Male infertility.

Clinical infertility is the inability of a couple to conceive after 12 months of trying. Male factors are estimated to contribute to 30-50% of cases of infertility. Infertility or reduced fertility can result from testicular dysfunction, endocrinopathies, lifestyle factors (such as tobacco and obesity), congenital anatomical factors, gonadotoxic exposures and ageing, among others. The evaluation of male infertility includes detailed history taking, focused physical examination and selective laboratory testing, including semen analysis. Treatments include lifestyle optimization, empirical or targeted medical therapy as well as surgical therapies that lead to measurable improvement in fertility. Although male infertility is recognized as a disease with effects on quality of life for both members of the infertile couple, fewer data exist on specific quantification and impact compared with other health-related conditions.

Effect of Distance From Fertility Center on Utilization of Fertility Preservation Referral in Men.

PURPOSE: Fertility preservation (FP) is underutilized in males with cancer or other diseases requiring gonadotoxic therapies. We sought to evaluate whether patient distance from FP center affected rates of providing a semen analysis after referral. MATERIALS AND METHODS: We performed a retrospective analysis of all males who were referred for FP at a single institution between 2013 and 2021. A multiple logistic regression model was conducted with semen sample submission as the variable of interest. Predictor variables were disease type, distance, and payment method. Secondary outcomes were number of semen samples submitted and number of vials collected. RESULTS: Records of 461 males referred to our center were analyzed. Of these patients, 326 (71%) provided a semen sample after referral and 135 (30%) did not. Further distance from our center was associated with lower odds of submitting a semen sample (OR, 0.85; 95% CI, 0.75 to 0.97; P < .05). For patients who submitted at least one sample, distance did not affect the total number of samples submitted but was associated with a small increase in total vials cryopreserved. CONCLUSION: Men referred for FP exhibit a high rate of sperm cryopreservation. Further distance from FP center was associated with decreased odds to provide semen sample after referral. Our model estimated a 15% decrease in odds of collection with every doubling of distance from our center. Efforts must be made to improve FP utilization for patients traveling far distances, but distance alone should not preclude referral.

Progress in translational reproductive science: testicular tissue transplantation and in vitro spermatogenesis.

Since the birth of the first child conceived via in vitro fertilization 40 years ago, fertility treatments and assisted reproductive technology have allowed many couples to reach their reproductive goals. As of yet, no fertility options are available for men who cannot produce functional sperm, but many experimental therapies have demonstrated promising results in animal models. Both autologous (stem cell transplantation, de novo morphogenesis, and testicular tissue grafting) and outside-the-body (xenografting and in vitro spermatogenesis) approaches exist for restoring sperm production in infertile animals with varying degrees of success. Once safety profiles are established and an ideal patient population is chosen, some of these techniques may be ready for human experimentation in the near future, with likely clinical implementation within the next decade.

Transurethral resection of the ejaculatory ducts: etiology of obstruction and surgical treatment options.

Ejaculatory duct obstruction is an uncommon but surgically correctable cause of male infertility. With the advent and increased use of high-resolution transrectal ultrasonography, anomalies of the ejaculatory ducts related to infertility have been well documented. Although there are no pathognomonic findings associated with ejaculatory duct obstruction, the diagnosis should be suspected in an infertile male with oligospermia or azoospermia with low ejaculate volume, normal secondary sex characteristics, testes, and hormonal profile, and dilated seminal vesicles, midline cyst, or calcifications on transrectal ultrasound (TRUS). Although additional larger prospective and comparative studies are needed, it appears that TRUS with aspiration is the most effective method for diagnosis. While intrusive, it is less invasive than vasography. The most robust and published evidence for treatment involves transurethral resection of ejaculatory duct (TURED). More recent experience with antegrade endoscopic approaches are promising and may also be considered. An alternative to surgeries for reversal of obstruction is sperm retrieval for in vitro fertilization/intracytoplasmic sperm injection. A thorough discussion of all alternatives, including risks and benefits, should be held with couples facing this uncommon condition to allow them to make informed decisions regarding management.

A 52-Week Study of Dose Adjusted Subcutaneous Testosterone Enanthate in Oil Self-Administered via Disposable Auto-Injector.

PURPOSE: In this open label, single arm, dose blinded, 52-week registration phase study we evaluated the efficacy and safety of a subcutaneous testosterone enanthate auto-injector administered weekly to men with hypogonadism. MATERIALS AND METHODS: A total of 150 patients were initiated on a 75 mg subcutaneous testosterone enanthate auto-injector self-administered weekly. Dose adjustments were made at week 7 to 50, 75 or 100 mg testosterone enanthate based on the week 6 total testosterone trough concentration. If required, dose adjustments continued through the extended treatment phase. Pharmacokinetic and clinical laboratory parameters, treatment emergent adverse events and injection site reactions were captured. RESULTS: The primary end point was met since 92.7% of patients achieved an average total testosterone concentration of 300 to 1,100 ng/dl (mean ± SD 553.3 ± 127.29) at week 12. A maximum concentration of less than 1,500 ng/dl was achieved by 91.3% of patients and no patient had a level greater than 1,800 ng/dl at week 12. The mean total testosterone trough concentration was 487.2 ± 153.33 ng/dl at week 52. Of the patients more than 95% reported no injection related pain. The most frequently reported treatment emergent adverse events were increased hematocrit, hypertension and increased prostate specific antigen, which led to discontinuation in 30 men. There were no study drug related serious adverse events. CONCLUSIONS: The dose adjusted subcutaneous testosterone enanthate auto-injector demonstrated a steady serum total testosterone pharmacokinetic profile with small peak and trough fluctuations. The device was safe, well tolerated and virtually painless, indicating that this subcutaneous testosterone enanthate auto-injector offers a testosterone delivery system that is a convenient weekly option to treat testosterone deficiency.

What's Gender Got to Do With It: Difference in the Proportion of Traditionally Female Cases Performed by General Urologists of Each Gender.

OBJECTIVE: To examine surgical case volume characteristics in certifying urologists to evaluate practice patterns, given the long-standing understanding but unproven hypothesis that non-fellowship trained female general urologists perform more urogynecologic procedures compared with their equally trained male counterparts. MATERIALS AND METHODS: Case log data from certifying and recertifying urologists from 2000 to 2015 were obtained from the American Board of Urology. Thirty-seven Current Procedural Terminology (CPT) codes were chosen to represent traditionally urogynecologic cases. Logistic regression analysis models were used to determine the percentage of total CPT codes logged during the certification period made up by traditionally urogynecologic cases. Male and female non-fellowship trained, self-described general urologists were compared. RESULTS: The case logs of 4032 non-fellowship trained general urologists were reviewed from 2000 to 2015, 297 of whom were female and 3735 of whom were male. Urogynecologic cases made up 1.27% of the total CPT codes logged by the women and 0.59% of those codes logged by the men (P <.001), an increase of 2.2 times (P <.001). This statistically significant difference persisted regardless of certification period, geographic location, population density, or full-time vs part-time employment. CONCLUSION: Traditional urogynecologic cases represented a significantly greater percentage of the total cases logged by non-fellowship trained female general urologists compared with their non-fellowship trained, generalist male colleagues. The percentage of total cases performed by both is very small. However, it supports a belief that patient populations differ for male and female general urologists, which may impact training or career choices.

Ghrelin modulates testicular damage in a cryptorchid mouse model.

Cryptorchidism or undescended testis (UDT) is a common congenital abnormality associated with increased risk for developing male infertility and testicular cancer. This study elucidated the effects of endogenous ghrelin or growth hormone secretagogue receptor (GHSR) deletion on mouse reproductive performance and evaluated the ability of ghrelin to prevent testicular damage in a surgical cryptorchid mouse model. Reciprocal matings with heterozygous/homozygous ghrelin and GHSR knockout mice were performed. Litter size and germ cell apoptosis were recorded and testicular histological evaluations were performed. Wild type and GHSR knockout adult mice were subjected to creation of unilateral surgical cryptorchidism that is a model of heat-induced germ cell death. All mice were randomly separated into two groups: treatment with ghrelin or with saline. To assess testicular damage, the following endpoints were evaluated: testis weight, seminiferous tubule diameter, percentage of seminiferous tubules with spermatids and with multinucleated giant cells. Our findings indicated that endogenous ghrelin deletion altered male fertility. Moreover, ghrelin treatment ameliorated the testicular weight changes caused by surgically induced cryptorchidism. Testicular histopathology revealed a significant preservation of spermatogenesis and seminiferous tubule diameter in the ghrelin-treated cryptorchid testes of GHSR KO mice, suggesting that this protective effect of ghrelin was mediated by an unknown mechanism. In conclusion, ghrelin therapy could be useful to suppress testicular damage induced by hyperthermia, and future investigations will focus on the underlying mechanisms by which ghrelin mitigates testicular damage.

Efficacy of Standardized Nursing Fertility Counseling on Sperm Banking Rates in Cancer Patients.

OBJECTIVE: To examine the effect of brief nurse counseling on sperm banking rates among patients prior to initiating chemotherapy. MATERIALS AND METHODS: A retrospective chart review was performed for men aged 18-50 with newly diagnosed cancer, from 1998 to 2003, prior to initiation of chemotherapy. A standardized nursing education session including brief fertility counseling was implemented at one institution in 2008 (Institution A). Rates of sperm banking among patients who received counseling were compared to those without counseling at institution A and to those at institution B where a counseling program was never initiated. RESULTS: A total of 766 male patients, 402 treated at institution A and 364 at institution B, were included. At institution A, sperm banking rates prior to 2008 were 6.4% and 8.3% after 2008 for those who did not receive counseling. The rate of sperm banking for those patients who did receive counseling was significantly higher at 17.6% (P = .002). The odds of banking increased 2.9 times for those who received counseling compared to those who did not (P = .003). At institution B, where counseling was never initiated, rates of banking remained low before and after 2008. Additional analysis revealed that younger patients and those patients who did not have children were more likely to perform sperm banking. CONCLUSION: The rates of sperm banking among cancer patients increased with the receipt of a brief, formalized nurse counseling session prior to initiation of chemotherapy. These findings may validate the use of a formalized fertility counseling prior to initiation of chemotherapy.

Ghrelin Inhibits Post-Operative Adhesions via Blockage of the TGF-ß Signaling Pathway.

Post-operative adhesions are a critical problem in pelvic and abdominal surgery despite a multitude of studies dedicated to finding modalities to prevent their occurrence. Ghrelin administration promotes an anti-fibrotic response in a surgical mouse model of adhesion-induction, but the mechanisms mediating this effect have not been established. In the current study, the molecular mechanisms that underlie the anti-adhesion effect of ghrelin were investigated. Post-surgical adhesions were experimentally created in C57BL/6 wild-type mice via a combination of ischemic peritoneal buttons and cecal multiple abrasions. Ghrelin or saline intraperitoneal injections were given twice daily from two days before surgery to selected time points post-surgically to assess the phenotypic and molecular effects of treatment (1 day (n = 20), 4 days (n = 20) and 20 days (n = 40) after surgery). Endpoints included the scoring of adhesions and gene and protein expression analysis of pro-fibrogenic factors conducted on peritoneal ischemic tissue by quantitative PCR and Western blot. Ghrelin administration significantly reduced post-surgical adhesions and down-regulated pro-inflammatory gene and protein expression, including Tgfb3 and Tgfbr2. The up-regulation of inhibitory proteins Smad6 and Smad7 confirmed the ghrelin-induced blockage of TGF-ß signaling. Ghrelin is a candidate therapeutic drug for post-operative adhesion prevention, inhibiting inflammatory responses via blockage of the TGF-ß signaling pathway at the onset of surgery before the occurrence of the granulation-remodeling phase.

Ghrelin ameliorates adhesions in a postsurgical mouse model.

BACKGROUND: Peritoneal adhesion formation is a well-recognized consequence of abdominal and pelvic surgery, causing infertility, chronic pelvic pain, and intestinal obstruction. We hypothesized that ghrelin, a 28-amino acid peptide predominantly found in the stomach, plays an important role in preventing postoperative surgical adhesions. The purpose of this study was to develop a new surgical peritoneal adhesion model to define the role that ghrelin plays in wound healing and adhesion formation. MATERIALS AND METHODS: C57BL/6 wild-type mice (n = 40) and growth hormone secretagogue receptor-knockout (GHSR KO) mice (n = 20) underwent a midline laparotomy to establish a peritoneal adhesion model characterized by the combination of two different techniques: ischemic peritoneal buttons and cecal multiple abrasion. All mice received intraperitoneal injections with ghrelin (0.16 mg/kg) or saline twice daily for 20 d after surgery. Peritoneal ischemic buttons were harvested to determine protein expression of collagen (Masson trichrome, picrosirius red stain, and Western blot). RESULTS: The novel mouse model demonstrated consistent and easily reproducible formation of intra-abdominal adhesions. Ghrelin administration significantly reduced postoperative adhesion formation (P < 0.001) in wild-type mice. The antifibrotic effect of ghrelin in wild-type mice was confirmed by measuring collagen I protein levels via Western blot analysis. The anti-adhesion effect of ghrelin seen in wild-type mice was not detected in GHSR KO mice demonstrating that this effect is mediated by the GHSR-1a receptor. CONCLUSIONS: Ghrelin administration may improve surgical outcome by reducing peritoneal adhesion formation and fibrotic response in a mouse model.

Rectal swab culture-directed antimicrobial prophylaxis for prostate biopsy and risk of postprocedure infection: a cohort study.

OBJECTIVE: To examine the effect of rectal swab culture-directed prophylaxis on the incidence of prostate biopsy-associated infections. Secondary objectives were to determine the rate of fluoroquinolone resistance and extended-spectrum beta-lactamase production in local rectal flora. METHODS: All men receiving prostate biopsies from February 2013 to February 2014 were included in a retrospective institutional review board-approved study. All received either a preprocedural rectal swab and culture-directed antimicrobial prophylaxis or routine fluoroquinolone antibiotics. Clinical information was collected on infectious complications treated within 30 days of biopsy. Chi-square test, Fisher exact test, and Welch t test were used for statistical analysis. Confounding variables were included in a multivariate logistic regression model. RESULTS: Of 487 total patients, 314 received preprocedure rectal cultures and 173 did not. Average ages were 62.7 and 64.1 years, respectively (P = .07). There was no difference in mean prostate-specific antigen value (P = .9), Charlson comorbidity score (P = .8), or ethnicity (P = .1). The rectal swab group was more likely to receive supplemental gentamicin (P < .001) and had fewer infectious complications (1.9% vs 2.9%; P = .5). On multivariate analysis, decreased odds of infection was associated with culture-directed antibiotics (odds ratio, 0.70; 95% confidence interval, 0.20-2.50; P = .6). However, the study was only powered to detect a 97% reduction in infections. The incidence of fluoroquinolone resistance and extended-spectrum beta-lactamase production was 12.1% and 0.64%, respectively. CONCLUSION: Our study was underpowered but suggests that there are lower odds of infection with rectal swab-directed antimicrobial prophylaxis. The local incidence of fluoroquinolone resistance is high. A prospective, randomized, controlled trial is warranted to further evaluate this intervention.

Biomarkers of chemotherapy-induced testicular damage.

Increasing numbers of men are having or wanting children after chemotherapy treatment. This can be attributed to improvements in cancer therapies that increase survival. However, a side effect of most chemotherapy drugs is disruption of spermatogenesis and a drastic reduction in sperm count and quality. Although many men eventually recover reproductive function, as indicated by normal semen analyses, there is no clinical test that can assess sperm quality at a high level of sensitivity. Sperm fluorescent in situ hybridization (i.e., FISH) and several different tests for deoxyribonucleic acid (DNA) fragmentation have been used infrequently in clinical assessment. Animal models of chemotherapy-induced testicular damage are currently being used to identify potential molecular biomarkers that may be translatable to humans-these include sperm messenger RNAs, microRNAs, histone modifications, and DNA methylation patterns. Changes in these molecular measurements are quantitative and sensitive, potentially making them important clinical biomarkers of testicular function after chemotherapy treatment.

Adult care of children from pediatric urology: part 2.

PURPOSE: We describe the outcomes of undescended testes and sex development disorders in adolescence and young adulthood. We reviewed the requirements for the long-term care of children born with these and other major congenital anomalies of the genitourinary system. MATERIALS AND METHODS: The current English language literature was retrieved with a PubMed® search for articles on these subjects. Only articles covering outcomes at ages past puberty were included in analysis. The material was supplemented from the database of the clinic for adults with sex development disorders at University College London Hospitals. RESULTS: An undescended testis has impaired spermatogenesis. In men in whom a unilateral undescended testis was corrected before puberty the incidence of paternity is normal at around 90% of those who attempt it. The equivalent rate for those with bilateral undescended testes is about 65%. If surgery for bilateral undescended testes is delayed until after puberty, fertility is unlikely. The risk of testicular neoplasms is overestimated and the relative risk is between 2.5 and 8. Children born with a sex development disorder receive multidisciplinary treatment throughout childhood and require the same care as adults. Males who are under virilized likely have a micropenis (greater than 2 SD below the mean stretched length) but they may have normal sexual function. Fertility depends on the underlying condition. Virilized females, who most commonly have congenital adrenal hyperplasia, currently present to adult clinics with an inadequate vagina after infantile surgery. Reconstruction is required to allow intercourse. CONCLUSIONS: The care of adults born with abnormalities of the genitalia is complex. Early management may define upbringing in childhood but requirements for sexuality and fertility in adult life are different. Multidisciplinary care is essential and a case can be made to establish a subspecialty of urology to coordinate it.

Clinical practice: surgical approaches to urolithiasis in children.

The incidence of urolithiasis in children is increasing. Adequate knowledge of treatment modalities and surgical options is therefore essential for every pediatrician. Surgical approaches to urolithiasis in children continue to evolve with advancements in technology and sophistication of current equipment and techniques. Perhaps the most significant development in new techniques is the advent of robotic-assisted laparoscopy. This review, for the general pediatrician, summarizes the most recent pediatric data and guidelines for surgical approaches to treatment of urolithiasis.

Diagnostic testicular biopsy before varicocele repair plays a realistic and important role.

We believe that diagnostic testicular biopsy before varicocele repair is important, despite the risks.

New advances on the expansion and storage of human spermatogonial stem cells.

PURPOSE OF REVIEW: Fertility in adult life can be severely impaired by gonadotoxic therapies and with remarkable advancements in the treatment of childhood cancers there is a growing population of adult survivors of childhood malignancies. The aim of the study is to review the developments that have been made in spermatogonial stem cell research and potential future utility in fertility preservation. RECENT FINDINGS: Whereas intense interest and subsequent research surrounds the regenerative potential of spermatogonial stem cells, a recent article highlights the in-vitro propagation of human spermatogonial stem cells from testicular biopsies for future transplantation and restoration of fertility. Whereas in-vitro propagation of spermatogonial stem cells has been established in animal models this is the first study in humans. SUMMARY: Spermatogonial stem cell transplantation began as a theoretical approach that currently is studied ardently by several research groups to make this a valid clinical option. Restoration of fertility following spermatogonial stem cell transplantation in animals suggests therapeutic potential for the technique in humans, and further research is proceeding to address the safety and efficacy of this technique.