Twin-Twin Transfusion Case File

Twin-Twin Transfusion Case File

Eugene C. Toy, MD, Edward Yeomans, MD, Linda Fonseca, MD, Joseph M. Ernest, MD

Case 39

A 22-year-old G1 P0 with a monochorionic diamniotic twin gestation is seen in your office at 24 weeks for follow-up sonogram. The patient notes fetal activity daily and occasional uterine contractions. Her vital signs are normal and she has gained 4 lb since her last visit at 20 weeks, when ultrasound revealed appropriate and concordant growth with normal amniotic fluid volume. Fundal height today is 30 cm.

On ultrasound, twin A appears normal and has grown appropriately since the last ultrasound, although the amniotic fluid volume appears moderately increased. Twin B’s estimated fetal weight (EFW) is equivalent to 22 weeks’ gestational age (GA). The bladder is difficult to visualize, and amniotic fluid volume is markedly decreased. No fetal movement of twin B is noted, although the fetal heart rate is 140 bpm.

➤ What is the most likely diagnosis?

➤ What is your next step?

➤ What are potential complications of the patient’s disorder?

ANSWERS TO CASE 39:

Twin-Twin Transfusion

Summary: This is a 22-year-old G1P0 woman with monozygotic twins at 24 weeks’ gestation with discordant growth and polyhydramnios in one sac and oligohydramnios in the other.

➤ Most likely diagnosis: Twin-twin transfusion syndrome (TTTS).

➤ Next step: Evaluate fetal well-being and the potential utility of various treatment modalities.

➤ Potential complications: Fetal polycythemia/fetal anemia; hydrops; intrauterine demise; preterm birth; preeclampsia.

ANALYSIS

Objectives

1. List risk factors for twin-twin transfusion syndrome.
2. Identify ultrasound findings that confirm the diagnosis of TTTS.
3. Explain a management scheme for TTTS.
4. Discuss situations in which laser ablation of placental vessels should be considered.

Considerations

This is a 22-year-old primigravida with a monochorionic, diamniotic twin gestation with a significant fluid discrepancy between the fetuses. One fetus has polyhydramnios and the other has oligohydramnios. Additionally, there is weight discordance between the two fetuses. This is highly suspicious for twin-twin transfusion syndrome (TTTS). Approximately 30% of all twin pregnancies are monochorionic, and the incidence of TTTS in monochorionic, diamniotic gestations is approximately 10% to 20%. Early identification is important due to the high perinatal mortality and the possible need for intervention. Because monochorionic twins have a higher perinatal morbidity, its identification is important, such as in the first trimester. This can be achieved by sonographic assessment of the dividing membrane.

APPROACH TO

Twin-Twin Transfusion

The diagnosis of TTTS is based on the presence of a monochorionic placenta and amniotic fluid discrepancy. Monochorionicity is diagnosed by the following sonographic findings:

• Same-sex twins
• A thin intertwin membrane
• The absence of a “twin peak” (also known as the “lambda”) sign
• The presence of a “T-sign,” in which the membranes diverge from the placental surface at a 90 degree angle
• A fused placenta
• Only two membranes between fetuses (if the ultrasound is done early enough and the membranes can be counted)

After monochorionicity is established, the remainder of the evaluation is based on fetal hemodynamics and growth. One fetus, the recipient, is volume overloaded, sometimes with signs of cardiac failure, and has polyhydramnios (maximum vertical pocket of over 8 cm). The recipient may be large for gestational age (LGA) or appropriate for gestational age (AGA). The other fetus, the donor, is dehydrated and has oligohydramnios (maximum vertical pocket of less than 2 cm). The donor may be SGA or AGA.

Growth discrepancy is many times a sign of chronic TTTS; however, in some cases the underlying etiology of growth discrepancy may be placental insufficiency or an abnormal placental cord insertion.

Once TTTS is suspected, Doppler analysis of the umbilical artery, middle cerebral artery, and of the ductus venosus, as well as echocardiograms of both fetuses are performed. The purpose of the echocardiogram is to evaluate cardiac function and signs of cardiac failure or valvular insufficiency.

Quintero et al1 designed a staging system for TTTS which consists of the following:

Stage I: Polyhydramnios in the recipient, severe oligohydramnios in donor but urine visible within the bladder of the donor.

Stage II: Polyhydramnios in the recipient; the appearance of a “stuck” donor fetus, urine not visible within the donor’s bladder and oligohydramnios.

Stage III: Polyhydramnios and oligohydramnios as well as critically abnormal Dopplers (at least one abnormal Doppler finding: absent or reverse enddiastolic flow in the umbilical artery, reverse flow in the ductus venosus or pulsatile umbilical venous flow) with or without urine visualized within the donor’s bladder.

Stage IV: Presence of ascites or hydrops (fluid collection in two or more cavities) in either donor or recipient.

Stage V: Demise of either fetus.

Other investigators have modified the Quintero staging system by further subdividing stage III based on cardiac function. There is a wide range of severity across the many patients who present in stage III. The cardiac function profile can be used to better define the severity of TTTS within this group. Signs of valvular incompetence, ventricular wall thickening, and cardiac dysfunction (as determined by the Tei index) are used to assess cardiac function and subdivide stage III into stage III a, b, c.

Pathophysiology

Sometimes in several combinations, 95% of monochorionic twin placentas contain inter-fetal vascular connections of some kind. These connections may be vein-to-vein, artery-to-vein, vein-to-artery, and artery-to-artery within a placental cotyledon. Depending on the number and type of vascular connections, the blood flow between the twins may be balanced or unbalanced. “Unbalanced” denotes net flow away from one fetus and toward another (see Figure 39–1). 

There is increasing evidence that the pathophysiology of TTTS may also include the renin and angiotensin system. The donor fetus—dehydrated and volume depleted—will produce angiotensin as a protective mechanism to maintain volume. However, because of the vascular shunting which underlies TTTS, the recipient is also exposed to the donor-produced angiotensin, further complicating the volume-overloaded recipient twin.

CLINICAL APPROACH

Once TTTS is diagnosed and the stage is determined, then the treatment approach is made. The treatment modalities can include:

• Microseptostomy
• Amnioreduction
• Laser ablation of the intertwin fetal vessels
• Selective fetal reduction

The treatment choice will depend on the gestational age at which TTTS presents as well as the severity. Prior to deciding upon a treatment plan, fetal evaluation should include the following:

• Ultrasound for growth
• Tests of fetal well-being—biophysical profile, umbilical artery Doppler, middle cerebral artery Doppler
• Assessment of the amniotic fluid volume
• Fetal echocardiogram for cardiac function and performance index

Treatment

Septostomy is performed in attempt to equalize the fluid dynamics between the fetuses. A small hole is created in the intertwin membrane to restore amniotic fluid in the donor fetus’ sac. This can be problematic if the defect

Figure 39–1. Twin-twin transfusion syndrome with the donor twin being smaller

and with oligohydramnios and the recipient twin being larger and with hydramnios.

Note the numerous arterial (donor) to venous (recipient) anatomoses which allows

for the TTTS.

expands, as the large septostomy creates a functional monoamniotic gestation, which carries inherent risks of cord entanglement. Because of this risk, a fetoscopic approach to septostomy has been proposed. In this case, a laser is used to create a microseptostomy; use of the laser creates very small holes and cautery of the edges is felt to prevent tearing. In a multicenter prospective trial, Saade et al2 compared amnioreduction to septostomy and found the survival in each arm was 65%.

Amnioreduction was initially performed to relieve maternal abdominal discomfort and shortness of breath. It was also thought to potentially decrease the risk of preterm delivery as a result of the uterine overdistension. It is likely that amnioreduction also improves placental function by decreasing intrauterine pressure created by the large amount of amniotic fluid in the recipient sac. The survival in one series with aggressive serial amnioreduction (reduction of amniotic fluid to normal) ranged widely, from 37% to 83%. However, this retrospective series contained small numbers and a wide range of gestational age and severity of TTTS. 

The earlier in pregnancy the diagnosis of TTTS is made, the worse the prognosis. The majority of patients who are treated with amnioreduction will require serial amnioreductions, sometimes performed on a weekly basis. This treatment approach addresses the problematic symptoms of TTTS. The benefit to amnioreduction is that it is easily available and less invasive for the mother, but it does not fully address the underlying pathophysiology of TTTS.

Cases presenting early in pregnancy may benefit from definitive treatment by fetoscopic laser ablation of the placental intertwin fetal vessels. Laser ablation aims to eliminate the unidirectional shunting of blood from the donor fetus to the recipient, balancing placental hemodynamics. Laser ablation is considered definitive treatment, since the underlying pathophysiology is directly addressed; a second procedure is rarely necessary. However, laser ablation is significantly more invasive for the patient.

When compared to serial amnioreduction, the overall survival is similar and was not statistically significantly different (61% vs 51% for laser ablation and serial amnioreductions, respectively) in one nonrandomized comparison of patients at two different centers (one performed laser ablation and the other serial amnioreduction). However, in this same study, the survival of at least one twin with laser ablation was 79%—survival of at least one twin with serial amnioreduction was 60%.

The Eurofetus trial is the only prospective, randomized trial to compare the efficacy of laser therapy with serial amnioreduction. Patients were eligible if they had stage I TTTS with a gestational age between 16 and 26 weeks. The study was stopped when an analysis revealed that the survival at 28 days of life and 6 months of life was significantly higher in the laser group when compared to serial amnioreduction (76% vs 56% and 76% vs 51%, respectively). Of note, the amnioreduction group had a survival of 38%, significantly lower than previously reported. In the Eurofetus trial, fewer fetuses in the laser group had neurologic abnormalities on neuroimaging studies when compared to the amnioreduction group (52% vs 31%). It must be noted, however, that this does not necessarily correlate with neurologic developmental delay or cerebral palsy.

Fetoscopic umbilical cord cauterization is reserved for end-stage TTTS, in which one fetus is so compromised that death is imminent. In this procedure, the umbilical cord of the severely compromised fetus is cauterized to protect the healthier fetus from death or neurologic damage as a result of co-twin death.

There is a small subset of patients who will respond to a single amnioreduction and do not require serial procedures. Since this is a less invasive approach to management of these pregnancies, an amnioreduction is recommended first before more aggressive and invasive therapies are chosen. If a single amnioreduction does not lead to lasting normalization of the amniotic fluid indices, more definitive therapy is recommended, particularly in early gestations.

Screening

The best time to determine chorionicity is early in the pregnancy. When the gestation is evaluated in the first or early second trimester, the positive predictive value for properly assigning chorionicity using sonographic findings (placental location[s], the lambda and T signs, and/or fetal gender) is as high as 98%. By the mid-second trimester the same ultrasound findings have a positive predictive value of only 88%.

All monochorionic pregnancies should be evaluated frequently for the onset of TTTS. It is not possible to accurately predict which pregnancies will go on to develop TTTS. It is especially important to watch carefully for TTTS in the earlier stages of pregnancy, since the more definitive and invasive treatment options may be preferable earlier in the pregnancy and become unavailable as the gestation advances. Screening monochorionic pregnancies every 2 weeks by evaluating growth and amniotic fluid volume is one method with which to aggressively monitor for TTTS.

Comprehension Questions

39.1 A 34-year-old G2P1001 woman at 32 weeks’ gestation is noted to have a twin gestation. The patient has been researching on the internet about different complications and asks about TTTS. The obstetrician reviews the records and specifically counsels the patient that she is not likely to develop TTTS. Which of the following is likely to be present in this patient?

A. Monochorionic diamniotic twin gestation

B. Polyhydramnios in the recipient sac

C. Oligohydramnios in the donor sac

D. Dichorionic twins with abnormal umbilical artery Dopplers

E. Growth restriction in one fetus of a monochorionic pair

39.2 A 29-year-old G1P0 woman at 30 weeks’ gestation with a diagnosis of TTTS. The obstetrician has counseled the patient about various therapy options that are available. Which of the following is LEAST likely to be a treatment of TTTS?

A. Microseptostomy

B. Laser ablation of the intertwin surface placental vessels

C. Amnioreduction with microseptostomy

D. Selective fetal reduction

E. Focused ultrasonic energy of the shared fetal vessels

39.3 to 39.5 Matching. Please match the following clinical vignette with the stage of the TTTS.

A. Stage I

B. Stage II

C. Stage III

D. Stage IV

E. Stage V

39.3 A 41-year-old G3P2002 woman at 25 weeks’ gestation is diagnosed with TTTS based on one fetus with oligohydramnios and the other with polyhydramnios. One fetus is noted to have loss of end-diastolic flow of the umbilical artery.

39.4 A 27-year-old G1P0 woman at 28 weeks’ gestation with TTTS, and one fetus with fetal ascites.

39.5 A 35-year-old G3P2011 woman at 23 weeks’ gestation with one fetus having oligohydramnios and the other with polyhydramnios, and cardiac dysfunction on echocardiogram.

39.6 A 32-year-old G4P2012 woman is at 25 weeks’ gestation. She had been diagnosed as having monochorionic twins based on a first-trimester ultrasound showing the “T sign” of the dividing membrane. Which of the following is most accurate regarding this patient?

A. Fetal gender is useful in determining zygosity.

B. Number of placentas is useful in determining zygosity.

C. The T sign is better visualized in the second trimester rather than the first trimester.

D. Once the pregnancy has progressed beyond 24 weeks’ gestational age and has not developed TTTS, then the patient is at low risk and can be followed monthly.

E. A family history of twins is useful in determining zygosity.

ANSWERS

39.1 D. Dichorionic placentation is not associated with TTTS since there are two separate placentas, one for each fetus and the hemodynamic shifts between the fetuses is not present as it can be in monochorionic placentas. 95% of monochorionic placentas have vascular connections and the risk of TTTS in monochorionic pregnancies is 10% to 20%. The diagnosis is made by finding a monochorionic gestation with oligohydramnios in one sac and polyhydramnios in the other. If the problem is chronic then a growth discrepancy can be appreciated.

39.2 E. Ultrasound energy to the fetal vessels is not a therapy. All of the other treatment modalities (A-D) are reasonable and can be done in sequence or in combination. A patient will often have an amnioreduction first to see if the pregnancy responds before proceeding with more invasive therapy. During the fetoscopic laser ablation procedure an amnioreduction is performed so that the final maximum vertical pocket is less than 5 cm. A microseptostomy is also done at the time of the fetoscopy at some centers. The selective fetal reduction is reserved for severe, terminal cases in which one fetus has a very poor prognosis and is expected to die.

39.3 C. Oligohydramnios and polyhydramnios in the face of critically abnormal Doppler flow studies such as absent or reverse end-diastolic flow is indicative of stage III TTTS.

39.4 D. Ascites or hydrops in either the recipient or donor twin is consistent with stage IV disease, and implies serious fetal compromise.

39.5 C. Oligohydramnios and polyhydramnios by themselves are consistent with stage I disease, but the presence of cardiac dysfunction upstages the severity to stage III. Thus, in general, every patient with TTTS in stage I to III should have cardiac echocardiography to assess for further severity. The use of echocardiogram is to stage all TTTS, and can help to subcategorize those in stage III, since this category is fairly broad. Based on cardiac dysfunction an initial assessment of stage I or II can be increased to stage III after the echocardiogram. All patients with TTTS should have an echocardiogram as part of staging.

39.6 A. Monozygotic twins are at greater risk for complications. Different fetal genders are highly suggestive of dizygotic gestations. The number of placentas is not helpful, as often the placentas will fuse. The fetal membranes are better seen in the first trimester rather than later in the pregnancy. Even after 24 weeks’ gestation TTTS can develop. It is difficult to predict which pregnancies will go on to develop TTTS and which will not. Sometimes TTTS can evolve very rapidly; therefore, it is recommended that the pregnancy be followed closely until delivery.

Clinical Pearls

See US Preventive Services Task Force Study Quality levels of evidence in Case 1

➤ The neonatal survival at 28 days of life and 6 months of life was significantly higher in the laser group when compared to serial amnioreduction (76% vs 56% and 76% and 51%, respectively) in the Eurofetus trial (Level I).

➤ Early ultrasound is useful in determining chorionicity and amnionicity in multifetal gestations (Level III).

➤ There is a wide range of severity across the many patients who present in stage III. The cardiac function profile can be used to better define the severity of TTTS within this group (Level III).

REFERENCES

1. Quintero RA, Morales WJ, Allen MH, et al. Staging of twin-twin transfusion syndrome. J Perinatol. 1999;19:550-555. 

2. 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. 

3. Barrea C, Alkazaleh F, Ryan G, et al. Prenatal cardiovascular manifestations in the twin-to-twin transfusion syndrome recipients and the impact of therapeutic amnioreduction. Am J Obstet Gynecol. 2005;192:892-902. 

4. Elliott JP, Urig MA, Clewell WH. Aggressive therapeutic amniocentesis for treatment of twin-twin transfusion syndrome. Obstet Gynecol. 1991;77:537-540. 

5. Lee YM, Cleary-Goldman J, Thaker HM, Simpson LL. Antenatal sonographic prediction of twin chorionicity. Am J Obstet Gynecol. 2006;195:863. 

6. Machin GA. Why is it important to diagnose chorionicity and how do we do it? Best Pract Res Clin Obstet Gynaecol. 2004 Aug;18(4):515-530. 

7. Mahieu-Caputo D, Dommergues M, Delezoide AL, et al. Twin-to-twin transfusion syndrome: role of the fetal renin-angiotensin system. Am J Pathol. 2000;156:629-636. 

8. Mahony BS, Petty CN, Nyberg DA, et al. The “stuck twin” phenomenon: ultrasonographic findings, pregnancy outcome, and management with serial amniocenteses. Am J Obstet Gynecol. 1990;163:1513-1521. 

9. Michelfelder E, Gottliebson W, Border W, et al. Early manifestations and spectrum of recipient twin cardiomyopathy in twin-twin transfusion syndrome: relation to Quintero stage. Ultrasound Obstet Gynecol. 2007 Dec;30(7):965-971. 

10. Pinette MG, Pan Y, Pinette SG, et al. Treatment of twin-twin transfusion syndrome. Obstet Gynecol. 1993;82:841-846. 

11. Reisner DP, Mahony BS, Petty CH, et al. Stuck twin syndrome: outcome in 37 consecutive cases. Am J Obstet Gynecol. 1993;169:991-995. 

12. Rodestal A, Thomassen PA. Acute polyhydramnios in twin pregnancy. A retrospective study with special reference to therapeutic amniocentesis. Acta Obstet Gynecol Scand. 1990;69:297-300. 

13. Saade GR, Olson G, Belfort MA, et al. Amniotomy: a new approach to the “stuck twin” syndrome. Am J Obstet Gynecol. 1995;172:429-434. 

14. Urig MA, Clewell WH, Elliott J. Twin-twin transfusion syndrome. Am J Obstet Gynecol. 1990;163:1522-1526.

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