The importance of the urologist in male oncology fertility preservation.

OBJECTIVES: To demonstrate that surgical sperm retrieval (SSR) and spermatogonial stem cell retrieval (SSCR) in an oncological context are safe and successful. PATIENTS AND METHODS: This a retrospective study in a tertiary hospital in the UK. Patients requiring fertility preservation from December 2017 to January 2020 were included. Data were analysed with Microsoft Excel 2016 and the Statistical Package for the Social Sciences (version 20). RESULTS: Among 1264 patients referred to the Reproductive Medical Unit at the University College of London Hospitals for cryopreservation prior to gonadotoxic treatment, 39 chose to go forward with SSR/SSCR because they presented as azoo-/cryptozoospermic or an inability to masturbate/ejaculate. Interventions were testicular sperm extraction (23 patients) or aspiration (one), electroejaculation (one), and testicular wedge biopsy for SSCR (14). The median (range) age was 15.0 (10-65) years and the median testosterone level was 4.4 nmoL/L. Primary diagnoses were sarcoma in 11 patients, leukaemia in nine, lymphoma in eight, testicular tumour in five, other oncological haematological entities in two, other solid cancers in two, while two patients had non-oncological haematological diseases. SSR/SSCR could be offered within 7.5 days on average. Chemotherapy could follow within 2 days from SSR/SSCR, and bone marrow transplant occurred within 19.5 days (all expressed as medians). The success rate for SSR was 68.0% (at least one vial/straw collected). The mean (SD) Johnsen score of testicular biopsies was 5.23 (2.25) with a trend towards positive correlation with SSR success (P = 0.07). However, age, hormonal profile and type of cancer did not predict SSR outcome. CONCLUSION: We show that SSR and SSCR in an oncological context are valid treatment options with a high success rate for patients in which sperm cryopreservation from semen is impossible. By providing an effective pathway, fertility preservation is possible with minimal delay to oncological treatment.

An analysis of the frequency of Y-chromosome microdeletions and the determination of a threshold sperm concentration for genetic testing in infertile men.

OBJECTIVE: To describe the prevalence of Y-chromosome microdeletions in a multi-ethnic urban population in London, UK. To also determine predictive factors and a clinical threshold for genetic testing in men with Y chromosome microdeletions. PATIENTS AND METHODS: A retrospective cohort study of 1473 men that were referred to a tertiary Andrology centre with male factor infertility between July 2004 and December 2016. All had a genetic evaluation, hormonal profile and 2 abnormal semen analyses. Those with abnormal examination findings also had targeted imaging performed. RESULTS: The prevalence of microdeletions was 4% (n = 58) in this study. These microdeletions were partitioned into the following regions: Azoospermia factors (AZF); AZFc (75%), AZFb+c (13.8%), AZFb (6.9%), AZFa (1.7%), and partial AZFa (1.7%). A high follicle-stimulating hormone level (P < 0.001) and a low sperm concentration (P < 0.05) were both found to be significant predictors for the identification of a microdeletion. Testosterone level, luteinising hormone level and testicular volume did not predict the presence of a microdeletion. None of the men with an AZF microdeletion had a sperm concentration of >0.5 million/mL. Lowering the sperm concentration threshold to this level retained the high sensitivity (100%) and increased the specificity (31%). This would produce significant cost savings when compared to the European Academy of Andrology/European Molecular Genetics Quality Network and European Association of Urology guidelines. The surgical sperm retrieval (SSR) rate after microdissection testicular sperm extraction was 33.2% in men with AZFc microdeletion. CONCLUSIONS: The prevalence of Y-chromosome microdeletions in infertile men appears to vary between populations and countries. A low sperm concentration was a predictive factor (P < 0.05) for identifying microdeletions in infertile males. A threshold for genetic testing of 0.5 million/mL would increase the specificity and lower the relative cost without adversely affecting the sensitivity. The rate of SSR was lower than that previously described in the literature.

Klinefelter syndrome: going beyond the diagnosis.

Although Klinefelter syndrome (KS) is common, it is rarely recognised in childhood, sometimes being identified with speech or developmental delay or incidental antenatal diagnosis. The only regular feature is testicular dysfunction. Postnatal gonadotropin surge (mini-puberty) may be lower, but treatment with testosterone needs prospective studies. The onset of puberty is at the normal age and biochemical hypogonadism does not typically occur until late puberty. Testosterone supplementation can be considered then or earlier for clinical hypogonadism. The size at birth is normal, but growth acceleration is more rapid in early and mid-childhood, with adult height greater than mid-parental height. Extreme tall stature is unusual. The incidence of adolescent gynaecomastia (35.6%) is not increased compared with typically developing boys and can be reduced or resolved by testosterone supplementation, potentially preventing the need for surgery. Around two-thirds require speech and language therapy or developmental support and early institution of therapy is important. Provision of psychological support may be helpful in ameliorating these experiences and provide opportunities to develop strategies to recognise, process and express feelings and thoughts. Boys with KS are at increased risk of impairment in social cognition and less accurate perceptions of social emotional cues. The concept of likely fertility problems needs introduction alongside regular reviews of puberty and sexual function in adolescents. Although there is now greater success in harvesting sperm through techniques such as testicular sperm extraction, it is more successful in later than in early adolescence. In vitro maturation of germ cells is still experimental.

Fertility preservation provision in the NHS: a national assessment of care policies.

Fertility preservation has gained momentum in recent years. As cancer survival rates improve, late effects of loss of gonadal function have increased the need to consider fertility preservation. NICE recommends offering cryopreservation of gametes or embryos to patients undergoing gonadotoxic therapy, highlighting that this should be extrapolated to those with non-malignant conditions that pose a risk to fertility. We investigated whether variation in fertility preservation provision exists across the United Kingdom, with a view to identifying equitable models of provision. In England, cryopreservation of gametes and embryos is funded for all patients undergoing treatment for cancer, but eligibility criteria and duration of storage funding vary widely. In Scotland, a national policy is applied, with health boards equitably providing funding for cryopreservation of gametes, embryos, and ovarian and testicular tissue for those undergoing treatment for benign and malignant conditions which impair fertility, including gender incongruence. In Wales and Northern Ireland, cryopreservation of gametes and embryos is funded for those undergoing treatment likely to make them infertile, but ovarian tissue cryopreservation is not funded. Funding criteria for fertility preservation in England, Wales, and Northern Ireland deviates from NICE guidance. Standardization of fertility preservation policies is needed to provide equity of access for patients.

Fertility preservation and realignment in transgender women.

Medical care for transgender people is multi-faceted and attention to individual reproductive aspirations and planning are an essential, yet often overlooked aspect of care. Given the impact of hormonal therapy and other gender affirmation procedures on reproductive function, extensive counselling and consideration of fertility preservation is recommended prior to their commencement. This review article explores the reproductive aspirations of transgender women and considers the current disparity between stated desires regarding utilisation of fertility preservation services. Current fertility preservation options and prospective treatments currently showing promise in the research arena are explored.

Stimulation of Leydig and Sertoli Cellular Secretory Function by Anti-Oestrogens: Clomiphene.

Leydig and Sertoli cells are essential for the testicular homeostasis. Clinically, the testicular homeostasis is impaired in hypogonadal and subfertile men. Therapeutically, the selective oestrogen receptor modulator clomiphene citrate (CC) is frequently used to treat these patients. In men, the mechanism of action of CC has long been thought to be limited to inhibition of the retro-control by oestrogen on the pituitary gland. However, oestrogen receptors are also expressed in the testis. Therefore, we will explore in this review the systemic effects as well as its action on reproductive function. We will describe in particular the possible effects of CC on the secretory functions of Leydig and Sertoli cells and their implication on the testicular microenvironment. CC is a costeffective and relatively safe off-label treatment for young hypogonadal men actively trying for a child or subfertile men with low testosterone with a positive effect on sperm concentration. Nevertheless, its effects on the oestrogen receptors and other signalling pathways at the testicular level remain poorly investigated. Further research, including combined treatment, could allow improving sperm morphology and sperm motility which do not seem to be significantly enhanced by CC alone.

Assessment of urodynamic and detrusor contractility variables in patients with overactive bladder syndrome treated with botulinum toxin-A: is incomplete bladder emptying predictable?

OBJECTIVE: To assess whether incomplete bladder emptying and the need for clean intermittent self-catheterization (CISC) is predictable, by analysing urodynamic and detrusor contractility variables in patients treated with botulinum toxin-A (BTX-A) for refractory idiopathic detrusor overactivity (IDO). PATIENTS AND METHODS: Sixty-seven patients (mean age 50.3) with IDO, from two centres, had bladder injections of 200 U BTX-A. Patients with difficulty in emptying their bladder and/or persistent overactive bladder symptoms, with postvoid residual volumes (PVR) of >150 mL after treatment were started on CISC. Urodynamics were conducted at baseline, 4 and 12-16 weeks after injection with BTX-A. Detrusor contractility was assessed using the projected isovolumetric pressure (PIP1) in women and bladder contractility index (BCI) in men. RESULTS: There were improvements in the mean maximum cystometric capacity, bladder compliance and maximum detrusor pressures during filling cystometry after BTX-A injections. The PVR was significantly increased at 4 but not at 12 weeks. Nineteen patients required CISC and when compared with those not needing CISC their pretreatment maximum flow rate (15 vs 22 mL/s, P = 0.003), PIP1 (43 vs 58, P = 0.02) and BCI (113 vs 180, P = 0.001) were lower. Receiver operator characteristic curve analysis suggested that a PIP1 of < or =50 in women (sensitivity 0.83; specificity 0.70; area under the curve 0.822) and BCI < or =120 (sensitivity 0.7; specificity 0.79; area 0.879) might predict the need for CISC. CONCLUSION: The maximum flow rate, PIP1 and BCI were significantly lower in patients who required CISC after BTX-A treatment than in those who did not. A PIP1 of < or =50 in women and a BCI of < or =120 might be predictive of a need for CISC in this setting, and might help when counselling patients.

Health economics and intradetrusor injections of botulinum for the treatment of detrusor overactivity.

Health economic aspects are crucial in arguing the feasibility of setting up a new service using an unlicensed treatment. Overall, the costs of intradetrusor botulinum neurotoxin-A treatment appear to be modest relative to the improvement in quality of life. However, in managing the overactive bladder, there is a need for a widely accepted definition of 'clinical improvement' or a common outcome measure to direct future clinical and health economic research.

The use of the 1 mm laparoscope to assist in port insertion in pelvic oncological surgery.

BACKGROUND: A 1 mm minilaparoscope (Lifeline Biotechnoligies, Florida, USA) was assessed for aiding port site insertions. METHODS: Ten consecutive patients having laparoscopic procedures in a gynaecological oncology unit were included. Minilaparoscopy was feasible in all cases and was used to insert the umbilical port under direct vision in all patients. In one case, a thick band of abdominal adhesions was identified and a further lateral port site was inserted to aid their dissection. RESULTS: The minilaparoscope correctly identified all 10 patients with peritoneal disease and identified all patients who were suitable for debulking procedures. CONCLUSION: Minilaparoscopy with the 1 mm endoscope appears to be safe and accurate and we feel that it has a place in helping the surgeon identify adhesions and peritoneal disease as well as assisting further port site insertion safely and with minimal complications.

Biomaterials in urinary incontinence and treatment of their complications.

Biomaterials integrate with the anatomy and provide support to the weakened area. They are generally synthetic, but natural substances are also used. These substances are being increasingly used in stress urinary incontinence. This article discusses the various biomaterials, minimally invasive techniques, and recent advances for the treatment of female stress urinary incontinence. In addition, their complications and subsequent management are explored.