Fetal cystoscopy to unblock severe bladder outlet obstruction before birth

Fetal Cystoscopy for Severe Lower Urinary Tract Obstruction (LUTO): A Prospective Trial

This procedure will try fetal cystoscopy in pregnant women carrying a male fetus with severe lower urinary tract obstruction and low amniotic fluid to see if it improves fetal kidney function and chances of survival.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: University of Miami (Academic / other)
• Locations: 2 sites (Miami, Florida and 1 other locations)
• Trial ID: NCT03281798 on ClinicalTrials.gov

What this trial studies

This interventional program uses a fetoscope to perform fetal cystoscopy with the aim of visualizing and, when possible, relieving severe bladder outlet obstruction in utero. Pregnant women with a singleton male fetus showing a dilated bladder, the ‘‘keyhole’’ sign, bilateral hydronephrosis, and oligohydramnios undergo detailed fetal urine electrolytes and invasive genetic testing before enrollment. Procedures are performed between 16 0/7 and 25 6/7 weeks at specialized fetal surgery centers after psychosocial evaluation and confirmation that the family has considered and declined termination. Maternal and fetal outcomes including renal function markers, amniotic fluid volume, survival to delivery, and neonatal status are tracked after the intervention.

Who should consider this trial

Good fit: Ideal candidates are pregnant women aged 18 or older with a singleton male fetus diagnosed with isolated severe LUTO (dilated bladder, keyhole sign, bilateral hydronephrosis), oligohydramnios, favorable fetal urine electrolytes, normal karyotype, and gestational age between 16 0/7 and 25 6/7 weeks who have considered and declined termination.

Not a fit: Patients with abnormal fetal urine biochemistry suggesting poor renal prognosis, chromosomal or other major anomalies, prior in utero urinary interventions, multifetal pregnancies, female fetuses, or those outside the gestational window are unlikely to benefit.

Why it matters

Potential benefit: If successful, fetal cystoscopy could preserve fetal kidney function, restore amniotic fluid, reduce lung underdevelopment, and improve survival and neonatal outcomes.

How similar studies have performed: Previous case series and trials using fetal cystoscopy or vesicoamniotic shunts have shown improved survival in some patients but variable long-term kidney outcomes, so the approach has precedent but results remain mixed.

Eligibility criteria

Inclusion Criteria:

1. Pregnant women
2. Singleton pregnancy
3. Maternal age ≥ 18 years
4. Male fetus with LUTO, dilated bladder, "keyhole sign" and bilateral hydronephrosis
5. Oligohydramnios or Anhydramnios
6. Favorable urine analysis defined as urinary sodium is \< 100 milliequivalents per liter (mEq/L), chloride \< 90 mEq/L, and osmolality \< 200 milliosmoles per kilogram (mOsm/kg) after 20 weeks and in the absence of previous in utero intervention for the disease (vesicoamniotic shunt placement or fetal cystoscopy).
7. Absence of chromosomal abnormalities and associated anomalies
8. Gestational age at the time of the procedure will be between 16 0/7 weeks and 25 6/7 weeks
9. Normal karyotype by invasive testing (amniocentesis or Chorionic Villus Sampling (CVS)). Patients declining invasive testing will be excluded.
10. Family have considered and declined the option of termination of the pregnancy at less than 24 weeks.
11. Family meets psychosocial criteria, including sufficient social support and ability to understand requirements of the study.
12. Parents or guardian are willing to provide signed informed consent.

Exclusion Criteria:

1. Fetal anomaly unrelated to LUTO
2. Congenital cardiac anomaly
3. Female fetus
4. Increased risk for preterm labor including short cervical length (\<1.5 cm), history of incompetent cervix with or without cerclage, and previous preterm birth
5. Placental abnormalities (previa, abruption, accreta) known at time of enrollment
6. Contraindications to surgery including previous hysterotomy in active uterine segment
7. Technical limitations precluding fetoscopic surgery, such as uterine fibroids, fetal membrane separation, uterine anomalies incompatible with fetoscopy
8. Maternal-fetal Rh isoimmunization, Kell sensitization or neonatal alloimmune thrombocytopenia affecting the current pregnancy
9. 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
10. Maternal medical condition that is a contraindication to surgery or anesthesia
11. Patient does not have health insurance to cover routine clinical care 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.
12. Inability to comply with travel and follow-up requirements of the trial
13. Participation in another intervention study that influences maternal and fetal morbidity and mortality or participation in this trial in a previous pregnancy
14. Patients declining invasive testing
15. Family does not meet psychosocial criteria including insufficient

Where this trial is running

Miami, Florida and 1 other locations

• University of Miami — Miami, Florida, United States (Recruiting)
• Mayo Clinic — Rochester, Minnesota, United States (Terminated)

Study contacts

• Principal investigator: Rodrigo Ruano, MD, PhD. — University of Miami
• Study coordinator: Rodrigo A Ruano, MD, PhD.

Conditions Lower Urinary Tract Obstructive Syndrome; Lower Urinary Tract Obstruction, Congenital; Bladder Outlet Obstruction; Bladder Outflow Obstruction