Craig Niederberger

The multinational Men's Attitudes to Life Events and Sexuality (MALES) study: I. Prevalence of erectile dysfunction and related health concerns in the general population.

Objective: The aims of the Mens Attitudes to Life Events and Sexuality (MALES) study were to identify prevalence of erectile dysfunction (ED) and related health issues in the general male population in Europe, North and South America, and to examine the attitudes and behavior of men in relation to these health issues. Research design and methods: Phase I of the MALES study involved 27839 men aged 20-75years who were interviewed in eight countries (United States, United Kingdom, Germany, France, Italy, Spain, Mexico, and Brazil) using a standardized questionnaire. Phase II of the MALES study involved 2912 men who were recruited from the sub-sample of Phase I MALES participants who reported ED together with additional men with ED recruited from other sources. Main outcome measure: Prevalence of ED and associated attitudes. Results:The overall prevalence of ED in the MALES sample was 16%. ED prevalence varied markedly by country, however, from a high of 22% of men in the US reporting ED to a low of 10% in Spain. The prevalence of self-reported ED increased with increasing age. Men with co-morbid medical conditions and risk factors, including cardiovascular disease, hypertension, dyslipidemia, and depression all reported higher prevalence of ED. Men with ED also reported increased prevalence rates of these co-morbid conditions. MALES Phase II data indicated that among men who reported ED, 58% had actively sought medical attention for their condition; however, only 16% of men with ED were currently being treated with oral PDE-5 therapy. Conclusions: The MALES study confirms the high prevalence rates of ED and its association with co-morbid medical conditions, such as diabetes and depression, reported in other large-scale, epidemiological studies. Despite the advent of oral phosphodiesterase inhibitors, only 58% of ED sufferers consult a physician about their problem, and only 16% of men with self-reported ED maintain their use of oral therapy.

Herniorrhaphy with polypropylene mesh causing inguinal vasal obstruction: a preventable cause of obstructive azoospermia.

Objective:To report a multiinstitutional experience of men presenting with infertility secondary to inguinal hernia repair using polypropylene mesh. Summary Background Data:An estimated 80% of inguinal hernia operations involve placement of a knitted polypropylene mesh to form a “tension-free” herniorrhaphy. The prosthetic mesh induces a chronic foreign-body fibroblastic response creating scar tissue that imparts strength to the floor and leads to fewer recurrences. However, little is known about the long-term effects of the polypropylene mesh on the vas deferens, especially with regard to fertility. Methods:Eight institutions in the United States reported a total of 14 cases of azoospermia secondary to inguinal vasal obstruction related to previous polypropylene mesh herniorrhaphy. Patient characteristics and operative findings were forwarded to 1 center for tabulation of data. Results:Mean patient age was 35.5 years with an average duration of infertility of 1.8 years. Mean number of years between urologic evaluation and herniorrhaphy was 6.3 years. Types of inguinal hernia repair previously performed were: open (10), laparoscopic (2), or both (2). Nine patients had bilateral obstruction and 5 patients had unilateral obstruction with contralateral testicular atrophy or epididymal obstruction. Surgical exploration revealed a dense fibroblastic response encompassing the polypropylene mesh with either trapped or obliterated vas in all patients. Surgical reconstruction was performed in 8 of 14 men (57%). Conclusion:Reconstruction to restore fertility can be difficult secondary to fibrotic reaction. Before undergoing polypropylene mesh herniorrhaphy, men, especially of young reproductive age or with a solitary testicle, need to be carefully advised of potential obstruction and compromise to future fertility.

THE ROLE OF TESTICULAR BIOPSY IN THE MODERN MANAGEMENT OF MALE INFERTILITY

PURPOSE We evaluate the traditional role of isolated testicular biopsy as a diagnostic tool, as opposed to the value as a therapeutic procedure for azoospermic men. MATERIALS AND METHODS The medical records of azoospermic patients who were evaluated, and treated between 1995 and 2000 were retrospectively analyzed for history, physical examination findings, endocrine profiles, testicular histology and sperm retrieval rates. Based on these parameters, cases were placed into diagnostic categories that included obstructive or nonobstructive azoospermia. Diagnostic parameters used to distinguish obstructive from nonobstructive azoospermia were subjected to statistical analysis with the t-test, analysis of variance and receiver operating characteristics curve. RESULTS A total of 153 azoospermic men were included in our analysis. Of men with obstructive azoospermia 96% had follicle-stimulating hormone (FSH) 7.6 mIU/ml. or less, or testicular long axis greater than 4.6 cm. Conversely, 89% of men with nonobstructive azoospermia had FSH greater than 7.6 mIU/ml., or testicular long axis 4.6 cm. or less. Receiver operating characteristics analysis revealed that FSH, testicular long axis, and luteinizing hormone were the best individual diagnostic predictors, with areas 0.87, 0.83 and 0.79, respectively. CONCLUSIONS In the vast majority of patients obstructive azoospermia may be distinguished clinically from nonobstructive azoospermia with a thorough analysis of diagnostic parameters. Based on this result, we believe that the isolated diagnostic testicular biopsy is rarely if ever indicated. Men with FSH 7.6 mIU/ml. or greater, or testicular long axis 4.6 cm. or less may be considered to have nonobstructive azoospermia and counseled accordingly. These men are best treated with therapeutic testicular biopsy and sperm extraction, with processing and cryopreservation for usage in in vitro fertilization and intracytoplasmic sperm injection if they accept advanced reproductive treatment. Diagnostic biopsy is of no other value in this group. Men with FSH 7.6 mIU/ml. or less, or testicular long axis greater than 4.6 cm. may elect to undergo reconstructive surgery with or without testicular biopsy and sperm extraction, or testicular biopsy and sperm extraction alone depending on their reproductive goals.

In vitro fertilization outcomes after intracytoplasmic sperm injection with fresh or frozen-thawed testicular spermatozoa

OBJECTIVE To compare the outcomes of intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) with fresh and cryopreserved testicular spermatozoa in patients with obstructive and nonobstructive azoospermia. DESIGN Retrospective analysis of consecutive ICSI cycles. SETTING Large urban reproductive medicine program. PATIENT(S) Twenty-nine patients with obstructive and nonobstructive azoospermia undergoing testicular sperm extraction for a total of 46 IVF-ICSI cycles (12 fresh, 34 frozen). INTERVENTION(S) Testicular sperm extraction, cryopreservation, and IVF-ICSI with fresh or frozen-thawed spermatozoa. MAIN OUTCOME MEASURE(S) Fertilization rates, embryo cleavage rates, embryo implantation rates, clinical pregnancy rates per cycle and per embryo transfer, and delivery and spontaneous abortion rates. RESULT(S) No statistically significant differences were noted in any of the parameters examined between IVF-ICSI cycles from fresh or frozen-thawed testicular spermatozoa. Fertilization rates were 56% with fresh vs. 61% with frozen-thawed testicular sperm, cleavage rates 92% vs. 95%, implantation rates 26% vs. 17%, clinical pregnancy rates per cycle 33% vs. 41%, and pregnancy rates per embryo transfer 33% vs. 45%, respectively. Delivery rates were 75% with fresh vs. 69.2% with frozen-thawed testicular sperm, and spontaneous abortion rates 25% and 30.8%, respectively. CONCLUSION(S) No differences were found in IVF-ICSI outcomes between cryopreserved and fresh testicular sperm. In addition, cryopreservation provides several advantages for the patients and reproductive team.

Genome-wide Association Study Identifies Candidate Genes for Male Fertility Traits in Humans

Despite the fact that hundreds of genes are known to affect fertility in animal models, relatively little is known about genes that influence natural fertility in humans. To broadly survey genes contributing to variation in male fertility, we conducted a genome-wide association study (GWAS) of two fertility traits (family size and birth rate) in 269 married men who are members of a founder population of European descent that proscribes contraception and has large family sizes. Associations between ∼250,000 autosomal SNPs and the fertility traits were examined. A total of 41 SNPs with p ≤ 1 × 10(-4) for either trait were taken forward to a validation study of 123 ethnically diverse men from Chicago who had previously undergone semen analyses. Nine (22%) of the SNPs associated with reduced fertility in the GWAS were also associated with one or more of the ten measures of reduced sperm quantity and/or function, yielding 27 associations with p values < 0.05 and seven with p values < 0.01 in the validation study. On the basis of 5,000 permutations of our data, the probabilities of observing this many or more small p values were 0.0014 and 5.6 × 10(-4), respectively. Among the nine associated loci, outstanding candidates for male fertility genes include USP8, an essential deubiquitinating enzyme that has a role in acrosome assembly; UBD and EPSTI1, which have potential roles in innate immunity; and LRRC32, which encodes a latent transforming growth factor β (TGF-β) receptor on regulatory T cells. We suggest that mutations in these genes that are more severe may account for some of the unexplained infertility (or subfertility) in the general population.

Optimization of spermatogenesis-regulating hormones in patients with non-obstructive azoospermia and its impact on sperm retrieval: A multicentre study

Study Type – Therapy (outcomes)

Cloning, expression analysis and chromosomal localization of the human nuclear receptor gene GCNF

Germ cell nuclear factor (GCNF) is an orphan member of the nuclear receptor gene superfamily. We report the cloning of a cDNA encoding a new variant of human GCNF from human testis and its expression analysis. Southern blot analysis of the human genomic DNA indicates that the GCNF gene is not closely related to other members within the nuclear receptor superfamily. Chromosomal localization of the GCNF gene shows that the gene is located on chromosome 9 at the locus q33–34.1. In situ hybridization analysis of GCNF expression in the testis shows that human GCNF is expressed exclusively in germ cells.

Phosphodiesterase 11: a brief review of structure, expression and function

Phosphodiesterase 11 (PDE11) is the latest isoform of the phosphodiesterase family to be identified. Interest in PDE11 has increased recently because tadalafil, an oral phosphodiesterase 5 inhibitor, cross reacts with PDE11. The function of PDE11 remains largely unknown, but growing evidence points to a possible role in male reproduction. The published literature on PDE11 structure, function and expression is reviewed.

In situ hybridization shows that Dazla expression in mouse testis is restricted to premeiotic stages IV-VI of spermatogenesis

JDepartment of Urology, University of Illinois at Chicago, Chicago, Illinois, USA 2Department of Genetics, University of Illinois at Chicago, Chicago, Illinois, USA 3Department of Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, Illinois, USA 4Department of Obstetrics and Gynecology, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA 5Department of Molecular and Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA 6Department of Urology, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA 7Department of Cell Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas 77030, USA

Predictors of general quality of life in patients with benign prostate hyperplasia or prostate cancer

PURPOSE Studies in disease specific populations have emphasized disease specific quality of life with little study of general quality of life. Furthermore, studies of general quality of life in disease specific populations have mostly examined the importance of disease specific variables, and have generally yielded poor correlations of such variables and general quality of life. We attempted to model the emotional component of general quality of life in patients with prostate disease. MATERIALS AND METHODS We integrated prospectively collected disease specific and nonspecific clinical and self-reported patient data. We also applied neural network and more conventional statistical tools to examine the relative use of various available analytical methodologies in modeling general quality of life. RESULTS Neural networks created reasonably good models of the emotional component of general quality of life. Logistic regression analysis also created reasonably good models and, given current computational schemes, allowed for identification of significant inputs in the models more readily than did the feed-forward, back propagation neural networks. All models of general quality of life relied primarily on disease nonspecific inputs, including social support, activities of daily living and coping. CONCLUSIONS Our observations suggested that efforts to optimize general quality of life in patients with prostate disease must integrate disease nonspecific variables.