Infertility

REVIEWING THE LITERATURE News and Views from the Literature Pediatric Urology Management Alternatives for Vesicoureteral Reflux Reviewed by Ellen Shapiro, MD, FACS, FAAP Department of Urology, New York University School of Medicine, New York, NY [Rev Urol. 2002;4(2):100–101] © 2002 MedReviews, LLC he treatment of vesicoureteral reflux continues to evolve. The following articles provide different approaches to the treatment of reflux and are timely, especially since Deflux, an injectable treatment, has recently been approved by the U.S. Food and Drug Administration. T Changing Concepts Concerning the Management of Vesicoureteral Reflux Herndon CD, DeCambre M, McKenna PH. J Urol. 2001;166:1439–1443. This study provides compelling evidence that pelvic floor dysfunction has a fundamental role in the pathogenesis of reflux. The authors propose aggressive treatment of dysfunctional voiding patterns as an important step in the diminution of recurrent urinary tract infections and the 100 VOL. 4 NO. 2 2002 REVIEWS IN UROLOGY ultimate resolution of reflux. They performed voiding cystourethrograms (VCUGs), renal sonogram, uroflowmetry with surface electromyography (EMG), and post-void residual (PVR) urine (defined as greater than 20% of predicted bladder volume) on every child presenting with urinary frequency, urgency, urinary tract infection, and diurnal enuresis. They enrolled only cases of voiding dysfunction and reflux. The study group was composed of 49 girls and 4 boys, ages 4 to 13 (average 8.8 years). There were 72 kidneys with grade 1–2 (48 [67%]) or high-grade 3–5 (24 [33%]) reflux. Reflux was bilateral in 19 and unilateral in 34. The patients’ presenting symptoms included nocturnal enuresis (38%), diurnal enuresis (64%), encopresis (30%), constipation (23%), and urinary tract infection (64%). All patients were placed on prophylactic antibiotics, and none were placed on anticholinergic medications. A bowel regimen for constipation was used when indicated. A VCUG was repeated in 1 year. Patients with voiding dysfunction entered into a previously described pelvic floor retraining program.1 EMG pads were placed on the perineum, and a commercially available biofeedback program was used for 1 hour. Anticholinergic agents were given to children who were refractory to medical regimens and biofeedback training. The mean follow-up period was 24 months. Four voiding patterns were identified, including staccato with no residual urine in 11%, staccato with increased PVR in 10%, flattened flow patterns with no PVR in 28%, and flattened flow pattern with increased PVR in 51%. An elevated PVR was found in 88% of the patients with high-grade reflux. Surgery was recommended for breakthrough urinary tract infections or increasing reflux. A breakthrough infection occurred in 5 patients (10%). One of these patients had res- Pediatric Urology olution of their reflux and 1 had only grade 1 reflux and was observed without surgery. Two patients did not want to undergo surgery and continued with their biofeedback training. Therefore, reimplantation surgery was performed in only 1 patient (2%). Resolution of reflux occurred in 25 ureters. Of those, 18 had low-grade reflux, whereas 7 had high-grade reflux, including 2 older patients with a chronic history of high-grade reflux. The average time to resolution was about 8 months, and the average age was 9.2 years. Patient age, uroflow patterns, voiding symptoms, and reflux history did not predict the resolution of reflux. Five patients with enuresis showed no improvement on biofeedback training, and oxybutynin chloride was started in 3 of those 5, with improvement seen in only 2 of these patients. Over 24 months, the primary author noted a 90% decrease in his reflux surgery. These authors observed that reflux resolution in their study approximated that of patients reported without known voiding dysfunction. They caution about the use of oxybutynin and recommend it only for patients with a small bladder capacity and low PVRs. Patients with high-grade reflux and a large PVR would most likely improve with double voiding. Because reimplantation surgery is usually recommended when there are recurrent urinary tract infections, the primary goal in these children should be to address the urinary tract infections, which are most commonly due to voiding dysfunction. Long-Term Follow-Up of Children Treated with Dextranomer/Hyaluronic Acid Copolymer for Vesicoureteral Reflux Lackgren G, Wahlin N, Skoldenberg E, Stenberg A. J Urol. 2001;166:1887–1892. This article presents the experience from Sweden with the use of dextranomer/hyaluronic acid copolymer or Deflux (Q-Med, Uppsala, Sweden). They assessed the long-term efficacy and safety of this product. Dextranomer/hyaluronic acid copolymer is a biodegradable material. Hydrolysis of the dextranomer microspheres has been identified as the likely cause for the decrease in implant volume.2 Because the microspheres constitute 50% of the volume of Deflux, substantial decreases in volume after implantation may be anticipated. However, in animal studies, ingrowth of collagen between the microspheres appears to stabilize the implant volume, and the 12-month volume reduction in rates was only 23%.2 This is important, because other agents, such as bovine collagen, are not durable and therefore lack longterm efficacy. Children, ages 1 to 15 years with vesicoureteral reflux were enrolled in this study. Of the 221 patients studied, there were 72 boys and 149 girls (mean age 4.7 years) who underwent cystoscopy with implantation of Deflux. Injections were performed using a 10-Fr Stortz cystoscope and a 3.5-Fr needle. All patients were given antibiotics. Most (94%) had grade 3 or 4 reflux, and 334 ureters were treated with an injection volume of 0.4 to 1.2 cc (mean 0.6 cc/ureter). A VCUG was performed at 3 and 12 months post-operatively. A renal sonogram was performed at 1 day and 1 month post-operatively. If necessary, a patient could undergo two additional injections before being considered for surgery. Sixty-seven patients received two injections, and 8 received three injections. The follow-up period was 2–7.5 years (mean 5 years). At the time of the last VCUG, 151 (68%) showed a satisfactory response (bilateral grade 1 or less), and 27 had only grade 2. Almost all (81%) had no dilating reflux (defined as less than grade 3). Only 27 patients (12%) underwent open surgery, and no technical difficulties were encountered. There were no gender differences and no difference in the grade of reflux in the surgical group. This low risk for recurrence of reflux was reported in those patients studied up to 5 years following treatment. Long-term follow-up in 49 patients at 2.5 years post-operatively showed that if there was no reflux at 3 and 12 months, then 96% of these patients had no reflux on the VCUG at that time. Response rate varied with reflux at baseline. Those patients with grade 3 had a 73% response rate; those with grade 4 had a response rate of 59%. Of 162 ureters with no reflux after 3 months, grade 3 or greater was seen in 14 (8%) long-term. Twenty percent (44/221) of patients had voiding dysfunction prior to endoscopic treatment. Of those patients, 77% had a favorable outcome, and most needed only one injection. Nineteen patients (8%) developed urinary tract infections (18 girls and 1 boy). Only 1 of 19 patients developed a urinary tract infection associated with the cystoscopy and injection. Almost half (8 of 19) had voiding dysfunction and developed pyelonephritis. Seven children had grade 3 or greater reflux and 3 of 7 underwent open surgery. There were 11 lower tract infections, and 6 patients had reflux on their last VCUG. On the post-operative renal sonogram performed at 24 hours, 4 patients had slight dilation, which did not progress. This study shows that endoscopic correction of reflux using Deflux is safe and durable in the long term, even when voiding dysfunction is present. However, one third of patients require more than one procedure. References 1. 2. McKenna PH, Herndon CD, Connery S, et al. Pelvic floor muscle retraining for pediatric voiding dysfunction using interactive computer games. J Urol. 1999;162:1056–1062. Steinberg A, Larsson E, Lindholm A, et al. Injectable dextranomer-based implant: histopathology, volume changes and DNA analysis. Scand J Urol Nephrol. 1999;33:355–361. VOL. 4 NO. 2 2002 REVIEWS IN UROLOGY 101 Infertility Infertility Timing of Sperm Retrieval in ICSI-IVF Reviewed by Jacob Rajfer, MD University of California at Los Angeles, Los Angeles, CA [Rev Urol. 2002;4(2):102] © 2002 MedReviews, LLC Timing of Testicular Sperm Retrieval Procedures and In Vitro FertilizationIntracytoplasmic Sperm Injection Outcome Levran D, Ginath S, Farhi J, et al. Fert Steril. 2001;76:380–383. T 102 oday, it is very common for testicular sperm to be utilized for ICSI (intracytoplasmic sperm injection) combined with in-vitro fertilization (IVF), particular- VOL. 4 NO. 2 2002 REVIEWS IN UROLOGY ly for a male partner who may have either obstructive (OA) or non-obstructive azoospermia (NOA). In both OA and NOA, testicular sperm can be harvested by aspiration of sperm from the testis (TESA) or by extraction (biopsy) of sperm from the testis (TESE). Because sperm have a finite life span, current protocols call for the sperm to be retrieved on the same day as the retrieval of the ova from the partner. This minimizes the time both sperm and egg are being kept alive in vitro before fertilization occurs with ICSI. However, in certain instances this may present a scheduling conflict. For example, the physician (commonly the urologist) may not be able to clear his schedule to accommodate the sperm aspiration procedure that day. What if there were more than a window of a few hours to harvest the sperm? To help answer this question, Levran and associates performed sperm retrieval (TESA and/or TESE) either on the day of or the day before ovum retrieval and ICSI and found that there was no difference in motile spermatozoa obtained, fertilization rate, and clinical pregnancy rate between the two groups, suggesting that sperm retrieval can be performed on the day before ova retrieval without compromising success.