With the growing acceptance of the concept that “the fetus is a patient,” intrauterine treatments focusing on the fetus as the primary subject have rapidly developed worldwide. A thorough evaluation is required to assess the risks of treatment for both the mother and the fetus, and surgical indications must be strictly followed.
Classification
Pharmacological Intervention
Pharmacological treatments are delivered to the fetus through the maternal-placental pathway or directly to the fetus. Examples include the administration of glucocorticoids to the mother for treating large congenital pulmonary airway malformation (CPAM) in the fetus, or the use of antiarrhythmic drugs delivered orally to the mother or via umbilical vein injection to manage fetal tachyarrhythmias.
Surgical Intervention
Surgical interventions can be divided based on approach into minimally invasive fetal surgery, ex-utero intrapartum treatment (EXIT), and open fetal surgery. They can also be classified by the surgical target:
- Surgeries directed at the fetus: Examples include in utero repair of open spina bifida, treatment of severe congenital diaphragmatic hernia, and pleuroamniotic shunting for fetal thoracic effusions.
- Surgeries targeting fetal appendages (placenta, umbilical cord, membranes): Examples include fetoscopic laser ablation of placental anastomotic vessels for twin-twin transfusion syndrome, laser or radiofrequency treatment for placental chorioangiomas, and fetoscopic procedures for releasing amniotic bands.
Common Intrauterine Surgical Interventions and Clinical Applications
Minimally Invasive Fetal Surgery
Fetal Reduction
Fetal reduction can be classified based on indications:
- Reduction of higher-order multiples: In cases of three or more fetuses, this procedure reduces the number of fetuses to lower maternal and fetal complications associated with multiple pregnancies.
- Selective reduction: Abnormal fetuses in twin or multifetal pregnancies are selectively terminated. Methods depend on chorionicity. For dichorionic multiples, potassium chloride injection into the fetal heart is often used. For monochorionic multiples, vascular occlusion techniques such as radiofrequency ablation, bipolar coagulation, or umbilical cord laser coagulation are preferred.
Fetoscopic Surgery
Fetoscopy allows direct visualization of the fetus and targeted tissue biopsy, initially used for diagnostic purposes, such as prenatal diagnosis of conditions like Duchenne muscular dystrophy or albinism. With advances in molecular diagnostic techniques, many single-gene disorders no longer require fetoscopic diagnosis. Currently, fetoscopic procedures include laser coagulation of placental anastomotic vessels for twin-twin transfusion syndrome, in utero repair of open spina bifida, endoluminal tracheal occlusion for severe congenital diaphragmatic hernia, laser ablation for posterior urethral valve, and release of amniotic bands.
Pleuroamniotic Shunt Surgery
For fetuses with severe thoracic effusions, pleuroamniotic shunting can provide continuous decompression of the chest cavity, facilitate lung expansion, and reduce neonatal mortality due to pulmonary hypoplasia. For fetuses with normal renal function and lower urinary tract obstruction, vesicoamniotic shunting can increase survival rates, restore normal amniotic fluid levels, and lower the likelihood of pulmonary hypoplasia. However, the effectiveness and potential complications of these procedures require further evaluation.
Intrauterine Blood Transfusion
For fetal anemia caused by various factors, especially immune-mediated anemia due to maternal-fetal blood type incompatibility, intrauterine blood transfusion may be performed before 34–35 weeks of gestation to prevent fetal hydrops and improve outcomes. Blood transfusion may be delivered via the umbilical vein, intrahepatic umbilical vein, or peritoneal cavity of the fetus. The donor blood is O-negative, with a hematocrit value of 0.75–0.85, irradiated with gamma rays, and tested to ensure negative cytomegalovirus status.
Severe Congenital Heart Disease
Severe conditions, such as aortic valve stenosis or pulmonary valve stenosis with an intact ventricular septum, can lead to obstructed blood flow that impairs the development of the pulmonary or systemic circulation. Theoretically, relieving structural obstructions in utero may promote normal heart development and increase the likelihood of a biventricular repair after birth rather than a univentricular repair. The clinical efficacy of fetal balloon valvuloplasty for congenital heart defects requires further investigation.
Ex-Utero Intrapartum Treatment (EXIT)
The EXIT procedure is designed to maintain uterine relaxation and uteroplacental circulation while providing treatment to the fetus. Its primary indications include:
- Maintaining airway patency during delivery: Addressing airway obstruction caused by neck masses, congenital high airway obstruction syndrome (e.g., tracheal or laryngeal hypoplasia), severe micrognathia, or balloon removal following fetoscopic endoluminal tracheal occlusion (FETO) for diaphragmatic hernia.
- Providing extracorporeal membrane oxygenation (ECMO) support: In cases of severe congenital diaphragmatic hernia (e.g., hepatic hernia), hypoplastic left heart syndrome, or severe aortic stenosis with an intact atrial septum.
- Performing tumor removal: For mediastinal or pericardial teratomas and lymphangiomas, as well as thoracic masses causing airway obstruction.
- Separating conjoined twins during delivery.
Some conditions, such as abdominal wall defects (e.g., omphalocele, gastroschisis), pulmonary abnormalities (e.g., severe CPAM, pulmonary sequestration, bronchogenic cysts), and congenital diaphragmatic hernia cases not requiring ECMO, are not considered indications for EXIT.
Open Fetal Surgery
Open fetal surgery is indicated for conditions such as open spina bifida, sacrococcygeal teratomas, and large fetal neck masses. Among these, open surgical repair of fetal spina bifida is the only procedure with proven efficacy based on randomized controlled trials. However, open fetal surgery carries significant risks for both the mother and the fetus, requiring careful patient selection.