Marcello Cocuzza

Clinical relevance of oxidative stress and sperm chromatin damage in male infertility: an evidence based analysis

Oxidative stress (OS) in the reproductive tract is now a real entity and concern due to the potential harmful effects of high levels of reactive oxygen species (ROS) on sperm number, motility, quality, and function including damage to sperm nuclear DNA. Evaluation of OS related damage to non-functional sperm is highly relevant as intracytoplasmic sperm injection (ICSI) technique, an effective therapy for severe male factor infertility, bypasses the majority of reproductive tract deficiencies. Despite the controversial findings in the existing literature, there is now enough evidence to show that sperm DNA damage is detrimental to reproductive outcomes. In addition, spermatozoa of infertile men are suggested to carry more DNA damage than do the spermatozoa from fertile men. Besides impairment of fertility such damage is likely to increase the transmission of genetic diseases during the assisted reproductive procedures. Standardization of protocols to assess reactive oxygen species and DNA damage is very important in introducing these tests in such clinical practice. Thus evaluation of seminal ROS levels and extent of sperm DNA damage especially in an infertile male may help develop new therapeutic strategies and improve success of assisted reproductive techniques (ART).

Age-related increase of reactive oxygen species in neat semen in healthy fertile men.

OBJECTIVESnThe effects of advancing paternal age on the male reproductive system are well known, but its effects on fecundity remain controversial. Although oxidative stress is associated with poor semen quality and function, a relationship with advancing male age has not been established. The objective of this study was to analyze the relationship between male age and seminal reactive oxygen species (ROS) levels in men presenting for voluntary sterilization.nnnMETHODSnWe prospectively evaluated 98 fertile men who were candidates for vasectomy. These were divided into 2 age groups: less than 40 years (n = 78) and 40 or more years (n = 20). We used 46 infertile patients as positive controls. Standard semen analysis, seminal leukocyte count and ROS levels were measured in all samples. Fertile men with leukocytospermia were excluded.nnnRESULTSnThe mean age of the men was 35.1 +/- 5.6 years. Men 40 years and older had significantly higher ROS levels compared with younger men (P <0.001). We observed a positive correlation between seminal ROS levels and age (r = 0.20; P = 0.040). In addition, ROS was negatively correlated with sperm concentration (r = -0.48; P <0.001) and motility (r = -0.21; P = 0.030).nnnCONCLUSIONSnReactive oxygen species levels are significant higher in seminal ejaculates of healthy fertile men older than 40 years. ROS levels in whole ejaculate are significantly correlated to age among fertile men. Because ROS are clearly implicated in the pathogenesis of male infertility, these data suggest that delayed fatherhood may reduce the chances of pregnancy as men become progressively less fertile with age.

Should seminal oxidative stress measurement be offered routinely to men presenting for infertility evaluation

OBJECTIVEnTo determine if seminal oxidative stress measurement should be offered routinely to men presenting for infertility evaluation.nnnMETHODSnWe performed an extensive review of the English-language literature by searching MEDLINE for studies published between 1980 and 2007.nnnRESULTSnResearch conducted during the last decade has provided growing support for the concept that excessive production of reactive oxygen species (ROS) is related to abnormal semen parameters and sperm damage. Routine semen analysis remains the backbone of clinical evaluation in male infertility, but determining the levels and sources of excessive ROS generation in semen is currently not included in the routine evaluation of subfertile men. However, the diagnostic and prognostic capabilities of seminal oxidative stress measurement exceed the capabilities of conventional sperm quality tests. An oxidative stress test may accurately discriminate between fertile and infertile men and identify those with a clinical diagnosis of male factor infertility who are likely to initiate a pregnancy if they are followed over a period of time. In addition, such a test can help select subgroups of patients with infertility in which oxidative stress is an important factor and those who may benefit from antioxidant supplementation. Although consensus is still required about the type and dosage of antioxidants to be used, rationale and evidence exist supporting their use in infertile men with elevated oxidative stress.nnnCONCLUSIONnConsensus is growing about the clinical utility of seminal oxidative stress testing in infertility clinics, but standardization of protocols to measure ROS is crucial before introducing these tests into routine clinical practice.

Combined retrograde flexible ureteroscopic lithotripsy with holmium YAG laser for renal calculi associated with ipsilateral ureteral stones.

PURPOSEnThe purpose of this study was to evaluate the effectiveness of combined ureteroscopic holmium YAG lithotripsy for renal calculi associated with ipsilateral ureteral stones.nnnMATERIALS AND METHODSnBetween August 2002 and March 2007, retrograde flexible ureteroscopic stone treatment was attempted in 351 cases. Indication for treatment was concurrent symptomatic ureteral stones in 63 patients (group I). Additional operative time and perioperative complication rates were compared to a group of 39 patients submitted to ureteroscopic treatment for ureteral calculi exclusively (group II).nnnRESULTSnMean ureteral stone size was 8.0 +/- 2.6 mm and 8.1 +/- 3.4 mm for groups I and II, respectively. Mean operative time for group I was 67.9 +/- 29.5 minutes and for group 2 was 49.3 +/- 13.2 minutes (p < 0.001). Flexible ureteroscopic therapy for renal calculi increased 18 minutes in the mean operative time. The overall complication rate was 3.1% and 2.5% for groups I and II, respectively (p = 0.87). Mean renal stone size was 10.7 +/- 6.4 mm, overall stone free rate in group I was 81%. However, considering only patients with renal stones smaller than 15 mm, the stone free rate was 88%. Successful treatment occurred in 81% of patients presenting lower pole stones, but only 76% of patients with multiple renal stones became stone free. As expected, stone free rate showed a significant negative correlation with renal stone size (p = 0.03; r = -0.36). Logistic regression model indicated an independent association of renal stones smaller than 15 mm and stone free rate (OR = 13.5; p = 0.01).nnnCONCLUSIONnCombined ureteroscopic treatment for ureteral and ipsilateral renal calculi is a safe and attractive option for patients presenting for symptomatic ureteral stone and ipsilateral renal calculi smaller than 15 mm.

MP66-04 GONADAL FUNCTION AND REPRODUCTIVE SYSTEM ANATOMY IN POST PUBERAL PRUNE BELLY SYNDROME PATIENTS

INTRODUCTION AND OBJECTIVES: Morrison’s survey of SPU members reported no clear consensus in managing peri-operative pain in pediatric patients undergoing common urological procedures. We posit that non-narcotic analgesia allows withholding narcotic use following simple urologic surgery in out-patient surgery in most patients. METHODS: We prospectively tracked analgesic use and pain scales of patients undergoing outpatient penile (non-hypospadias) or groin surgery (hernia, orchidopexy). Parents marked an analgesic usage form and Wong-Baker FACES pain scale on the day of surgery (DOS) and post-operative day 1 (POD1). Patients received a caudal nerve block, unless contraindicated or refused by parents, or a penile block. Postoperative analgesics were either non-narcotic agents or narcotics prescribed at surgeon’s discretion. Descriptive statistics, contingency table analyses, and t-test were performed. RESULTS: 249 male patients, median age 36 mo (2-216mo) underwent penile (64%) or groin (36%) surgery. Caudal (92) or local block (147) was used in 96% of cases. Narcotics prescribed in 152 (61%) was associated with older age (74mo vs 47mo; p 1⁄40.0002). Overall, no difference in analgesic use was noted (p1⁄4NS) on DOS (72%) and POD (62%) and were not affected by surgery or block type. Among patients prescribed narcotics, 76% used any analgesic on DOS and 66% on POD 1 (p1⁄4NS); narcotic use on DOS (91 cases 65 took 1 dose) declined on POD1 (57; p1⁄40.0001) and was unaffected by surgery type or block type. Analgesic type used was similar between surgery types and between DOS and POD1 regardless of block used. Among patients not prescribed narcotics, 72% took 1+ doses of analgesics on DOS which declined to 59% on POD 1 (p1⁄4NS); usage was similar based on surgery type and from DOS to POD1 for both surgery and block types. Pain scale differences were not significant on DOS between non-narcotics and narcotic users (3.2 v 3.6, p1⁄4NS) but were on POD 1 (2.8 v 3.6, p1⁄40.0003). Pain significantly decreased for those using non-narcotics between DOS and POD1 (p1⁄40.004) but not for those using narcotics, perhaps due to pain perception in older children. CONCLUSIONS: Narcotic availability leads to its usage following uncomplicated urologic surgery. Given the efficacy of nonnarcotic analgesics, and the associated costs and potential side effects, prescribing narcotics should be highly selective.