The role of sperm aneuploidy as a predictor of the success of intracytoplasmic sperm injection?

BACKGROUND: We present the first powered prospective study to assess whether sperm aneuploidy can predict the outcome of ICSI. METHODS: Our null hypothesis was that aneuploidy rates (AR) are identical in men who achieve successful (Group A) and unsuccessful (Group B) ICSI outcome. A power calculation yielded a sample number of 56 to achieve 80% power to reject our hypothesis at the 5% significance level. Samples for testing were obtained on the day of embryo transfer and tests were performed on raw pre-preparation samples. Sperm AR of chromosomes 13, 18, 21, X/Y were assessed using fluorescence in-situ hybridization (FISH) techniques (mean of 1223 sperm). RESULTS: There was no significant difference in any patient, seminal, cycle or laboratory characteristic between groups that may have affected outcome. Total AR (2.37 versus 1.18%, P = 0.01), as well as AR of chromosomes 18, X/Y and 18 + X/Y (1.48 versus 0.67%, P = 0.005) were significantly higher in Group B compared with Group A. Regression analysis confirmed these differences to be independent of other variables and showed a 2.6-fold change in odds of achieving a pregnancy for every 1% change in total AR. CONCLUSIONS: Our findings confirm a potential role for aneuploidy testing in the work-up of ICSI patients as a predictor of success, as well as in future genetic counselling. If confirmed, there may also be a place for a study of preimplantation genetic screening to improve ICSI success in men found to have high AR and ICSI failure.

Male-factor infertility: do we really need urologists? A gynaecological view.

The Royal College of Obstetricians and Gynaecologists state that male factor infertility is responsible for up to 25% of all cases of infertility and may contribute in a further 25%. Where the role of the urologist ends and gynaecologist begins in these couples is a matter of debate. We therefore discuss the management of these couples and the need for a multidisciplinary approach.

Does the cause of obstructive azoospermia affect the outcome of intracytoplasmic sperm injection: a meta-analysis.

OBJECTIVE: To define whether the outcome of intracytoplasmic sperm injection (ICSI) using sperm surgically retrieved from men with obstructive azoospermia (OA) depends on the cause of obstruction. PATIENTS AND METHODS: We first analysed our data and then used a meta-analysis of published data (including ours) to compare the outcome of ICSI in OA, classified in terms of congenital and acquired causes. The present study comprised 82 couples who underwent 127 ICSI cycles using surgically retrieved sperm. The cause was classified as congenital bilateral absence of vas deferens (CBAVD, in 20), after vasectomy (56), infective/inflammatory (21), noninfective (24) and ejaculatory (five). Five reports (687 cycles) including the present were identified as suitable for meta-analysis. RESULTS: Analysis of the present data showed that fertilization and live-birth rates were highest in men with a previous vasectomy and no infective cause (vasectomy 51% and 23%; not infective 53% and 29%, respectively) and lowest in men with infective or inflammatory causes. There was no difference in outcome if the sperm was fresh or frozen, or whether epididymal or testicular. Meta-analysis comparing congenital (CBAVD) and acquired causes showed a significantly increased fertilization rate (95% confidence interval, 0.84-1) with acquired causes. Meta-analysis of the three papers reporting delivery outcome showed no difference in live-birth rate but a significantly higher miscarriage rate in the congenital group (relative risk 2.67). CONCLUSION: In ICSI cycles in men with OA the cause appears to influence the outcome, but outcome is not affected by whether the retrieved sperm is fresh, frozen, epididymal or testicular. The meta-analysis suggested a higher fertilization rate and lower miscarriage rate in acquired causes of OA.

The results of 154 ICSI cycles using surgically retrieved sperm from azoospermic men.

BACKGROUND: The effects of source of sperm, aetiology and sperm cryopreservation on ICSI cycles in azoospermic men were evaluated. The effect of aetiology of azoospermia on embryo development was also assessed. METHODS: This study was a retrospective analysis of 154 cycles (91 couples) using surgically retrieved sperm. Outcome measures were fertilization rate (FR), implantation rate (IR), and clinical pregnancy rate (CPR) and livebirth rate (LBR) per transfer. RESULTS: Our data demonstrated similar outcome between the use of epididymal or testicular sperm in men with obstructive azoospermic (OA). FR and IR were significantly lower (P < 0.05) using sperm from men with non-obstructive azoospermic (NOA), but although pregnancy outcome appeared lower, this did not reach statistical significance (P = 0.08). Cryopreservation of epididiymal sperm did not alter outcome, but the use of frozen-thawed testicular sperm did demonstrate a lower FR, with no statistical difference in IR or pregnancy outcome. Embryos derived from NOA sperm had impaired development beyond day 2 post-oocyte retrieval (OA, 44% <5 cell; NOA, 71% <5 cell; P = 0.002). CONCLUSIONS: The use of sperm from men with NOA significantly affects fertilization and implantation in ICSI cycles. The use of frozen-thawed testicular sperm affects fertilization rate without significantly altering pregnancy outcome. The use of such data on which to base clinical decisions needs to be supported by the meta-analyses of previous reports.

From zero to one hundred million in six months: the treatment of azoospermia in congenital adrenal hyperplasia.

In the majority of the 25% of couples in which a male factor is responsible for their infertility, no identifiable pathology is found. It is unusual to be faced with an etiology that is readily amenable to successful treatment without the eventual dependence on assisted reproductive techniques for pregnancy. The diagnosis of congenital adrenal hyperplasia has variable implications on fertility. A case is presented of azoospermia in a man diagnosed with classical non-salt-losing congenital adrenal hyperplasia. Within 9 months of treatment with dexamethasone, his sperm count had risen to above 100 million per milliliter, enough to overcome very poor morphology and a naturally conceived pregnancy ensued. The pregnancy is ongoing. Although an increase in sperm count has been shown in such cases, the degree of improvement in semen parameters is unique, especially in an azoospermic patient.

Khat chewing and bladder neck dysfunction. A randomized controlled trial of alpha 1-adrenergic blockade.

OBJECTIVE: To assess whether the effect of chewing khat leaves (Catha edulis) on the urodynamics of healthy males is altered by the selective alpha 1-adrenergic blocking agent indoramin in a prospective randomized double-blind controlled trial. SUBJECTS AND METHODS: The urodynamics of 11 healthy males were studied before and during a khat chewing session preceded by indoramin or placebo. RESULTS: Khat chewing produced a fall in average and maximum urine flow rate. This effect was inhibited by indoramin. CONCLUSIONS: The urinary side-effects of khat chewing are probably mediated through stimulation of alpha 1-adrenergic receptors.

Sham versus transurethral microwave thermotherapy in patients with symptoms of benign prostatic bladder outflow obstruction.

Transurethral microwave thermotherapy (TUMT) is a single-session, minimally invasive outpatient treatment for patients with symptoms of benign prostatic bladder outflow obstruction. We designed a prospective randomised trial to identify any placebo response. Patients with a Madsen symptom score over 8 for at least 6 months were eligible for study. Two measurements of urinary flow less than 15 mL/s and a residual urine of under 350 mL were also required for entry. Patients with renal dysfunction, upper urinary tract disease, co-existing bladder disease, and malignant prostatic change were excluded. 43 patients were studied: 21 were randomised to receive a sham treatment and 22 to thermotherapy. Sham treatments were done with the urethral applicator in situ. 40 patients were available for evaluation at 3 months. 2 patients had delayed follow-up and 1 patient randomised to TUMT has undergone transurethral resection. The thermotherapy group showed a 70% decrease (from 14.5 to 4.3) in the mean Madsen score, a 53% increase in flow-rate (8.5 to 13.0 mL/s), and 92% decrease in residual urine volume (147 to 12 mL). No significant change was seen in these mean indices in the sham group. There was no difference in the main complication of transient haematuria between the two groups. However, there was a 22% frequency of acute retention in the TUMT group. The results show little significant placebo component to the subjective and objective improvement that occurs in patients who have received TUMT.

Endometriosis of the ureter.

Five patients with ureteric endometriosis are described. Extensive pre-operative investigation failed to reveal the aetiology of the unilateral upper urinary tract obstruction seen in all of these patients. Due to the dense fibrosis that invariably accompanies ureteric endometriosis, early surgical excision of the ureteric stricture permits effective resolution of upper tract dilatation and improved renal salvage.

Fournier's gangrene of the scrotum following day case vasectomy.

PIP: A case of Fournier's gangrene of the scrotum is reported in a 31-year old man who had outpatient vasectomy during an intercurrent diarrheal illness. The surgery was done through a midline incision, under local anesthesia of plain 2% lignocaine, with a preoperative chlorhexidine scrub. Although his scrotum was red and swollen within 3 hours, he did not have medical care until admission to hospital 48 hours later. At admission he had Fournier's gangrene of the scrotum and penis, Gram-negative septic shock, and acute renal failure. In the intensive care unit he was treated with continuous dialysis, parenteral metronidazole, benzylpenicillin, Ceftazidime and inotropes. He had a cardiorespiratory arrest after emergency radical debridement. After resuscitation he developed adult respiratory distress syndrome and disseminated intravascular coagulation. Pathological exam showed necrosis of the dermis and subcutaneous layers, thrombosis and beta-hemolytic streptococci. After adding gentamicin and vancomycin, 2 weeks of ventilator care, 4 more surgical debridements, a left orchidectomy, and a despite a grossly abnormal EEG recording, the man regained consciousness and recovered. His scrotal and penile skin re-epithelialized over 3 months. Patients requesting vasectomy should be assessed for local and systemic illness before performing the procedure.^ieng

Biofilms, bacteria and bladder catheters. A clinical study.

Biofilms were present on 16 of 33 urethral catheters examined. In 11 cases the catheter carried a different microbial flora from that of the bladder urine. The length of time the catheter was in situ did not influence biofilm formation, and all types of materials tested supported biofilm growth. Biofilms were seen on 2 of the 7 catheters where prophylactic antibiotics had been used.

Plasma lignocaine levels during transurethral prostatectomy.

It has been reported that transurethral absorption of lignocaine may cause systemic toxicity when associated with mucosal damage within the urethra. We measured the serum levels of lignocaine in 30 patients after the transurethral administration of 400 mg lignocaine gel just before transurethral prostatectomy. In 11 patients additional lignocaine was given as part of the anaesthetic induction (Group A). In 19 patients no additional lignocaine was given (Group B). Two patients in Group A and three patients in Group B also underwent Otis urethrotomy. The mean peak plasma lignocaine concentration as measured by sequential venous samples was 1424 ng/ml in Group A and 72 ng/ml in Group B. We conclude that 400 mg lignocaine gel applied endourethrally before transurethral resection of the prostate results in plasma concentrations well below the toxic levels.

Irrigation and acute ureteric dilatation--as for ureteroscopy.

The effects of irrigation with sterile and infected saline after acute ureteric dilatation by graded Teflon dilators were evaluated renographically and histologically in minipigs. The minipig ureter was dilated from its normal calibre of 4 F to 10 F, and 100 ml of sterile or infected saline were then introduced from a height of 60 cm under gravity. One week after irrigation and dilatation the ipsilateral kidney was either functioning less than 10% or there was an obstructive nephropathy. Histology at 3 months suggested that extravasation of infected irrigating fluid was the most likely cause of ureteric stricture formation.

The effects of double J stents on renal pelvic dynamics in the pig.

Intra-pelvic pressure and peristaltic activity were measured before and during diuresis in 26 minipigs, immediately, one week and three weeks following ureteric intubation with 5 and 6F polyethylene double J stents. Changes in these dynamic parameters were seen which indicate that these stents caused renal outflow obstruction. The severity of this obstruction appears dependent upon the size of the catheter and the temporal length of intubation. This study indicates that double J stents provide sub-optimal drainage of the renal pelvis and damaged ureter.

Suprapubic endoscopy: a percutaneous approach.

We have assessed whether suprapubic endoscopic surgery can be helpful in situations where transurethral access is inadequate, difficult or likely to be associated with urethral damage and have applied a modified version of the well known techniques for creating and dilating a track for percutaneous renal access to the bladder. This method has been used in a series of clinical cases and in certain experimental studies. Assessment of the techniques has allowed their modification and the development of a specially designed access cannula--the St Peter's Hospital cannula.

Acute ureteric dilatation for ureteroscopy. An experimental study.

The effects of three methods of acute ureteric dilatation (by graded Teflon dilators, low and high pressure balloon dilators) were evaluated radiologically, renographically and histologically in minipigs. The minipig ureter was dilated from its normal calibre of 4 F to 10 F. All three methods caused upper urinary tract dilatation and an obstructive nephropathy which had not resolved 96 h after dilatation. Histology at 24 h showed destruction of the transitional epithelium, with inflammation throughout the ureteric wall. Four weeks after dilatation the ureter was still dilated and urothelial nests were seen in the lamina propria and in the muscle coats. There was no evidence of ischaemic necrosis or ureteric stricture formation. The implications of these findings for clinical practice are discussed.