In Utero Treatment of Obstructive Ureterocele.

Lower urinary tract obstruction consists of a heterogeneous group of conditions in which the normal urethral egress of urine from the fetal bladder is impaired. The most frequent diagnoses are posterior urethral valves, urethral atresia, and less common obstructive ureterocele. We report a case of a fetus with prenatal diagnosis of obstructive ureterocele who presented progressive bilateral hydronephrosis. A fetal cystoscopy with laser ablation was performed.

Z-scores of fetal bladder size for antenatal differential diagnosis between posterior urethral valves and urethral atresia.

OBJECTIVE: To construct reference values for fetal urinary bladder distension in pregnancy and use Z-scores as a diagnostic tool to differentiate posterior urethral valves (PUV) from urethral atresia (UA). METHODS: This was a prospective cross-sectional study in healthy singleton pregnancies aimed at constructing nomograms of fetal urinary bladder diameter and volume between 15 and 35 weeks' gestation. Z-scores of longitudinal bladder diameter (LBD) were calculated and validated in a cohort of fetuses with megacystis with ascertained postnatal or postmortem diagnosis, collected from a retrospective, multicenter study. Correlations between anatomopathological findings, based on medical examination of the infant or postmortem examination, and fetal megacystis were established. The accuracy of the Z-scores was evaluated by receiver-operating-characteristics (ROC)-curve analysis. RESULTS: Nomograms of fetal urinary bladder diameter and volume were produced from three-dimensional ultrasound volumes in 225 pregnant women between 15 and 35 weeks of gestation. A total of 1238 urinary bladder measurements were obtained. Z-scores, derived from the fetal nomograms, were calculated in 106 cases with suspected lower urinary tract obstruction (LUTO), including 76 (72%) cases with PUV, 22 (21%) cases with UA, four (4%) cases with urethral stenosis and four (4%) cases with megacystis-microcolon-intestinal hypoperistalsis syndrome. Fetuses with PUV showed a significantly lower LBD Z-score compared to those with UA (3.95 vs 8.83, P < 0.01). On ROC-curve analysis, we identified 5.2 as the optimal Z-score cut-off to differentiate fetuses with PUV from the rest of the study population (area under the curve, 0.84 (95% CI, 0.748-0.936); P < 0.01; sensitivity, 74%; specificity, 86%). CONCLUSIONS: Z-scores of LBD can distinguish reliably fetuses with LUTO caused by PUV from those with other subtypes of LUTO, with an optimal cut-off of 5.2. This information should be useful for prenatal counseling and management of LUTO. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal lower urinary tract obstruction: a current overview of intrauterine diagnosis and treatment.

OBJECTIVE: The aim of this review article is to provide a practical and concise overview of diagnosis and management of pregnancy with fetal lower urinary tract obstruction. METHODS: Review of literature and current studies. CONCLUSION: Proper diagnosis and management of isolated fetal lower urinary tract obstruction with oligohydramnios allows appropriate implementation of intrauterine treatment in indicated cases. The treatment is a prevention of pulmonary hypoplasia and also improves renal function; this  finally contributes to the improvement of overall perinatal morbidity and mortality.

Biometric and morphological features on magnetic resonance imaging of fetal bladder in lower urinary tract obstruction: new perspectives for fetal cystoscopy.

OBJECTIVES: Incompatibility between currently available fetoscopes and the anatomical constraints of the distended fetal bladder, with the resulting curvature around the bladder neck, account for most technical difficulties during fetal cystoscopy in lower urinary tract obstruction (LUTO). The aim of this anatomical study was to assess by magnetic resonance imaging (MRI) the variation in three bladder angles (bladder-neck angle (BNA), vesicourethral angle (VUA) and angle between bladder dome and posterior urethra (DUA)), according to gestational age (GA), bladder volume and the presence of LUTO. METHODS: From our fetal medicine database, we retrieved for review 46 MRI examinations of male fetuses between 2015 and 2019, including 17 with LUTO, examined at a mean GA of 28.1 (range, 17.3-35.0) weeks and 29 age-matched controls, examined at 29.9 (range, 21.9-35.0) weeks. We measured bladder volume, bladder-wall thickness and the three bladder angles, and used the Mann-Whitney U-test to compare values between groups. Variations according to GA and bladder volume were determined using analysis of variance (ANOVA). A reliability study was performed using the Bland-Altman method and Lin's correlation coefficient was calculated. RESULTS: Both bladder volume and bladder-wall thickness were significantly greater in the LUTO group (P < 0.01). BNA was significantly larger in LUTO compared with control fetuses: the mean (range) was 127.1° (101.6-161.6°) vs 111.2° (88.5-157.3°) (P < 0.01). DUA averaged 117° and showed no difference between the groups (P = 0.92). No statistical comparison was performed on VUA since this was not measurable in most control fetuses. ANOVA showed no variation of any angle with bladder volume in both LUTO fetuses and control fetuses. BNA in LUTO fetuses was the only angle to vary with GA, being larger after, compared with at or before, 25 weeks (P = 0.04). The reliability study showed an acceptable bias for both intra- and interobserver reproducibility for all three angles. CONCLUSION: The findings that BNA is increased by approximately 15° in fetuses with LUTO and DUA averages 117° could aid in development of a customized fetal cystoscope and help to overcome the current technical challenges of fetal cystoscopy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Fetal Cystoscopy and Vesicoamniotic Shunting in Lower Urinary Tract Obstruction: Long-Term Outcome and Current Technical Limitations.

BACKGROUND: In utero therapeutic approaches for lower urinary tract obstruction (LUTO) have been developed to salvage the fetal kidney function. OBJECTIVE: The aim of this work was to report the long-term survival, nephrological, and urological outcome of children treated prenatally for LUTO using operative fetal cystoscopy (FC) and vesicoamniotic shunting (VAS) or both. METHODS: A retrospective study of 48 procedures (23 FC, 25 VAS) was performed on 33 patients (between 2008 and 2018). Reviewed data included prenatal management and clinical follow-up by a pediatric nephrologist and a pediatric urologist. Both intention-to-treat and per-protocol analyses were conducted. RESULTS: The median follow-up was 3.6 years (0.5-7) for FC and 2.5 years (1.1-5.1) for VAS. There was no difference between FC and VAS in terms of survival (92 vs. 83%, p = 1), complication rate (74 vs. 92%, p = 0.88), or chronic kidney disease (58 vs. 50%, p = 1). The number of procedures was higher in the VAS group: 1.7 (1-3) versus 1.1 (1-2), p = 0.01. With a 30% rate of technical failure, FC added diagnostic value in 3 out of 21 cases. CONCLUSIONS: No difference was found between FC and VAS regarding survival, long-term kidney function, or urological outcome. Despite overly optimistic reports on FC, it lacks reproducibility due to posterior-urethra inadequate visualization and inappropriate instrumentation.

Current State of Fetal Intervention for Lower Urinary Tract Obstruction.

PURPOSE OF THE REVIEW: In this article, we explore the origins of intervention of fetal lower urinary tract obstruction, and we specifically discuss the background and recent outcomes of vesicoamniotic shunt placement and fetal cystoscopy. The article seeks to provide a comprehensive overview of the field while bringing the reader quickly up to speed on the pertinent literature and the critical data that are available to guide decision-making regarding intervention. RECENT FINDINGS: Appropriate patient selection for fetal intervention remains challenging despite advances in prenatal imaging. Both a randomized controlled trial and multiple systematic reviews show evidence of a perinatal survival benefit following fetal intervention but rates of renal morbidity remain very high. Despite 30 years of research, fetal lower urinary tract obstruction remains a difficulty entity to treat. Intervention may lead to survival, but physicians and caregivers must remain alert for the distinct possibility of long-term renal morbidity in survivors.

New minimally invasive technique for cystoscopic laser treatment of fetal ureterocele.

Prenatal ultrasound detection of fetal ureterocele with bilateral hydroureteronephrosis, obstruction of the bladder outlet and progressive amniotic fluid reduction have been associated with a significant risk of end-stage chronic renal disease after birth. Fetal cystoscopic laser incision of the ureterocele, using standard 3.5-mm fetoscopic access to the amniotic cavity and the fetal bladder with the aim of relieving the bladder outflow obstruction to preserve renal function, has been reported previously in a case with a favorable outcome. We report on two additional cases of fetal ureterocele treated by cystoscopic laser decompression. In the first case, a standard 3.3-mm uterine entry was used. In the second case, a new approach was adopted using an 'all-seeing needle' 1.6-mm endoscope. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Lower urinary tract obstruction: fetal intervention based on prenatal staging.

The authors present an overview of lower urinary tract obstruction (LUTO) in the fetus with a particular focus on the insult to the developing renal system. Diagnostic criteria along with the challenges in estimating long-term prognosis are reviewed. A proposed prenatal LUTO disease severity classification to guide management decisions with fetal intervention to maintain or salvage in utero and neonatal pulmonary and renal function is also discussed. Stage I LUTO (mild form) is characterized by normal amniotic fluid index after 18 weeks, normal kidney echogenicity, no renal cortical cysts, no evidence of renal dysplasia, and favorable urinary biochemistries when sampled between 18 and 30 weeks; prenatal surveillance is recommended. Stage II LUTO is characterized by oligohydramnios/anhydramnios, hyperechogenic kidneys but absent renal cortical cysts or apparent signs of renal dysplasia and favorable fetal urinary biochemistry; fetal vesicoamniotic shunting (VAS) or fetal cystoscopy is indicated to prevent pulmonary hypoplasia and renal failure. Stage III LUTO is oligohydramnios/anhydramnios, hyperechogenic kidneys with cortical cysts and renal dysplasia and unfavorable fetal urinary biochemistry after serial evaluation; fetal vesicoamniotic shunt may prevent severe pulmonary hypoplasia but not renal failure. Stage IV is characterized by intrauterine fetal renal failure, defined by anhydramnios and ultrasound (US) findings suggestive of severe renal dysplasia, and is associated with death in 24 h of life or end-stage renal disease (ESRD) within the first week of life; fetal vesicoamniotic shunt and fetal cystoscopy are not indicated.

Urological fistulas after fetal cystoscopic laser ablation of posterior urethral valves: surgical technical aspects.

OBJECTIVE: To describe the surgical technical aspects associated with the development of urological fistulas after fetal antegrade cystoscopic laser fulguration of the posterior urethral valves (PUV). METHODS: The perioperative data for all fetal cystoscopies performed between January 2004 and August 2013 at three institutions in the USA, France and Brazil were reviewed, with particular emphasis on surgical technical aspects of the procedure and the complications encountered. RESULTS: A total of 40 fetal cystoscopies were performed at the three institutions. Laser fulguration of the PUV was performed in 23 of these cases, with a survival rate of 60.9% (14/23) and normal renal function in 85.7% (12/14) of these infants. Urological fistulas were diagnosed postnatally in four (10%) newborns. The presence of fistulas was associated with a higher gestational age at diagnosis of PUV (P < 0.01) and with the use of semi-curved rather than curved sheaths (P < 0.01), the use of a diode laser (P < 0.01) and the use of higher laser power and energy (P < 0.01 and P < 0.01, respectively), as well as with less operator experience (P < 0.01) and with absence of fetal anesthesia/immobilization (P = 0.02). CONCLUSION: Urological fistulas are a severe complication of fetal cystoscopic laser fulguration of PUV and are associated with type, energy and power settings of the laser and instrumentation. The use of appropriate technique and proper training of the operator are necessary to perform this fetal intervention safely.

Fetal intervention for severe lower urinary tract obstruction: a multicenter case-control study comparing fetal cystoscopy with vesicoamniotic shunting.

OBJECTIVE: To evaluate the efficacy of fetal intervention using fetal cystoscopy or vesicoamniotic shunting in the treatment of severe lower urinary obstruction (LUTO). METHODS: A cohort of 111 fetuses with severe LUTO attending two centers between January 1990 and August 2013 were included retrospectively. Fetuses were categorized into three groups based on the method of intervention: (1) fetal cystoscopy, (2) vesicoamniotic shunting or (3) no intervention. Multivariate analyses were performed to determine the probability of survival and normal renal function until 6 months of age by comparing fetal cystoscopy and vesicoamniotic shunting to no fetal intervention. RESULTS: Of the 111 fetuses with severe LUTO that were included in the analysis, fetal cystoscopy was performed in 34, vesicoamniotic shunting was performed in 16 and there was no fetal intervention in 61. Gestational age at diagnosis, method of fetal intervention and cause of bladder obstruction were associated with prognosis. In multivariate analysis and after adjustment for potential confounders (considering all causes of LUTO) the overall probability of survival was significantly higher with fetal cystoscopy and vesicoamniotic shunting when compared to no intervention (adjusted relative risk (ARR), 1.86 (95% CI, 1.01-3.42; P = 0.048) and ARR, 1.73 (95% CI, 1.01-3.08; P = 0.04) respectively). A clear trend for normal renal function was present in the fetal cystoscopy group (ARR, 1.73 (95% CI, 0.97-3.08; P = 0.06)) but was not observed in the vesicoamniotic shunt group (ARR, 1.16 (95% CI, 0.86-1.55; P = 0.33)). In cases in which there was a postnatal diagnosis of posterior urethral valves, fetal cystoscopy was effective in improving both the 6-month survival rate and renal function (ARR, 4.10 (95% CI, 1.75-9.62; P < 0.01) and 2.66 (95% CI, 1.25-5.70; P = 0.01) respectively) while vesicoamniotic shunting was associated only with an improvement in the 6-month survival rate (ARR, 3.76 (95% CI, 1.42-9.97; P < 0.01)) with no effect on renal function (ARR, 1.03 (95% CI, 0.49-2.17, P = 0.93)). CONCLUSION: Fetal cystoscopy and vesicoamniotic shunting improve the 6-month survival rate in cases of severe LUTO. However, only fetal cystoscopy may prevent impairment of renal function in fetuses with posterior urethral valves. Our data support the idea of performing a subsequent randomized controlled trial to compare the effectiveness of fetal cystoscopy vs vesicoamniotic shunting for severe fetal LUTO.

Fetal bladder outflow obstruction: Interventions, outcomes and management uncertainties.

Fetal lower urinary tract obstruction (LUTO) is classically based on prenatal ultrasound identification of a dilated/ thick-walled bladder, bilateral hydronephrosis, dilated ureters and a dilated posterior urethra (also known as the "keyhole sign") in a male fetus. Although the most common underlying diagnosis is posterior urethral valves, the prenatal appearance may be similar with urethral atresia or stenosis, the Prune-Belly Syndrome, or even a cloacal anomaly in a female. These conditions form part of the Congenital Anomalies of Kidney and Urinary Tract (CAKUT) spectrum, which is the commonest cause of end-stage renal disease in children. Although it is difficult to predict postnatal renal function from the prenatal appearance, studies have recently identified predictive features (based on ultrasound findings and fetal biochemistry), and established staging systems to assist with counselling, and, where indicated, patient selection for in-utero intervention. Current in-utero therapy includes amnio-infusion, vesico-amniotic shunting, and fetal cystoscopy with valve ablation or urethral stenting. Postnatal survival and renal functional outcomes, complications and management uncertainties are described, highlighting areas of future development.

Report on The Society for Fetal Urology panel discussion on the selection criteria and intervention for fetal bladder outlet obstruction.

INTRODUCTION: The Society for Fetal Urology panel section at the 2016 Fall Congress featured a multidisciplinary discussion on appropriate patient selection, the conservative versus surgical management, and postnatal renal outcome of fetuses with lower urinary tract obstruction (LUTO). SELECTION CRITERIA FOR INTERVENTION: Rodrigo Ruano shared his experience of prenatal intervention, presenting the outcome of 111 fetuses with severe LUTO treated with vesicoamniotic shunting (VAS) (n = 16), cystoscopy (n = 34) or no intervention (n = 61) in a non-randomized series. Multivariate analysis at the 6-month follow-up suggested a significantly higher probability of survival with fetal intervention versus no intervention. A clear trend for normal renal function was present in the fetal cystoscopy group, but not in the VAS group. In cases in which there was a postnatal diagnosis of posterior urethral valves (n = 57), fetal cystoscopy was effective in improving both the 6-month survival rate and renal function, while VAS was associated with an improvement in the 6-month survival rate. In an attempt to better define which fetuses would benefit from intervention, Michael Braun explained the proposed LUTO classification system that incorporates: (1) fetal urinary biomarkers of renal injury; (2) amniotic fluid levels as a surrogate for the severity of obstruction; and (3) imaging studies to identify signs of renal dysplastic or cystic changes. Intervention was not recommended in patients at low risk of either renal disease or pulmonary hypoplasia (Stage 1). Vesicoamniotic shunting was performed in patients at high risk of either progressive renal injury or pulmonary hypoplasia without evidence of severe pre-existing renal damage (Stage 2). For those patients, who at the time of evaluation had evidence of severe renal disease (Stage 3), fetal intervention was individualized and often based on bladder capacity and bladder refilling after vesicocentesis. He went on to present the nephrologic outcome of fetuses managed over the last 3 years utilizing the selection criteria. Craig Peters supported the concept of selective criteria and discussed the cautious viewpoint, namely: (1) the procedure may be unnecessary, as it is possible for patients to do well, in spite of severe prenatal obstruction; and (2) the risk of giving partial treatment by allowing the baby to survive to delivery with the daunting postnatal journey of renal and pulmonary insufficiency. CONCLUSION: Standardized patient selection utilizing a staging system is undoubtedly the way forward and will enable comparable long-term renal and bladder functional outcome studies.

Fetal bladder outlet obstruction: Embryopathology, in utero intervention and outcome.

Fetal bladder outlet obstruction (BOO), most commonly caused by posterior urethral valves (PUV), remains a challenging and multi-faceted condition. Evolving techniques, and refinement in ultrasound, optics and instrumentation, have increased our rate of prenatal diagnosis, and enabled valve ablation not only in smaller newborns, but also in fetuses. Long-term outcome studies have raised our awareness of the silent damage caused by bladder dysfunction and polyuria and encouraged their proactive management. In spite of our best efforts, the proportion of boys with PUV who progress to chronic and end-stage renal disease (ESRD) has not changed in the last 25 years. Evidence suggests a reduction in perinatal mortality following prenatal intervention, probably resulting from amelioration of oligohydramnios at the crucial time of lung development between 16 and 28 weeks' gestation, but no improvement in postnatal renal outcome. There are no bladder functional outcome studies in patients who have undergone prenatal intervention and hence the long-term effect of in utero defunctionalisation of the bladder is not known. This aim of this review is to revisit the embryopathology of fetal BOO, in particular the renal and bladder structural and functional changes that occur with in utero obstruction. The effect of earlier prenatal diagnosis, and therapy, on postnatal outcome is also explored and compared with outcomes published for traditional postnatal treatment.