INTRA-UTERINE FETAL SURGERY -- WHERE DO WE STAND

PROLOGUE

Intra-uterine fetal surgery is relatively new and a costly procedure. It requires a large, collaborative team in which each member is aware of their co-worker's role. Though considered a unique speciality, intra-uterine fetal surgery evolved alongside advances in ultrasonography, the establishment of fetal medicine, and the increased acceptance of fetoscopy for diagnosis and therapy in desperate situations. As a surgeon, my perspective is consistently shaped by a desire to dispel misconceptions and alleviate apprehension about surgical procedures prevalent among the general public. In this endeavour, I have gained invaluable knowledge about the rapidly evolving field of fetal medicine. Until recently, it was unimaginable that the fetus could be considered a patient and that surgical interventions could be performed on it while still within the mother’s womb. In the article, I describe the evolution of that concept and the procedures currently practised. Essentially, the fetus has to be born twice ---- the first time during the extraction from the intra-uterine milieu for the necessary correction, and the second time, during the final Cesarean delivery. The fetus is returned to a recreated intra-uterine environment for residual growth, development, and organogenesis till term.

THE "CRAZY IDEA" & THE EVOLUTION OF FETAL SURGERY

The concept of fetal surgery comes from first identifying the need for a corrective process in a fetus, diagnosing the anomaly by a detailed ultrasound examination, then evaluating whether it is a surgically correctable condition and whether the surgery needs to be done while still in the mother's womb. If not done, it can compromise the fetal well-being or even survival [6]. For example, in a twin pregnancy. If one of the twins is acardiac (has not developed a heart of its own) and thrives on the heart and circulation of the other healthy twin, then the healthy twin’s heart has to work twofold and will soon go into failure. This demands an immediate severance of the vascular connections between the twins to ensure the healthy twin’s survival. Likewise, if there is an amniotic band that is cutting through one of the limbs of the fetus, and if severed, it can save that limb, then it should be tried during the intrauterine life. Intrauterine fetal surgery is fraught with risks and requires strong conviction, determination, and an optimistic outlook for positive results. The hospital unit where such procedures are performed must have a sound financial back-up. This challenging speciality operates within a wide spectrum in which advanced ultrasound, Seldinger techniques, fetoscopic laser for adhesiolysis, band dissolution, and vascular ablation, etc., are all necessary skills. Where a uterine incision is needed, the best results are with life-threatening neural canal defects with skin loss, complex meningomyelocoels, sacrococcygeal teratomas, and similar defects. These pictures became viral on the internet in the '90s. Though these had a fair share of criticism, modern medicine saw the spread and recognition of the new intrauterine fetal surgery as a new speciality.

The fetal hand spontaneously coming out of the uterine incisions and held the surgeon's finger.

Enlarged view of the foetal hand. This particular surgery was carried out at Vanderbilt hospitals and the results of a landmark, seven-year National Institutes of Health-funded trial, Management of Myelomeningocele Study (MOMS), demonstrate clear benefit for babies who undergo fetal surgery to treat spina bifida, the most common birth defect in the central nervous system. The picture appears in the newsletter published by Vanderbilt hospital.

Fetal surgery is also called in-utero prenatal surgery or fetal intervention and helps in the --

1. Early identification of congenital defects incompatible with meaningful postnatal life.

2. Pre-planning and modification of the post-natal life by the parents.

3. Termination of and discontinuation of such incompatible pregnancies within the legal time.

4. Improving the quality of life for all concerned.

   
   

A 'crazy idea' taxed Dr Michael Harrison while observing the renowned pediatric surgeon, Hardy Hendren, performing a flawless congenital diaphragmatic repair sometime after birth. Unfortunately, the baby died early, and Michael Harrison thought that further in-utero lung development was necessary for survival, and he hypothesised intra-uterine feto-placental intervention in high-risk selected situations. This was in Boston, Massachusetts. Harrison's opinion was met with scepticism and disbelief at that time. Harrison realised that he himself would have to perform and show everybody that his idea is worth a risk. In his own unit at the University of California (UCSF) Hospital, he successfully performed the first surgery on an intra-uterine fetus-- a suprapubic cystostomy for the relief of hydronephrosis. The offending space-occupying-lesion was surgically removed in the post-natal period.

Experience taught obstetricians that the developing fetus within the mother's body, together with the mother, has certain special needs. Regular and periodic visits to the obstetrician help recognise troubles during the natal period and plan a method for managing detected defects. The goal is not only for the welfare of the pregnant mother but also to ensure early detection of gestational impairment of blood sugar, pregnancy-related hypertension and imminent seizure disorders, intrauterine growth anomalies, cervical incompetence threatening a pregnancy, pre-empting early labour, etc. Repeat and frequent miscarriages and a blighted ovum at the embryo stage often suggest severe congenital anomalies not compatible with life. Non-invasive investigations, especially obstetric ultrasound, improved exponentially in the intervening period and added to a check-up during the antenatal period to help identify feto-maternal problems early and institute measures accordingly. Ian Donald introduced ultrasound in the late '50s and early '60s, enabling an obstetrician to have a view of the intrauterine fetal activity and other abnormalities.

Ultrasound image of an intrauterine pregnancy.

The minimum number of antenatal visits and timing of the required investigations are protocolised, and WHO guidelines are universally available online. Still, a prenatal visit to an obstetrician is situation-dependent and individualised.

Fetal ultrasound improved by leaps and bounds, courtesy of Kypros Nicolaides, and accurate localisation of intrauterine fetal structures became possible. Obstetricians also came to understand that during pregnancy, the hormonal milieu in the mother's body is changed, and most of the drugs have unwanted effects while organogenesis is in progress. Selective drugs can be used only in exceptional circumstances, and most are used for maternal causes - only a few cross the fetoplacental barrier to affect fetal organogenesis. Fetal medicine is an all-encompassing obstetric speciality where a detailed ultrasound follows clinical examination and counselling. Routine haematological examinations are done at the same time. The primary aim is the well-being of both the mother and the child inside the womb, early detection of any fetal structural anomalies, and early identification of genetic and chromosomal abnormalities. The majority of subjects incompatible with a meaningful post-natal life abort spontaneously. Elective termination is planned for fetuses having serious defects, but they can continue growing inside the uterus.

Hobbins and Mahoney introduced fetal endoscopy - fetoscopy - in 1974, triggering a dream in the medical fraternity. Fetal surgery began modestly, with diagnostic and therapeutic fetoscopy at the forefront. In 1961, Sir William Liley (New Zealand) did the first percutaneous fetal transfusion and in 1964, Asensio and Adamsons (Puerto Rico) reported success in direct access to fetal circulation by open hysterotomy. The'70s saw a parallel exponential development of obstetric ultrasound and both diagnostic and therapeutic fetoscopy. A combination of uterine ultrasound and therapeutic fetoscopy allowed percutaneous access and approach to the fetus, placenta, and umbilical cord. Percutaneous relief from rhesus incompatibility in severe cases befor'e birth became a reality.

Fetoscope inside the uterus.

Lysis of bands entrapping fetal structures in the amniotic band syndrome and the delivery of targeted laser beams in twin-to-twin transfusion syndrome (TTTS) or the twin reversed arterial perfusion syndrome (TRAP) ensured healthy pregnancy outcomes. These complications are common in monochorionic twins.

Michael Harrison is unequivocally regarded as the father of intrauterine fetal surgery because of his belief, dedication, and giving a final form to his "crazy idea", from 1981 onwards, He led from the front. He was instrumental in the innovations and the continued evolution of a speciality that challenged several surgeons' skills. The premature death of a congenital diaphragmatic hernia (CDH) in the postnatal period gave him the"crazy idea" which taxed him, and it was a long way before a final form with acceptable mortality was realised. With time, more procedures were added to its ambit. Fetal surgery in the mother's womb is still evolving and has a wide spectrum. After withstanding countless religious, social, cultural, and ethnic criticisms and objections, gradual innovations by daring clinicians allowed a quantum increase in the ambit of fetal surgery.

PROCEDURAL POSSIBILITIES

The recent day options include --

• Fetoscopic major fetal vascular and cord needle access.

• Therapeutic fetoscopic tracheal occlusion with external clips,

• Endoluminal tracheal occlusion (FETO) for severe congenital diaphragmatic hernia (CDH),

• Fetal vesicoamniotic shunt (VAS) and fetal cystoscopy for bladder obstruction,

• Open fetal surgery for sacrococcygeal teratoma (or SCT, a tumour on the tailbone of the fetus) resection,

• Open fetal surgery to remove a congenital cystic adenomatoid malformation (CCAM) of the lung,

• Fetoscopic laser ablation for twin-twin transfusion syndrome (TTTS) and twin anaemia-polycythemia sequence (TAPS), conditions in which twins have problems with blood flow,

• Radiofrequency ablation for fetal tumours

• Bipolar cord coagulation for twin reversed arterial perfusion (or TRAP,  which can happen when twins develop unequally) sequence,

• Fetal cardiac intervention,

• Intrauterine blood transfusion,

• Serial amnioinfusions for bilateral renal agenesis and complex renal diseases,

• Spina bifida /myelomeningocele,

• Twin anaemia-polycythemia sequence (TAPS),

• Twin reversed arterial perfusion (TRAP) sequence,

• Twin-twin transfusion syndrome (TTTS),

• Amniotic band syndrome (ABS),

• Bronchopulmonary sequestration of the lung,

• Lower urinary tract obstruction (LUTO),

• Mediastinal teratoma,

• Neck mass that interferes with airflow,

• Sacrococcygeal teratoma (SCT),

• Congenital cystic adenomatoid malformation (CCAM) of the lung,

• Congenital diaphragmatic hernia (CDH),

• Congenital high airway obstruction syndrome (CHAOS),

• Fetal anaemia.

• Repair of spina bifida/meningomyelocele (MOM), Twin-to-twin transfusion syndrome surgery,

• Ex-utero intrapartum treatment/surgeries (EXIT procedures) for rare conditions,

Positioning the fetus and the uterus for a uterine incision in Congenital meningomyelocoel reair.

Most cases are managed by fetoscopy, laser ablation of errant vessels, and fetoscopic shunt placements. A trans-abdominal approach utilising the modified Seldinger technique makes it a minimally invasive procedure.

CDH repair in intrauterine life is radically different and may not require surgery. The simple application of a tracheal occluder, which may be a fetoscopic external clip or an intratracheal sponge/balloon occluder, helps the developing lung bud to grow normally in the trapped fluid. Therapeutic endoscopic surgery with a fetoscope is also known as 'Fetendo' and has obvious advantages.

INTRA-UTERINE FETAL SURGERY BY HYSTEROTOMY

Advanced intrauterine ultrasound allowed for an appropriate short hysterotomy, with the lesion accessible and facing the surgeon. Spina bifida and meningomyloceles, considered the most difficult correctable lesions, are managed thus. Bigger tumours like sacrococcygeal teratomas, some varieties of congenital cystic malformation of the lung, major lung lobar sequestration, mediastinal dermoid, and the congenital high airway obstruction syndrome (CHAOS) require a larger hysterotomy with partial delivery of the fetus, which gets an arterial supply via the intact umbilical cord and undisturbed placenta. Blood loss is minimised by using staplers and a specialised retractor. The partially delivered fetus is returned to the uterine cavity of the mother after the procedure. Continuous amnioinfusion is maintained during the procedure, and the fluid is replenished with isotonic Ringer's or Hartman's solution to make the baby float and cushion the cord just before tying the last uterine closure stitch.

THE EXIT PROCEDURE

The ex-utero intrapartum (EXIT) surgery needs a word or two. This is a grey area, and the combined skill of an obstetric surgeon, a pediatric surgeon, or a neonatal cardiac surgeon is necessary. Typically, an EXIT procedure is performed in conditions where a secondary source of oxygen is required for the survival of the freshly delivered neonate. Lines for extracorporeal membrane oxygenation may have to be instituted in rare cases. The umbilical cord is clamped, tied, and cut only after securing the oxygen supply. Separating the membranes and placenta occurs next, and the obstetrician proceeds with uterine and abdominal closure. The neonatal surgeon, meanwhile, does whatever is necessary for the baby.

Securing the fetal airway during an intra-uterine fetal surgery

Pediatric and neonatal cardiac surgeons may prefer early surgical correction in certain congenital cyanotic cardiac defects to limit the ill effects of hypoxic blood and related circulatory changes.

SET-UP

Intrauterine fetal surgery is a new subspeciality that was only recognised as unique from 1981 onwards. A large team comprising an obstetrician, a pediatric surgeon, their associates, two anesthesiology teams, the nursing personnel, the machine operators, and class IV operation theatre assistants and cleaners are minimum requirement.

A usual set-up of an intra-uterine fetal surgery or an EXIT procedure.

A collaborative and coordinated role among the operators is essential for success. The mortality and fetal outcomes vary and are still high (around 6-12%). Direct counselling, confidence in the team, and comprehensive consent are all important. Intrauterine fetal surgery is rare and evolving. Few centres can offer the full gamut. An international Fetal Medicine Foundation (FMF) was established by Nicolaides in 1995, and the watchdog bodies publish yearly medical and surgical procedural guidelines online.

CONCLUSION

Ultrasound localisation, planning, intuition, and innovation are the hallmarks of fetal surgery. Mortality is still high and varies (6-12%). The speciality is practised only in a few centres that can boast of appropriately qualified personnel and appliances. The procedures are costly and only practised in desperate situations.