Surgical Principles of Fetal Interventions

Ahmed A. Nassr

Michael A. Belfort

Alireza A. Shamshirsaz

GENERAL PRINCIPLES

In the United States, structural congenital anomalies are detected in up to 3% of all children (1). Some of the major anomalies and fetal conditions can cause mortality or significant postnatal morbidity.
Recent advances in diagnostic prenatal imaging as well as open and endoscopic surgical techniques have allowed us to offer a variety of procedures in pregnancies associated with a high risk of fetal demise or lifelong morbidity if not timely corrected.

PREOPERATIVE PLANNING

Curvilinear ultrasound transducers are commonly used for needle guidance in fetal interventions. These transducers allow some degree of flexibility in guiding the needle toward the target.
Simulation models and simple invasive procedures (e.g., amniocentesis) are of great value in initial training and improving the operator’s needle orientation skills.
Two operators are generally needed for complex fetal interventions, with one person holding the ultrasound transducer and the second operator performing the needle procedure. This allows for fine adjustment as the operator directs and advances the needle. A reasonable degree of coordination between the two operators is required for the successful completion of the procedure, and this comes from practice and experience working as a team. Many interventionists, based on their training and experience, prefer to direct the needle and hold the ultrasound probe themselves, and this is a perfectly acceptable alternate approach.
Careful planning regarding the ideal site of surgical access is the first step for safe and successful fetal intervention or surgery. The target should be clearly seen, and a clear path to that target should be identified. The placental location is often a determining factor in the location of the access site, and under most circumstances, avoidance of the placenta and the immediate placental edge is wise because of the risk of hemorrhage. Care should be taken to exclude the presence of uterine vessels, other pelvic structures, and bowel loops along
the intended path of the needle, particularly so with lateral abdominal access.
We prefer to perform invasive fetal procedures in an operating room using standard sterile procedures. A transparent sterile plastic sheet is usually used to cover the ultrasound panel, and a probe cover is used to keep the probe sterile. This setup allows the ultrasound operator to control the image settings during the procedure.

Procedures and Techniques

Closed Fetal Interventions

Closed fetal interventions refer to those procedures that can be completed using ultrasoundguided needles, laser fibers, trocars/cannulas, and endoscopes without the need to create a hysterotomy. This group includes two main categories: Percutaneous interventions without laparotomy and laparotomy-assisted endoscopic procedures.

General Principles for Closed Fetal Interventions

Tocolysis: Indomethacin 50 mg orally (PO) (followed by 25 mg orally q6 hours for 24 hours) in pregnancies at <30 weeks’ gestational age. In some cases, nifedipine 10 to 20 mg PO is added preoperatively and continued q6 hours for 24 hours after the procedures.
Prophylactic antibiotics: Preoperative intravenous (IV) cefazolin (2 g) or IV clindamycin (900 mg) if the patient is allergic to penicillin
Anesthesia: Closed fetal interventions are usually performed using infiltrated local anesthesia supplemented with IV sedation (midazolam and/or remifentanil).
Laparotomy-assisted interventions are generally performed under general endotracheal anesthesia supplemented by epidural anesthesia for postoperative pain control.

Acquisition of Uterine Access in Closed Fetal Procedures

Invasive closed fetal procedures are best performed in the operating theater using standard sterile techniques.
Ultrasound is universally used for guidance during such procedures. The ultrasound transducer is placed in a sterile cover, and the control panel of the ultrasound machine is covered with a sterile plastic sheet. This allows an assistant to remain sterile during the procedure and provide both ultrasound guidance and procedural assistance.
The track of the needle or access port is carefully imaged to avoid injuring placental tissue, bowel, and uterine vessels.
Placing an access port using Seldinger technique:
- An 18-gauge needle is inserted into the amniotic cavity under ultrasound guidance, the trocar is removed, and a guidewire is slipped into the uterus. The needle is then removed, leaving the wire in place.
- An appropriately sized vascular access port (usually 9-12F) with a tapered dilator is then advanced together over the guidewire into the uterus, and the wire and dilator are removed leaving an access port through which the fetoscope can be inserted.

Intrauterine Transfusion for Fetal Anemia

Intrauterine transfusion of red blood cells is the standard therapy for severe fetal anemia from a number of different etiologies: Alloimmunization, congenital infection (e.g., Parvovirus B19), fetomaternal hemorrhage, other rare causes of fetal anemia such as Fanconi anemia.
Fetal middle cerebral artery peak systolic velocity ≥1.50 multiples of the median is used as the cutoff for considering cordocentesis (and subsequent transfusion if needed) in at-risk pregnancies (2).
Both the intravascular and intraperitoneal routes have been described for the intrauterine transfusion of red blood cells. Although intravascular transfusion (IVT) has become the generally accepted and preferred method, intraperitoneal transfusion (IPT) remains an option in technically challenging cases (e.g., extremely early gestational age, inability to visualize a safe IV transfusion site) and may provide life-saving capacity to sustain the fetus until the intravascular route can be safely accessed (3). Some authors advocate for a combined approach (IVT and IPT) to prolong transfusion intervals (4,5).
Accessing the umbilical vein (UV) at the placental insertion site is the preferred approach for intrauterine IVT (Tech Figures 3.10.1 and 3.10.2). The intrahepatic portion of the UV provides an alternative site in cases where the placental UV insertion cannot be safely accessed owing to fetal position or placental location (6).
In general, O RhD-negative, Kell-negative, irradiated, washed, cytomegalovirus-negative, leucocyte-depleted, packed red blood cells are used for intrauterine transfusion.

Fetoscopic Laser Photocoagulation of Abnormal Placental Anastomoses in Twin-to-Twin Transfusion Syndrome

Twin-to-twin transfusion syndrome (TTTS) complicates 9% to 15% of monochorionic diamniotic twin pregnancies (7) and is associated with high perinatal mortality and morbidity (up to 90% fetal loss if left untreated).

Tech Figure 3.10.1. Approach for intrauterine transfusion in patients with anterior placenta. Arrow shows needle tip inside UV insertion on anterior placenta. UV, umbilical vein.

Tech Figure 3.10.2. Approach for intrauterine transfusion in patients with posterior placenta. Arrow shows needle tip inside UV insertion on posterior placenta. UV, umbilical vein.
TTTS develops as a result of unbalanced placental vascular connections caused primarily by unidirectional anastomoses (arteriovenous and venoarterial) (8). Bidirectional arterial-arterial connections are often protective and help to balance pressures, whereas veno-venous connections are deleterious and worsen outcomes.
Diagnosis of TTTS depends on the demonstration of polyhydramnios/oligohydramnios sequence in monochorionic diamniotic twins. Quintero staging has been widely used for classifying disease severity and guiding the timing of intervention if deemed necessary (9) (Tech Figure 3.10.3).
Laser photocoagulation is currently the standard treatment for TTTS that has been classified as stages II, III, or IV. Treatment of stage I TTTS is recommended in those cases complicated by progressive symptomatic polyhydramnios and/or those with a short/shortening cervix (10). Although routine treatment of stage I TTTS has been suggested by one study, this practice has not shown to improve outcomes (11,12).
Timing of the procedure: Generally, laser photocoagulation is offered for TTTS cases between 17 and 26 weeks’ gestation. Similar technical success has been achieved for cases treated before 17 weeks and after 26 weeks by some authors (13).
Selective laser coagulation of the placental vessels (SLCPV) describes a technique in which the vascular anastomoses are initially identified and then ablated in a selective approach that favors coagulation of the higher flow/pressure arterial feeding vessel before coagulation of the lower pressure venous arm (Tech Figures 3.10.4 and 3.10.5). This selective technique has been shown to be more effective and to be associated with better outcomes when compared with the nonselective technique (ablating all vessels crossing the membranous equator) (14).
Connecting all the ablation points on the placental surface (Tech Figure 3.10.6) from one edge of the placenta to the other (Solomonization or Solomon technique) significantly decreases the risk of persistent/reopened anastomoses, which may lead to twin anemia polycythemia sequence and recurrent TTTS (15,16).
Several techniques have been used in cases in which there is an anterior placenta blocking usable access to the placental surface. These include the use of 30-degree offset and/or curved endoscopes, laser fiber deflecting devices, and the deployment of the laser from inside the vascular access canula (17,18,19). Laparotomy and exteriorization of the uterus as well as laparoscopic-assisted tilt of the uterus to enable access to the posterior uterine wall have been described for cases with complete anterior placenta and difficult anterior percutaneous access (20).
Practical points
- Avoid accessing the uterus in close proximity to the donor sac to reduce the risk of septostomy, which can occur in the region of overlapping membranes caused by the collapsed donor sac.
- A 70-degree scope can help initial placental mapping in difficult cases with an anterior placenta.
  
  Tech Figure 3.10.3. Stages of twin-to-twin transfusion syndrome. (Printed with permission from Texas Children’s Hospital.)
  
  Tech Figure 3.10.4. Selective laser coagulation of placental vessels. (Printed with permission from Texas Children’s Hospital.)
  
  Tech Figure 3.10.5. Fetoscopic laser photocoagulation of the anastomoses.
  
  Tech Figure 3.10.6. Solomon technique. (Printed with permission from Texas Children’s Hospital.)
- Follow each set of vessels suspected of being involved in an abnormal anastomosis from beginning to end before obliterating any of them. Frequently what may initially appear to be an aberrant vessel may be found simply to have a more tortuous route back to the correct cord insertion. In this way, functional cotyledons can be preserved and fetal loss diminished. This may result in a curved nonlinear vascular equator.
- To enhance the speed of SLCPV and reduce the time needed for complete ablation of all anastomoses, mark the vascular equator with the laser by burning small “dots” along the intended line of ablation. Because of the narrow field of view of the endoscope, this allows more
  efficient endoscope use while performing the Solomon technique along the vascular equator from one placental edge to the other.
- Always look for the immediate surface of the placenta for anastomoses that may not be on the placental surface.

Fetoscopic Endoluminal Tracheal Occlusion (FETO)

Congenital diaphragmatic hernia (CDH) is a rare anomaly encountered in ˜1 to 5,000/10,000 live births, with most cases occurring on the left side (85%). Right-sided (13%) and bilateral (2%) (21) are much less frequently seen.
CDH is classified into mild, moderate, and severe degrees based on the size of the lungs and the degree of liver herniation. The classification systems most often used rely on both ultrasound and magnetic resonance imaging (MRI) parameters such as lung-to-head ratio (LHR) (21), observed/expected lung-to-head ratio (o/e LHR) (22), observed/expected total lung volume (o/e TLV) (23).
Temporary balloon occlusion of the fetal trachea (Tech Figure 3.10.7) is believed to stimulate pulmonary growth, vascular proliferation, and vascular development by preventing the escape of pulmonary fluid during mid-gestation lung development and increasing airway pressure during a critical developmental time point (24).
Although FETO is still considered an experimental procedure, it has been investigated in both isolated severe and moderate cases of CDH. Early studies demonstrated improved survival from 24.1% to ˜49.1% in severe left-sided CDH, and from 0% to 35.3% in severe right-sided CDH (25,26).
In severe CDH, FETO is typically performed between 26 and 29 weeks’ gestation. Earlier balloon placement as early as 22 weeks has been evaluated in extremely severe cases with reported potential benefit in this group (27).
FETO has been shown, in one study, to be independently associated with an increased resolution of pulmonary hypertension by 1 year of age in infants with severe CDH (28).
Removal or deflation of the balloon (referred to as FETO unplug) is typically scheduled around 34 weeks’ gestation. Cases with unexpected preterm labor before FETO unplug may require emergency balloon puncture, removal by emergency fetoscopy, or delivery by ex-utero intrapartum therapy (EXIT) to secure the neonatal airway (29).