Testosterone levels among non-obstructive azoospermic patients 2 years after failed bilateral microdissection testicular sperm extraction: a nested case-cohort study.

PURPOSE: To define the risk of hypogonadism following microdissection testicular sperm extraction in cases of non-obstructive azoospermia. While sperm retrieval by open testicular sperm extraction can be associated with an increased risk of hypogonadism, there is limited data addressing which procedures and which patients harbor the greatest risk. METHODS: We report on a community-acquired, nested, case-cohort of non-obstructive azoospermic patients referred to one clinic after failed bilateral microdissection testicular sperm extraction. Patients were health-matched (1:2) to surgically naïve controls and divided into 2 cohorts based on risk factors for hypogonadism. Among microdissection patients, we compared total testosterone and gonadotropin levels before and > 6 months after surgery. Biochemical hypogonadism was defined as a total serum testosterone level ≤ 300 ng/dL. Hormone levels were compared to risk-matched controls. Comparative statistics were used to assess hormone levels within and between cohorts. RESULTS: There were no significant differences in baseline testosterone levels between microdissection patients (n = 26) and risk-matched controls (n = 52). At a mean of 26 months (range 6.2-112.8) post-procedure, mean testosterone levels decreased significantly (73 ng/dL or 16%; CI - 27, - 166; p < 0.01, paired t-test). Among microdissection patients with baseline testosterone > 300 ng/dL, 8/22 (36%) experienced hypogonadism post-procedure. There was a corresponding increase in follicle stimulating hormone (p = 0.05) and a trending increase in luteinizing hormones (p = 0.10). CONCLUSION: A durable decrease in testosterone levels occurs after failed microdissection testicular sperm extraction regardless of baseline risk of hypogonadism. In addition, a significant proportion of eugonadal patients will become hypogonadal after failed testicular microdissection procedures.

Isolation of human testicular cells and co-culture with embryonic stem cells.

Our overall goal is to create a three-dimensional human cell-based testicular model for toxicological and spermatogenesis studies. Methods to purify the major somatic testicular cells, namely Leydig cells (LCs), peritubular myoid cells (PCs) and Sertoli cells (SCs), from rats, mice and guinea pigs have been reported. In humans, the isolation of populations enriched for primary LCs, PCs or SCs also have described. One objective of this study was to determine if populations of cells enriched for all three of these cell types can be isolated from testes of single human donors, and we were successful in doing so from testes of three donors. Testes tissues were enzymatically digested, gravity sedimented and Percoll filtered to isolate populations enriched for LCs, PCs and SCs. LCs and PCs were identified by colorimetric detection of the expression of prototypical enzymes. Division of PCs and SCs in culture has been reported. We observed that primary human LCs could divide in culture by incorporation of 5-ethynyl-2'-deoxyuridine. SCs were identified and their functionality was demonstrated by the formation of tight junctions as shown by the expression of tight junction proteins, increased transepithelial electrical resistance, polarized secretion of biomolecules and inhibition of lucifer yellow penetration. Furthermore, we found that human SC feeder layers could facilitate germ cell progression of human embryonic stem cells (hESCs) by microarray analysis of gene expression.

Reproductive genetics and the aging male.

PURPOSE: To examine current evidence of the known effects of advanced paternal age on sperm genetic and epigenetic changes and associated birth defects and diseases in offspring. METHODS: Review of published PubMed literature. RESULTS: Advanced paternal age (> 40 years) is associated with accumulated damage to sperm DNA and mitotic and meiotic quality control mechanisms (mismatch repair) during spermatogenesis. This in turn causes well-delineated abnormalities in sperm chromosomes, both numerical and structural, and increased sperm DNA fragmentation (3%/year of age) and single gene mutations (relative risk, RR 10). An increase in related abnormalities in offspring has also been described, including miscarriage (RR 2) and fetal loss (RR 2). There is also a significant increase in rare, single gene disorders (RR 1.3 to 12) and congenital anomalies (RR 1.2) in offspring. Current research also suggests that autism, schizophrenia, and other forms of "psychiatric morbidity" are more likely in offspring (RR 1.5 to 5.7) with advanced paternal age. Genetic defects related to faulty sperm quality control leading to single gene mutations and epigenetic alterations in several genetic pathways have been implicated as root causes. CONCLUSIONS: Advanced paternal age is associated with increased genetic and epigenetic risk to offspring. However, the precise age at which risk develops and the magnitude of the risk are poorly understood or may have gradual effects. Currently, there are no clinical screenings or diagnostic panels that target disorders associated with advanced paternal age. Concerned couples and care providers should pursue or recommend genetic counseling and prenatal testing regarding specific disorders.

Is human fecundity changing? A discussion of research and data gaps precluding us from having an answer.

Fecundity, the biologic capacity to reproduce, is essential for the health of individuals and is, therefore, fundamental for understanding human health at the population level. Given the absence of a population (bio)marker, fecundity is assessed indirectly by various individual-based (e.g. semen quality, ovulation) or couple-based (e.g. time-to-pregnancy) endpoints. Population monitoring of fecundity is challenging, and often defaults to relying on rates of births (fertility) or adverse outcomes such as genitourinary malformations and reproductive site cancers. In light of reported declines in semen quality and fertility rates in some global regions among other changes, the question as to whether human fecundity is changing needs investigation. We review existing data and novel methodological approaches aimed at answering this question from a transdisciplinary perspective. The existing literature is insufficient for answering this question; we provide an overview of currently available resources and novel methods suitable for delineating temporal patterns in human fecundity in future research.

Environmental toxicants perturb human Sertoli cell adhesive function via changes in F-actin organization mediated by actin regulatory proteins.

STUDY QUESTION: Can human Sertoli cells cultured in vitro and that have formed an epithelium be used as a model to monitor toxicant-induced junction disruption and to better understand the mechanism(s) by which toxicants disrupt cell adhesion at the Sertoli cell blood-testis barrier (BTB)? SUMMARY ANSWER: Our findings illustrate that human Sertoli cells cultured in vitro serve as a reliable system to monitor the impact of environmental toxicants on the BTB function. WHAT IS KNOWN ALREADY: Suspicions of a declining trend in semen quality and a concomitant increase in exposures to environmental toxicants over the past decades reveal the need of an in vitro system that efficiently and reliably monitors the impact of toxicants on male reproductive function. Furthermore, studies in rodents have confirmed that environmental toxicants impede Sertoli cell BTB function in vitro and in vivo. STUDY DESIGN, SIZE AND DURATION: We examined the effects of two environmental toxicants: cadmium chloride (0.5-20 µM) and bisphenol A (0.4-200 µM) on human Sertoli cell function. Cultured Sertoli cells from three men were used in this study, which spanned an 18-month period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human Sertoli cells from three subjects were cultured in F12/DMEM containing 5% fetal bovine serum. Changes in protein expression were monitored by immunoblotting using specific antibodies. Immunofluorescence analyses were used to assess changes in the distribution of adhesion proteins, F-actin and actin regulatory proteins following exposure to two toxicants: cadmium chloride and bisphenol A (BPA). MAIN RESULTS AND THE ROLE OF CHANCE: Human Sertoli cells were sensitive to cadmium and BPA toxicity. Changes in the localization of cell adhesion proteins were mediated by an alteration of the actin-based cytoskeleton. This alteration of F-actin network in Sertoli cells as manifested by truncation and depolymerization of actin microfilaments at the Sertoli cell BTB was caused by mislocalization of actin filament barbed end capping and bundling protein Eps8, and branched actin polymerization protein Arp3. Besides impeding actin dynamics, endocytic vesicle-mediated trafficking and the proper localization of actin regulatory proteins c-Src and annexin II in Sertoli cells were also affected. Results of statistical analysis demonstrate that these findings were not obtained by chance. LIMITATIONS, REASONS FOR CAUTION: (i) This study was done in vitro and might not extrapolate to the in vivo state, (ii) conclusions are based on the use of Sertoli cell samples from three men and (iii) it is uncertain if the concentrations of toxicants used in the experiments are reached in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Human Sertoli cells cultured in vitro provide a robust model to monitor environmental toxicant-mediated disruption of Sertoli cell BTB function and to study the mechanism(s) of toxicant-induced testicular dysfunction.

New Traditional Chinese Medicine Supplement Reduces Pain Faster than Conventional Pain Pills Alone: A Phase I/II Prospective, Double-Blinded Placebo-Controlled Randomized Trial.

BACKGROUND: The opioid crisis demands novel solutions for postoperative pain control. Traditional Chinese medicine (TCM) has used herbs for the treatment of pain for thousands of years. We studied whether a synergistic multimodal TCM supplement could reduce the need for conventional pain pills for low risk surgical procedures. METHODS: In a Phase I/II, prospective, double-blind, placebo-controlled, randomized clinical trial (PRCT), 93 patients were randomized to either TCM supplement or placebo oral medication for low-risk outpatient surgical procedures. Study medications began 3 days preoperatively and continued for 5 days postoperatively. Conventional pain pill use was not restricted. Patients were monitored postoperatively for all forms of pain pill use (Pain Pill Scoring Sheet) and subjective pain ratings (Brief Pain Inventory Short Form). Primary outcomes included type and number of pain pills used and subjective pain ratings. Secondary outcomes included an assessment of mood, general activity, sleep, and enjoyment of life. RESULTS: TCM use well tolerated. Conventional pain pill use was similar between groups. Linear regression analysis revealed that TCM reduced postoperative pain 3 times faster than placebo (P < .0001) with a 4-fold greater magnitude of relief by postoperative day 5 (P = .008). TCM also significantly improved sleep habits (P = .049) during the postoperative period. TCM effect was independent of type of surgery or amount of preoperative pain. DISCUSSION: This PRCT is the first to show that a multimodal, synergistic TCM supplement is safe and can effectively reduce acute postoperative pain more rapidly, and to a lower level, than conventional pain pills alone.

Roles of Spermatogonial Stem Cells in Spermatogenesis and Fertility Restoration.

Spermatogonial stem cells (SSCs) are a group of adult stem cells in the testis that serve as the foundation of continuous spermatogenesis and male fertility. SSCs are capable of self-renewal to maintain the stability of the stem cell pool and differentiation to produce mature spermatozoa. Dysfunction of SSCs leads to male infertility. Therefore, dissection of the regulatory network of SSCs is of great significance in understanding the fundamental molecular mechanisms of spermatogonial stem cell function in spermatogenesis and the pathogenesis of male infertility. Furthermore, a better understanding of SSC biology will allow us to culture and differentiate SSCs in vitro, which may provide novel stem cell-based therapy for assisted reproduction. This review summarizes the latest research progress on the regulation of SSCs, and the potential application of SSCs for fertility restoration through in vivo and in vitro spermatogenesis. We anticipate that the knowledge gained will advance the application of SSCs to improve male fertility. Furthermore, in vitro spermatogenesis from SSCs sets the stage for the production of SSCs from induced pluripotent stem cells (iPSCs) and subsequent spermatogenesis.

Bioethics in human embryology: the double-edged sword of embryo research.

There has been a significant increase in the use of assisted reproductive therapies (ARTs) over the past several decades, allowing many couples with infertility to conceive. Despite the achievements in this field, a mounting body of evidence concerning the epigenetic risks associated with ART interventions such as ovarian hormonal stimulation, intracytoplasmic sperm injection (ICSI), and in vitro culture (IVC) of oocytes and embryos has also emerged. Induced development of multiple follicles, the IVC media itself, and extended culture may alter the epigenome of both gametes and embryos, resulting in yet to be fully understood developmental, postnatal, and adult life health consequences. Investigators have attempted to decipher the molecular mechanisms mediating ART-induced epigenetic changes using either human samples or animal models with some success. As research in this field continues to expand, the ethical responsibilities of embryologists and researchers have become critically important. Here, we briefly discuss the ethical aspects of ART research, concentrating on the constraints arising from the perceived 'unnaturalness' of many of these procedures. Secondly, we focus on the bioethics and morality of human embryo research in general and how ethically acceptable model systems may be used to mimic early human embryogenesis. Lastly, we review the 14-day culture limit of human embryos and the notion that this rule could be considered of taken into account using new technologies and cues from animal models. The 'black box' of early post-implantation embryogenesis might be revealed using embryo models. As long as this distinct moral line has been drawn and closely followed, we should not fear scientific growth in embryo research. Although in vitro fertilization (IVF) is ethically acceptable, research with human embryos to improve its success raises serious ethical concerns that are in need of constant revisiting.Glossary index: Moral status: the ascription of obligations and rights to embryos on the basis of sentience; Sentience: the capacity of the developing embryo to experience feelings and sensations, such as the awareness of pain; Ectogenesis: the growth of the embryo in an artificial environment outside the mother's body.

Narrative review of the history of microsurgery in urological practice.

The clinical need for magnified visualization during surgery spurred the evolution of microscope and microsuture technology. Innovative surgeons across various surgical specialties recognized the importance of utilizing and advancing these technologies. Operative microscopy allows human dexterity to perform beyond direct visual limitations. Microsurgery started in otolaryngology and ophthalmology, became popular in reconstruction and transplantation, and was then adopted in urology. Microsurgery in urology involves renal and penile revascularization, penile transplantation and free flap phalloplasty, testicular autotransplantation, reproductive tract reconstruction of the vas deferens and epididymis, varicocele repair, and sperm retrieval. By examining the peer reviewed and lay literature, this review discusses the history of microsurgery and its subsequent development as a subspecialty in urology.

A study of pregnancy rates in "cleared" male factor couples.

BACKGROUND: Among couples with male factor infertility, the natural pregnancy rates associated with classic male factor treatments are well described. In couples with unexplained infertility, the proportion due to occult male factor is unclear. We hypothesized that many men diagnosed with unexplained infertility are actually fertile. We describe the 1-year natural pregnancy rates among couples in whom the male partner has been "cleared" of infertility on urologic evaluation. METHODS: Consecutive infertile couples were recruited from a single practice (PJT) over a 3-year period. A thorough male factor evaluation was performed, including a history, physical examination and 2 semen analyses. Based on this assessment, male partners in whom bulk semen parameters were normal were "cleared" from further evaluation. Lifestyle modifications were allowed, but no medical or surgical treatments were offered. The presence or absence of a female factor evaluation was not required for study inclusion. Subjects were followed for 12 months or until a pregnancy was achieved. Subjects were contacted via telesurvery 1-year later and pregnancy status ascertained. Simple descriptive statistics were used to evaluate the significance of observations. RESULTS: Fifty-four men were enrolled in the study. The mean duration of infertility was 1.5 years (range, 0.4 to 4.0 years) and the mean male and female partner ages were 38.6 and 35.1 years, respectively. On evaluation, 40% of men were noted to have significant fertility risks that included a clinical varicocele, exposures, and androgen altering medications. Among n=31 couples with known pregnancy outcomes, 20/31 (65%) conceived naturally at a mean of 9 months after evaluation (range, 3-30 mos). Another 1/31 (3%) couples conceived with intrauterine insemination (IUI) and 4/31 (13%) conceived with IVF-ICSI. CONCLUSIONS: A significant proportion of men diagnosed with unexplained infertility have lifestyle risk factors on urologic evaluation. Care in the form of counseling at-risk patients regarding lifestyle issues, in the absence of formal treatment, may have value in improving the fertility potential in this population. Indeed, natural conception rates among men identified with unexplained infertility are substantial and suggest that many of these men are truly fertile.

Successful Targeted Testicular Sperm Extraction Using Microsurgical Technique (microTESE) Following Fine Needle Aspiration (FNA) Mapping in a Non-Obstructive Azoospermia (NOA) Patient: A Case Report.

BACKGROUND: Management for male infertility can be difficult for some cases. Surgical intervention has long been thought as the last resort to help married couples to conceive. The current guideline recommends testicular sperm extraction with micro-surgery technique (microTESE) in severe cases of male infertility. However, the success rate still varies. Thus, a new strategy was needed to further increase the sperm retrieval success rate. CASE PRESENTATION: A 39-year-old male with a history of failed sperm extraction, non-obstructive azoospermia (NOA) and Y-chromosomal microdeletion came to the fertility center to undergo sperm retrieval. Fine needle aspiration (FNA) Mapping was performed prior to microTESE to increase the accuracy of sperm retrieval. After further examination with laser assisted immotile sperm selection (LAISS), five spermatozoa were found. CONCLUSION: The combination of FNA Mapping and microTESE increases the chance of a successful sperm extraction.

COVID-19 and human reproduction: A pandemic that packs a serious punch.

The COVID-19 pandemic has led to a worldwide health emergency that has impacted 188 countries at last count. The rapid community transmission and relatively high mortality rates with COVID-19 in modern times are relatively unique features of this flu pandemic and have resulted in an unparalleled global health crisis. SARS-CoV-2, being a respiratory virus, mainly affects the lungs, but is capable of infecting other vital organs, such as brain, heart and kidney. Emerging evidence suggests that the virus also targets male and female reproductive organs that express its main receptor ACE2, although it is as yet unclear if this has any implications for human fertility. Furthermore, professional bodies have recommended discontinuing fertility services during the pandemic such that reproductive services have also been affected. Although increased safety measures have helped to mitigate the propagation of COVID-19 in a number of countries, it seems that there is no predictable timeline to containment of the virus, a goal likely to remain elusive until an effective vaccine becomes available  and widely distributed across the globe. In parallel, research on reproduction has been postponed for obvious reasons, while diagnostic tests that detect the virus or antibodies against it are of vital importance to support public health policies, such as social distancing and our obligation to wear masks in public spaces. This review aims to provide an overview of critical research and ethics issues that have been continuously emerging in the field of reproductive medicine as the COVID-19 pandemic tragically unfolds.Abbreviations: ACE2: angiotensin- converting enzyme 2; ART: Assisted reproductive technology; ASRM: American Society for Reproductive Medicine; CCR9: C-C Motif Chemokine Receptor 9; CDC: Centers for Disease Control and Prevention; COVID-19: Coronavirus disease 2019; Ct: Cycle threshold; CXCR6: C-X-C Motif Chemokine Receptor 6; ELISA: enzyme-linked immunosorbent assay; ESHRE: European Society of Human Reproduction and Embryology; ET: Embryo transfer; FSH: Follicle Stimulating Hormone; FFPE: formalin fixed paraffin embedded; FYCO1: FYVE And Coiled-Coil Domain Autophagy Adaptor 1; IFFS: International Federation of Fertility Societies; IUI: Intrauterine insemination; IVF: In vitro fertilization; LH: Luteinizing Hormone; LZTFL1: Leucine Zipper Transcription Factor Like 1; MAR: medically assisted reproduction services; MERS: Middle East Respiratory syndrome; NGS: Next Generation Sequencing; ORF: Open Reading Frame; PPE: personal protective equipment; RE: RNA Element; REDa: RNA Element Discovery algorithm; RT-PCR: Reverse=trascriptase transcriptase-polymerase chain reaction; SARS: Severe acute respiratory syndrome; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; SLC6A20: Solute Carrier Family 6 Member 20; SMS: Single Molecule Sequencing; T: Testosterone; TMPRSS2: transmembrane serine protease 2; WHO: World Health Organization; XCR1: X-C Motif Chemokine Receptor.

A novel application of 1H magnetic resonance spectroscopy: non-invasive identification of spermatogenesis in men with non-obstructive azoospermia.

BACKGROUND: About 10% of infertile men have no sperm in their ejaculate due to poor or absent spermatogenesis, also known as non-obstructive azoospermia (NOA). Testis (1)H magnetic resonance spectroscopy ((1)H-MRS) is a non-invasive imaging tool that can potentially identify and localize spermatogenesis in the testis. This study sought to identify metabolic signatures associated with various histological states of spermatogenesis in infertile men. METHODS: Quantitative high resolution magic angle spinning spectroscopy was performed on snap frozen testicular tissue from 27 men with three classic histological patterns: (i) normal spermatogenesis (men with prior paternity undergoing vasectomy reversal), (ii) maturation arrest (early or late, MA) or (iii) Sertoli-cell only (SCO). Concentrations of 19 tissue metabolites were acquired from each biopsy specimen. One-way ANOVA analysis was used to determine inter-group differences in metabolite concentrations among the three histologic groups. RESULTS: Phosphocholine (PC) and taurine tissue concentrations were significantly different between normal and SCO tissue. Mean PC concentrations were three times higher in normal testes compared with SCO (5.4 +/- 1.4 versus 1.5 +/- 0.3 mmol/kg; P = 0.01). No differences in metabolite concentrations were observed between normal and MA testes or between SCO and MA testes. Further histologic stratification of MA testes into subsets of those with (early) and without (late) spermatids or mature sperm, identified differences in PC concentrations. A predictive model for sperm presence with (1)H-MRS was developed based upon PC tissue concentrations. CONCLUSIONS: PC concentrations are significantly higher in testes with spermatogenesis. This suggests that a unique metabolic signature for spermatogenesis is possible using (1)H-MRS which could aid in the non-invasive diagnosis of sperm in men with NOA.

Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells.

Several reports have documented the derivation of pluripotent cells (multipotent germline stem cells) from spermatogonial stem cells obtained from the adult mouse testis. These spermatogonia-derived stem cells express embryonic stem cell markers and differentiate to the three primary germ layers, as well as the germline. Data indicate that derivation may involve reprogramming of endogenous spermatogonia in culture. Here, we report the derivation of human multipotent germline stem cells (hMGSCs) from a testis biopsy. The cells express distinct markers of pluripotency, form embryoid bodies that contain derivatives of all three germ layers, maintain a normal XY karyotype, are hypomethylated at the H19 locus, and express high levels of telomerase. Teratoma assays indicate the presence of human cells 8 weeks post-transplantation but limited teratoma formation. Thus, these data suggest the potential to derive pluripotent cells from human testis biopsies but indicate a need for novel strategies to optimize hMGSC culture conditions and reprogramming.

The evolution of testicular sperm extraction and preservation techniques.

Along with the advent of intracytoplasmic sperm injection in 1992, sperm retrieval procedures now allow the possibility of conception from male sterility. In cases of sterility due to blockages in the reproductive tract, sperm retrieval procedures are relatively straightforward and reliable. In nonobstructive azoospermia or testis failure, sperm often can be difficult to retrieve. For this reason, the field of testicular sperm retrieval has witnessed tremendous change and innovation to achieve higher sperm yields, increasing efficiency and safety, along with fewer complications. We review the history and evolution of testicular sperm retrieval since its inception. Using the findings from randomized controlled trials, basic science studies, meta-analyses, case-controlled or cohort studies, best-practice policies, and literature reviews, we outline the concepts, facts, and principles that have been elucidated over several decades of experience with sperm retrieval. We also appraise the merits and issues of the most popular sperm retrieval techniques and strategies. Finally, we define areas of future clinical and laboratory development that will further refine the field of testicular sperm retrieval.

Vardenafil allows successful intercourse initiated rapidly after dosing in Japanese patients with diabetes mellitus and erectile dysfunction.

INTRODUCTION: Vardenafil is reported to improve success rates in the maintenance of an erection sufficient for completion of intercourse (SEP-3) compared with placebo in erectile dysfunction (ED) patients who attempted intercourse from as early as 15 minutes after dosing. However, these data were based on general ED patients, using time from administration to initiation of intercourse. It is unclear whether the results can be applied to difficult-to-treat ED patients, such as those with diabetes mellitus (DM), with the time between dosing and insertion into vagina. AIM: To determine whether early onset of activity with vardenafil is also achievable in ED patients with DM. METHODS: Data from a 12-week Phase III clinical trial (randomized, placebo-controlled, double-blind, parallel-group comparison) in Japanese men with ED and DM was used for analysis. In this study, patients received vardenafil 10 mg, 20 mg, or placebo, and were instructed to start sexual activity 1 hour after dosing. Mean per-patient SEP-3 success rates (intent-to-treat; ITT population), based on patient diary question, were calculated by the time between dosing and insertion. The least-squares means and nominal P values for differences versus placebo were derived by analysis of covariance with terms for baseline. MAIN OUTCOME MEASURES: SEP-3 success rates in each time interval. RESULTS: The majority of inserts occurred between 60-90 minutes after dosing, but 100 of inserts in 52 patients occurred in the first 30 minutes. SEP-3 success rates in patients who inserted in each interval from 0-15 minutes (P = 0.0268), 15-30 minutes (P = 0.0094) through > 120 minutes were all higher in vardenafil-treated patients than those in placebo. CONCLUSIONS: In this retrospective analysis, a rapid onset of activity was also demonstrated in difficult-to-treat ED patients. Vardenafil improved successful intercourse rates compared with placebo in Japanese DM patients who inserted from as early as 15 minutes to >120 minutes after dosing.

Sexual, marital, and social impact of a man's perceived infertility diagnosis.

INTRODUCTION: Male factor infertility is a relatively common problem. This diagnosis may increase sexual, marital, and relationship strain in male partners of infertile couples. AIM: To measure the personal, social, sexual, and marital impacts of a male factor infertility diagnosis among men in couples evaluated for infertility. METHODS: Cross-sectional analysis of 357 men in infertile couples from eight academic and community-based fertility clinics. Participants completed written surveys and face-to-face and telephone interviews at study enrollment. This interview queried each participant's perception of their infertility etiology to determine the primary study exposure (i.e., male factor only, male and female factors, female factor only, unknown). MAIN OUTCOME MEASURES: Personal Impact, Social Impact, Marital Impact, and Sexual Impact scales. RESULTS: Among the 357 men, no male factor was reported in 47%, isolated male factor was present in 12%, combined male and female factors were present in 16%, and unexplained infertility was present in 25% of couples. Male factor infertility was independently associated with worse Sexual (mean 39 vs. 30, standard deviation [SD] 2.7, P = 0.004) and Personal (mean 37 vs. 29, SD 3.8, P = 0.04) Impact scores relative to men in couples without male factor infertility. These differences remained statistically significant after controlling for male age, partner age, race, religion, educational level, employment status, prior pregnancy, duration of infertility, and prior paternity. CONCLUSIONS: Male partners in couples who perceive isolated male factor infertility have a lower sexual and personal quality of life compared with male partners of couples without perceived male factor infertility. Social strain is highest among couples without a clear etiology for infertility. These findings highlight the clinically significant negative sexual, personal, and social strains of a perceived infertility diagnosis for men.

The relative accuracy of a questionnaire compared with pedigree analysis in genetic risk assessment for infertility.

PURPOSE: For infertile couples family history assessment can add valuable information about genetic infertility and possible risks for offspring. We created a genetic questionnaire for eliciting family history and asked whether it could capture information similar to a pedigree. MATERIALS AND METHODS: Infertile male patients completed a genetic questionnaire and had a pedigree obtained by a genetic counselor. We assessed the accuracy of the questionnaire to elicit family history information compared to the gold standard pedigree. RESULTS: Of 93 patients 76 (82%) patients indicated relevant genetic information. A comparison of the 2 methods revealed that 61 (80%) patients failed to report key genetic information on the questionnaire that was ascertained by the pedigree. Assessment of 5 relevant family history elements revealed that the questionnaire missed 75% or more of stillbirths, birth defects, developmental delay/learning disabilities/mental retardation, recurrent miscarriages and congenital heart defects. The positive predictive value and the negative predictive value of the questionnaire ranged from 67% to 100% and 74% to 87%, respectively. The sensitivity and specificity of the questionnaire ranged from 12% to 30% and 98% to 100%, respectively. CONCLUSIONS: A comprehensive family history questionnaire is not as reliable for capturing relevant, genetic information as a pedigree. The optimal method will become more important as our knowledge of genetic infertility and its implications expands.

Racial differences among boys with testicular germ cell tumors in the United States.

PURPOSE: There are marked racial differences in the incidence of testicular germ cell tumors among United States men, with whites having 5 times the incidence of blacks and 3 times that of Asians. Testicular germ cell tumors in boys are rare, and limited racial classification by cancer registries has made attempts to discern racial patterns difficult. We hypothesize that recent diversification of race data by cancer registries may allow for more accurate racial classification, and that there are racial differences in the incidence of testicular germ cell tumors in prepubertal boys. MATERIALS AND METHODS: We identified all cases of histologically confirmed testicular germ cell cancer in boys 0 to 14 years old between 1992 and 2004 through the Surveillance, Epidemiology and End Results Program. We performed subgroup analysis in boys 0 to 9 years old. Race was categorized as white, black, American Indian/Alaska Native or Asian/Pacific Islander. Variables analyzed included age, tumor histology and year of diagnosis. RESULTS: A total of 695 cases of testicular germ cell tumors were diagnosed among boys of all races, with an overall incidence of 6.3 per 1 million person-years. Testicular germ cell tumors were 1.4-fold more likely to develop in Asian/Pacific Islanders compared to whites (RR 1.4, 95% CI 1.1 to 1.8). Increased rates among Asian/Pacific Islanders were constant across all age strata, in cases of yolk sac tumor/embryonal, teratoma and seminoma, and were maintained from 1992 to 2004. CONCLUSIONS: Asian/Pacific Islander boys are more likely to have testicular germ cell tumors compared to whites. Similar to adults, race appears to have a significant role in the incidence of testicular germ cell tumors among prepubertal boys.