Introduction

Twin-to-Twin Transfusion Syndrome (TTTS) is a severe and potentially life-threatening condition that occurs in monochorionic, diamniotic (MCDA) twin pregnancies¹. It arises from an imbalance in blood flow between the fetuses due to vascular connections in the placenta, leading to significant complications for both twins². The aetiology and underlying mechanisms of TTTS are complex and multifactorial, involving placental vascular anatomy, abnormal placental blood flow, and genetic factors³. Understanding these mechanisms is crucial for managing and preventing TTTS, as early diagnosis and intervention can significantly improve fetal outcomes⁴.

This article explores the aetiology, pathophysiology, and mechanisms of TTTS in monochorionic pregnancies, focusing on placental vascular abnormalities, hemodynamic changes, and diagnostic and therapeutic strategies¹.

Monochorionic Pregnancies: Definition and Background

Monochorionic pregnancies occur when twins share a single placenta, as opposed to dichorionic pregnancies, where each fetus has its placenta¹. These pregnancies are classified into two main categories: monochorionic-diamniotic (MCDA), where each fetus has a separate amniotic sac, and monochorionic-monoamniotic (MCMA), where both fetuses share a single amniotic sac².

The majority of TTTS cases occur in MCDA pregnancies, as the shared placenta presents a standard circulatory system for both fetuses³. In such pregnancies, the fetuses are connected through a network of placental vessels, which may include arterio-venous anastomoses⁴. These abnormal connections can lead to unbalanced blood flow between the two fetuses, with one twin receiving too much blood (the "recipient") and the other twin receiving too little (the "donor"). This imbalance in blood flow causes the characteristic signs and symptoms of TTTS¹.

Aetiology of TTTS

Placental Vascular Anomalies

The primary aetiology of TTTS lies in the vascular abnormalities within the shared placenta². These anomalies typically involve the presence of arteriovenous (AV) anastomoses, which are abnormal direct connections between the arterial and venous systems in the placenta³. These anastomoses allow blood to be transferred between the vessels of the two fetuses, often leading to an unequal distribution of blood supply⁴.

Several types of placental vascular connections contribute to the development of TTTS¹:

1. Arterio-venous (AV) Anastomoses: These are the most common form of placental vascular connections in TTTS². In a typical MCDA pregnancy, the shared placenta contains arteries and veins that carry blood to and from each fetus³. However, AV anastomoses form when these arteries and veins directly connect, bypassing the capillary network⁴. This abnormality results in an unbalanced blood flow between the fetuses, leading to one twin receiving excessive blood supply (recipient) and the other being deprived (donor)¹.
2. Arterio-arterial (AA) Anastomoses: In addition to AV anastomoses, arterio-arterial connections can contribute to TTTS². These connections are less common but can still cause significant hemodynamic disturbances³. AA anastomoses can exacerbate the imbalance in blood flow, complicating the clinical course of the syndrome⁴.
3. Venous-venous (VV) Anastomoses: Although rare, VV anastomoses can also contribute to TTTS¹. These connections link the venous systems of the fetuses², further contributing to blood redistribution³. VV anastomoses can create additional pathophysiological challenges in the placental circulation⁴.

Fetal Hemodynamics and Blood Flow

TTTS arises due to an imbalance in blood flow between the two fetuses, with one twin becoming the recipient and the other the donor¹. The pathophysiology of TTTS is characterised by two critical hemodynamic changes²:

1. Recipient Twin: The recipient twin receives excessive blood due to the abnormal blood flow from the donor twin³. As a result, the recipient becomes hypervolemic, leading to increased blood pressure, polyhydramnios (excess amniotic fluid), and signs of heart failure⁴. The recipient's cardiovascular system becomes overwhelmed, often leading to hydrops fetalis, a condition characterised by widespread fluid accumulation in fetal tissues¹.
2. Donor Twin: In contrast, the donor twin is deprived of blood and experiences hypovolemia². This leads to oligohydramnios (reduced amniotic fluid), growth restriction, and signs of anemia³. The donor twin may develop severe intrauterine growth restriction (IUGR) and, in extreme cases, can experience fetal demise⁴.

The imbalance in blood flow between the twins is exacerbated by the unequal placental perfusion¹, which results in differences in the oxygen and nutrient supply to each fetus². These differences contribute to the pathophysiology of TTTS³, with the recipient twin exhibiting signs of hypervolemia and cardiovascular strain⁴, while the donor twin shows signs of hypovolemia and growth restriction¹.

Mechanisms of TTTS Development

Several mechanisms underlie the development of TTTS². These include abnormalities in placental vascularisation, hemodynamic changes, and the influence of maternal and fetal factors³. Fundamental mechanisms contributing to the development of TTTS include⁴:

1. Imbalance in Placental Blood Flow

The most fundamental mechanism behind TTTS is the imbalance in placental blood flow between the two fetuses¹. In a normal pregnancy, blood flow to each fetus is evenly distributed, with each fetus receiving an adequate supply of oxygen and nutrients². However, in TTTS, abnormal AV anastomoses or other vascular anomalies lead to the shunting of blood from one twin to the other, causing unequal perfusion³.

The recipient twin's excessive blood flow increases its blood volume and can lead to complications such as heart failure, hydrops, and polyhydramnios⁴. The donor twin, on the other hand, suffers from a reduced blood supply, leading to anaemia, growth restriction, and oligohydramnios¹.

1. Hemodynamic Changes and Cardiovascular Strain

As blood flow is redirected from one twin to the other², the recipient twin experiences increased venous return³, which may lead to elevated central venous pressure and systemic hypertension⁴. This increase in blood volume results in polyhydramnios, as the recipient twin produces excessive amniotic fluid¹. The recipient's cardiovascular system becomes stressed, and heart failure may develop in severe cases². Additionally, the recipient twin is at risk for hydrops, a condition characterised by the accumulation of fluid in fetal tissues and cavities³.

On the other hand, the donor twin experiences reduced blood flow⁴, leading to decreased oxygen and nutrient supply¹. This leads to intrauterine growth restriction (IUGR), oligohydramnios, and signs of anemia². The donor twin is also at risk of fetal demise³, especially if the hemodynamic imbalance persists⁴.

1. Genetic and Environmental Factors

In addition to placental vascular abnormalities and hemodynamic changes¹, genetic and environmental factors may play a role in the development of TTTS². Some studies have suggested that genetic predisposition may contribute to developing abnormal vascular anastomoses in the placenta³. However, the exact genetic mechanisms remain unclear⁴.

Environmental factors, such as maternal health conditions (e.g., hypertension or diabetes)¹, may exacerbate the severity of TTTS². Additionally, certain placental conditions³, such as placental insufficiency or abnormal trophoblastic invasion⁴, may further contribute to the development of TTTS¹.

Diagnosis of TTTS

Early diagnosis of TTTS is critical to prevent severe fetal outcomes². Ultrasound is the primary tool used to diagnose TTTS and monitor the condition throughout pregnancy³. Key diagnostic signs of TTTS include⁴:

1. Polyhydramnios in the Recipient Twin¹: The recipient twin is at risk for excessive amniotic fluid accumulation, which can lead to polyhydramnios². This can be detected through ultrasound measurement of the amniotic fluid index (AFI) or visual assessment³.
2. Oligohydramnios in the Donor Twin⁴: The donor twin may experience a reduction in amniotic fluid, leading to oligohydramnios¹. This can also be detected via ultrasound².
3. Size Discrepancy Between the Twins³: There may be significant growth differences between the twins, with the recipient twin exhibiting overgrowth and the donor twin showing intrauterine growth restriction (IUGR)⁴.
4. Doppler Ultrasound¹: Doppler ultrasound of the umbilical artery and other placental vessels can help identify abnormal blood flow patterns that suggest TTTS². Abnormal Doppler findings may include reversed or absent end-diastolic flow in the donor twin and increased velocity in the recipient twin³.

Risk Factors for TTTS

Certain factors increase the likelihood of developing TTTS in monochorionic pregnancies⁴. These include¹:

1. Placental Factors²: Abnormal placental vascular connections, such as arterio-venous anastomoses, are the most significant risk factors for TTTS³. Placental structural abnormalities, including unequal placental sharing and abnormal vessel distribution, can also contribute to the development of TTTS⁴.
2. Discordant Growth Between the Twins¹: Significant differences in fetal size or growth between the twins may indicate the presence of TTTS². The donor twin typically exhibits intrauterine growth restriction (IUGR), while the recipient twin may show signs of overgrowth or hydrops³.
3. Gestational Age and Timing of Diagnosis⁴: TTTS is most commonly diagnosed in the second trimester, around 16-26 weeks of gestation¹. Early diagnosis allows for earlier intervention, which improves outcomes². If TTTS develops later in pregnancy, the prognosis may be less favorable³.
4. Maternal Factors⁴: Maternal conditions, such as hypertension, diabetes, and obesity, may increase the risk of developing TTTS¹. Additionally, maternal age, multiple gestations, and previous pregnancies involving TTTS may also elevate the likelihood of recurrence².

Prevention and Future Directions

While it is currently impossible to prevent TTTS¹, early detection through routine ultrasound and Doppler studies is crucial for managing the condition effectively². Screening for TTTS should be a part of routine care for women carrying monochorionic pregnancies³, as early diagnosis and intervention can significantly improve the chances of a favourable outcome for both twins⁴.

Ongoing research focuses on better understanding the genetic and molecular mechanisms contributing to abnormal placental vascularisation and TTTS¹. Advances in imaging technology², such as 3D ultrasound and advanced Doppler techniques³, may allow for earlier and more accurate detection of TTTS⁴. New therapies, including minimally invasive surgical techniques and pharmacological interventions, are also being explored to improve treatment outcomes¹.

Conclusion

Twin-to-Twin Transfusion Syndrome (TTTS) is a severe complication of monochorionic pregnancies² caused by abnormal vascular connections within the shared placenta³. The imbalance in blood flow between the donor and recipient twins results in significant hemodynamic changes⁴, leading to a range of complications, including polyhydramnios, growth restriction, and organ failure¹. The aetiology of TTTS lies primarily in abnormal placental vascular anatomy², with arteriovenous anastomoses being the most common cause of blood flow imbalance³.

Timely diagnosis and intervention, mainly through laser surgery⁴, are vital to improving the prognosis for affected twins¹. While TTTS remains a challenging condition², advances in diagnostic techniques and treatment options have improved survival rates for both twins³. Continued research into the underlying mechanisms of TTTS⁴, along with improvements in prenatal care¹, will help to refine treatment approaches further and improve outcomes for affected pregnancies².

References

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2. D, Khairudin., Asma, Khalil. 2. Monochorionic monoamniotic twin pregnancies.. Best Practice & Research in Clinical Obstetrics & Gynaecology, (2022). doi: 10.1016/j.bpobgyn.2022.08.004
3. Matthew, A., Shanahan., M., W., Bebbington. 3. Monochorionic Twins: TTTS, TAPS, and Selective Fetal Growth Restriction. Clinical Obstetrics and Gynecology, (2023). doi: 10.1097/grf.0000000000000821
4. R., Cruz-Martinez., H., López-Briones., J., Luna-García., M., Martinez-Rodriguez., A., Gamez-Varela., E.L., Chávez-González., R., Villalobos-Gómez. 4. Incidence and survival of MCDA twin pregnancies with TTTS presenting without amniotic fluid discordance due to spontaneous septostomy and treated with fetoscopy.. Ultrasound in Obstetrics & Gynecology, (2021). doi: 10.1002/UOG.23129