Fertility considerations in men with testicular cancer.
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ABSTRACT:
SUBMITTER: Parekh NV
PROVIDER: S-EPMC6995852 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Publications
Fertility considerations in men with testicular cancer.
Parekh Neel V NV Lundy Scott D SD Vij Sarah C SC
Translational andrology and urology 20200101 Suppl 1
The modern approach to cancer management has evolved into a multidisciplinary initiative focused not only on cancer specific and overall survival, but also patient quality of life and survivorship. Future fertility is often a major concern for young patients undergoing cancer therapy. Fertility preservation has emerged as a viable but significantly underutilized option. Patients and families should be aware of the varying effects of antineoplastic therapy on their future fertility to allow for a ...[more]
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Project description:PurposePatients with non-seminoma testicular cancer (NSTC) cancer can be subfertile or infertile, and present reduced sperm quality, but the underlying mechanisms are unknown. The aim of this study was to compare the sperm proteome of patients with NSTC, who cryopreserved their sperm before starting cancer treatment, with that from healthy fertile men.Materials and methodsSemen volume, sperm motility and sperm concentration were evaluated before the cryopreservation of samples from patients with NSTC (n=15) and the control group (n=15). Sperm proteomic analysis was performed by liquid chromatography-tandem mass spectrometry and the differentially expressed proteins (DEPs) between the two groups were identified using bioinformatic tools.ResultsA total of 189 DEPs was identified in the dataset, from which five DEPs related to sperm function and fertilization were selected for validation by Western blot. We were able to validate the underexpression of the mitochondrial complex subunits NADH:Ubiquinone Oxidoreductase Core Subunit S1 (NDUFS1) and ubiquinol-cytochrome C reductase core protein 2 (UQCRC2), as well as the underexpression of the testis-specific sodium/potassium-transporting ATPase subunit alpha-4 (ATP1A4) in the NSTC group.ConclusionsOur results indicate that sperm mitochondrial dysfunction may explain the observed decrease in sperm concentration, total sperm count and total motile count in NSTC patients. The identified DEPs may serve as potential biomarkers for the pathophysiology of subfertility/infertility in patients with NSTC. Our study also associates the reduced fertilizing ability of NSTC patients with the dysregulation of important sperm molecular mechanisms.
| S-EPMC7076305 | biostudies-literature
Project description:STUDY QUESTION:Is marijuana smoking associated with semen quality, sperm DNA integrity or serum concentrations of reproductive hormones among subfertile men? SUMMARY ANSWER:Men who had ever smoked marijuana had higher sperm concentration and count and lower serum FSH concentrations than men who had never smoked marijuana; no differences were observed between current and past marijuana smokers. WHAT IS KNOWN ALREADY:Studies of marijuana abuse in humans and animal models of exposure to marijuana suggest that marijuana smoking adversely impacts spermatogenesis. Data is less clear for moderate consumption levels and multiple studies have found higher serum testosterone concentrations among marijuana consumers. STUDY DESIGN, SIZE, DURATION:This longitudinal study included 662 subfertile men enroled at the Massachusetts General Hospital Fertility Center between 2000 and 2017. The men provided a total of 1143 semen samples; 317 men also provided blood samples in which we measured reproductive hormones. PARTICIPANTS/MATERIALS, SETTING, METHODS:Use of marijuana and other drugs was self-reported at baseline. Standard protocols were followed for measuring semen quality, sex hormones and DNA integrity. We used linear mixed effect models with a random intercept to evaluate the associations of self-reported marijuana smoking at enrolment with semen parameters from subsequently collected samples, and linear regression models for sperm DNA integrity and serum reproductive hormones, while adjusting for confounders including smoking and cocaine use. MAIN RESULTS AND THE ROLE OF CHANCE:Men who had ever smoked marijuana (N = 365) had significantly higher sperm concentration (62.7 (95% confidence interval: 56.0, 70.3) million/mL) than men who had never smoked marijuana (N = 297) (45.4 (38.6, 53.3) million/mL) after adjusting for potential confounders (P = 0.0003). There were no significant differences in sperm concentration between current (N = 74) (59.5 (47.3, 74.8) million/mL) and past marijuana smokers (N = 291) (63.5 (56.1, 72.0) million/mL; P = 0.60). A similar pattern was observed for total sperm count. Furthermore, the adjusted prevalence of sperm concentration and total sperm motility below WHO reference values among marijuana smokers was less than half that of never marijuana smokers. Marijuana smokers had significantly lower follicle stimulating hormone (FSH) concentrations than never marijuana smokers (-16% (-27%, -4%)) and there were no significant differences between current and past marijuana smokers (P = 0.53). Marijuana smoking was not associated with other semen parameters, with markers of sperm DNA integrity or with reproductive hormones other than FSH. Chance findings cannot be excluded due to the multiple comparisons. LIMITATIONS, REASONS FOR CAUTION:Our results may not be generalisable to men from the general population. Marijuana smoking was self-reported and there may be misclassification of the exposure. WIDER IMPLICATIONS OF THE FINDINGS:These findings are not consistent with a deleterious effect of marijuana on testicular function. Whether these findings are reflective of the previously described role of the endocannabinoid system in spermatogenesis or a spurious association requires confirmation in further studies. STUDY FUNDING/COMPETING INTEREST(S):The project was funded by grants R01ES009718 and P30ES000002 from the National Institute of Environmental Health Sciences (NIEHS). None of the authors has any conflicts of interest to declare. TRIAL REGISTRATION NUMBER:N/A.
| S-EPMC6443114 | biostudies-literature
Project description:Study questionIs self-reported type of underwear worn associated with markers of testicular function among men at a fertility center?Summary answerMen who reported most frequently wearing boxers had higher sperm concentration and total count, and lower FSH levels, compared to men who did not.What is known alreadyElevated scrotal temperatures are known to adversely affect testicular function. However, the epidemiologic literature on type of underwear, as a proxy of scrotal temperature, and male testicular function is inconsistent.Study design, size, durationThis is a cross-sectional study including 656 male partners of couples seeking infertility treatment at a fertility center (2000-2017).Participants/materials, setting, methodsSelf-reported information on type of underwear worn was collected from a take-home questionnaire. Semen samples were analyzed following World Health Organization guidelines. Enzyme immunoassays were used to assess reproductive hormone levels and neutral comet assays for sperm DNA damage. We fit linear regression models to evaluate the association between underwear type and testicular function, adjusting for covariates and accounting for multiple semen samples.Main results and the role of chanceMen had a median (interquartile range) age of 35.5 (32.0, 39.3) years and BMI of 26.3 (24.4, 29.9) kg/m2. About half of the men (53%; n = 345) reported usually wearing boxers. Men who reported primarily wearing boxers had a 25% higher sperm concentration (95% CI = 7, 31%), 17% higher total count (95% CI = 0, 28%) and 14% lower serum FSH levels (95% CI = -27, -1%) than men who reported not primarily wearing boxers. Sperm concentration and total count were inversely related to serum FSH. Furthermore, the differences in sperm concentration and total count according to type of underwear were attenuated after adjustment for serum FSH. No associations with other measured reproductive outcomes were observed.Limitations, reasons for cautionOur results may not be generalizable to men from the general population. Underwear use was self-reported in a questionnaire and there may be misclassification of the exposure. The cross-sectional design limits causal inference, and residual confounding is still possible owing to lack of information on other modifiable life styles that can also modify scrotal heat (e.g. type of trousers worn, textile fabric of the underwear). Blood sampling was not limited to the morning and, as a result, we may have missed associations with testosterone or other hormones with significant circadian variation despite statistical adjustment for time of blood draw.Wider implications of the findingsCertain styles of male underwear may impair spermatogenesis and this may result in a compensatory increase in gonadotrophin secretion, as reflected by higher serum FSH levels among men who reported most frequently wearing tight underwear. Confirmation of these findings, and in particular the findings on FSH levels suggesting a compensatory mechanism, is warranted.Study funding/competing interest(s)The project was financed by Grants (R01ES022955, R01ES009718, P30ES000002, and K99ES026648) from the National Institutes of Health. None of the authors has any conflicts of interest to declare.
| S-EPMC6530653 | biostudies-literature
Project description:IntroductionWe sought to better understand the baseline knowledge and practices of the general population regarding testicular cancer (TC) and testicular self-examination (TSE) in an effort to understand whether current screening guidelines reflect their viewpoint. The U.S. Preventive Services Task Force (USPSTF) currently recommends against TSE for TC screening due to a lack of data to support a benefit. Early detection of TC may reduce the required burden of therapy and associated long-term toxicities.MethodsThis was a cross-sectional survey study. Participants (median age 33 years, IQR 28-39) were recruited via Amazon Mechanical Turk, a validated crowdsourcing platform used to recruit minimally compensated participants.ResultsA total of 250 men rated themselves as "somewhat unknowledgeable" about TC, with no respondents considering themselves "very knowledgeable." Only 26.4% of men knew that TC was curable most of the time. Despite 90.8% of men feeling that their doctor had some role in discussing TC/TSE, only 17.2% had discussed these topics with their doctor. Even after being informed of the rationale behind USPSTF recommendations, only 8% of men thought that potential false positives of TSE would be more important than the rare chance of finding early TC.ConclusionsAmerican men do not feel knowledgeable about TC, have a favorable attitude toward TSE and want their doctor to discuss these topics. Shared decision making regarding TC screening is warranted given the low risk of harm and patient interest, and continued accrual of data on this topic is necessary given the lack of prospective work to date.
| S-EPMC9661737 | biostudies-literature
Project description:Testicular germ cell tumours (TGCT) cluster in families, but responsible genes remain unidentified. The association between testicular microlithiasis (TM) and testicular carcinoma in situ (CIS) suggests that TM may be a TC risk factor. We report testicular ultrasound findings in men with familial TGCT (FTGCT) and their unaffected relatives. A total of 81 men (48 affected and 33 unaffected) from 31 families with > or =2 TC cases underwent testicular ultrasound. Testicular microlithiasis was defined as either 'classic' (> or =5 microliths) or 'limited' (<5 microliths). Statistical analyses used Fisher's exact test and permutation testing. Testicular microlithiasis was more frequent in the contralateral testicles of men with a history of TGCT (affected men) than in unaffected men (48 vs 24%, P=0.04). The association appeared stronger for classic TM (21 vs 9%) than for limited TM (27 vs 15%). Testicular microlithiases were bilateral in six out of seven (87%) unaffected men. Among affected men, TM was not associated with histology, age at diagnosis or cancer treatment. Of the 31 families, 10 accounted for a majority (61%) of the TM cases identified (P=0.11). Testicular microlithiasis was more prevalent among FTGCT family members than described previously in the general population, and was more common among FTGCT cases vs unaffected blood relatives. Testicular microlithiasis appeared to cluster in certain families. These findings suggest both a familial predisposition to TM and an association between TM and FTGCT. If proven, this could be clinically important to men in FTGCT families, and may be useful in identifying specific genes involved in FTGCT.
| S-EPMC2584936 | biostudies-other
Project description:Spermatogenesis is an essential precursor for successful sexual reproduction. Recently, there has been an expansion in the knowledge of the genes associated with particular stages of normal, physiological testicular development and pubertal activation. What has been lacking, however, is an understanding of those genes that are involved in specifically regulating sperm production, rather than in maturation and elaboration of the testis as an organ. By using the reversible (seasonal) fertility of the Syrian hamster as a model system, the authors sought to discover genes that are specifically involved in turning off sperm production and not involved in tissue specification and/or maturation. Using gene expression microarrays and in situ hybridization in hamsters and genetically infertile mice, the authors have identified a variety of known and novel factors involved in reversible, transcriptional, translational, and posttranslational control of testicular function, as well those involved in cell division and macromolecular metabolism. The novel genes uncovered could be potential targets for therapies against fertility disorders.
| S-EPMC3398136 | biostudies-literature
Project description:BackgroundThe incidence of testicular cancer in the United States (US) has substantially increased in recent decades. The majority of testicular cancers are germ cell tumors (TGCT), which are the most commonly occurring malignancies among men aged 15-44 years in the US. To date, few studies have focused on testicular cancer among men aged ≥ 50 years. Thus, we sought to examine detailed descriptive features, including incidence rates and age patterns, of tumors that arise in the testes among men aged ≥ 50 years.MethodsData from forty-one US cancer registries were included for the years 1999-2014. Incidence rates per 100,000 person-years and their 95% confidence intervals (CI) were calculated by race/ethnicity, histology, and age at diagnosis. Estimates of annual percent change (APC) were also calculated.ResultsAge-specific incidence rates of spermatocytic tumors, sex cord stromal tumors and lymphomas rose with age, while age-specific incidence rates of seminomas and nonseminomas declined. Between 1999 and 2014, the incidence of nonseminoma (APC = 3.26, 95% CI: 2.27-4.25) increased more than any other tumor type. The incidence of seminoma (APC: 1.15, 95% CI: 0.59-1.71) also increased, while rates of testicular lymphoma (APC: -0.66, 95% CI: -1.16 to -0.16), spermatocytic tumors (APC: 0.42, 95% CI: -1.42 to 2.29), and sex cord stromal tumors (APC: 0.60, 95% CI: -3.21 to 4.55) remained relatively unchanged.ConclusionGiven the distinct time-trends and age-specific patterns of testicular cancer in men aged ≥50 years, additional investigation of risk factors for these tumors is warranted.
| S-EPMC6668029 | biostudies-literature
Project description:ObjectiveTo explore the associations between semen characteristics and subsequent risk of testicular cancer.DesignCohort study.Participants32 442 men who had a semen analysis done at the Sperm Analysis Laboratory in Copenhagen during 1963-95.Main outcome measureStandardised incidence ratios of testicular cancer compared with total population of Danish men.ResultsMen in couples with fertility problems were more likely to develop testicular cancer than other men (89 cases, standardised incidence ratio 1.6; 95% confidence interval 1.3 to 1.9). The risk was relatively constant with increasing time between semen analysis and cancer diagnosis. Analysis according to specific semen characteristics showed that low semen concentration (standardised incidence ratio 2.3), poor motility of the spermatozoa (2.5), and high proportion of morphologically abnormal spermatozoa (3.0) were all associated with an increased risk of testicular cancer. The only other cancer group that showed increased incidence was "peritoneum and other digestive organs" (six cases; 3.7, 1.3 to 8.0). Of these, two cases were probably and two cases were possibly extragonadal germ cell tumours.ConclusionsThe results point towards the existence of common aetiological factors for low semen quality and testicular cancer. Low semen quality may also be associated with increased incidence of extragonadal germ cell tumours.
| S-EPMC27489 | biostudies-literature
Project description:BackgroundChildren with cancer often face infertility as a long-term complication of their treatment. For boys, compromised testicular function is common after chemotherapy and currently there are no well-established options to prevent this damage. Platinum-based agents are used to treat a wide variety of childhood cancers. However, platinum agents are not currently included in the cyclophosphamide equivalent dose (CED), which is used clinically to assess the risks to fertility posed by combination chemotherapy in children with cancer.Objective and rationaleThis was a systematic search of the literature designed to determine the evidence for effects of platinum-based cancer treatment on the prepubertal human testis in relation to subsequent testicular function and fertility.Search methodsPubMed and EMBASE were searched for articles published in English between 01 January 1966 and 05 April 2020 using search terms including 'cancer treatment', 'chemotherapy', 'human', 'prepubertal', 'testis', 'germ cells', 'testosterone' and related terms. Abstracts were screened and full-text articles were obtained for those that met the three major inclusion criteria (age ≤12 years at treatment, exposure to platinum-based chemotherapeutic and measure of reproductive function). Screening of bibliographies for full-text articles was used to identify additional studies.OutcomesOur initial search identified 1449 articles of which 20 (1.3%) studies (n = 13 759 males) met all inclusion criteria. A control group (healthy individuals or siblings) was included for 5/20 (25%) studies. A total of 10/20 (50%) studies provided sub-analysis of the relative gonadotoxicity of platinum-based agents.The primary outcome measures were: pregnancies and fatherhood; semen analysis; and hormonal function. For pregnancies and fatherhood, three studies (n = 10 453 males) reported negative associations with platinum-agents, including the largest (n = 5640) controlled study (hazard ratio = 0.56, P = 0.0023), whilst two other studies (n = 1781) with platinum sub-analysis reported no association. For semen analysis (based on World Health Organization criteria), platinum-based chemotherapy was associated with azoospermia in one study (n = 129), whilst another (n = 44) found no association and the remainder did not perform platinum-based sub-analysis. For hormone analysis, conflicting results were obtained regarding potential associations between platinum-based agents and elevated FSH (a proxy for impaired spermatogenesis); however, the majority of these studies were based on low numbers of patients receiving platinum-based chemotherapy.Wider implicationsOverall, these results indicate that platinum-based chemotherapy should be included in clinical calculators, for example CED, used to determine gonadotoxicity for childhood cancer treatment. These findings have important implications for clinicians regarding counselling patients and their carer(s) on fertility risk, guiding requirements for fertility preservation strategies (e.g. testicular tissue cryopreservation) and modification of treatments to reduce or eliminate the risk of infertility in childhood cancer survivors.
| S-EPMC7600277 | biostudies-literature
Project description:Background: An association between testicular microlithiasis (TM) and both carcinoma in situ (CIS) of the testis and testicular germ cell tumors (TGCTs) has been reported. Furthermore, TM seems to be significantly more prevalent in men with male-factor infertility, representing itself a risk factor for TGCT. Nevertheless, the evidence of the association of TM with a higher prevalence of testicular cancer in infertile men remains inconclusive. The aim of this study was to systematically evaluate whether, and to what extent, TM is associated to a significantly higher prevalence of testicular cancer in infertile males. Methods: A thorough search of MEDLINE, SCOPUS, CINAHL, WEB OF SCIENCE, and Cochrane Library databases was carried out to identify case-control studies comparing the prevalence of testicular cancer in infertile men with and without TM. Methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. In the absence of heterogeneity, odds ratios (ORs) with 95% confidence intervals (CIs) for testicular cancer were combined using a fixed effect model. Funnel plots and trim-and-fill analysis were used to assess publication bias. Results: Eight studies met the inclusion criteria and provided information on 180 infertile men with TM and 5,088 infertile men without TM. The pooled OR indicated that the presence of TM is associated with a ~18-fold higher odd for testicular cancer (pooled OR:18.11, 95%CI: 8.09, 40.55; P < 0.0001). No heterogeneity among the studies was observed (P for heterogeneity = 0.99, I 2 = 0%). At the sensitivity analysis, similar pooled ORs and 95%CIs were generated with the exclusion of each study, indicating the high degree of stability of the results. The funnel plot revealed a possible publication bias and the trim-and-fill test detected two putative missing studies. Nevertheless, even when the pooled estimate was adjusted for publication bias, there was a still significantly higher odd for testicular cancer in the TM group (adjusted pooled OR: 16.42, 95%CI: 7.62, 35.37; P < 0.0001). Conclusions: In infertile men the presence of TM is associated to an ~18-fold higher prevalence of testicular cancer. Longitudinal studies are warranted to elucidate whether this cross-sectional association actually reflects a higher susceptibility of infertile men with TM to develop testicular cancer over time.
| S-EPMC6437042 | biostudies-literature