Fetal Surgery in Germany (Intrauterine Fetal Surgery)

Twin-to-twin transfusion syndrome (TTTS) is a serious complication of monochorionic multiple pregnancy in which the fetuses develop a disproportionate blood flow. In other words, in this condition twins sharing a single placenta exchange blood with each other through so-called "anastomoses" — connections between blood vessels. If in this situation one twin, the donor, gives the other, the recipient, more blood than it receives, TTTS may develop.

TTTS develops in approximately 10–15% of monochorionic twins. Given the widespread use of assisted reproductive technologies, the prevalence of twins — and in some countries of triplets — continues to rise, which increases the risk of TTTS.

Monochorionic multiple pregnancy is a high-risk pregnancy in terms of adverse perinatal outcomes. The vascular system of the placenta shared by the two fetuses determines both the nature of the specific complications and the approaches to correcting TTTS — one of the most serious conditions occurring exclusively in monochorionic multiple pregnancy.

Numerous superficial anastomoses compensate for the redistribution of blood in monochorionic pregnancies and play a protective role in twin-to-twin transfusion syndrome. The main trigger for the development of TTTS is decompensation of this redistribution of blood between the twins.

The cause of TTTS is the presence of vascular anastomoses that connect the placental circulatory systems of both fetuses.  The leading role in the development of TTTS is played by "deep" arteriovenous anastomoses located not on the surface but within the thickness of the placenta. The severity of TTTS (5 stages) depends on the degree of blood redistribution through these anastomoses, which vary in size, number and direction, as well as  on the compensatory capacity of the fetuses. It is assumed that the main triggering factor in the formation of TTTS is abnormal development of the donor fetus's placenta, which increases the peripheral resistance of placental blood flow and leads to the shunting of blood to the recipient fetus. The recipient develops polyhydramnios, hypervolaemia, cardiomegaly, tricuspid regurgitation and, in some cases, obstruction of the pulmonary trunk. The severity of the pathological changes depends on the degree of blood redistribution through the anastomoses.

Ultrasound diagnosis of TTTS becomes possible at 16–24 weeks of pregnancy and is based on establishing the monochorionicity of the fetuses, detecting discordance in the size of the "donor" and "recipient" fetuses and in the amount of their amniotic fluid, and examining fetoplacental haemodynamics; the detection of increased afterload and preload
indicates the severity of TTTS. The prognosis for the pregnancy is least favourable when the syndrome develops before 25 weeks.

Without any intervention the fetuses die (in about 80% of cases) or suffer severe morbidity. Today the most effective procedure is fetoscopic laser coagulation of the placental anastomoses in TTTS. Neonatal outcomes depend on the stage of the disease at which the intervention is performed. The earlier the operation is carried out, the better the expected results.

For many years TTTS was diagnosed retrospectively in the neonatal period on the basis of the difference in haemoglobin levels in the twins' peripheral blood and the difference in the newborns' birth weight (20% or more). However, a considerable difference in haemoglobin level and birth weight is also typical of some dichorionic twins, and for this reason these indicators have in recent years ceased to be regarded as signs of TTTS.

In the recipient's plasma, as well as in the amniotic fluid, a multi-fold increase is found in ANP (atrial natriuretic peptide), hBNP (human brain natriuretic peptide) and in the concentration of endothelin-1. Hypovolaemia in the donor, caused by the redistribution of blood through the anastomoses to the recipient, leads to overexpression of renin.

In 2000 a group of researchers found increased renin secretion in the donor and a corresponding decrease in secretion in the recipient. Stimulation of the renin-angiotensin cascade leads to the conversion of angiotensin I into angiotensin II (AT II). The threefold increase in the donor's vasopressin concentration reduces urine production and additionally causes hypo-osmolality, which leads to the loss of the donor's water across the placenta to the mother.

The Quintero classification of TTTS distinguishes five stages:

    • Stage I: polyhydramnios in the recipient combined with oligo-anhydramnios in the donor;
    • Stage II: absence of bladder filling in the donor;
    • Stage III: cardiovascular changes in both fetuses, manifested by abnormal Doppler findings in the umbilical arteries and the ductus venosus;
    • Stage IV: hydrops (fetal hydrops) of the recipient fetus;
    • Stage V: intrauterine death of one or both fetuses.

The pathognomonic sonographic signs of severe TTTS are: a large bladder in the recipient fetus with polyuria against a background of marked oligohydramnios, and an "absent" bladder in the donor fetus with anuria, which is characterised by reduced motor activity against a background of marked oligohydramnios.

Clinical studies show that the best treatment for severe TTTS is ultrasound-guided fetoscopic laser coagulation of the placental anastomoses, which is based on endoscopic (fetoscopic) technique.

Indications for fetoscopic laser therapy in twin-to-twin transfusion syndrome are established in the presence of:

    • polyhydramnios in the recipient with a vertical  amniotic fluid pocket  >8cm up to 20+0 weeks of pregnancy or  >10cm from the 21st week of pregnancy;
    • oligo-/anhydramnios in the donor; a stuck twin with a vertical amniotic fluid pocket  <2 cm;
    • viability of both twins; gestational age between  17 and 25+0 weeks of pregnancy.

The outcome of these operations depends largely on the experience of the operating surgeons. Insufficient experience means that anastomoses are missed, so that Re-TTTS develops before birth. According to some data, missed anastomoses are found in 32% of cases after fetoscopic laser coagulation.

As mentioned above, if nothing is done both fetuses die in 80% of cases, but even performing the necessary surgical intervention does not rule out stillbirth caused by injuries from the surgical instruments. In order to eliminate intrauterine mortality, Professor Michael Tchirikov (Germany) developed and patented the world's thinnest fetoscopic laser scalpel: after the operations performed by Professor Tchirikov, survival of one twin has risen to 97% and of both twins to 90%; these are the best fetal survival rates in the world.

Michael Tchirikov's use of 1.0/1.2 mm optics and the reduction of the trocar diameter from 3.8 / 4.3 (13 F, 11.27 mm2) to 2.3 mm (7F, 2.65 mm²) has led to a significant improvement in neonatal outcomes. During the operation the connecting vessels are closed off with a laser using fetoscopic technique. With the ultra-fine technique with 1 mm optics used by Professor Tchirikov, the opening in the amniotic membrane is reduced  from the standard 11.27 mm² to 2.65 mm². This markedly reduces the risk of preterm rupture of the membranes  and of the associated premature birth, and consequently increases fetal survival rates. After laser coagulation, survival of at least one child has risen from 94.9% to 100% and of both fetuses from 74.3% to 90%.

Fetoscopic laser operations are carried out at the Centre for Fetal Surgery under sterile conditions in an operating theatre under local anaesthesia, by injecting 20 ml of 1% Scandicain solution under ultrasound guidance down to the peritoneum. In practice, local anaesthesia has proved better than other methods.

After a skin micro-incision of no more than 2-3 mm (7 F trocar and 1 mm optics), the fetoscope is introduced into the recipient's amniotic cavity under ultrasound guidance. The anastomoses are localised and coagulated with an Nd:YAG laser at 50-60 W by means of a 0.6 mm laser fibre. At the end of the operation a careful check is made that all anastomoses are closed, and amnioreduction is performed through the trocar.

For two days before the operation the patient receives indomethacin suppositories 100 mg. During the laser coagulation, Mg2+ 1 g/h and cefazolin 2 g are administered intravenously.

After laser coagulation the risk of TAPS (twin anaemia-polycythaemia sequence) is about 13%.  In such cases the former recipients are anaemic after the operation, while the donor twins are polycythaemic. Because the Centre for Perinatal Diagnosis and Micro-Invasive Fetal Surgery pays great attention to the meticulous closure of all anastomoses, not a single case of TAPS has been recorded in the entire history of the Centre. If even one anastomosis is missed during the operation, the consequences for both fetuses may be more serious than if no operation had been performed at all. Careful selective laser coagulation of all the placental anastomoses between the two fetuses makes it possible to avoid this complication.

The situation in monochorionic twin pregnancy differs considerably from that in dichorionic pregnancy, because intrauterine death of the growth-restricted twin sharply increases the risk of death and of morbidity for the second twin. If intrauterine death of one twin in the second trimester after 24 weeks of pregnancy cannot be avoided and is expected on the basis of Doppler ultrasound findings, the doctor faces a dilemma: to induce preterm labour with a highly uncertain prognosis for both twins, or to choose expectant management with a 26% risk of mortality and increased morbidity for the healthy twin. Some clinics perform selective termination of the affected fetus by laser coagulation of the cord insertion site using bipolar forceps, or radiofrequency ablation of the umbilical vessels, which may improve the neonatal outcome for the healthy twin.

In the event of intrauterine death of one twin, the patient should be observed in hospital for several days in order to rule out fetal anaemia. Alongside cardiotocography (CTG), Doppler sonography of the peak blood flow velocity in the middle cerebral artery is required in order to rule out fetal anaemia in the event of bleeding. If signs of fetal anaemia appear, cordocentesis should be performed and then, if necessary, an intrauterine blood transfusion. Endoscopic laser coagulation makes it possible to prolong the pregnancy by an average of 14 weeks, which reduces intrauterine fetal death.

Advantages of diagnosing and treating TTTS at the Centre for Perinatal Diagnosis and Micro-Invasive Fetal Surgery, Halle (Germany):

    • open statistics;
    • low cost of services compared with similar centres in other countries;
    • unique, innovative 1 mm optics for fetal surgical interventions from Karl Storz, the world's leading manufacturer of endoscopic equipment,  which reduces the risk of preterm rupture of the membranes  and of the associated premature birth;
    • the best statistics in the world since 2008 for the survival of both fetuses after laser operations for twin-to-twin transfusion syndrome (after laser coagulation, survival of at least one child has risen from 94.9% to 100% and of both fetuses from 74.3% to 90%);
    • the risk of TAPS reduced to 0;
    • 22 years of experience in fetal surgery on the part of its head, Prof. Dr. med. M. Tchirikov, with outstanding clinical results;
    • scrupulous review of the indications for surgery;
    • meticulous closure of absolutely all anastomoses;
    • a modern operating theatre with laser equipment;
    • ongoing certification and recertification procedures  and quality management monitoring.
    • geographical proximity to Berlin and the possibility of travelling by rail during pregnancy.

Diaphragmatic hernia is a developmental anomaly characterised by a congenital defect of the diaphragm through which, during intrauterine life, the abdominal organs (loops of bowel, the stomach, the spleen, sometimes part of the liver) move into the chest. The incidence of this developmental anomaly is 1 case per 2,200 newborns. A distinction is made between left-sided and right-sided diaphragmatic hernia, false and true hernia, and also eventration of the diaphragm. There are hernias of the diaphragm itself and hernias of the natural openings of the diaphragm (hiatal hernia, para-aortic hernia). Congenital diaphragmatic hernia is associated with concomitant developmental anomalies of other organs and systems (defects of the nervous system, heart defects, malrotation).

At present this malformation is diagnosed antenatally at 18-20 weeks of intrauterine development. On fetal ultrasound the abdominal organs are visualised in the chest, the mediastinum is displaced towards the healthy side, and polyhydramnios is noted.

Clinical symptoms develop within a few minutes of birth in the form of respiratory failure (cyanosis, rapid breathing, retraction of the sternum). An asymptomatic course over several months or even years is possible. The earlier the clinical picture of diaphragmatic hernia appears, the worse the prognosis of this condition. If diaphragmatic hernia is suspected, immediate admission to a specialised hospital is required.

In fetal diaphragmatic hernia the diaphragm is not completely closed — there is no separation between the abdominal cavity and the chest during the development of the fetus. As a result, the abdominal organs (for example, the liver and loops of bowel) move up into the area of the chest. The main problem of this intrauterine condition is lung development, which is restricted by the upward pressure of the abdominal organs.

How does congenital diaphragmatic hernia of the fetus develop?

The causes of this developmental disorder are unclear. There are theories that it is caused by adverse environmental influences. In some cases the cause lies in a genetic error. To date there is no single definite cause of diaphragmatic hernia.

The main problem of the condition is compression of the lungs during the development of the fetus, which leads to their abnormal development, so- called pulmonary hypoplasia. This deficiency means that the child's lungs may be unable to supply the body with enough oxygen after birth.

How is congenital diaphragmatic hernia of the fetus diagnosed?

Fetal diaphragmatic hernia can be detected during an ultrasound examination in pregnancy.

If diaphragmatic hernia is not diagnosed before birth, the newborn will develop respiratory distress immediately after birth (laboured breathing, cyanosis, displacement of the heart sounds towards the healthy side, weakened or absent breath sounds on the affected side, a scaphoid abdomen, retraction of the sternum ). This situation is particularly serious if the child is born in a hospital that cannot provide the necessary medical care immediately, and also in the case of home births or births outside hospital. Children with congenital diaphragmatic hernias need immediate comprehensive care from qualified paediatricians straight after birth, in hospitals with properly equipped intensive care and resuscitation units for infants.

What are the chances of survival of a child with fetal diaphragmatic hernia?

The chances (prognosis) for children with CDH vary widely and depend, above all, on the size of the hernia. There are cases of mild diaphragmatic hernias that were detected only by chance and quite late. In most cases, however, this condition leads to severe respiratory disorders immediately after birth which, if left untreated, cause the child's death.

The most important indicator for assessing the chances of survival of an unborn child is the index of the ratio of the size of the child's head to the lungs, the so-called lung-to-head ratio, or LHR; the size of the fetal head is used as a reference variable for assessing the size of the lung in relation to the body. This index is usually determined by ultrasound examination. At the Centre for Fetal Surgery at the Martin Luther University Hospital in Halle, lung volume can also be measured by fetal MRI.

If the LHR<1 (i.e. the lungs are smaller than the head) or the volume of the lungs is less than one third of the normal size for the current week of pregnancy, it is assumed that the child has no chance of survival.

How is congenital diaphragmatic hernia of the fetus treated?

Treatment of fetal diaphragmatic hernia is carried out in close cooperation between the paediatricians, paediatric surgeons and obstetricians of the perinatal centre. Immediately after delivery the child is placed under continuous observation by paediatricians in the neonatal intensive care unit. The initial aim of monitoring is to stabilise cardiovascular function. If the child's circulation is stable, paediatric surgeons carry out surgical treatment. During the intervention the displaced organs are moved back into the abdominal cavity and the diaphragmatic opening is closed.

Intrauterine treatment of congenital diaphragmatic hernia at the Centre for Perinatal Diagnosis and Micro-Invasive Fetal Surgery, Halle

As already mentioned, the decisive factor limiting the child's chances of survival is pulmonary hypoplasia, which requires intrauterine intervention.

At 26 weeks of pregnancy a surgical intervention is performed during which an air-filled latex balloon is placed in the child's trachea using an ultra-thin fetoscope under real-time 3D ultrasound guidance (the so-called procedure of balloon tracheal occlusion). The aim of the occlusion is to raise the pressure of the fluid produced in the lungs by closing off the trachea; the lung thereby expands. Two months later the balloon is punctured with a syringe used for amniotic fluid sampling.

Fetoscopic tracheal occlusion is currently performed only in fetuses with a lung-to-head ratio <1. In these children, tracheal occlusion with an air balloon can significantly improve the chances of survival.

The main method of treating congenital diaphragmatic hernia at the Centre for Fetal Surgery headed by Professor Tchirikov, after careful assessment of the indications for intrauterine intervention, is also balloon tracheal occlusion. This procedure has proved itself in absolutely all the largest European, American and Japanese centres of intrauterine medicine, but in Halle the fetal survival rate after such an intervention is the highest in the world — 85%.

What has made balloon tracheal occlusion at the Centre for Fetal Surgery in Halle the most successful, safest and gentlest?

Firstly, the use of unique fetoscopic instruments and a large balloon dilator with an extended tail, which have received European and American patents. The Long-Tail-Ballonsystem balloon system is used to occlude the trachea in congenital diaphragmatic hernia. Occlusion of the trachea prevents the fluid contained in the lungs from escaping through the fetus's mouth. Because the volume of fluid increases sharply, the lungs are stretched, which stimulates the development they need in order for the fetus to survive.

Secondly, the balloon dilators used in other centres of fetal surgery are smaller. At the same time, the balloon system described is removed from the trachea either after the birth of the child by caesarean section, or by an additional minimally invasive intervention (puncture of the balloon with a syringe used for amniotic fluid sampling) 4 weeks before the expected date of natural delivery. The Long-Tail-Ballonsystem balloon system therefore does not require additional surgical removal, unlike in other centres of fetal surgery. Often, closer to delivery, the child can pull the balloon out of the trachea itself by its long tail; if this does not happen, the balloon is punctured with a syringe used for amniotic fluid sampling.

The method described is notable not only for its low risks for mother and fetus, but also for major cost savings: there is no need to pay separately for an intervention to remove the balloon; and there are none of the requirements, mandatory in other centres, for the mother to stay nearby because of the high risk of preterm rupture of the membranes and loss of amniotic fluid.

All the advantages described above have made the Centre for Fetal Surgery in Halle an internationally recognised world scientific and clinical leader in the field of intrauterine surgery.

Twin reversed arterial perfusion (TRAP) is one of the complications of monochorionic twin pregnancy, in which one of the twins develops as an acardius and often also as an acranius. In this twin, which in the absence of a heart and a head should functionally be regarded rather as a tumour, cystic structures in the upper part of the body, limb malformations and fetal hydrops are relatively common. The affected twin is supplied with nutrients by the healthy one through arteriovenous anastomoses (hence the name reversed arterial perfusion). TRAP sequence is rare in obstetric practice and occurs with a frequency of 1:35,000. Because the heart of the healthy fetus has to serve two bodies, this often causes heart failure in that fetus, polyhydramnios and early delivery, with a mortality of up to 41%.

The prognosis depends on the weight of the affected twin. If the weight difference is more than 50% in favour of the healthy child, the survival rate of the healthy child is 91%. There are a number of methods for separating the twin with acardius-acranius syndrome from the circulation of the healthy fetus. Laser coagulation of the placental anastomoses is usually performed. If for technical reasons this procedure is unsuccessful, the umbilical cord of the affected fetus is coagulated with bipolar forceps. A second method is used for this, which in turn increases the risk of preterm rupture of the membranes. One American centre prefers sonographically guided radiofrequency ablation of the intra-abdominal portion of the umbilical cord of the affected fetus.

A group of paediatricians from San Francisco (USA) recently reported on 76 patients with TRAP sequence and a weight difference of more than 50%. Radiofrequency ablation of the umbilical cord of the affected fetus could not significantly improve the chances of survival of the healthy twin. The chances of survival of the healthy fetus are 80% in the case of laser coagulation and 86% after radiofrequency ablation. The mean gestational age at delivery was 37 + 4 weeks, and in 67% of cases a full 36 weeks. Periventricular leukomalacia of stages I and II occurred in 2 of the 46 surviving children.