Twin-twin transfusion syndrome (TTTS), a complication of monochorionic multiple pregnancies, is defined sonographically as the combined presence of polyhydramnios in one sac and oligohydramnios in the other sac in a monochorionic-diamniotic twin gestation. Polyhydramnios is defined as a maximum vertical pocket (MVP) > 8 cm, and oligohydramnios as an MVP <2 cm. Monochorionicity is established by the presence of a single placenta, absence of a twin-peak sign, thin dividing membrane, and same gender.

Variations in the definition

TTTS can also occur in triplet or higher order multiple gestations , provided that at least two fetuses are monochorionic. In monochorionic triplet pregnancies, two or all three fetuses may be involved. TTTS may also occur in monoamniotic twins. In these patients, the absence of a dividing membrane does not allow development of oligohydramnios in the donor. Rather, the single amniotic cavity has polyhydramnios. The diagnosis is made by noting polyhydramnios and differences in bladder filling or Doppler studies as will be discussed below.

Definitions no longer used

Previous neonatal criteria, weight difference >25% or hemoglobin differences >5g/dl are no longer used.

Incidence

TTTS occurs in approximately 5.5-17.5% of all monochorionic pregnancies. Variations in the reported incidences may reflect variations in the definitions used.

Etiology

The syndrome appears to result from a net unbalanced flow of blood between two monochorionic fetuses through placental vascular communications. This results in a donor twin and a recipient twin.

Two general types of anastomoses may be present: superficial or deep. Superficial anastomoses include arterio-arterial and veno-venous anastomoses. Deep anastomoses correspond to shared cotyledons, perfused by an artery and a vein from each twin. An average of 3.1 anastomoses per placenta are present in each twin pair. In addition to vascular anastomoses, monochorionic placentas have individually-perfused cotyledons, within which exchange of blood between the fetuses does not take place. Vascular anastomoses may responsible per se for the development of TTTS if the vascular design is such that it forces a net flow from Donor to Recipient. Alternatively, vascular anastomoses may play a passive role in the development of the syndrome as in the case of monochorionic twins discordant for congenital heart disease, cardiomyopathies, cord anomalies or other conditions associated with uneven hemodynamic balance.

Diagnosis

The diagnosis of TTTS is made by ultrasound by noting the presence of combined polyhydramnios and oligohydramnios in a monochorionic-diamniotic twin pregnancy. Polyhydramnios is defined as a maximum vertical pocket (MVP) of >8 cm, and oligohydramnios as an MVP of < 2cm. Differences in estimated fetal weight are no longer used to define the syndrome. Adherence to these criteria is important to distinguish TTTS from other entities.

The use of Doppler to define the syndrome is unwarranted, but it is useful in staging the disease and in monoamniotic twins.

Differential diagnosis

1. Simple amniotic fluid volume discordance. Differences in amniotic fluid volume not meeting the above criteria can be present in up to 26% of all monochorionic twins.
2. Isolated polyhydramnios. Discordance may include an MVP >8 cm in one sac, but an MVP >2 cm in the other (isolated polyhydramnios). Occasionally, isolated polyhydramnios may be significant enough to warrant therapy (MVP >10 cm).
3. Isolated oligohydramnios. Alternatively, the MVP in one sac may be < 2 cm, but the MVP in the other sac is < 8 cm (isolated oligohydramnios). This may occur in cases of bilateral renal agenesis or other urinary tract abnormalities of one fetus, undiagnosed premature of membranes, or in selective intrauterine growth retardation.

Staging of TTTS

The sonographic presentation of TTTS is not homogeneous. In 1998, Quintero et al. proposed a staging system as follows:
Stage I: The bladder of the Donor twin is still visible.
Stage II: The bladder of the Donor twin is no longer visible (in over 60 minutes of observation). This fetus is in renal failure.
Stage III: Critically Abnormal Doppler studies characterized by absent or reverse end-diastolic velocity in the umbilical artery, or pulsatile umbilical venous flow, or reverse flow in the ductus venosus in either twin.
Stage IV: Hydrops of one or both fetuses.
Stage V: Demise of one or both fetuses.
Stage III and Stage IV patients can present in symptomatically treated patients in a classic form (bladder of the donor is not visible) or in an atypical form (bladder of the Donor is visible). Stage III or Stage IV patients are further classified as Donor, Recipient, or both. (e.g. Stage III Donor)

Expectant management of patients may show no progression from one Stage to the next, or sequential or non-sequential progressive disease. The proposed Staging system has prognostic value for patients managed expectantly or symptomatically.

Treatment

EXPECTANT MANAGEMENT

Expectant management of TTTS has been associated with almost 100% perinatal mortality. Medical treatment either with Digoxin, or indomethacin is also ineffective. It is possible to follow Stage I patients expectantly, provided the degree of polyhydramnios is not large (MVP 8-9 cm) and the cervical length is adequate (>2.5 cm in length), particularly if disease is diagnosed after 22-24 weeks of gestation. Such pregnancies may remain stable and not require invasive therapy.

SERIAL AMNIOCENTESIS

The goal of this therapy is to decrease the likelihood of miscarriage or preterm labor by reducing the amniotic fluid volume in the sac of the recipient twin. The procedure is repeated as often as necessary, depending on the rate of reaccumulation of fluid in the sac of the recipient twin. Occasionally, no further reaccumulation of fluid occurs, and a single procedure is all that is necessary. We normally do not start treatment until an MVP of 9-10 cm is reached, unless the cervical length is 2.5 cm or less. Serial amniocenteses is associated with an overall success rate of 66% (likelihood of at least one twin surviving), with an average risk of cerebral palsy of 15% and an average gestational age at delivery of 29 weeks.

TECHNIQUE OF SERIAL AMNIOCENTESIS

There is no standard technique for the performance of serial amniocentesis. How much fluid should be removed, at what rate, what needle or what type of anesthesia should be used are issues that could benefit from standardization. Our technique involves the use of an 18-gauge Echotip needle (Cook Ob/Gyn, Spencer , IN ) under local anesthesia. The needle is inserted in a placenta-free area, with care not to disrupt the dividing membrane. An extension tubing is attached to the needle with a luer-lock adaptor, connected to wall suction (maximum vacuum pressure 300 mmHg). The patient is previously sedated with 5-10 mg of IV Morphine Sulfate and 5-10 mg of PO Diazepam. This pre-medication, aside from the sedation of the mother, results in decreased fetal movements of the recipient twin, thus facilitating the procedure. Fluid is removed until an MVP of approximately 6-7 cm is reached. We do not attempt to reach a particular level of MVP, but rather limit the amount of fluid extracted by the amount space surrounding the Donor twin. Indeed, if too much fluid is removed, the Donor twin may become compromised from cord compression and die, as it is unable to change its position within the uterine cavity.

LASER THERAPY

The goal of this approach is to eliminate all and any blood exchange between the fetuses. This halts the disease process altogether, allowing each fetus to continue the pregnancy from its individually-perfused placenta. For many years, endoscopic identification of the communicating vessels remained an unresolved issue. The original technique, while fundamentally correct, did not specify how the vessels could be identified. The next step in the evolution of the technique involved targeting all vessels that crossed the dividing membrane. Although this effectively interrupted the vascular communications between the twins, it could also target many non-communicating vessels. In 1998, Quintero et al. described an anatomical, reproducible technique capable of discerning communicating vessels from normal individually-perfused areas of the placenta. We called this technique: selective laser photocoagulation of communicating vessels, or SLPCV. Basically, each placental artery is followed to its terminal end in the placenta (arteries cross over veins). A returning vein from that cotyledon should normally drain back to the same twin. If blood is drained to the other twin, a deep arterio-venous anastomosis (AV) is present. Arterio-arterial or veno-venous anastomoses are easily identified by noting lack of a terminal end for an artery or a vein respectively. We also developed reliable techniques to treat patients with anterior placentas. SLPCV is associated with an 85% success rate (likelihood that at least one fetus survives), and a 3-5% risk of cerebral palsy and an average gestational age at delivery of 33-34 weeks.

UMBILICAL CORD OCCLUSION

The goal of this technique is to stop blood exchange between the fetuses at the level of the umbilical cord of one of the twins. This can be accomplished by ligating the umbilical cord either endoscopically or under ultrasound guidance, or by using bipolar electrocautery under ultrasound. The procedure is reserved for severe cases where spontaneous fetal death of one of the twins is likely to occur, particularly with the presence of hydrops. Our rate of cord occlusion has dropped from approximately 20% in 1997 to less than 4% in 2004. We currently have a 85% successful pregnancy rate, with no quotable risk of cerebral palsy in patients treated with umbilical-cord ligation.

IATROGENIC DISRUPTION OF THE DIVIDING MEMBRANE, OR "SEPTOSTOMY"

The goal of this procedure is to "equilibrate" the pressures between the two amniotic cavities. Under ultrasound guidance, the dividing membrane is pierced repeatedly with a needle, allowing fluid from the Recipient twin's sac to enter the Donor twin's sac. Proponents of this technique have actually not shown that different amniotic fluid pressures exist in the two cavities. Instead, we have shown in fact that the amniotic fluid pressures are similar, despite large differences in amniotic fluid volumes. Iatrogenic membrane disruption may result in a pseudo-monoamniotic twin pregnancy, with cord entanglement and fetal demise. In addition, the resulting artificial improvement in the amniotic fluid volume of the Donor twin's sac no longer reflects the urinary function of this fetus (this also applies to cases where purposeful amnioinfusion of the Donor twin is performed), which precludes adequate monitoring of the disease status of this twin. Lastly, disruption of the dividing membrane significantly hampers the performance of laser therapy, or subsequent amniocenteses, as the floating dividing membrane interferes with either procedure. Because septostomy is ill- based, does not result in improvement of the disease, and may actually harm the pregnancy, we strongly disagree with its use and discourage its practice.

Amniocentesis vs. Laser

The controversy regarding the optimal treatment of TTTS has centered on the use of amniocentesis or laser. Unfortunately, lack of standard sonographic criteria, different inclusion criteria for gestational age, dogmatic views about the merits of each technique, and the shortcomings of a surgical technique in development led to almost irreconcilable positions between the proponents of each approach. Despite these limitations, two prospective non-randomized clinical studies have shown laser therapy to be superior to amniocentesis, subsequently confirmed by a randomized clinical trial in Europe (Eurofetus study).

Single intrauterine fetal demise

Death of one of the twins is not an infrequent phenomenon in twin-twin transfusion, and has been associated with death or significant morbidity of the co-twin, provided that the vascular communications between the fetuses are patent. Morbidity in the co-twin includes porencephalic cysts and other major neurological complications. Originally, these complications were thought to result from the release of thromboplastic substances from the dead twin into the surviving twin. More recently, acute anemia in the surviving twin has been demonstrated with cordocentesis. This suggests that post-mortem feto-fetal hemorrhage may be responsible for the development of acute hypotension for the observed complications. Demise or morbidity of the co-twin after demise of one twin can be averted altogether by occluding all placental vascular anastomoses or the umbilical cord of the unhealthy fetus prior to its death. Umbilical cord-occlusion or laser therapy of the vascular anastomoses is unwarranted once fetal demise has occurred.

Referrals

You may download the TTTS evaluation form or contact us to fax the form to your office. For further information, feel free to contact us.

Phone Toll Free: 1-877-FETAL-77
Phone: (813)259-8513
Fax: 813- 259-0839
E-mail: sdzabel@tgh.org 

References

1. Bebbington MW, Wittmann BK. Fetal transfusion syndrome: Antenatal factors predicting outcome. Am J Obstet Gynecol 1989; 160:913-915.
2. Bejar R, Vigliocco G, Gramajo H, al. e. Antenatal origin of neurologic damage in newborn infants. Part II. Multiple gestations. Am J Obstet Gynecol 1990; 162:1230.
3. Benirschke K, Driscoll S. The Pathology of the Human Placenta. Springer-Verlag , New York 1967.
4. Benirschke K. Twin placenta in perinatal mortality. NY State J Med 1961; 61:1499-1508.
5. Brennan JN, Diwan R, V., Rosen MG, Bellon EM. Fetofetal Transfusion Syndrome: Prenatal Ultrasonographic Diagnosis. Radiology 1982; 143:535-536.
6. Brown G, Macaskill S. Acute Hydramnios, with Twins, Successfully Treated by Abdominal Paracentesis. Br Med J 1961; 1:1739-40.
7. Brown G. Letter. Br J Obstet Gynecol 1980; 87:255.
8. Brown GR. Acute Hydramnios Treated By Abdominal Paracentesis. J Obstet Gynaecol Br Emp 1958; 65:61-63.
9. Chescheir NC , Seeds JW. Polyhydramnios and Oligohydramnios in Twin Gestations. Obstetrics & Gynecology 1988; 71:882-884.
10. Danziger RW, Chir B. Twin Pregnancy witn Acute Hydramnios Treated by Paracentesis Uteri. Br Med J 1948; 2:205-206.
11. De Lia J, Cruiskshank D, Keye W. Fetoscopic Neodymium: Yttrium-aluminum-garnet laser occlusion of placental vessels in severe twin-twin transfusion syndrome. Obstet Gynecol 1990; 75:1046-53.
12. De Lia J, Emery M, Sheafor S, al. e. Twin transfusion syndrome: successful in utero treatment with digoxin. Int J Gynecol Obstet 1985; 23:197.
13. De Lia J, Kuhlman R, Harstad T, al. e. Twin-twin transfusion syndrome treated by fetoscopic neodymium: YAG laser occusion of chorioangiopagus. Am J Obstet Gynecol 1993; 168 (1, part 2):308.
14. Deprest JA, Audibert F, Van Schoubroeck D, Hecher K, Mahieu-Caputo D. Bipolar coagulation of the umbilical cord in complicated monochorionic twin pregnancy. Am J Obstet Gynecol 2000; 182:340-5.
15. Dudley D, D'Alton M. Single fetal death in twin gestation. Semin Perinatol 1986; 10:65-72.
16. Elliott JP, Sawyer AT, Radin TG, Strong RE. Large-volume therapeutic amniocentesis in the treatment of hydramnios. Obstet Gynecol 1994; 84:1025-7.
17. Elliott JP, Urig MA, Clewell WH. Aggressive Therapeutic Amniocentesis for Treatment of Twin-Twin Transfusion Syndrome. Obstetrics & Gynecology 1991; 77:537-540.
18. Erskine JP. A Case of Acute Hydramnios Successfully Treated by Abdominal Paracentesis. Obstet Gynecol Br Emp 1944; 51:549-551.
19. Farmakides G, Schulman H, Saldana L, al. e. Surveillance of twin pregnancy with umbilical arterial velocimetry. Am J Obstet Gynecol 1985; 153:789.
20. Feingold M, Cetrulo CL, Newton ER, Weiss J, Shakr C, Shmoys S. Serial Amniocentesis in the Treatment of Twin to Twin Transfusion Complicated with Acute Polyhydramnios. Acta Genet Med Germellol 1986; 35:107-113.
21. Gilbert W, Davis S, Kaplan C, Pretorius D, Merrit T, Benirschke K. Morbidity associated with prenatal disruption of the dividing membrane in twin gestations. Obstet Gynecol 1991; 78:623-30.
22. Gonsoulin W, Moise KJ, Kirshon B, Cotton DB, Wheeler JW, Carpenter RJ. Outcome of Twin-Twin Transfusion Diagnosed Before 28 Weeks of Gestation. Obstetrics & Gynecology 1990; 75:214-216.
23. Hecher K, Plath H, Bregenzer T, Hansmann M, Hackeloer BJ. Endoscopic laser surgery versus serial amniocenteses in the treatment of severe twin-twin transfusion syndrome. Am J Obstet Gynecol 1999; 180:717-24.
24. Jones J, Sbarra A, Dilillo L, al. e. Indomethacin in severe twin-to-twin transfusion syndrome. Am J Perinatol 1993; 10:24.
25. Lemery D, Vanlieferinghen P, Gasq M, Finkeltin F, Beaufrere M, Beytout M. Fetal umbilical cord ligation under ultrasound guidance. Ultrasound Obstet Gynecol 1994; 4:399-401.
26. Mari G. International TTTS registry group. Am J Obstet Gynecol 1998:s28.
27. Melnick M. Brain damage in survivor after in utero death inmonozygous co-twin (letter). Lancet 1977; 2 (8051):1287.
28. Mills W. Letter. Br J Obstet Gynecol 1980; 87:256.
29. Montan S, Jorgensen C, Sjoberg N. Amniocentesis in treatment of acute polyhydramnios in twin pregnancies. Acta Obstet Gynecol Scand 1985; 64:537-39.
30. Nageotte M, Hurwitz S, Kaupke C, Vaziri N, Pandian M. Atriopeptin in the twin transfusion syndrome. Obstet Gynecol 1989; 73:867-70.
31. Okamura K, Murotsuki J, Tanigawara S, Uehara S, Yahima A. Funipuncture for evaluation of hematologic and coagulation indices in the surviving twin following co-twin's death. Obstet Gynecol 1994; 83:975-8.
32. Quintero R, Dickinson J, Morales W, et al. Stage-based treatment of twin-twin transfusion syndrome. Am J Obstet Gynecol Accepted for publication Oct. 2002.
33. Quintero R, Morales W, Allen M, Bornick P, Johnson P, Krueger M. Staging of twin-twin transfusion syndrome. J Perinatol 1999; 19:550-555.
34. Quintero R, Morales W, Mendoza G, et al. Selective photocoagulation of placental vessels in twin-twin transfusion syndrome: Evolution of a surgical technique. Obstet Gynecol Surv 1998; 53:s97-s103.
35. Quintero R, Quintero L, Bornick P, Allen M, Johnson P. The donor-recipient (D-R) score: in vivo endoscopic evidence to support the hypothesis of a net transfer of blood from donor to recipient in twin-twin transfusion syndrome. Prenat Neonat Med 2000; 5:84-91.
36. Quintero R, Quintero L, Morales W, Allen M, Bornick P. Amniotic fluid pressures in severe twin-twin transfusion syndrome. Prenat Neonat Med 1998; 3:607-10.
37. Quintero R, Romero R, Reich H, et al. In utero percutaneous umbilical cord ligation in the management of complicated monochorionic multiple gestations. Ultrasound Obstet Gynecol 1996; 8:16-22.
38. Quintero RA, Bornick PW, Allen MH, Johson PK. Selective laser photocoagulation of communicating vessels in severe twin-twin transfusion syndrome in women with an anterior placenta. Obstet Gynecol 2001; 97:477-81.
39. Quintero RA, Comas C, Bornick PW, Allen MH, Kruger M. Selective versus non-selective laser photocoagulation of placental vessels in twin-twin transfusion syndrome. Ultrasound Obstet Gynecol 2000; 16:230-6.
40. Robertson E, Neer K. Placental injection studies in twin gestation. Am J Obstet Gynecol 1983; 147:170-3.
41. Saade GR, Belfort MA , Berry DL, et al. Amniotic septostomy for the treatment of twin oligohydramnios-polyhydramnios sequence. Fetal Diagn Ther 1998; 13:86-93.
42. Saunders NJ, Snijders RJ, Nicolaides KH. Therapeutic amniocentesis in twin-twin transfusion syndrome appearing in the second trimester of pregnancy. Am J Obstet Gynecol 1992; 166:820-4.
43. Schinzel A, Smith D, Miller J. Monozygotic twinning and structural defects. J Pediatr 1979; 95:921-30.
44. Schneider KTM, Vetter K, Huch R, Huch A. Acute Polyhydramnios Complicating Twin Pregnancies. Acta Genet Med Gemellol 1985; 34:179-184.
45. Senat MV, Deprest J, Boulvain M, Paupe A, Winer N, Ville Y. Endoscopic laser surgery versus serial amnioreduction for severe twin-to-twin transfusion syndrome. N Engl J Med 2004;351:136-44.
46. Tan K, Tan R, Tan A. The twin transfusion syndrome. Clin Pediatr 1979; 18:111-4.
47. Urig M, Clevell W, Elliot J. Twin-twin transfusion syndrome. Am J Obstet Gynecol 1990; 163:1522-6.
48. Ville Y, Hecher K, Gagnon A, Sebire N, Hyett J, Nicolaides K. Endoscopic laser coagulation in the management of severe twin-to-twin transfusion syndrome. Br J Obstet Gynaecol 1998; 105:446-53.
49. Ville Y, Hyett J, Hecher K, Nicolaides K. Management of severe twin-twin transfusion: amniodrainage compared to endoscopic surgery (abstract). Ultrasound in Obstetrics and Gynecology 1994; 4(suppl 1):130.
50. Ville Y, Hyett J, Hecher K, Nicolaides K. Preliminary experience with endoscopic laser surgery for severe twin-twin transfusion syndrome. N Engl J Med 1995; 332:224-7.
51. Ville Y, Van Peborgh P, Gagnon A, Frydman R, Fernandez H. [Surgical treatment of twin-to-twin transfusion syndrome: coagulation of anastomoses with a Nd:YAG laser, under endosonographic control. Forty four cases]. J Gynecol Obstet Biol Reprod 1997; 26:175-81.
52. Yoshioka H, Kadomoto Y, Mino M, al. e. Multicystic encephalomalacia in liveborn twin with a still-born macerated co-twin. J Pediatr 1979; 95:798.