Pregnancy rate after vasectomy reversal in a contemporary series: influence of smoking, semen quality and post-surgical use of assisted reproductive techniques

Study Type – Outcomes (cohort series) Level of Evidence 2b What's known on the subject? and What does the study add? Microsurgical vasectomy reversal is an effective and cost‐effective method of reinstating fertility in a man who has previously had a vasectomy. The current literature indicates that the success rate (i.e. potency and pregnancy rates) are dependent primarily on the time elapsed since vasectomy and the age of the female partner. Using a multivariate Cox regression model, evaluation of the influence of preoperative data (including smoking) and semen parameters indicates a significant influence of post‐surgical sperm motility only, on time to first pregnancy. The use of assisted reproductive techniques, when natural pregnancy failed, was successful in ≈50% of couples who attempted this procedure and accounted for an absolute increase in pregnancy rate of 14%.

OBJECTIVE

• ? To determine the influence of smoking, postoperative semen characteristics and the use of an assisted reproductive technique (ART) on pregnancy rate in a contemporary series of men undergoing vasectomy reversal.

PATIENTS AND METHODS

• ? Between January 2002 and January 2009, 186 vasectomy reversals were performed. Of the 171 patients who could be contacted for follow‐up, 162 attempted pregnancy and constitute the study group.
• ? Semen analysis was performed 3 months after the procedure and at subsequent 3‐monthly intervals.
• ? Patient characteristics and surgical information were obtained from a computerized database, and follow‐up data were collected by telephone interview.
• ? A multivariate Cox regression model was used to discern possible prognosticators with respect to pregnancy outcome.

RESULTS

• ? The overall patency rate was 91.4%, with a natural pregnancy rate of 44.4% and a subsequent 14.2% of patients conceiving using a ARTs resulting in a total pregnancy rate of 58.6%. Multiple pregnancies were obtained by 20.4% of couples.
• ? Smoking of the male or female partner did not influence the probability of conception.
• ? In a multivariate model that included, among other factors, time since vasectomy, female age and semen characteristics, only sperm motility was significantly related to natural pregnancy outcome.
• ? The probability of obtaining a natural pregnancy within 2 years after surgery is 53% for men with sperm motility >20% (WHO a+b) compared to 19% for men with sperm motility <5% (P= 0.003).

CONCLUSIONS

• ? A clear and significant association between sperm motility and the probability of conception was found, whereas smoking, female age and time since vasectomy appeared to have no influence on pregnancy outcome in this patient cohort.
• ? The use of ARTs accounted for an absolute increase in pregnancy rate of 14.2%.

     

UK practice regarding reversal of vasectomy 2001-2010: relevance to best contemporary patient management

Study Type – Practice trends (survey) Level of Evidence 2c What's known on the subject? and What does the study add? Approximately 6% of men who have had a vasectomy subsequently decide to have it reversed. For such men there are various options available, including vasal reconstruction, surgical sperm retrieval with assisted reproductive techniques, use of donated sperm or adoption. The decision‐making process with regard to the most appropriate management is challenging and the urologist requires both an intimate knowledge of the advantages and disadvantages of each of the available options and the opportunity to counsel a couple appropriately. The study confirms that patient management after previous vasectomy is a complex process, demanding detailed knowledge about the availability and outcomes of alternatives to vasectomy reversal. It recommends that couples should not be seen by urologists with diverse interests but by those with appropriate knowledge of all of the factors influencing outcome and the available management options and their costs. Urologists should also have appropriate facilities to offer intra‐operative demonstration of and, potentially, storage of sperm.

OBJECTIVES

• ? To review the management of men presenting for reversal of vasectomy amongst consultant members of the British Association of Urological Surgeons (BAUS) between 2001 and 2010.
• ? To make recommendations for contemporary practice.

SUBJECTS AND METHODS

• ? Three consecutive questionnaire‐based surveys were undertaken by BAUS consultant members in 2001, 2005 and 2010.
• ? Standard questionnaires were sent on each occasion asking urologists about their counselling of couples regarding options in achieving a conception, expectation of outcome from reconstructive surgery and the techniques of vaso‐vasostomy used.
• ? In 2005 additional information was obtained about the availability of fertility treatments and sub‐specialization of the urologist and in 2010 about the eligibility criteria for in‐vitro fertilization (IVF) treatment and synchronous sperm retrieval.

RESULTS

• ? Overall there was a 47% response rate with >80% of respondents still performing vaso‐vasostomy.
• ? More than 75% of respondents were doing <15 procedures a year and <50% of respondents counselled couples about other management options.
• ? Only 41% gave their personalized outcomes from vaso‐vasostomy, whilst >80% were using some form of magnification intra‐operatively.
• ? Members of the BAUS section of andrology were more likely to discuss options for becoming a parent and criteria for IVF treatment, to present their individualized outcomes from vaso‐vasotomy and to carry out >15 procedures a year than urologists with no andrological affiliation.

CONCLUSIONS

• ? Patient management after previous vasectomy is a complex process necessitating detailed knowledge concerning the availability and outcomes of alternatives to vaso‐vasostomy.
• ? Couples should not be seen by urologists with diverse interests but by those with appropriate knowledge of all of the factors influencing outcome.
• ? Vaso‐vasostomy should no longer be seen as a procedure within the remit of any adequately trained urologist but as one option to be considered by a sub‐specialist with access to appropriate micro‐surgical training and assisted reproductive technologies.

     

Fulguration of the lumen does not improve vasectomy sterilization rates

OBJECTIVES

To assess the effect of adding lumen diathermy fulguration to our standard technique of vas ligation with polyglactin 910 (Vicryl^TM, Ethicon, Sommerville, NJ, USA) excision and fascial interposition, in an attempt to improve our sterilization rates. We previously reported the effect of changing suture material on vasectomy success rates; 3005 post‐vasectomy semen analyses (PVSA) revealed a decrease in sterilization rates after surgery on changing from chromic catgut to polyglactin 910.

PATIENTS AND METHODS

We retrospectively reviewed PVSA undertaken for vasectomies performed by urological surgeons at the Mid‐Yorkshire NHS Trust for 18 months from September 2005 to February 2007.

RESULTS

There were 592 vasectomies in all; the age distribution of patients between the groups treated with the standard and new method was similar. Overall, 166 patients (28%) failed to provide two semen samples as instructed, and so were excluded from further analyses. Sterility was achieved in 367 patients (86%); a further 28 (7%) have indeterminate analyses to date, with one of the last two PVSAs showing sperm, with the PVSA of 32 (7%) patients showing persisting sperm. For the eight surgeons reviewed the sterility rates were broadly similar.

CONCLUSIONS

The introduction of diathermy fulguration of the lumen has not improved vasectomy sterilization rates, with up to 14% having sperm on PVSA.     

Vasectomy reversal with ultrasonography‐guided spermatic cord block

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Vasectomy reversal is often performed in general or neuraxial anaesthesia. Even though the site of vasectomy reversal is easily amenable to regional/local anaesthesia, spermatic cord blocks are rarely applied because of their risk of vascular damage within the spermatic cord. Recently, we described the technique of ultrasonography (US)‐guided spermatic cord block for scrotal surgery, which, thanks to the US guidance, at the same time avoids the risk of vascular damage of blindly performed injections and the risks of general and neuraxial anaesthesia. Vasectomy reversal can easily be done in regional anaesthesia with the newly described technique of US‐guided spermatic cord block without the risks of vascular damage by a blindly performed injection and the risks of standard general and neuraxial anaesthesia. In addition, this technique grants long‐lasting postoperative pain relief and patients recover more quickly. Microsurgical conditions are excellent and patient satisfaction is high. Thanks to these advantages, more patients undergoing vasectomy reversal might avoid general or neuraxial anaesthesia.

OBJECTIVE

• ? To assess the success rate, microsurgical conditions, postoperative recovery, complications and patient satisfaction of ultrasonography (US)‐guided spermatic cord block in patients undergoing microscopic vasectomy reversal and to compare them to a control group with general or neuraxial anaesthesia.

PATIENTS AND METHODS

• ? The present study comprised a prospective series of 10 consecutive patients undergoing US‐guided spermatic cord block for microscopic vasectomy reversal.
• ? The cohort was compared with 10 patients in a historical control group with general or neuraxial anaesthesia.

RESULTS

• ? Nineteen of 20 (95%) blocks were successful, defined as no pain >3 on the Visual Analogue Scale (VAS), no additional analgesics and/or no conversion to general anaesthesia. Median pain was 0 on the VAS (range 0–5). Additional analgesics were requested in one (5%) block, and there was no conversion to general anaesthesia.
• ? Microsurgical conditions were excellent.
• ? In the spermatic cord block vs general/neuraxial anaesthesia groups, median times (range) between surgery and first postoperative analgesics, alimentation, mobilization and hospital discharge were 12 (2–14) vs 3 (1–6), 1 (0.25–3) vs 4 (3–6), 2 (1–3) vs 6 (3–10), and 4 (3–11) vs 8.5 (6–22) h, respectively.
• ? No complications were reported after the spermatic cord block.
• ? Patient satisfaction was excellent.

CONCLUSIONS

• ? US‐guided spermatic cord block for microscopic vasectomy reversal is highly successful and provides long‐lasting perioperative analgesia.
• ? Times to alimentation, mobilization and hospital discharge are shorter under US‐guided spermatic cord block than under general/neuraxial anaesthesia.
• ? Additional anaesthetic pain management might, however, be required unexpectedly with US‐guided spermatic cord block.

     

Outcomes of the management of post-chemotherapy retroperitoneal lymph node dissection-associated anejaculation

Study Type – Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Modern surgical techniques have allowed preservation of fertility in most patients after post‐chemotherapy retroperitoneal lymph node dissection (PC‐RPLND), but some patients still have infertility after surgery. We reviewed our experience treating infertility in 26 men after PC‐RPLND. Using a structured clinical pathway we obtained sperm in 81% of men for use in assisted reproduction.

OBJECTIVE

• ? To evaluate the effectiveness of a clinical pathway on sperm retrieval outcomes in patients presenting with infertility after post‐chemotherapy (PC) retroperitoneal lymph node dissection (RPLND).

PATIENTS AND METHODS

• ? We carried out a retrospective review of patients with advanced testicular cancer, presenting with infertility after PC‐RPLND in a large reproductive urology practice.
• ? We implemented a clinical pathway where pseudoephedrine was first administered. If this medication failed, electroejaculation (EEJ) and/or testicular sperm extraction (TESE) was carried out.
• ? The primary outcome was retrieval of sperm for use in assisted reproduction.

RESULTS

• ? Four men had retrograde ejaculation, of whom two converted to antegrade ejaculation with medical therapy.
• ? In all, 22 patients had failure of emission (FOE) and, of these, no patient converted to antegrade ejaculation with medication.
• ? In patients with FOE, sperm was found in 15/20 of those experiencing a successful EEJ.
• ? Seven patients underwent TESE for azoospermia on EEJ or no ejaculate on EEJ, three of whom had sperm found on TESE.
• ? Sperm was found for assisted reproduction in 81% (21/26) patients.

CONCLUSIONS

• ? There appears to be no role for the use of pseudoephedrine therapy in patients with FOE after PC‐RPLND.
• ? The use of a structured clinical pathway may optimize patient care.

     

Biochemical outcome after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy: 12 years of experience

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Biochemical control from series in which radical prostatectomy is performed for patients with unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal. The treatment regimen of HDR brachytherapy and external beam radiotherapy is a safe and very effective treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity.

OBJECTIVE

• ? To investigate the long‐term oncological outcome, during the PSA era, of patients with prostate cancer who were treated using high‐dose‐rate (HDR) brachy therapy (BT) combined with external beam radiation therapy (EBRT).

PATIENTS AND METHODS

• ? From June 1998 to April 2007, 313 patients with localized prostate cancer were treated with 46 Gy of EBRT to the pelvis with a HDR‐BT boost.
• ? The mean (median) follow‐up was 71 (68) months.
• ? Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, V.4.

RESULTS

• ? The 10‐year actuarial biochemical control was 100% for patients with no high‐risk criteria, 88% for patients with two intermediate‐risk criteria, 91% with one high‐risk criterion and 79% for patients with two to three high‐risk criteria (P= 0.004).
• ? The 10‐year cancer‐specific survival was 97% (standard deviation ±1%).
• ? The multivariate Cox regression analyses identified, Gleason score and T stage as independent prognostic factors for biochemical failure.
• ? Gleason score was the only factor to significantly affect distant metastases.
• ? Grade ≥3 late toxicity was not detected.

CONCLUSION

• ? The 10‐year results confirm the feasibility and effectiveness of EBRT with conformal HDR‐BT boost for patients with localised prostate cancer.

     

Clearance after vasectomy with a single semen sample containing < than 100 000 immotile sperm/mL: analysis of 1073 patients

Study Type – Diagnostic (non‐consecutive)
Level of Evidence 3b

OBJECTIVE

To evaluate the safety and efficacy of a new semen analysis protocol after vasectomy, where clearance is given to patients who provide a single semen sample with <100 000 immotile sperm/mL at ≥3 months after vasectomy.

PATIENTS AND METHODS

Between 1 July 2005 and 31 March 2008, 1073 men provided a first semen sample at ≥3 months after vasectomy. Semen was first evaluated on a wet‐slide preparation. Those samples with no (‘azoospermia’) or sporadic immotile spermatozoa could be cleared without further analysis. Samples with motile sperm were immediately labelled as potentially fertile, while those with a significant number of immotile sperm were re‐analysed using a Neubauer haemocytometer. All samples with <100 000 immotile sperm/mL were cleared.

RESULTS

Of men providing semen at 3 months after vasectomy, 96% could be cleared. No sperm were seen (‘azoospermia’) in 51.3% of samples, and 44.7% of samples contained <100 000 immotile sperm. No paternity has been reported in the cleared group after a follow‐up of at least 1 year.

CONCLUSIONS

A protocol stipulating that patients can be cleared after a single semen sample containing <100 000 immotile sperm/mL at ≥3 months after vasectomy is safe and dramatically reduces the number of men who cannot be cleared at 3 months after vasectomy.     

Cost-effectiveness and efficiency of shockwave lithotripsy vs flexible ureteroscopic holmium:yttrium-aluminium-garnet laser lithotripsy in the treatment of lower pole renal calculi

Study Type – Therapy (cost effectiveness) Level of Evidence 2b What’s known on the subject? and What does the study add? Stone management economics is a complex issue. FURS and SWL are recognised treatment option for lower pole kidney stones. There are paucity of data comparing cost implication and effectiveness of both treatment options. Both treatment modalities are equally efficacious. FURS incurred greater cost burden compared to SWL in the UK setting. In the present economic circumstance, clinicians should also consider cost‐impact, patient’s preference and specific clinical indication when counselling patients for treatment.

OBJECTIVE

• ? To compare the cost‐effectiveness and outcome efficiency of extracorporeal shockwave lithotripsy (SWL) vs intracorporeal flexible ureteroscopic laser lithotripsy (FURS) for lower pole renal calculi ≤20 mm.

PATIENTS AND METHODS

• ? Patients who had treatment for their radio‐opaque lower pole renal calculi were categorized into SWL and FURS group.
• ? The primary outcomes compared were: clinical success, stone‐free, retreatment and additional procedure rate, and perceived and actual costs.
• ? Clinical success was defined as stone‐free status or asymptomatic insignificant residual fragments <3 mm.
• ? Perceived cost was defined as the cost of procedure alone, and the actual cost included the cost of additional procedures as well as the overhead costs to result in clinical success.

RESULTS

• ? The FURS (n= 37) and SWL (n= 51) group were comparable with respect to sex, age, stone size and the presence of ureteric stent.
• ? The final treatment success rate (100% vs 100%), stone‐free rate (64.9% vs 58.8%), retreatment rate (16.2% vs 21.6%) and auxillary procedure rate (21.6% vs 7.8%) did not differ significantly.
• ? The mean perceived cost of each FURS and SWL procedure was similar (£249 vs £292, respectively); however, when all other costs were considered, the FURS group was significantly more costly (£2602 vs £426, P= 0.000; Mann–Whitney U‐test).

CONCLUSION

• ? SWL was efficacious and cost‐effective for the treatment of lower pole renal calculi ≤20 mm.

     

In the era of micro‐dissection sperm retrieval (m‐TESE) is an isolated testicular biopsy necessary in the management of men with non‐obstructive azoospermia?

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? There are a number of ways to retrieve sperm from the testis however there is no universal consensus as to which is the best approach. Furthermore, there is controversy as to whether a diagnostic biopsy has a role in management of non‐obstructive azoospermia (NOA). This study gives support to the growing consensus that micro‐dissection TESE (m‐TESE) is the optimum approach to retrieve sperm in patients with NOA even when previous attempts have failed. Moreover, it strongly suggests that histology is unreliable in determining success rates with m‐TESE and therefore isolated diagnostic biopsies should not be performed.

OBJECTIVES

• ? To assess the outcome of sperm retrieval using micro‐dissection‐TESE (m‐TESE) and simultaneous diagnostic biopsy in NOA to determine if the final definitive histology correlated with the outcome of sperm retrieval by m‐TESE in men with NOA.
• ? To determine if there was a correlation between FSH levels and positive sperm retrieval rates and assessed the success rate of m‐TESE as either a primary or a salvage procedure after previous negative sperm retrieval.
• ? The EAU guidelines (2010) recommend that in men with non obstructive azoospermia ‘a testicular biopsy is the best procedure to define the histological diagnosis and the possibility of finding sperm’. However, these guidelines do not identify which patients should have a diagnostic biopsy and if this biopsy should be performed as an isolated procedure or synchronously with sperm retrieval. It is also suggested that there is a correlation between the histological diagnosis and possibility of finding sperm on testis biopsy.

PATIENTS AND METHODS

• ? 100 men with NOA underwent a m‐TESE sperm retrieval between 2005 and 2010 at a single centre.
• ? All patients underwent hormonal analysis (serum FSH, Testosterone and LH levels) and genetic analyses after full counselling including; Y‐deletion, CF‐gene analysis and karyotype.
• ? Thirty five men had previously undergone unsuccessful TESA/TESE or diagnostic biopsy at other centres. All patients underwent synchronous sperm retrieval and biopsy of the testis, which was sent for histopathological examination on the day of an ICSI cycle or as an isolated procedure.

RESULTS

• ? Mean age of patients was 37.25 (range 29–56 years). The mean serum FSH levels in the Sertoli cell only, maturation arrest and hypospermatogenesis groups were 21.3 IU/L (2.8–75), 16.18 (1.6–67) and 14.17 IU/L (0.8–42.3) respectively. SR rates in the respective groups were 42.85%, 26.6% and 75.86% (P= 0.023). There were no post‐operative complications.
• ? In the 35 men who had previously undergone unsuccessful procedures elsewhere, the SR rates were 57.1%. The overall sperm retrieval rate was 50%. There was no correlation between SR and FSH levels (P= 0.28).

CONCLUSION

• ? M‐TESE should be considered the gold standard for retrieval of testicular sperm in NOA, even in cases where there has been previously unsuccessful attempts. FSH levels and histology cannot be used to predict the success of sperm retrieval. An isolated diagnostic testicular biopsy is not recommended in men with NOA, as a significant proportion of men undergoing m‐TESE will have successful a sperm retrieval irrespective of previous histology or previous unsuccessful surgery.

     

Maintenance therapy with bacillus Calmette-Guérin Connaught strain clearly prolongs recurrence-free survival following transurethral resection of bladder tumour for non-muscle-invasive bladder cancer

Study Type – Therapy (RCT) Level of Evidence 1b

OBJECTIVE

• ? To confirm the recurrence‐preventing efficacy and safety of 18‐month bacillus Calmette‐Guérin (BCG) maintenance therapy for non‐muscle‐invasive bladder cancer.

PATIENTS AND METHODS

• ? The enrolled patients had been diagnosed with recurrent or multiple non‐muscle‐invasive bladder cancer (stage Ta or T1) after complete transurethral resection of bladder tumours (TURBT).
• ? The patients were randomized into three treatment groups: a maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks as induction therapy, followed by three once‐weekly instillations at 3, 6, 12 and 18 months after initiation of the induction therapy), a non‐maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks) and an epirubicin group (epirubicin, 40 mg, intravesically instilled nine times). The primary endpoint was recurrence‐free survival (RFS).

RESULTS

• ? Efficacy analysis was performed for 115 of the full‐analysis‐set population of 116 eligible patients, including 41 maintenance group patients, 42 non‐maintenance group patients and 32 epirubicin group patients.
• ? At the 2‐year median point of the overall actual follow‐up period, the final cumulative RFS rates in the maintenance, non‐maintenance and epirubicin groups were 84.6%, 65.4% and 27.7%, respectively.
• ? The RFS following TURBT was significantly prolonged in the maintenance group compared with the non‐maintenance group (generalized Wilcoxon test, P= 0.0190).

CONCLUSION

• ? BCG maintenance therapy significantly prolonged the post‐TURBT RFS compared with BCG induction therapy alone or epirubicin intravesical therapy.

     

Tubeless vs standard percutaneous nephrolithotomy: a meta-analysis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? This study showed that tubeless PCNL could reduce hospital stay with little need for postoperative analgesia. This study discussed the clinical feasibility of tubeless PCNL, which is the tendency of PCNL. Our results are reliable by using veta‐analysis from individual studies.

OBJECTIVE

• ? To systematically review and compare tubeless percutaneous nephrolithotomy (PCNL) with standard PCNL.

MATERIALS AND METHODS

• ? We conducted a review of the English language literature on studies involving randomized controlled trials for PCNL. The studies chosen to be included in our review compared tubeless PCNL with standard PCNL and described the advantages of each in the outcomes.
• ? Two reviewers independently screened the studies for eligibility, evaluated their quality and extracted the data from the eligible studies, with confirmation by cross‐checking.
• ? Data were processed using Rev Man 5.0.

RESULTS

• ? Seven studies involving 1365 cases met the inclusion criteria, and these were included in the meta‐analysis.
• ? The patients' baseline characteristics were comparable in all the studies. By comparing the four common characteristics, we found no difference in efficacy between the two surgical approaches in terms of mean operation duration and postoperative haematocrit change (P > 0.05).
• ? We found that the mean analgesic requirement and number of days in hospital were lower for tubeless PCNL (P < 0.05).

CONCLUSIONS

• ? Our results show that tubeless PCNL is a good option in non‐complicated cases, with the advantages of reduced hospital stay and little need for postoperative analgesia. There was no difference between the two approaches in operation duration, or haematocrit change after surgery.
• ? As only few studies with small study populations were available, more high quality larger trials with longer follow‐up are recommended.

     

Is joint hypermobility associated with vesico‐ureteral reflux? An assessment of 50 patients

Study Type – Aetiology (individual cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Recent studies have already shown associations between generalized joint hypermobility (GJH) and voiding and defecation dysfunction and/or slow transit constipation. Changes in extracellular matrix composition in vesico‐ureteric junction of vesico‐ureteral reflux (VUR) patients were also observed previously. This study is the first to assess joint mobility as a parameter for connective tissue composition in vesico‐ureteral reflux. We convincingly demonstrate that VUR patients have significantly more hypermobile joints compared to controls and this provides a new angle to the intriguing subjects of development of VUR and susceptibility to VUR.

OBJECTIVE

• ? To assess whether there is an increased prevalence of joint hypermobility in patients with vesico‐ureteric reflux (VUR).

MATERIALS AND METHODS

• ? We studied 50 patients with primary VUR and matched controls drawn from a reference population.
• ? Joint mobility was assessed using the Bulbena hypermobility score.

RESULTS

• ? We identified significantly more patients with VUR with generalized joint hypermobility than controls (24% vs 6.7%, P= 0.007).

CONCLUSION

• ? Our findings confirm our clinical observation of an increased rate of joint hypermobility in patients with VUR. We speculate that an altered composition of the connective tissue may contribute to the severity of the (pre‐existing) VUR phenotype.

     

Association between obesity and alteration of sperm DNA integrity and mitochondrial activity

Study Type – Prognosis (cohort) Level of Evidence 3a What's known on the subject? and What does the study add? The relationship between high levels of BMI and changes in altered standard semen analysis parameters are described in the literature. However, the functional characteristics of the sperm are essential to complete the evaluation of male infertility. Thus, this study provides important information about the functionality of the sperm of men with different levels of BMI.

OBJECTIVE

• ? To assess the effect of obesity on semen analysis, sperm mitochondrial activity and DNA fragmentation.

MATERIALS AND METHODS

• ? A transversal study of 305 male patients, presenting for clinical evaluation, was carried out. The patients were divided into three groups according to body mass index (BMI) as follows: eutrophic (BMI < 25 kg/m², n= 82), overweight (BMI ≥ 25 kg/m² and <30, n= 187) and obese (BMI ≥ 30 kg/m², n= 36).
• ? The variables analysed were semen analysis, rate of sperm DNA fragmentation and sperm mitochondrial activity.
• ? Groups were compared using one‐way analysis of variance followed by a least significant difference post‐hoc test. A P‐value of <0.05 was considered to indicate statistical significance.

RESULTS

• ? No differences were observed in age, ejaculatory abstinence, ejaculate volume, sperm vitality, morphology or round cell and neutrophil count among the groups.
• ? The eutrophic group had a higher percentage of sperm with progressive motility (P= 0.001). Mitochondrial activity was lower in the obese group (P= 0.037) when compared to the eutrophic, and the percentage of sperm with DNA damage was higher in the obese group (P= 0.004) than the other two groups.

CONCLUSION

• ? Increased BMI values are associated with decreased mitochondrial activity and progressive motility and increased DNA fragmentation.

     

Open non‐microsurgical,laparoscopic or open microsurgical varicocelectomy for male infertility: a meta‐analysis of randomized controlled trials

Study Type – Therapy (systematic review) Level of Evidence 1a What's known on the subject? and What does the study add? There are several surgical techniques for the treatment of varicocele in infertile men, including open non‐microsurgical, laparoscopic and microsurgical varicocelectomy. It is currently unclear, however, which is the most beneficial method for patients. The present meta‐analysis found that microsurgical varicocelectomy is the most effective and least morbid method among the three varicocelectomy techniques for treating varicocele in infertile men.

OBJECTIVE

• ? To compare various techniques of open non‐microsurgical, laparoscopic or microsurgical varicocelectomy procedures to describe the best method for treating varicocele in infertile men.

PATIENTS AND METHODS

• ? We searched PubMed, Embase, the Cochrane Library, the Institute for Scientific Information (ISI) – Science Citation Index and the Chinese Biomedicine Literature Database up to June 2011. Only randomized controlled trials (RCTs) were included in the present study.
• ? The outcome measures assessed were pregnancy rate (primary), the incidence of recurrent varicocele, time to return to work, the incidence of postoperative hydrocele and operation duration (secondary).
• ? Two authors independently assessed the study quality and extracted data. All data were analysed using Review Manager (version 5.0).

RESULTS

• ? The present study included four randomized controlled trials comprising 1,015 patients in total.
• ? At the follow‐up endpoints, patients who had undergone microsurgery showed a significant advantage over those who had undergone open varicocelectomy in terms of pregnancy rate (odds ratio [OR]= 1.63, 95% confidence interval [CI]: 1.19–2.23].
• ? There was no significant difference between laparoscopic and open varicocelectomy (OR = 1.11, 95% CI: 0.65–1.88) or between microsurgery and laparoscopic varicocelectomy (OR = 1.37, 95% CI: 0.84–2.24).
• ? The incidences of recurrent varicocele and postoperative hydrocele were significantly lower after microsurgery than after laparoscopic or open varicocelectomy.
• ? The time to return to work after microsurgery and laparoscopic varicocelectomy was significantly shorter than that after open varicocelectomy.
• ? The operation duration of microsurgical varicocelectomy was longer than that of laparoscopic or open varicocelectomy.

CONCLUSIONS

• ? Current evidence indicates that microsurgical varicocelectomy is the most effective and least morbid method among the three varicocelectomy techniques for treating varicocele in infertile men.
• ? More high‐quality, multicentre, long‐term RCTs are required to verify the findings.

     

Early oncological outcomes for bladder urothelial carcinoma patients treated with robotic-assisted radical cystectomy

Study Type – Therapy (case series) Level of Evidence 4

OBJECTIVE

• ? To determine oncological outcomes including early survival rates among unselected bladder urothelial carcinoma (BUC) patients treated with robotic‐assisted radical cystectomy (RRC).

PATIENTS AND METHODS

• ? Clinicopathologic and survival data were prospectively gathered for 85 consecutive BUC patients treated with RRC.
• ? The decision to undergo a robotic rather than open approach was made without regard to tumor volume or surgical candidacy.
• ? Kaplan–Meier survival rates were determined and stratified by tumor stage and LN positivity, and multivariate analysis was performed to identify independent predictors of survival.

RESULTS

• ? Patients were relatively old (25% >80 years; median 73.5 years), with frequent comorbidities (46% with ASA class ≥3). Of these patients 28% had undergone previous pelvic radiation or pelvic surgery, and 20% had received neoadjuvant chemotherapy.
• ? Extended pelvic lymphadenectomy was performed in 98% of patients, with on average 19.1 LN retrieved.
• ? On final pathology, extravesical disease was common (36.5%).
• ? Positive surgicalmargins were detected in five (6%) patients, all of whom had extravesical tumors with perineural and/or lymphovascular invasion, and most of whom were >80 years old.
• ? At a mean postoperative interval of 18 months, 20 (24%) patients had developed recurrent disease, but only three (4%) patients had recurrence locally. Disease‐free, cancer‐specific and overall survival rates at 2 years were 74%, 85% and 79%, respectively. Patients with low‐stage/LN(?) cancers had significantly better survival than extravesical/LN(?) or any‐stage/LN(+) patients, with stage being the most important predictor on multivariate analysis.

CONCLUSION

• ? RRC can achieve adequately high LN yields with a low positive margin rate among unselected BUC patients.
• ? Early survival outcomes are similar to those reported in contemporary open series, with an encouragingly low incidence of local recurrence, however long‐term follow‐up and head‐to‐head comparison with the open approach are still needed.

     

Meta-analysis showing the beneficial effect of α-blockers on ureteric stent discomfort

Study Type – Therapy (systematic review) Level of Evidence 1a What’s known on the subject? and What does the study add? Ureteric stents cause significant discomfort and this is probably related to ureteric smooth muscle spasm and trigonal irritation. Alpha‐adrenoceptor antagonists reduce smooth muscle activity and are already widely used in medical expulsive therapy to aid passage of ureteric calculi. This meta‐analysis incorporating five randomized controlled trials provides evidence that alpha‐adrenoceptor antagonists reduce stent‐related pain and storage symptoms as assessed by the Ureteric Stent Symptoms Questionnaire (USSQ).

OBJECTIVES

• ? To evaluate the efficacy of α‐blockers with respect to improving stent‐related symptoms.
• ? Ureteric stents remain a source of marked discomfort and their placement is often required after certain ureteroscopic procedures or in the acute setting. This analysis identifies and reviews the several studies that have investigated the role of α‐blockers after stent placement.

MATERIALS AND METHODS

• ? Pubmed/Medline, EMBASE, CINAHL and Cochrane Library databases were scrutinized using standard MeSH headings.
• ? Randomized or controlled trials comparing α‐blockers with control or standard therapy were included.
• ? In all studies, patients completed the Ureteral Stent Symptom Questionnaire (USSQ).
• ? The study data were independently reviewed by two assessors.

RESULTS

• ? In total, five studies of varying quality were identified, including 461 patients receiving either tamsulosin or alfuzosin, or control.
• ? On meta‐analysis, all five studies showed a reduction in USSQ urinary symptom score and body pain scores. There was mean reduction of 8.4 (95% CI, 5.6–11.1) in the urinary symptom score and 7.2 (95% CI, 2.5–11.8) in the body pain score.
• ? In three studies, the numbers of patients experiencing stent related pain were stated: 45% (51/114) of patients receiving an α‐blocker experienced painful episodes within the follow‐up period defined for that study compared to 76% (88/116) in the control groups, which is equivalent to a relative risk of pain of 0.59 (95% confidence interval, 0.47–0.71).
• ? There were also reductions in other aspects of the USSQ, such as the general health score and sexual matters score, although these were not statistically significant or uniformly reported.

CONCLUSION

• ? There is evidence that α‐blockers provide an improvement in discomfort after placement of a ureteric stent.

     

The use of estramustine phosphate in the modern management of advanced prostate cancer

What’s known on the subject? and What does the study add? Estramustine phosphate has anti‐tumour properties and it improves patient outcomes if combined with other chemotherapy agents such as doeetaxel. The efficacy of estramustine phosphate in selected patients and its safety profile, provided used with any low‐molecular‐weight heparin support its use as a second‐line treatment in hormone‐resistant prostate cancer.

OBJECTIVES

• ? Estramustine phosphate is a nitrogen mustard derivative of estradiol‐17β‐phosphate and has anti‐tumour properties.
• ? Interest in estramustine has been renewed because of the results of clinical studies showing improved patient outcomes if estramustine is combined with other chemotherapy agents such as docetaxel.

PATIENTS AND METHODS

• ? Relevant clinical studies using chemotherapy combinations including estramustine are discussed.
• ? Efficacy and safety outcomes are summarized.

RESULTS

• ? Combination therapy with estramustine and docetaxel can increase PSA response rates, improve quality of life and increase median patient survival compared with chemotherapy regimens that do not include estramustine.
• ? Although the overall tolerability of estramustine is favourable, its use can be associated with an increased risk of thromboembolic events.

CONCLUSIONS

• ? The identification of suitable patient groups and the effective management of the risk of thromboembolism with the adjunct of low‐molecular‐weight heparins support the use of estramustine as an effective second‐line treatment strategy in hormone‐resistant prostate cancer.
• ? These promising findings warrant further investigation in a randomized clinical trial.

     

Use of fluorescein isothiocyanate-human serum albumin for the intravesical photodiagnosis of non-muscle-invasive bladder cancer: an in vitro study using multicellular spheroids composed of normal human urothelial and urothelial cell carcinoma cell lines

OBJECTIVE

• ? To evaluate human serum albumin (HSA), fluorescently labelled with fluorescein isothiocyanate (FITC), as a potential intravesical photodiagnostic method for the early detection of non‐muscle‐invasive bladder cancer.

PATIENTS AND METHODS

• ? By using multicellular spheroids prepared from normal human urothelial (NHU) cells and from different urothelial cell carcinoma (UCC) cell lines (T24, J82), we simulated three‐dimensionally the normal urothelium and non‐muscle‐invasive UCCs present in the bladder of patients.
• ? The distribution of FITC‐HSA in these spheroids was investigated.

RESULTS

• ? Our data showed that fluorescently labelled albumin is quite evenly dispersed throughout the spheroids. However, in the case of the 10 mg/mL incubations, the fluorescence intensity seems to increase slightly towards the spheroid core.
• ? Using 1 mg/mL, the penetration of FITC‐HSA in T24 differed significantly from the penetration in NHU spheroids, but this was not the case for J82 spheroids.
• ? When the concentration of FITC‐HSA was increased 10‐fold, all UCC spheroids exhibited a significantly different accumulation of FITC‐HSA.

CONCLUSIONS

• ? As spheroids represent a suitable in vitro model for predicting the in vivo behaviour of compounds, our data suggest that FITC‐HSA could be used for the early detection of non‐muscle‐invasive bladder cancer.
• ? Human serum albumin conjugates of new or already available intravesical drugs could be generated to create alternative bladder cancer therapies with increased selectivity.

     

Cost-effectiveness analysis of degarelix for advanced hormone-dependent prostate cancer

Study Type – Therapy (cost‐effectiveness analysis) Level of Evidence 2b What's known on the subject? and What does the study add? The European Medicines Evaluation Agency recognised that the principal advantage of degarelix is the avoidance of the transient rise in testosterone. This paper compares the cost‐effectiveness of degarelix with the most common treatment in the UK (LHRHa plus short‐term anti‐androgen) for the management of prostate cancer, focusing on the costs and clinical consequences that might be associated by the avoidance of the transient rise in testosterone. Our analysis suggests that, at the current UK list price, degarelix would not represent good value for money for the NHS.

OBJECTIVE

• ? To evaluate the cost‐effectiveness of degarelix vs luteinizing hormone‐releasing hormone analogue (triptorelin) plus short‐term antiandrogen treatment for advanced prostate cancer.

METHODS

• ? We developed a decision analytic model based on a clinical trial and literature review. The two interventions evaluated were: (i) monthly injection of degarelix and (ii) 3‐monthly triptorelin therapy plus short‐term flutamide, cyproterone or bicalutamide treatment.
• ? The model consisted of a decision tree monitoring a hypothetical cohort of patients aged 70 years from the start of hormonal treatment to the end of the first month, and a Markov model monitoring patients from the end of month 1 for a time horizon of 10 years (i.e. when 96% of patients are assumed to have died).
• ? The base‐case analysis assumed patients present with asymptomatic metastatic prostate cancer. Costs and outcomes were collected over the model time horizon. Outcome measures were quality‐adjusted life years (QALYs), lifetime costs and incremental cost‐effectiveness ratios.
• ? Sensitivity analyses (one‐way and multi‐way) and probabilistic sensitivity analyses were conducted to explore the uncertainties around the assumptions.

RESULTS

• ? In the base‐case analysis, the incremental cost‐effectiveness ratio (ICER) for degarelix vs triptorelin plus antiandrogen was £59 000 per QALY gained.
• ? The model was most sensitive to the rate of significant adverse events in the triptorelin plus antiandrogen group. The model was also sensitive to the assumed survival of patients with metastatic prostate cancer and the price of degarelix.
• ? The results of the probabilistic sensitivity analyses suggested that there was a low probability (9.6%) of degarelix being the most cost‐effective treatment option when a willingness‐to‐pay threshold of £30 000 per QALY gained is assumed.

CONCLUSION

• ? Degarelix is unlikely to be cost‐effective compared to triptorelin plus short‐term antiandrogen in the management of advanced prostate cancer with respect to the usual thresholds of cost‐effectiveness used in the UK: £20 000–30 000 per QALY gained (used by the National Institute for Health and Clinical Excellence).