Samuel Ohlander

Impact of fresh versus cryopreserved testicular sperm upon intracytoplasmic sperm injection pregnancy outcomes in men with azoospermia due to spermatogenic dysfunction: a meta-analysis

OBJECTIVE To determine if clinical pregnancy rates and fertilization rates with the use of cryopreserved sperm for intracytoplasmic sperm injection (ICSI) in patients with azoospermia due to spermatogenic dysfunction (i.e., nonobstructive azoospermia) are similar to those with fresh sperm. DESIGN Systematic review and meta-analysis. SETTING Academic medical center. PATIENT(S) Azoospermic men secondary to spermatogenic dysfunction. INTERVENTION(S) Not applicable. MAIN OUTCOME MEASURE(S) Clinical pregnancy rate, fertilization rate. RESULT(S) Eleven studies met criteria for the outcome of clinical pregnancy rate. Seventy-nine (28.7%) of 275 intracytoplasmic sperm injection cycles using fresh testicular sperm resulted in a clinical pregnancy, compared with 84 (28.1%) of 299 intracytoplasmic sperm injection cycles using cryopreserved sperm (relative risk [RR] 1.00, 95% confidence interval [CI] 0.75-1.33). Ten studies met criteria for the outcome of fertilization rate. A total of 1,422 (52.9%) of 2,687 oocytes injected with fresh testicular sperm were fertilized, compared with 1,490 (54.0%) of 2,757 oocytes injected with cryopreserved sperm (RR 0.97, 95% CI 0.92-1.02). CONCLUSION(S) In men with azoospermia due to spermatogenic dysfunction, there is no statistical difference between the use of fresh versus cryopreserved-thawed testicular sperm when assessing clinical pregnancy or fertilization rates in couples undergoing ICSI.

Erythrocytosis Following Testosterone Therapy

INTRODUCTION A rapid increase in awareness of androgen deficiency has led to substantial increases in prescribing of testosterone therapy (TTh), with benefits of improvements in mood, libido, bone density, muscle mass, body composition, energy, and cognition. However, TTh can be limited by its side effects, particularly erythrocytosis. This review examines the literature on testosterone-induced erythrocytosis and polycythemia. AIM To review the available literature on testosterone-induced erythrocytosis, discuss possible mechanisms for pathophysiology, determine the significance of formulation, and elucidate potential thromboembolic risk. METHODS A literature review was performed using PubMed for articles addressing TTh, erythrocytosis, and polycythemia. MAIN OUTCOME MEASURES Mechanism, pharmacologic contribution, and risk of testosterone-induced erythrocytosis. RESULTS For men undergoing TTh, the risk of developing erythrocytosis compared with controls is well established, with short-acting injectable formulations having the highest associated incidence. Potential mechanisms explaining the relation between TTh and erythrocytosis include the role of hepcidin, iron sequestration and turnover, erythropoietin production, bone marrow stimulation, and genetic factors. High blood viscosity increases the risk for potential vascular complications involving the coronary, cerebrovascular, and peripheral vascular circulations, although there is limited evidence supporting a relation between TTh and vascular complications. CONCLUSION Short-acting injectable testosterone is associated with greater risk of erythrocytosis compared with other formulations. The mechanism of the pathophysiology and its role on thromboembolic events remain unclear, although some data support an increased risk of cardiovascular events resulting from testosterone-induced erythrocytosis. Ohlander SJ, Varghese B, Pastuszak AW. Erythrocytosis Following Testosterone Therapy. Sex Med Rev 2018;6:77-85.

Variants in DPF3 and DSCAML1 are associated with sperm morphology.

PurposeAbnormalities in semen parameters are often associated with reduced fertility in males, and may, in part, be attributed to genetic variation. Aim of this study is to determine if genetic variants that were previously shown to be predictors of family size and birth rate in healthy men are also associated with sperm morphology in men recruited from an infertility laboratory.MethodsGenetic associations with sperm morphology phenotypes in 126 ethnically diverse men from Chicago at 41 independent loci, previously shown to be predictors of family size and birth rate in healthy men, were tested.ResultsTwo intronic SNPs, rs680730 (in DSCAML1) and rs10129954 (in DPF3), were associated with the percent of normal sperm morphology in Chicago men (P = 0.017 and 0.023, respectively). Furthermore, both loci were associated with increased occurrence of sperm head defects.ConclusionsSNPs in two genes, both of which have roles in nervous system development, were associated with poor sperm morphology. These results may be helpful in identification of other novel genes and biological pathways whose proper functioning is crucial for sperm production and male reproductive processes.

Implications of Sperm Source on ICSI Outcome: Assessment of TESE and Other Surgical Sperm Retrieval Methods

This chapter addresses the options for sperm origin for couples requiring intracytoplasmic sperm injection (ICSI) for advanced fertility treatment. Sperm from various sources have been shown to have differing properties, which are thought to affect ICSI outcomes. One of these key differences is in the DNA fragmentation index (DFI). It has been postulated that sperm DFI increases during transit through the male genital tract and that this may impact fertilization and pregnancy rates. Sperm may be either ejaculated or surgically retrieved from the testicle, vas deferens, or epididymis. Various retrieval methods exist. In men with azoospermia, epididymal and testicular sperm have been utilized for ICSI with varied results; therefore, a conclusive superior source cannot be identified. In men with cryptozoospermia, ejaculated sperm or surgically retrieved sperm can be used. Comparing testicular and ejaculated sperm, combining all studies no statistically significant difference in pregnancy or fertilization rates have been seen.

Environmental Toxins and Male Fertility

Purpose of ReviewGlobal industrialization has increased population exposure to environmental toxins. A global decline in sperm quality over the last few decades raises questions about the adverse impact of environmental toxins on male reproductive health.Recent FindingsMultiple animal- and human-based studies on exposure to environmental toxins suggest a negative impact on semen quality, in terms of sperm concentration, motility, and/or morphology. These toxins may exert estrogenic and/or anti-androgenic effects, which in turn alter the hypothalamic-pituitary-gonadal axis (HPGA), induce sperm DNA damage, or cause sperm epigenetic changes.SummaryThis chapter will discuss the most recent literature about the most common environmental toxins and their impact on spermatogenesis and its consequences on male fertility. Understanding the presence and underlying mechanism of these toxins will help us preserve the integrity of the male reproduction system and formulate better regulations against their indiscriminate use.

Growth Hormone Secretagogue Treatment in Hypogonadal Men Raises Serum Insulin-Like Growth Factor-1 Levels:

Realizing the reported misuse of human growth hormone (GH), investigation of a safe alternative mechanism for increasing endogenous GH is needed. Several GH secretagogues are available, including GH-releasing peptides (GHRPs) GHRP-2 and GHRP-6, and the GH-releasing hormone analog, sermorelin (SERM). Insulin-like growth factor 1 (IGF-1) serves as a surrogate marker for GH. Here, the effect of GHRP/SERM therapy on IGF-1 levels is evaluated. A retrospective review of medical records was performed for 105 men on testosterone (T) therapy seeking increases in lean body mass and fat loss who were prescribed 100 mcg of GHRP-6, GHRP-2, and SERM three times daily. Compliance with therapy was assessed, and 14 men met strict inclusion criteria. Serum hormone levels of IGF-1, T, free T (FT), estradiol (E), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were evaluated. Mean (SD) age of the cohort was 33.2 (2.9) years, and baseline IGF-1 level was 159.5 (26.7) ng/mL. Mean (SD) duration of continuous GHRP/SERM treatment was 134 (88) days. Mean posttreatment IGF-1 level was 239.0 (54.6) ng/mL (p < .0001). Three of the 14 men were on an aromatase inhibitor and/or tamoxifen prior to treatment and another 4 men were coadministered an aromatase inhibitor and/or tamoxifen during treatment. Inhibition of E production or estrogen receptor blockade resulted in smaller increases in IGF-1 levels. GHRP/SERM therapy increases serum IGF-1 levels with strict compliance to thrice-daily dosing. The results suggest that combination therapy may be beneficial in men with wasting conditions that can improve with increased GH secretion.

MP47-05 LOW SERUM TESTOSTERONE IS ASSOCIATED WITH ELEVATIONS IN HIGH-SENSITIVITY CARDIOVASCULAR DISEASE BIOMARKERS

INTRODUCTION AND OBJECTIVES: Significant controversy exists regarding the relationship between serum testosterone (T) levels and cardiovascular risk, with evidence supporting increased risk in men with both low and high T levels. However, few studies have assessed cardiovascular (CV) risk as a function of plasma testosterone (T) level using objective biomarkers. Here we examine the relationship between T levels and a panel of high sensitivity CVD markers. METHODS: 10,041 unique male patients were identified in the database of the Singulex Clinical Laboratory (SCL), which specializes in high sensitivity (hs) CVD biomarker testing using single molecule counting (SMC) technology. Results were evaluated for total T, hscardiac troponin I (cTnI), endothelin-1 (ET), N-terminal pro-B-type natriuretic peptide (NTproBNP), interleukin-6, (IL-6), tumor necrosis factor-a (TNF-a), and interleukin-17A (IL-17A). Patients were grouped by total T concentration and associations with the above biomarkers were determined. RESULTS: Median (interquartile range) age within the cohort was 58 (48-68) years, and serum T level was 421 (305-565) ng/dL; T levels did not change with patient age (p1⁄40.78), but were inversely related with body mass index (BMI) (P<0.0001). An inverse relationship between plasma T level and the number of men with increased CV risk was observed for 6 of 7 cardiovascular markers, including IL-6, cTnI, TNF-a, ET, NTproBNP and leptin (Table 1). In men with T <250 ng/dL, after adjusting for age, BMI, hemoglobin A1c (HbA1c) levels, hsCRP and HDL cholesterol levels, IL-6, ET, NTproBNP, and leptin remained significantly associated with increased CV risk. As plama T levels increased, however, the fraction of men with marker values above the reference range, and therefore considered at increased risk, decreased (Figure 1). CONCLUSIONS: Our findings support prior reports demonstrating increased CV risk in hypogonadal men and argue against the controversial current clinical conclusion that men on testosterone therapy may have an increased incidence of CVD. Source of Funding: AWP and AH are National Institutes of Health (NIH) K12 Scholars supported by a Male Reproductive Health Research Career (MRHR) Development PhysicianScientist Award (HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program (to Dolores J. Lamb).

MP76-05 TWICE PER WEEK DOSING OF INTRAMUSCULAR TESTOSTERONE (T) IS ASSOCIATED WITH GREATER RISK OF ERYTHROCYTOSIS

INTRODUCTION AND OBJECTIVES: It is well known that testosterone plays a critical role in regulation of erectile function (EF). Veno-occlusive insufficiency is a causal or accompanying symptom in 20e45% of patients with ED. The conventional therapy of venogenic ED may be useless if unrecognized andogendeficiency. There are limited data shown that testosterone improves EF in hypogonadal patients with veno-occlusive dysfunction. In this multiclinical study we evaluated the results of testosterone therapy (TT) in the hypogonadal patients with corporal venous leakage. METHODS: 49 hypogonadal men with ED and venous leakage from corpora cavernosa, aged 32 e 56 (44 8, 3) non-responded to PDE-5 inhibitors, were examined. Comorbidities included diabetes mellitus (4 pts), arterial hypertension (5 pts), alcohol abuse ( 8pts). Testosterone levels were 2,3 -11,2 (6,8 3,1) nmol/l. After lab tests each patient underwent penile duplex ultrasound for reveling signs of venous deficiency. Arterial inflow was normal at all patients while the end diastolic velocity was >5 ml/sec. All patients underwent the treatment with 1,000 mg testosterone undecanoate on day 1, followed by another injection after 6 weeks and every 3 months thereafter 5 injections totally. Pharmacocavernosography (PCG) (7 pts) or magnetic resonance imaging (MRI) with contrast enhancement (14 pts) were used for visualization of venous leakage pathways prior to TT and after 6 -8 months of TT for the detection of venous leakage decreasing. Design of the investigation: open, prospective, non-control, non-randomize. RESULTS: All patients responded to the therapy and noted the considerable improvement in EF domain (IIEF scores increased to 24,5 0,5) and SD domain (IIEF scores increased to 9 0.3) 41/49 pts (84%) restore satisfactory coitus with monotherapy of testosterone. 8/49 pts (16%) poor responded to monotherapy had satisfactory coitus after combine therapy with PDE-5 inhibitors. After 6 months treatment the control penile duplex ultrasound revealed in 45 pts the end diastolic velocity <5 ml/sec. PCG or MRI was repeated in 12 patients. Compared with baseline investigation, repeat radiological studies after TT showed significant decreasing or even absence of the venous leakage from the corporal bodies. CONCLUSIONS: These results demonstrate that testosterone regulates the veno-occlusive mechanism of erection and improves the EF in hypogonadal patients with venous leakage. The combination of TT with PDE-5 inhibitors will be useful in poor responders to the testosterone monotherapy.

Device and method to determine perineal artery occlusion during road bicycling.

Greater than 60 million American men who ride bicycles are at risk of developing erectile dysfunction. One possible reason is occlusion of the perineal arteries. Researchers relied on indirect methods and stationary models to study this problem. We developed a novel system to quantify occlusion among bicycle riders during a road bike ride. Our verification and validation activities show that this system can be safely used on human subjects to measure perineal artery occlusion. The method described in this paper provides a valuable tool to the researchers to study or to develop new solutions that alleviate this problem. The outcomes of these efforts will help millions of cyclists worldwide.

Fourier transform infrared spectroscopic imaging identifies early biochemical markers of tissue damage

Fourier Transform Infrared (FT-IR) spectroscopic imaging can allow for the rapid imaging of tissue biochemistry in a label-free and non-perturbing fashion. With the rapid adoption of new minimally invasive surgery (MIS) technologies over the last 20 years, adequate skill to safely and effectively use these technologies may not be achieved and risk of undue physical pressure being placed on tissues is a concern. Previous work has demonstrated that a number of histological stains can detect tissue damage, however, this process requires the initiation and progression of a signaling cascade that results in the epitope of interest being expressed. We proposed to identify the early biochemical markers associated with physical tissue damage from applied forces, thus not requiring transcriptional and translational protein synthesis as traditional immunohistochemistry does. To demonstrate that FT-IR can measure biochemical changes in tissues that have undergone physical force, we took ex-vivo lamb’s liver that had been freshly excised and applied varying levels of physical pressure (0kPa to 30kPa). Tissues were then formalin-fixed, paraffin-embedded, and sectioned on to glass for H and E staining to identify damage and on to an IR slide for FT-IR imaging. Regions of interest containing hepatocytes were identified and average FT-IR spectra were extracted from the damaged and undamaged livers. FT-IR spectra showed clear biochemical changes associated with tissue damage. In addition, chemical changes could be observed proceeding histological changes observed when using conventional staining approaches.