Kathleen Hwang

Concomitant Intramuscular Human Chorionic Gonadotropin Preserves Spermatogenesis in Men Undergoing Testosterone Replacement Therapy

PURPOSE Testosterone replacement therapy results in decreased serum gonadotropins and intratesticular testosterone, and impairs spermatogenesis, leading to azoospermia in 40% of patients. However, intratesticular testosterone can be maintained during testosterone replacement therapy with co-administration of low dose human chorionic gonadotropin, which may support continued spermatogenesis in patients on testosterone replacement therapy. MATERIALS AND METHODS We retrospectively reviewed the records of hypogonadal men treated with testosterone replacement therapy and concomitant low dose human chorionic gonadotropin. Testosterone replacement consisted of daily topical gel or weekly intramuscular injection with intramuscular human chorionic gonadotropin (500 IU) every other day. Serum and free testosterone, estradiol, semen parameters and pregnancy rates were evaluated before and during therapy. RESULTS A total of 26 men with a mean age of 35.9 years were included in the study. Mean followup was 6.2 months. Of the men 19 were treated with injectable testosterone and 7 were treated with transdermal gel. Mean serum hormone levels before vs during treatment were testosterone 207.2 vs 1,055.5 ng/dl (p <0.0001), free testosterone 8.1 vs 20.4 pg/ml (p = 0.02) and estradiol 2.2 vs 3.7 pg/ml (p = 0.11). Pretreatment semen parameters were volume 2.9 ml, density 35.2 million per ml, motility 49.0% and forward progression 2.3. No differences in semen parameters were observed during greater than 1 year of followup. No impact on semen parameters was observed as a function of testosterone formulation. No patient became azoospermic during concomitant testosterone replacement and human chorionic gonadotropin therapy. Nine of 26 men contributed to pregnancy with the partner during followup. CONCLUSIONS Low dose human chorionic gonadotropin appears to maintain semen parameters in hypogonadal men on testosterone replacement therapy. Concurrent testosterone replacement and human chorionic gonadotropin use may preserve fertility in hypogonadal males who desire fertility preservation while on testosterone replacement therapy.

Contemporary concepts in the evaluation and management of male infertility

Infertility in men is a common condition. At the core of the medical evaluation of the male partner in a couple who are unable to conceive is the history and physical examination. Special attention should be directed to the patients developmental history and any use of testosterone products. The physical examination focuses on the genitals, and includes assessments of the size and consistency of the testicles, epididymis, vas deferens, and presence of varicoceles. Although many sophisticated tests are available, semen analysis is still the most important diagnostic tool used to assess fertility, and includes parameters such as sperm count, motility and viability. Treatment of male factor infertility can involve targeted agents, in the case of specific conditions such as hypogonadotropic hypogonadism, or it can be empirical—using medical therapy or assisted conception techniques—for patients in whom no underlying cause has been identified. Although an all-encompassing treatment for male factor infertility has not yet been developed, the field offers many promising avenues of research.

Mendelian genetics of male infertility

Infertility is defined as the inability of a couple to conceive despite trying for a year, and it affects approximately 15% of the reproductive‐age population. It is considered a genetically lethal factor, as the family lineage stops at that individual with no progeny produced. A genetic defect associated with an infertile individual cannot be transmitted to the offspring, ensuring the maintenance of reproductive fitness of the species. However, with the advent of assisted reproductive techniques (ART), we are now able to overcome sterility and bypass natures protective mechanisms that developed through evolution to prevent fertilization by defective or deficient sperm.

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.

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.

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.

Use of Diagnostic Testing to Detect Infertility

The evaluation of the infertile male continues to be a clinical challenge of increasing significance with considerable emotional and financial burdens. Many physiological, environmental and genetic factors are implicated; however, the etiology of suboptimal semen quality is poorly understood. This review focuses on the diagnostic testing currently available, as well as future directions that will be helpful for the practicing urologist and other clinicians to fully evaluate the infertile male.

Controversies in testosterone replacement therapy: testosterone and cardiovascular disease

The role of testosterone in the cardiovascular (CV) health of men is controversial. Data suggest that both the condition and treatment of clinical hypogonadism is associated with decreased CV mortality; however, two recent studies suggest that hypogonadal subjects treated with testosterone replacement therapy have a higher incidence of new CV events. There has been increased media attention concerning the risk of CV disease in men treated with testosterone. Until date, there are no long-term prospective studies to determine safety. Literature spanning over the past 30 years has suggested that not only is there a possible increased CV risk in men with low levels of testosterone, but the benefits from testosterone therapy may even lower this risk. We review here the recent studies that have garnered such intense scrutiny. This article is intended as a thorough review of testosterone levels and CV risk, providing the clinician with the facts needed to make informed clinical decisions in managing patients with clinical hypogonadism.

The use of fluorescent in situ hybridization in male infertility

Male factors are implicated in up to 50% of couples being evaluated and treated for infertility with advanced assisted reproductive technologies. Genetic abnormalities, including sperm chromosome aneuploidy as well as structural aberrations, are one of the major causes of infertility. The use of chromosome-specific DNA probes labeled with fluorochromes, particularly the combination with multiple probes, has been used to indirectly study the sperm chromosome by fluorescent in situ hybridization (FISH). Clinically, this technique is also used to assess the sperm of men recovering from gonadotoxic treatment. Recent advances in this technology facilitate the evaluation of sperm aneuploidy. Sperm FISH is a widely used screening tool to aid in counseling couples with severe male factor infertility, especially in cases of prior repeated in vitro fertilization/intracytoplasmic sperm injection failure or recurrent pregnancy loss. Automation of FISH imaging and analysis, as well as the development of emerging techniques such as comparative genomic hybridization, will all contribute to the promise of future diagnostic approaches aimed at improving the quality, ease, and efficiency of aneuploidy analysis.