiago, Chile

KEYWORDS Twin-to-twin transfusion syndrome; Laser coagulation; Review

Summary Twin-to-twin transfusion syndrome (TTTS) is a severe fetal condition that has regained attention since surgical endoscopic treatment proved beneficial in a randomized controlled trial. Our objective is to review published series of cases treated with fetoscopic surgery. Diagnostic criteria, surgical technique, and perinatal outcome of series of TTTS cases treated by laser were reviewed. Over 1300 cases from 17 publications have been included, with a median perinatal survival rate of 57% (50e100%); brain lesions were present in 2e7% of the survivors at the age of 1e6 months. The percutaneous technique has gained wide acceptance, with an acceptable risk of maternal morbidity but a significant risk of miscarriage or preterm rupture of the membranes, presenting in 6.8e23% and 5e30%, respectively. The conclusion is that standardization of the technique and stability to improvement of the initial results should broaden the use of this technique. The overall survival rate at birth was 66% (1894/2869). However, variations in survival rates between centres and inconsistency in the reporting of complications call for more homogeneity in the pre- and post-operative assessment. ª 2007 Elsevier Ltd. All rights reserved.

Introduction Twin-to-twin transfusion syndrome (TTTS) affects 15% of all monochorionic twin pregnancies and has a dismal prognosis in up to 80% of the cases if untreated. Since publication of the first series,1,2 over 1000 cases have been treated worldwide, in an increasing number of centres, following the results of the randomized controlled trial establishing the benefit of fetoscopic laser surgery * Corresponding author. Tel.: þ33 1 39275380; fax: þ33 1 39274412. E-mail address: [email protected] (Y. Ville).

(FLS) over amnioreduction.4 The objective of this chapter is to review series of cases treated by FLS.

Methods A PubMed search for ‘twin-to-twin transfusion syndrome’ was performed to identify all series of TTTS treated by FLS of placental anastomoses. Reports of 5 cases were excluded. The numbers of cases included in earlier publications were taken into account. The review included only written information, and no unpublished data were requested from the authors. Only publications in which consecutive cases of TTTS were published were included.

1744-165X/$ - see front matter ª 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.siny.2007.07.005

Laser treatment in TTTS Table 1

451

Publications, authors, number of cases treated

Authors (year of publication)

Performed

Gestational age (range)

n

Institutions

% of cases previously published

Triplets

Ville et al., 19951 De Lia et al., 19952 Ville et al., 199813 De Lia et al., 19993 Hecher et al., 19999 Hecher et al., 20006 Quintero et al., 20005 Quintero, et al., 200314 Senat et al., 20044 Sepulveda et al., 200515 Yamamoto et al., 200516 Robyr et al., 200611 Huber et al., 200617 Ishii et al., 200718 Ierullo et al., 20077 Middeldorp et al., 200719 Middeldorp et al., 200720

1992e1994 1988e1994 1992e1996 1995e1998 1995e1997 1995e1999 1994e1999 1997e2000 1999e2002 1997e2002 1999e2004 2002e2004 1999e2003 2002e2005 2002e2006 2000e2004 1991e2006

15e28 18e24 15e27 18e24 17e25 16e25 16e26 16e25 15e26 16e23 15e26 NA 15e25 <26 16e26 16e26 26e28

45 26 132 69 73 200 92 95 72 10 175 151 200 55 77 100 10

1 1 3 1 1 1 1 1 3 1 1 2 1 4 1 1 1

No No 34 No 24 36 No Yes, % not mentioned No No 41 No No No No No No

0 1 0 0 0 0 0 0 0 10 3 0 0 0 0 0 0

The results were analysed taking into consideration the gestational age at surgery, participating institution, number of cases, and year of publication. The diagnostic criteria for surgery, differences in the procedure, premedication, and Table 2 staging

fetal and maternal outcomes were compared between studies. A non-selective technique was defined as coagulation of all vessels crossing the insertion of the inter-twin membrane. A selective technique was defined on intention-

Diagnostic criteria for laser indication and other sonographic parameters such as placental location, hydrops and

Authors

Weight Polyhydramnios Donor discordance in recipient amniotic fluid

Collapsed Anterior bladder placenta (%) in donor

Hydrops

Ville et al., 1995 De Lia et al., 1995 Ville et al., 1998 De Lia et al., 1999 Hecher et al., 1999

Yes No No No No

Yes Yes >9 cm Yes Yes Yes >8 cm

Stuck twin Oligoamnios Oligoamnios Oligoamnios Yes <1 cm

40 None 43 46 38

NA NA 4/30 NA NA NA Some, NA NA 6/73 NA

Hecher et al., 2000 Quintero et al., 2000 Quintero et al., 2003 Senat et al., 2004

No No No No

Yes Yes Yes Yes

NA 46.7 NA 30

NA 9/92 11/95 1/72

NA 52/32 56/39 37/35

Sepulveda et al., 2005

No

Yes >8 cm Yes >8 cm Yes >8 cm Yes >8 cm or >10 cm over 20 weeks’ GA Yes

Yes No Yes No Small or empty Yes No No No

Yes

NA

1/10

NA

Yamamoto et al., 2005

No

Oligoamnios, stuck Yes <2 cm

No

44

8/175

101/74

Robyr et al., 2006

No

Yes <2 cm

No

NA

NA

NA

Huber et al., 2006 Ishii et al., 2007 Ierullo et al., 2007 Middeldorp et al., 2007

No No No No

Yes Yes Yes Yes

No Yes Yes No

NA NA 15

10/200 NA 9 7/100

110/90 6/49 0/77 52/48

Middeldorp et al., 2007

No

No

0

0

2/8

GA, gestational age.

Yes >8 cm or >10 cm over 20weeks’ GA Yes >8 cm or >10 cm over 20 weeks’ GA Yes >8 cm Yes >8 cm Yes >8 cm Severe polyhydramnios Yes >10 cm

<1 cm <2 cm <2 cm <2 cm

<2 cm <2 cm <1 cm <2 cm

Yes <2 cm

Stages 1/2 and 3/4

452

M. Yamamoto, Y. Ville

to-treat as a procedure in which coagulation was aimed at preserving normal cotyledons.5 Survival rates were expressed in comparable ways; some authors expressed them in live births and others in survival at 6 months. Cases with secondary pregnancy termination or selective termination were not excluded. Neonatal deaths were presented as a percentage of treated cases and not of live births, because neonatal death is largely a consequence

of preterm delivery and because the neonatal death rate may be decreased if pregnancies reach later gestations.

Results Of 1046 articles found using the key words ‘twin-to-twin transfusion syndrome’, Table 1 includes all published series

Table 3

Description of surgery

Authors

Anaesthesia

Access

Laser/power

Endoscope

Technique

Ville et al., 1995

Local, lidocaine

Percutaneous

Nd:YAG

Non-selective

De Lia et al., 1995

General

Nd:YAG/60 W

Ville et al., 1998 De Lia et al., 1999

Local, lignocaine General

Hecher et al., 1999

Local, lidocaine

7e10 cm laparotomy with purse-string suture Percutaneous Minilaparotomy or midline incision and exteriorize the uterus in cases with an anterior placenta Percutaneous

2.7 mm; Keymed, UK and Storz, Germany 2.9  3.8 mm

Hecher et al., 2000

NA

Percutaneous

Nd:YAG

Quintero et al., 2000 Quintero et al., 2003 Senat et al., 2004

NA

Percutaneous

NA

Non-selective

Nd:YAG/30e50 W Nd:YAG/60 W

2.7 mm; Keymed 2.9  3.8 mm; Comeg, USA

Non-selective Selective

Nd:YAG/50e60 W

Selective

Nd:YAG/20e40 W

2 mm; Olympus, Germany and Storz, Germany 2 mm; Olympus, Germany and Storz, Germany 3 mm; Wolff

Percutaneous

Nd:YAG

3 mm; Wolff

Local

Percutaneous

Local, lidocaine

Percutaneous

Nd:YAG or diode/ 30e60 W Nd:YAG

Percutaneous

Nd:YAG or diode/ 30e50 W

Robyr et al., 2006

Local, xylocaine and 1 mg oral flunitrazepam Local or regional

3.3 mm; Storz, Germany 3.3 mm; Olympus, Germany 3.3 mm; Storz, Germany

Percutaneous

Diode/30e60 W

Huber et al., 2006

Local

Percutaneous

Nd:YAG

Ishii et al., 2007 Ierullo et al., 2007

NA 1% Lignocaine and 5e10 mg oral diazepam Regional and general

Percutaneous Percutaneous

Nd:YAG Ktp/Nd:Yag/30e 60 W

Percutaneous, minilaparotomy (8), open-entry laparotomy (7) Percutaneous

Sepulveda et al., 2005 Yamamoto et al., 2005

Middeldorp et al., 2007

Middeldorp et al, 2007

Regional

Selective

Non-selective and selective Selective Selective Non-selective Selective

3.3 mm; Storz, Germany 2 mm and 30 for anterior placenta; Storz, Germany 3 mm 2.8 mm; Olympus

Selective

Nd:YAG

3.3 mm; Storz, Germany

Selective

Nd:YAG

3.3 mm; Storz, Germany

Selective

Selective

Selective Vascular equator coagulation

Laser treatment in TTTS Table 4

453

Premedication and hospitalization

Authors

Antibiotics

Preoperative tocolysis

Procedure duration

Prophylactic tocolysis

Duration of hospitalization

Ville et al., 1995 De Lia et al., 1995

Yes, not described 3rd generation cephalosporin IV

Yes, not described Indomethacin 50 mg

30e90 NA

<1 day NA

Ville et al., 1998

3rd generation cephalosporin IV

40 min, 15e85

De Lia et al., 1999

No

Indomethacin or diclofenac per rectum Doses NA 50 mg indomethacin sup 1 h before

Hecher et al., 1999

Yes, not described

NA

NA Indomethacin 50 mg/6 h for 2 day, then 25 mg/ 6 h for 2 day Indomethacin IR, diclofenac IR or salbutamol IV Doses NA Indomethacin 50 mg/6 h for 1 day, then 25 mg/ 6 h for 2 day NA

24e48 h

Hecher et al., 2000 Quintero et al., 2000

NA

NA

NA

NA

60 min, 20e188

Same drug for 48 h

24e48 h

Quintero et al., 2003

3rd generation cephalosporin IV

NA

Same drug for 48 h

24e48 h

Senat et al., 2004 Sepulveda et al., 2005 Yamamoto et al., 2005

Yes, not described Yes, not described

NA 45e90

NA Yes, not described

24e48 h NA

Cefazolyn 2 g IV

Indomethacin 100 mg the night before and 1 h before procedure

30 min, 14e55

Not used

12e48 h

Robyr et al., 2006 Huber et al., 2006 Ishii et al., 2007

Yes, not described NA 3rd generation cephalosporin IV

NA NA 62 min, 20e188

NA NA Same drug for 48 h

24e48 h NA 24e48 h

Ierullo et al., 2007

Cefuroxime 750 mg IV Amoxicillin/ clavulanate Amoxycilin/ clavulanate

Yes, not described NA Magnesium sulphate, terbutaline, indomethacin 5 mg trinitrate patch for 24 h Indomethacin

15 min, 5e25

NA

NA

5 mg trinitrate patch for 24 h Not used

NA

Indomethacin

NA

Not used

NA

Middeldorp et al., 2007 Middeldorp et al., 2007

3rd generation cephalosporin IV

Magnesium sulphate or indomethacin NA Magnesium sulphate, terbutaline, indomethacin Magnesium sulphate, terbutaline, indomethacin Yes, not described Yes, not described

of TTTS treated by FLS, i.e., 1507 cases included in 17 papers. Some cases were reported twice as part of ongoing growing series in many centres. There was one publication in which the number of cases included previously was not mentioned.14 Gestational age at surgery was similar. In the first study FLS was performed up until 28 weeks of gestation; however, it was limited to 26 weeks thereafter, except for a recent series of 10 cases treated after 26 weeks.20 One publication was dedicated to triplets and

NA

6e48 h

NA

showed a significant difference in results when comparing dichorionic with monochorionic triplet placentas15 (Table 1). Table 2 describes the inclusion criteria on ultrasound and information on Quintero staging,8 used since 1999. Diagnostic criteria appear similar within studies. Weight discordance was not always used for diagnostic purposes and was abandoned in the more recent studies. Unfortunately, none of the series reports on how often and how much inter-twin discordance was present. The donor’s

454 Table 5

M. Yamamoto, Y. Ville Maternal complications and delivery

Authors

Gestational age at delivery (mean or median, interval), weeks

PPROM <24 weeks, %

% of miscarriage (delivery <24 weeks)

PPROM >24 weeks, %

Laser-to-delivery interval median (interval), weeks

Ville et al., 1995 De Lia et al., 1995 Ville et al., 1998 De Lia et al., 1999 Hecher et al., 1999 Hecher et al., 2000 Quintero et al., 2000 Quintero et al., 2003 Senat et al., 2004 Sepulveda et al., 2005 Yamamoto et al., 2005 Robyr et al., 2006 Huber et al., 2006 Ishii et al., 2007 Ierullo et al., 2007 Middeldorp et al., 2007 Middeldorp et al., 2007

Median 35 (25e40) Mean 32 (26e37) Mean 32 (26e37) NA Median 20 (17e25) Median 20 (16e26) Mean 32 (24e39) Median 32 (17e40) Median 33.3 Median 30 NA NA Median 34 (23e40) Median 31 (26e38) NA Median 33 Median 31

NA 13 NA NA NA NA NA NA NA NA 6.8 NA 1 1.8 NA NA NA

11 23 9.8 NA 12 11 5.4 8.4 12 10 6.8 6 3.5 1.8 6.5 8 8

NA 30 9.8 NA NA NA NA NA 13.8a NA 21 17 NA NA NA 5b 5b

14 11.7 NA 9.9 12.9 13 NA 10.3 NA 11.5 NA NA 13 NA 9 NA NA

(0e21) (6e17) (1e19) (0.3e19.1) (0.7e22.7) (0e21.4) (1e19)

(0e21)

PPROM, preterm premature rupture of membranes. a Only PPROM within 4 weeks of the procedure were included. b Only PPROM within 2 weeks of the procedure were included.

empty bladder is not considered a requisite for laser in later series, and Quintero staging has become an important landmark in classifying cases and has been used in most publications since 2000 (Table 2). Amniotic fluid discordance Table 6

criteria have varied, as oligohydramnios of <1 cm was changed to <2 cm from 2000.5 One centre uses variable polyhydramnios criteria, >10 cm deepest vertical amniotic fluid sac after 20 weeks and >8 cm before 20 weeks4 (Table 2).

Recurrence and second procedures

Authors

Poly/ oligohydramnios recurrence

Second laser (for recurrence)

Need for amnioreduction

Delivery as a treatment of TTTS

Selective termination (for recurrence or fetal complication)

Pregnancy termination (for recurrence or fetal complication)

Ville et al., 1995 De Lia et al., 1995 Ville et al., 1998 De Lia et al., 1999 Hecher et al., 1999 Hecher et al., 2000 Quintero et al., 2000 Quintero et al., 2003 Senat et al., 2004 Sepu ´lveda et al., 2005 Yamamoto et al., 2005 Robyr et al., 2006 Huber et al., 2006 Ishii et al., 2007 Ierullo et al., 2007 Middeldorp et al., 2007 Middeldorp et al., 2007

2.2% 3.8% 9.1% No 1.3% NA 2.2% NA 4.1% NA NA

1 No 5 No 1 NA No NA 2 NA NA

No No 6 No No NA No NA 1 NA NA

No No 1 No No NA No NA No NA NA

3 No 6 No 1 NA No NA No 1 NA

No No 1 2 2 7 3 NA No No NA

9% (14) 0 0 0 5% (5)

6 0 0 0 2

8 0 0 0 NA

3 0 0 0 3

7 0 No No No

2 4 No 6 No

0

0

0

0

No

No

(1) (1) (12) (1) (2) (3)

Perinatal outcome

Authors

Treated pregnancies (n)

Ville et al., 1995 De Lia et al., 1995 Ville et al., 1998 De Lia et al., 1999 Hecher et al., 1999 Hecher et al., 2000 Quintero et al., 2000 Quintero et al., 2003 Senat et al., 2004 Sepu ´lveda et al., 2005 Yamamoto et al., 2005 Robyr et al., 2006 Huber et al., 2006 Ishii et al., 2007 Ierullo et al., 2007 Middeldorp et al., 2007 Middeldorp et al., 2007

Triplets cases in the series (n)

Pregnancies with three survivors

Pregnancies with two survivors

Pregnancies with one survivor

Pregnancies without survivors

Pregnancies with at least one survivor (%)

Neurological sequelae in liveborns (n)

Neonatal deaths (n)

Perinatal survival (%)

45

0

e

13

19

13

71

0

3

50

26

1

1

8

9

8

69

1

2

53

132

0

e

47

50

35

81

6

12

55

67

0

e

38

17

12

82

6

5

69

73

0

e

31

27

15

79

5

6

61

127

0

e

69

34

24

81

5

9

68

92

0

e

35

35

22

76

3

17

57

95

0

e

43

36

16

83

4

14

64

72

0

e

26

29

17

82

8

12

56

10

10

2

3

4

1

90

2

0

53

175

3

0

61

67

47

73

NA

19

54

151

0

e

66

59

26

82

NA

NA

200

0

e

119

48

33

84

NA

19

55

0

e

39

12

4

93

NA

NA

77

0

e

31

26

20

74

0

10

57

100

0

e

58

23

19

81

NA

8

69

10

0

e

10

0

0

100

3

0

100

Laser treatment in TTTS

Table 7

NA 72 NA

455

456 Most centres use endoscopes of 2e3 mm in diameter made of either fibre-optics or rod-lenses. A percutaneous technique is the most widely used. This involves the introduction of either the operative sheath loaded with a trocar or the use of a Seldinger technique to introduce a canula through which the scope and its sheath can be passed. Only three papers describe a laparotomy for the insertion of the endoscope in the uterus (Table 3), with comparable overall fetal and maternal results. Middeldorp’s group is the only one among the more recent series to use a laparotomy, but they confine the indication to anterior placenta.19,20 Nevertheless, transplacental entry for cases with anterior placenta is rarely described in any publication. Local anaesthesia is the most popular mode of analgesia; however, when a maternal laparotomy is performed general anaesthesia is used (Table 3). An alternative is epidural analgesia (Table 3). Premedication almost always includes the use of a cephalosporin; one centre uses amoxycillin/clavulanate (Table 4). Indomethacin is preferred for prophylactic tocolysis (Table 4). Complications such as miscarriage, preterm premature rupture of membranes (PPROM), and preterm delivery are inconstantly specified in the papers (Table 5). Reports on series should record miscarriages, PPROM before and after 24 weeks and within 1 and 3 weeks from surgery, as well as spontaneous preterm labour. In this review, miscarriage occurred in 6.8e23% of the cases2,13. The need for repeat laser or subsequent amnioreduction is also important to record, as it reflects incomplete coagulation and persistent inter-twin transfusion (Table 6).10 In at least 2.8% (39/1374) of the cases recurrence leading to amnioreduction, repeat laser or delivery was diagnosed. Another 1.7% (24/1507) of the cases were subjected to selective termination or pregnancy termination in cases of recurrence or severe fetal complication. This may reflect under-reporting of these complications since they may end up with fetal death or preterm delivery. Therefore, at least 4.5% of the cases require a second procedure for the management of a specific complication. This highlights the need for exact indication, close follow-up, recognition and management11,12 of the complication and delivery. This is likely to be underestimated, as most centres do not monitor the follow-up of all the cases they treat (Table 6). The overall 6-month survival ranged from 50% to 69% in cases treated up to 26 weeks’ gestation (Table 7). The rate of brain lesions varies from 1.9% to 6.8% in the surviving infants in the neonatal period. The way the intrauterine follow-up and postnatal brain imaging are performed also has to be set into the same protocol within different centres (Table 7).

Conclusions Laser treatment in TTTS is now established as the best firstline treatment in severe TTTS between 16 and 26 weeks of gestation, with over 1000 cases treated worldwide. The surgical approach is similar between centres, and survival rates are comparable. Cases with anterior placenta are generally accepted for treatment, as are all Quintero stages.

M. Yamamoto, Y. Ville Future problems consist in decreasing the rate of preterm rupture of the membranes and miscarriage. Evaluation of new indications and the diagnosis of complications of laser surgery will become factors critical to the development of the technique. Some authors have suggested that a learning curve improved their results, but the way the technique changed or improved is not mentioned in their paper. The overall survival rate at birth was 66% (1894/2869). However, variations in survival rates between centres and inconsistency in the reporting of complications call for more homogeneity in the pre- and post-operative assessment.

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Laser treatment in TTTS 15. Sepulveda W, Surerus E, Vandecruys H, Nicolaides K. Fetofetal transfusion syndrome in triplet pregnancies: outcome after endoscopic laser surgery. Am J Obstet Gynecol 2005;192:161e4. 16. Yamamoto M, El Murr L, Robyr R, Leleu F, Takahashi Y, Ville Y. Incidence and impact of perioperative complications in 175 fetoscopy-guided laser coagulation of chorionic plate anastomoses in feto-fetal transfusion syndrome before 26 weeks of gestation. Am J Obstet Gynecol 2005;193(3 Pt 2): 1110e6. 17. Huber A, Diehl W, Bregenzer T, Hackelo ¨er BJ, Hecher K. Stagerelated outcome in twinetwin transfusion syndrome treated by fetoscopic laser coagulation. Obstet Gynecol 2006;108:333e7.

457 18. Ishii K, Hayashi S, Nakata N, Murakoshi T, Sago H, Tanaka K. Ultrasound assessment prior to laser photocoagulation for twin-twin transfusion syndrome for predicting intrauterine fetal demise after surgery in Japanese patients. Fetal Diagn Ther 2007;22:149e54. 19. Middeldorp FM, Sueters M, Lopriore E, et al. Fetoscopic laser surgery in 100 pregnancies with severe twin-to-twin transfusion syndrome in the Netherlands. Fetal Diagn Ther 2007;22: 190e4. 20. Middeldorp J, Lopriore E, Sueters M, et al. Twin-to-twin transfusion syndrome after 26 weeks of gestation: is there a role for fetoscopic laser surgery? BJOG 2007;114:694e8.