Fetal Cystoscopy for Lower Urinary Tract Obstruction
Fetal Cystoscopy for Lower Urinary Tract Obstruction
This is a pilot study to evaluate the safety, feasibility, and effectiveness of fetal
 cystoscopy as an experimental procedure in avoiding perinatal death and renal impairment and
 to compare to the investigators clinical experience with fetal vesicoamniotic shunting.
Patients with severe LUTO will come for clinical evaluation as part of the standard clinical
 care at the Fetal Center at Texas Children's Hospital. Once the diagnosis of fetal severe
 LUTO is confirmed and the patient is considered for fetal intervention, patient will be
 invited to participate in the present study. Fetal cystoscopy will be offered as an optional
 experimental procedure.

 The following information will be obtained in the standard clinical care visit as usual: a.
 demographics (maternal age, parity); b. gestational age at the diagnosis of LUTO; c. fetal
 ultrasound findings including documentation of cervical length, gestational age,fetal bladder
 size, bladder wall thickness, degree of fetal hydronephrosis, amount of amniotic fluid, fetal
 biometry; d. fetal urinary biochemistry; e. fetal echocardiogram findings.

 The standard management options for fetal LUTO include expectant management, fetal
 vesico-amniotic shunting or termination of pregnancy according to the law. These options will
 be offered to all patients as the first set of management options and the gold standard. In
 addition, the investigators group will offer the procedure as an alternative experimental
 option, with a full explanation of the experimental nature of the procedure, the technical
 benefits and difficulties, and the risks and potential benefits of the procedure and the
 limited long-term outcomes information. Those patients who request participation in the
 present study will be informed that they can, a priori, select a crossover arm if for any
 reason the fetal cystoscopic procedure is not possible. They can elect that a fetal
 vesico-amniotic shunting be performed or prenatal expectant management or even termination of
 pregnancy (as part of the standard management of fetuses with LUTO).

 Participation in the study:

 Once the patient is deemed eligible, all prenatal standard management options will be offered
 first to the patient. Fetal cystoscopy will be offered as an investigational procedure for
 evaluation. If the patient opts for the fetal cystoscopy, we will explain that this procedure
 can be diagnostic and therapeutic. In order to prevent coercion, the investigation procedure
 will be presented to the patient in a manner that is an option and voluntary, if the patient
 chooses not to participate in the investigational procedure, the clinical care will not be
 affected. Informed consent to participate in the present study will be obtained. We will also
 include non-English speaking subjects in the present study. We will submit a full Spanish
 consent via amendment for IRB approval after approval of the English consent. We will not
 enroll any non-English subjects until we receive final approval. The study flow is
 demonstrated in Figure 1 (see attached document).

 Description of the fetal cystoscopy procedure (experimental procedure):

 Fetal cystoscopy will be performed between 16 0/7 and 25 6/7 weeks at the Pavilion for Women
 - TCH. This procedure will be performed under maternal local anesthesia and sedation. In some
 cases, according to the anesthesiologist's indication, maternal epidural may be performed.
 Fetal anesthesia will be performed by ultrasound-guided injection into fetal arm or leg of a
 combination of fentanyl (15µglKg), atropine and vecuronium (0.5-2mg/Kg).

 Prophylactic tocolysis will be used in all patients with a protocol employing magnesium
 sulfate - 6 gram IV loading dose followed by a 2 gram/hour continuous infusion for 24 hours,
 followed by nifedipine 10mg Q6 during until 36 weeks of gestation.

 Prophylactic antibiotics will also be used during the procedure using Cefazolin 2 g IV
 immediately before the procedure. Nafcillin will be injected into the amniotic cavity at the
 conclusion of the procedure. In case the patient has allergies to cephalosporin, clindamycin
 600 mg will be used as alternative.

 Steroids for fetal lung maturation will be given between 24 and 25 6/7 weeks (two doses of 12
 mg betamethasone given 24 hours apart, with the last dose given 48-72 hours before the
 procedure), if the procedure is performed during this gestational period.

 The procedure will be performed percutaneously under ultrasound-fetoscopic guidance. An 18G
 needle will be introduced into the fetal bladder through the maternal abdominal wall and
 uterus under ultrasound guidance. Using a Seldinger technique an 8-9Fr Cook trocar will be
 inserted through the maternal wall towards the fetal bladder. A curved Storz sheath for 1.3
 mm (11530AA, Karl Storz, Tuttlinglen, Germany) or 2.0 mm fetoscopy (26120BA, Karl Storz,
 Tuttlingen, Germany) or flexible ureteroscope will be introduced into the Cook catheter into
 the fetal bladder. After confirming that the trochar is inside the fetal bladder, urine
 samples will be collected for further renal function analysis. The fetoscope will be advanced
 toward the bladder neck and the dilated posterior urethra. If a membrane-like obstruction of
 the urethral lumen is seen, the diagnosis of PUV will be confirmed and at this time the
 valves will be fulgurated using a Diode laser with low energy (15-20W). If necessary, we will
 use a guide-wire to perforate the valves. Fulguration of the valves will be performed very
 cautiously with the laser fiber almost touching them in order to avoid damaging peripheral
 tissues. When the valves are completely disrupted, the urine will be released through the now
 patent urethra, which results in emptying the bladder. A transurethral shunt may be placed
 depending on the cause of the obstruction (urethral stenosis). In addition, power Doppler
 will be applied to confirm passage of fluid through the patent urethra into the amniotic
 cavity. However, if a non membrane-like structure is found, even with the fluid injection or
 the guide-wire, urethral atresia (UA, US or Prune Belly syndrome) will be diagnosed and we
 will not attempt to perforate this structure. A vesicoamniotic shunting placement will be
 performed in this situation depending on the patient's consent prior to the surgery.

 The postsurgical care is going to follow the same standard prenatal care after fetal
 vesico-amniotic shunting. The expected hospital course is 72 hours as it is also expected for
 fetal vesico-amniotic shunting; however, it is possible that the patient will be hospitalized
 for complications or preterm labor. The patient will then be discharged home with
 recommendations for modified bed rest for the first 2 weeks post discharge, but will
 subsequently be allowed to graduate to moderate activity if the uterus is quiescent. Patients
 will return on a weekly basis for clinical and ultrasound evaluation. On ultrasound, fetal
 kidneys, bladder thickness and dilatation, and amniotic fluid volume will be assessed. Fetal
 Surveillance by biophysical profiles and Doppler studies will begin at 34 weeks

 Delivery mode will be performed based on the obstetrical management following the
 investigators clinical algorithm.

 The subjects that undergo fetal cystoscopy will have exactly the same postnatal routine
 (standard of care) clinical follow-up that is provided to all infants with LUTO. All infants
 with LUTO are followed-up by the pediatric urology and nephrology services and may need
 postnatal surgical intervention. At birth, the clinical evaluation will include a renal
 ultrasound, voiding cysto-urethrogram (VCUG) as well as clinical laboratory examinations such
 as serum creatinine, sodium, calcium, potassium and chloride, and a urine analysis will be
 performed as part of the standard clinical care. Information from these routine examinations
 will be collected and documented.
Inclusion Criteria:

 -  Fetus with LUTO, dilated bladder, "keyhole sign" and bilateral hydronephrosis

 -  Oligohydramnios or Anhydramnios after 18 weeks

 -  "Favorable urine analysis after 18 weeks (urinary sodium is < 100mEq/L, chloride <
 90mEq/L, osmolarity <200mOsm/L and β2-microglobulin <6mg/L 7)

 -  Absence of chromosomal abnormalities and associated anomalies (Normal karyotype by
 invasive testing (amniocentesis or CVS))

 -  Gestational age at the time of the procedure will be between 16 0/7 weeks and 25 6/7
 weeks

 Exclusion Criteria:

 -  Fetal anomaly unrelated to LUTO

 -  Congenital cardiac anomaly

 -  Increased risk for preterm labor including short cervical length (<1.5 cm), history of
 incompetent cervix with or without cerclage, and previous preterm birth

 -  Placental abnormalities (previa, abruption, accreta) known at time of enrollment - A
 body-mass index ≥ 35

 -  Contraindications to surgery including previous hysterotomy in active uterine segment

 -  Technical limitations precluding fetoscopic surgery, such as uterine fibroids, fetal
 membrane separation, uterine anomalies incompatible with fetoscopy

 -  Maternal-fetal Rh isoimmunization, Kell sensitization or neonatal alloimmune
 thrombocytopenia affecting the current pregnancy

 -  Maternal HIV, Hepatitis-B, Hepatitis-C status positive because of the increased risk
 of transmission to the fetus during maternal-fetal surgery. If the patient's HIV or
 Hepatitis status is unknown, the patient must be tested and found to have negative
 results before enrollment

 -  Maternal medical condition that is a contraindication to surgery or anesthesia

 -  Patient does not have a support person (ie. Spouse, partner, mother) available to
 support the patient for the duration of the pregnancy at Texas Children's
 Hospital/Ronald McDonald House

 -  Patient does not have healthy insurance to cover routine clinical care at Texas
 Children's Hospital including prenatal care, prenatal ultrasound, amniocentesis,
 tocolysis, admission, delivery, and fetal vesico-amniotic shunting. The exception will
 be fetal cystoscopy which is considered an experimental procedure.

 -  Inability to comply with the travel and follow-up requirements of the trial

 -  Participation in another intervention study that influences maternal and fetal
 morbidity and mortality or participation in this trial in a previous pregnancy

 -  Patients declining invasive testing

 -  Family does not meet psychosocial criteria.