Occupational exposure to organic solvents and the risk of developing testicular germ cell tumors (TESTIS study): Effect of combined exposure assessment on risk estimation.

OBJECTIVES: Etiological factors of testicular germ cell tumors (TGCT) remain largely unknown, but a causal role of occupational exposures to solvents has been suggested. Previous studies analyzing these exposures reported discordant results, potentially related to exposure assessment methods. The aim of this study was to investigate the role of occupational exposure to solvents on the risk of developing TGCT among young men. METHODS: This study examined occupational exposures to solvents and TGCT risk based on the lifetime work histories of 454 cases and 670 controls, aged 18-45 years, of the French national TESTIS case-control study. Solvent exposure was estimated using: (i) exposure assignment by job-exposure matrix (JEM) and (ii) JEM combined with self-reported exposure data from specific questionnaires (SQ) and expert assessment (EA). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression models. RESULTS: Both approaches (JEM and JEM+SQ+EA) showed a consistent association between TGCT and trichloroethylene exposure (exposed versus not exposed; JEM=OR 1.80 [95% confidence interval (CI) 1.12-2.90] and JEM+SQ+EA= OR 2.59 (95% CI 1.42-4.72). Both approaches also observed positive associations with ketone esters and fuels & petroleum-based solvents. CONCLUSION: The results suggest that some organic solvents might be involved in the pathogenesis of TGCT among occupationally exposed men. The combined use of JEM+SQ+EA seemed to limit misclassification by considering individual exposure variability and is, therefore, an appealing approach to assess occupational exposures in epidemiological studies.

Sperm DNA methylation dynamics after chemotherapy: a longitudinal study of a patient with testicular germ cell tumor treatment.

BACKGROUND: An important issue for young men affected by testicular germ cell tumor (TGCT) is how TGCT and its treatment will affect, transiently or permanently, their future reproductive health. Previous studies have reported that xenobiotics can induce changes on human sperm epigenome and have the potential to promote epigenetic alterations in the offspring. OBJECTIVES: Here, we report the first longitudinal DNA methylation profiling of frozen sperm from a TGCT patient before and up to 2 years after a bleomycin, etoposide, and cisplatin (BEP) chemotherapy. MATERIALS AND METHODS: A TGCT was diagnosed in a 30-year-old patient. A cryopreservation of spermatozoa was proposed before adjuvant BEP treatment. Semen samples were collected before and after chemotherapy at 6, 9, 12, and 24 months. The DNA methylation status was determined by RRBS to detect DNA differentially methylated regions (DMRs). RESULTS: The analysis revealed that among the 74 DMRs showing modified methylation status 6 months after therapy, 17 remained altered 24 months after treatment. We next associated DMRs with differentially methylated genes (DMGs), which were subsequently intersected with loci known to be important or expressed during early development. DISCUSSION AND CONCLUSION: The consequences of the cancer treatment on the sperm epigenome during the recovery periods are topical issues of increasing significance as epigenetic modifications to the paternal genome may have deleterious effects on the offspring. The altered methylated status of these DMGs important for early development might modify their expression pattern and thus affect their function during key stages of embryogenesis, potentially leading to developmental disorders or miscarriages.

Efficient pathway for men fertility preservation in testicular cancer or lymphoma: a cross-sectional study of national 2018 data.

BACKGROUND: In 15-49 years-old men, the main cancers are testicular cancer (TC) and lymphomas (L): freezing of ejaculated sperm is primarily used for male fertility preservation (FP) before cancer treatment. Our objective was to analyze the French FP rate in 15-49 years-old men diagnosed with TC or L in 2018. We designed a national descriptive cross-sectional study of sperm banking rate in men with a diagnosis of TC, Hodgkin L (HL) or non-Hodgkin L (NHL). From the French National Cancer Institute (INCa) 2018 data, we extracted the estimated incidence of TC and L in metropolitan France. From the 2018 activity report of CECOS network (Centers for Study and Banking of Eggs and Sperm), we extracted the number of men with TC or L who banked ejaculated sperm. We estimated the proportion of 15-49 years-old men diagnosed with TC or L who banked sperm. RESULTS: Among 15-49 years-old men, INCa estimated 38,048 new cancer diagnoses in metropolitan France in 2018: 2,630 TC and 3,913 L (943 HL and 2,970 NHL). The CECOS network provided data from 26/27 metropolitan centers (96% response rate): 1,079 sperm banking for men with TC, 375 for HL and 211 for NHL. We estimated that the 2018 sperm banking rate in France was 41% for TC, 40% for HL, and 7% for NHL. CONCLUSIONS: To our knowledge, our paper is the first cross-sectional study with multicenter and national data analyzing FP rate in cancer men: it suggests an efficient pathway for men to FP before cancer treatment, compared to previously published studies. Although sperm banking rate in 15-49 years-old men could definitely be improved, further studies should evaluate the information given to patients before gonadotoxic treatments, the factors associated with the absence of sperm banking and whether this lack of referral induces a loss of chance for these men.

RéSUMé: CONTEXTE: Chez les hommes de 15 à 49 ans, les principaux cancers sont le cancer du testicule (CT) et les lymhomes (L): la congélation de spermatozoïdes éjaculés est utilisée en première intention pour leur préservation de fertilité (PF) avant traitement du cancer. Notre objectif était d'analyser le taux de PF chez les hommes de 15 à 49 ans diagnostiqués avec un CT ou un L en 2018 en France. Nous avons réalisé une étude nationale transversale descriptive du taux de congelation de spermatozoïdes chez les hommes âgés de 15 à 49 ans diagnostiqués avec un CT, un L de Hodgkin (LH) ou un L non-Hodgkinien (LNH). A partir des données de l'Institut National du Cancer (INCa) de 2018, nous avons extrait l'incidence estimée de CT et de L en France métropolitaine. A partir des données du bilan d'activité 2018 de la Federation Française des CECOS (Centre d'Etude et de Conservation des Oeufs et du Sperme), nous avons extrait le nombre d'hommes avec un CT ou un L qui ont congelé leurs spermatozoïdes. Nous avons enfin estimé la proportion d'hommes de 15 à 49 ans diagnostiqués avec un CT ou un L qui ont congelé leurs spermatozoïdes. RéSULTATS: Chez les hommes de 15 à 49 ans, l'INCa a estimé en 2018 38 048 nouveaux cas de cancers diagnostiqués en France métropolitaine en 2018: 2 630 CT et 3 913 L (943 LH et 2 970 LNH). Le réseau des CECOS a produit les résultats issus de 26/27 centres métropolitains (taux de réponse de 96%): 1 079 congélations de sperme pour des hommes atteints de CT, 375 pour LH et 211 pour LNH. Nous avons estimé que le taux de congelation de spermatozoïdes de 2018 en France était de 41% pour le CT, 40% pour le LH et 7% pour le LNH. CONCLUSIONS: A notre connaissance, notre travail est la première étude transversale multicentrique de données nationales analysant le taux de PF chez les hommes atteints de cancer: il suggère un parcours patient efficace pour la PF des hommes avant traitement d'un cancer, par rapport aux études précédemment publiées. Bien que le taux de PF chez les hommes puisse certainemen être amélioré, des études futures devraient évaluer l'information donnée aux patients avant traitement gonadotoxique, les facteurs associés à l'absence de PF et si le défaut d'adressage au CECOS induit un perte de chance pour ces hommes. MOTS-CLéS: Chimiothérapie, Radiothérapie, Oncofertiité, Azoospermia, Paternité.

Parental occupational exposure to solvents and risk of developing testicular germ cell tumors among sons: a French nationwide case-control study (TESTIS study).

OBJECTIVES: The etiology of testicular germ cell tumors (TGCT) is suspected to be related to prenatal environmental risk factors. Some solvents have potential endocrine disrupting or carcinogenic properties and may disrupt male genital development in utero. The aim of this study was to examine the association between parental occupational exposure to solvents and TGCT risk among their offspring. METHODS: A French nationwide case-control study, TESTIS included 454 TGCT cases and 670 controls frequency-matched on region and 5-year age strata. Participants were interviewed via telephone and provided information on parental occupations at birth. Job-exposure matrices (JEM) developed in the French Matgéné program were used to assign exposure to five petroleum-based solvents, five solvents or groups of oxygenated solvents, and five chlorinated solvents. Odds ratios (OR) for TGCT and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for TGCT risk factors. RESULTS: Occupational exposure to at least one solvent during the year of their son's birth was 41% among fathers and 21% among mothers. Paternal exposure to at least one solvent showed OR 0.89 (95% CI 0.68-1.15). Exposure to perchloroethylene (OR 1.41, 95% CI 0.55-3.61), methylene chloride (OR 1.13, 95% CI 0.54-2.34) and diesel/kerosene/fuel oil (OR 1.17, 95% CI 0.80-1.73) disclosed OR >1 but with low precision. Our results suggest a possible modest increase in non-seminoma risk for sons whose fathers were highly exposed to trichloroethylene (OR 1.44, 95% CI 0.79-2.63). Maternal exposure to at least one solvent showed OR 0.90 (95% CI 0.65-1.24). When stratifying by birth year, men born in the 1970s experienced an increased TGCT risk following maternal exposure to fuels and petroleum-based solvents (OR 2.74, 95% CI 1.11-6.76). CONCLUSION: Overall, no solid association was found between parental occupational exposure to solvents and TGCT risk. The association found with maternal occupational exposure to fuels and petroleum solvents among older men needs further investigation.

International cooperation and the challenge of internet accessibility in Caribbean territories: example of a collaborative platform between the University Hospital of Martinique and Ramón González Coro Hospital in Cuba, through the French PRPH-3 program.

BACKGROUND: Martinique shares with the other Caribbean countries specific public health issues, particularly in the diagnostic and therapeutic management of cancer patients. Mutualization of human and material resources by promoting cooperation is the most appropriate response to the challenges of the health systems of the Caribbean territories. Through the French PRPH-3 program, we propose to set up a collaborative digital platform adapted to the specificities of the Caribbean to strengthen professional links and skills in oncofertility and oncosexology and reduce inequalities in access to reproductive and sexual health care for cancer patients. METHODS: Within the context of this program, we have developed of an open-source platform based on a Learning Content Management System (LCMS), with an operating system developed by UNFM for low speed internet. LO libraries have been created and interaction between trainers and learners were done in asynchronous mode. This training management platform is based on: a TCC learning system (Training, Coaching, Communities); a web-hosting with pedagogical engineering appropriate to low bandwidth; a reporting system and a responsibility for processing. RESULTS: We have carried out a flexible, multilingual and accessible digital learning strategy functionality called e-MCPPO according to low-speed internet ecosystem. In close connection with the e-learning strategy we conceived (i) a multidisciplinary team; (ii) an appropriate training program for expert health professionals and (iii) a responsive design. DISCUSSION AND CONCLUSION: This low-speed web-based infrastructure allows communities of experts to cooperate in creating, validating, publishing and managing academic learning content. The self-learning modules provide the digital layer for each learner to extend their skills. Learners, as well as trainers, would gradually take ownership of this platform and encourage its promotion. Innovation in this context is both technological (low-speed Internet broadcasting, free interactive software) and organizational (moderating educational resources). This collaborative digital platform is unique in its form and content. This challenge could contribute to the digital transformation of the Caribbean ecosystem for capacity building in this specifics topics.

Testicular germ cell tumour risk by occupation and industry: a French case-control study - TESTIS.

OBJECTIVE: Testicular germ cell tumours (TGCT) are the most common cancer in men of working age and its incidence has increased notably over the past 40 years. Several occupations have been identified as potentially associated with TGCT risk. The aim of this study was to further explore the relationship between occupations, industries and TGCT risk in men aged 18-45 years. METHODS: The TESTIS study is a multicenter case-control study conducted between January 2015 and April 2018 in 20 of 23 university hospital centers in metropolitan France. A total of 454 TGCT cases and 670 controls were included. Full job histories were collected. Occupations were coded according to the International Standard Classification of Occupation 1968 version (ISCO-1968) and industry according to the 1999 version of Nomenclature d'Activités Française (NAF-1999). For each job held, ORs and 95% CIs were estimated using conditional logistic regression. RESULTS: A positive association was observed between TGCT and occupation as agricultural, animal husbandry worker (ISCO: 6-2; OR 1.71; 95% CI (1.02 to 2.82)), as well as salesman (ISCO: 4-51; OR 1.84; 95% CI (1.20 to 2.82)). An increased risk was further observed among electrical fitters and related, electrical and electronics workers employed for 2 years or more (ISCO: 8-5; OR≥2 years 1.83; 95% CI (1.01 to 3.32)). Analyses by industry supported these findings. CONCLUSIONS: Our findings suggest that agricultural, electrical and electronics workers, and salesmen workers experience an increased risk of TGCT. Further research is needed to identify the agents or chemicals in these high-risk occupations which are relevant in the TGCT development. TRIAL REGISTRATION NUMBER: NCT02109926.

Parental occupations at birth and risk of adult testicular germ cell tumors in offspring: a French nationwide case-control study.

Background: Testicular germ cell tumors (TGCT) are the most frequent cancer in young men in developed countries. Parental occupational exposures during early-life periods are suspected to increase TGCT risk. The objective was to estimate the association between parental occupations at birth and adult TGCT. Methods: A case-control study was conducted, including 454 TGCT cases aged 18-45 from 20 French university hospitals, matched to 670 controls based on region and year of birth. Data collected from participants included parental jobs at birth coded according to the International Standard Classification of Occupation-1968 and the French nomenclature of activities-1999. Odds ratios (OR) for TGCT and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for TGCT risk factors. Results: Paternal jobs at birth as service workers (OR = 1.98, CI 1.18-3.30), protective service workers (OR = 2.40, CI 1.20-4.81), transport equipment operators (OR = 1.96, CI 1.14-3.37), specialized farmers (OR = 2.66, CI 1.03-6.90), and maternal jobs as secondary education teachers (OR = 2.27, CI 1.09-4.76) or in secondary education (OR = 2.35, CI 1.13-4.88) were significantly associated with adult TGCT. The risk of seminoma was increased for the above-mentioned paternal jobs and that of non-seminomas for public administration and defence; compulsory social security (OR = 1.99, CI 1.09-3.65); general, economic, and social administration (OR = 3.21, CI 1.23-8.39) for fathers; and secondary education teacher (OR = 4.67, CI 1.87-11.67) and secondary education (OR = 3.50, CI 1.36-9.01) for mothers. Conclusion: Some paternal jobs, such as service workers, transport equipment operators, or specialized farmers, and maternal jobs in secondary education seem to be associated with an increased risk of TGCT with specific features depending on the histological type. These data allow hypotheses to be put forward for further studies as to the involvement of occupational exposures in the risk of developing TGCT, such as exposure to pesticides, solvents, or heavy metals.

Paternal Occupational Exposure to Heavy Metals and Welding Fumes and Testicular Germ Cell Tumours in Sons in France.

Testicular cancer is the most common cancer in young men. Its causes are largely unknown, although prenatal occupational and environmental exposures have been suggested. We investigated paternal occupational exposure to heavy metals and welding fumes and the risk of testicular germ cell tumors (TGCT) in their offspring. A total of 454 cases and 670 controls were included from a French nationwide case-control study. The INTEROCC job exposure matrix was used to assign occupational exposures (cadmium, chromium, iron, nickel, lead, and welding fumes) to the fathers' jobs. Odds ratios (ORs) for TGCT were estimated using conditional logistic regression models for frequency-matched sets. Three complementary analytical approaches were used: (1) single-agent analysis, (2) analysis by groups, and (3) principal component analysis (PCA). The proportion of paternal exposure to different heavy metals and welding fumes ranged from 0.7% (cadmium) to 11.3% (lead). Based on PCA, three principal components explained 93.5% of the cumulative variance. No associations were found between heavy metals or welding fumes and TGCT. In this study, paternal occupational exposure to heavy metals or welding fumes was not associated with TGCT development in their sons.

Domestic use of pesticides during early periods of development and risk of testicular germ cell tumors in adulthood: a French nationwide case-control study.

BACKGROUND: Testicular germ cell tumours (TGCT) are the most frequent cancers in young men in developed countries and their incidence rate has doubled worldwide over the past 40 years. Early life exposures to pesticides are suspected to increase TGCT risk. Our research aimed at estimating adult TGCT risk associated with parental domestic use of pesticides during early periods of child development. METHODS: We conducted a case-control study of 304 TGCT cases, aged 18-45 years old, recruited in 20 French university hospitals, and 274 controls frequency-matched on hospital and birth year. Participants' mothers provided information on their domestic use of pesticides from 1 year before start of pregnancy to 1 year after their son's birth, for gardening activities, treatment of indoor plants, pets, wood and mold, and pest control. Odds ratios (OR) for TGCT (overall and by histological subtype) and 95% confidence intervals (CI) were estimated using conditional logistic regression. RESULTS: Prevalence of reported domestic use of pesticides was 77.3% for insecticides, 15.9% for fungicides and 12.1% for herbicides. While no association was found for any use of insecticides (OR = 1.27, CI = 0.80-2.01) or herbicides (OR = 1.15, CI = 0.67-2.00), elevated risks of TGCT overall (OR = 1.73, CI = 1.04-2.87) and non-seminoma subtype (OR = 2.44, CI = 1.26-4.74) were observed for any use of fungicides. When specific purposes were examined, using fungicides and/or insecticides for woodwork (OR = 2.35, CI = 1.06-5.20) and using insecticides on cats and dogs (OR = 1.95, CI = 1.12-3.40) were associated with increased risk of non-seminoma subtype. We found no association for seminoma subtype. CONCLUSIONS: Although recall bias may partially explain the elevated ORs, our study provides some evidence of a positive association between domestic use of pesticides during early periods of development, particularly fungicides and risk of adult TGCT and non-seminoma. Given the common domestic use of pesticides in France, further research on TGCT risk is warranted.

Collaborative digital platform France - Cuba: oncorehabilitation in reproductive and sexual health.

BACKGROUND: In the French West-Indies, few studies have been performed on fertility and sexual problems in cancer survivors, which are frequent and recurring issues reported by surveys on unmet needs. Additionally, mutualizing human and material resources and promoting cooperation through a collaborative platform are the most appropriate response to complex health pathways in the Caribbean territories. Implementation of such a collaborative platform will help to launch a strategic Caribbean partnership to transfer theoretical and technical skills and care standards in oncofertility and oncosexuality. METHODS: We propose to set up a collaborative digital platform to strengthen, from the French expertise, Cuban health professionals' knowledge, know-how, and skills in oncofertility and oncosexuality. The project will be coordinated by a coordinating, scientific, and supervisory committee, and the main activities will include: 1. Theoretical training in e-learning adapted to low-speed Internet. 2. Practical training in fertility preservation and sexual rehabilitation. 3. Digital multidisciplinary consultation meetings for medical decisions to be taken for complex clinical cases. The platform will benefit from a recurrent evaluation, by the two cancer registries of Martinique and Cuba, with the following performance indicators: number of Cuban professionals trained, number of professionals sensitized, hourly volumes (or number of training courses provided), satisfaction of trained professionals, number of e-RCPs carried out online and number of missionaries supported. These indicators will be set up and analyzed by the registers. This project meets the Cuban and French health policies (cancer plans and national sexual health strategies) and will be implemented in liaison with the Health Agencies of both countries and the Embassy of France in Cuba. DISCUSSION: This project aims to provide support through bilateral exchanges to improve reproductive and sexual health in Cuba's cancer patients. This collaboration will be based on a long-lasting French expertise and a solid Cuban health system. Consequently, this collaborative digital platform will contribute to data collection for cancer surveillance, and the two participating countries will ultimately be identified in the Caribbean as having centers of competence and excellence in oncofertility and oncosexuality with care standards.

Male partners of infertile couples with congenital unilateral absence of the vas deferens are mainly non-azoospermic.

BACKGROUND: Men with congenital unilateral absence of vas deferens were reported to be mainly azoospermic, with both unilateral renal absence and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) but some have neither. OBJECTIVES: To assess whether in infertile couples the male partners with congenital unilateral absence of vas deferens are mainly azoospermic men. MATERIAL AND METHODS: Retrospective study in a unique university hospital; reproductive, clinical, CFTR analysis and seminal data of male partners of infertile couples (from 1998 to 2018) were analysed. Diagnosis of congenital unilateral absence of vas deferens was based on transrectal ultrasounds (TRUS): complete or partial absence of one vas deferens with complete contralateral vas deferens confirmed in 63 men. Distribution of sperm count in three classes: azoospermia, oligozoospermia or normozoospermia. Ultrasound determination of renal status; seminal biomarkers assays; and search for CFTR mutations. RESULTS: Among the 63 men, 39.7% displayed azoospermia, 27% oligozoospermia and 33.3% normozoospermia; 42% of the non-azoospermic men (16/38) had previously obtained a natural pregnancy. We found unilateral renal absence in 17/59 patients (29%). Among 50 men with CFTR testing, five carried an allele associated with cystic fibrosis belonging to the 29 men without renal anomalies, indicating a high allelic frequency (8.6%). The 63 patients displayed high rates of surgical histories for undescended testicles or inguinal hernia, low values of semen volume and of total seminal glycerophosphocholine. CONCLUSIONS: Our results indicate that men with congenital unilateral absence of vas deferens mainly display oligozoospermia or normozoospermia and that they were previously fertile. They clearly confirm, first, that CFTR testing is recommended in congenital unilateral absence of vas deferens men and it should be mandatory for those with normal kidneys; and, second, that TRUS is needed for the diagnosis of congenital unilateral absence of vas deferens. As congenital unilateral absence of vas deferens may be present whatever the sperm count, biological warnings are represented by semen volume and seminal epididymal markers and clinical warnings by surgical histories of undescended testes or inguinal hernia.

Upper and lower genital tract Zika virus screening in a large cohort of reproductive-age women during the Americas epidemic.

RESEARCH QUESTION: To determine whether there is a risk of localized Zika virus (ZIKV) infection in the upper genital tract, specifically the oocytes, follicular fluids and endometrium, in exposed and/or recently infected reproductive-age women. ZIKV is an Aedes mosquito-borne Flavivirus that can lead to birth defects and to developmental anomalies when it infects pregnant women. DESIGN: Controlled observational clinical study following 179 female patients undergoing oocyte vitrification cycles in an academic fertility centre during the ZIKV epidemic in the French territories of the Americas. At the time, the French Ministry of Health issued a ban on medically-induced pregnancies. Oocyte vitrification cycles were the only means of preserving fertility options and ensuring Zika-free oocyte cryopreservation for currently exposed and/or recently infected patients. Samples of serum, urine, lower genital tract, endometrium, follicular fluid and immature oocytes were tested for ZIKV RNA (vRNA) by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Serological analysis for ZIKV antibodies was performed in succession for the duration of the study. The follow-up protocol was set up for more than 6 months post-exposure or post-onset. RESULTS: No vRNA was detected in the various samples from exposed patients. Furthermore, no vRNA was found in the upper genital tracts of women with a recent (3 months) history of acute infection. CONCLUSION: These findings represent evidence of a lack of vRNA persistence in the reproductive tract in ZIKV exposed and/or recently infected reproductive-age women and could help simplify current guidelines.

Sperm cryopreservation incidence in men with testicular cancer: towards a stabilization in testicular cancer incidence? Results from the CECOS network.

BACKGROUND: Testicular cancer (TC) represents 1% of all new male cancer cases but remains the most frequent cancer in adolescents and young adults in industrialized countries. In this study, we assessed time trends in use of sperm cryopreservation by men with TC from 1990 to 2013 in France. METHODS: We collected data from patients diagnosed with TC who underwent sperm cryopreservation in the French national network of sperm banks. Trends in the incidence of sperm cryopreservation were estimated through two statistical models: the commonly used Poisson regression model and the Verhulst model. RESULTS: Between 1990 and 2013, the overall incidence of sperm cryopreservation rose from 1.73 to 5.57 per 100,000 person-years. Poisson regression predicted an incidence of 9 per 100,000 [95% CI = 8.66-9.34] in 2020. However, since 2005, the observed sperm cryopreservation rate seems to be attenuating. The Verhulst model predicted an incidence of 6 per 100,000 after 2020. CONCLUSIONS: Limitations include the impossibility of analyzing age-standardized incidence. Based on the Verhulst model, results suggest that it is still relevant to follow up TC incidence and sperm cryopreservation in order to confirm or refute the potential decrease already observed in this disease.

CONTEXTE: Le cancer des testicules (CT) représente environ 1% de l'ensemble des cas de cancer chez les hommes, mais il demeure néanmoins le cancer le plus fréquent chez les adolescents et les jeunes adultes dans les pays industrialisés. Dans cette étude, nous avons évalué les variations temporelles des autoconservations de sperme réalisées par les hommes atteints d'un CT entre 1990 et 2013 en France. MÉTHODES: Les données proviennent des autoconservations de sperme réalisées auprès de patients diagnostiqués avec CT, issues du réseau national français des banques de sperme. Les tendances de l'incidence des autoconservations de sperme ont été estimées à l'aide de deux modèles statistiques: la régression de Poisson, couramment utilisée, et le modèle de Verhulst. RÉSULTATS: Entre 1990 et 2013, l'incidence globale des autoconservations de sperme est. passée de 1,73 à 5,57 pour 100,000 personnes-années. La régression de Poisson montre une estimation de l'incidence de près de 9 pour 100,000 [IC à 95% = 8,66-9,34] en 2020. Cependant, depuis 2005, le taux observé des autoconservations de sperme semble s'atténuer. Le modèle de Verhulst estime alors une incidence aux alentours de 6 pour 100,000 après 2020. CONCLUSIONS: Les limites de cette étude comprennent l'impossibilité d'analyser l'incidence standardisée sur l'âge. Sur la base du modèle de Verhulst, les résultats suggèrent qu'il est. toujours et encore pertinent d'étudier l'évolution de l'incidence du cancer du testicule et des autoconservations de sperme afin de confirmer ou non la diminution/stagnation potentielle déjà observée dans cette maladie.

[CECOS: missions and expertise]. / Les CECOS : des missions et une expertise.

Diagnosis and treatment of HIV primary infection : the earlier, the better ! In France, the HIV epidemic is far from being controlled and it is estimated that more than 7000 new infections still occur each year. HIV primary infection is a critical time in terms of the risk of contagion of the partners. The risk of evolution of the infection is clearly decreased if the treatment is initiated at the earliest since the benefits of early treatment are now well established. Moreover, the low toxicity of actual treatments facilitates long-term adherence. The challenges of reducing the HIV epidemic in France are therefore to encourage the medical community to widely offer an HIV test to those exposed and to initiate treatment as soon as possible.

Diagnostic et traitement de la primo-infection par le VIH : le plus tôt est le mieux ! En France, l'épidémie d'infection par le virus de l'immunodéficience humaine (VIH) est loin d'être maîtrisée et il est estimé que plus de 7 000 nouvelles infections ont encore lieu chaque année. La primo-infection est un moment critique en termes de risque de contagion des partenaires. Le risque d'évolution de l'infection est clairement diminué si le traitement est initié au plus tôt. L'intérêt du traitement précoce est désormais bien établi et la faible toxicité des traitements facilite l'adhésion au long cours. Les enjeux de la réduction de l'épidémie de VIH en France sont donc d'inciter la communauté médicale à proposer largement une sérologie pour le VIH aux personnes exposées et d'initier au plus tôt un traitement.

Sperm aneuploidy after testicular cancer treatment: data from a prospective multicenter study performed within the French Centre d'Étude et de Conservation des Oeufs et du Sperme network.

OBJECTIVE: To study sperm aneuploidy in a population of testicular cancer (TC) patients treated with the use of either bleomycin-etoposide-cisplatin (BEP) chemotherapy or radiotherapy. DESIGN: Multicenter prospective longitudinal study of TC patients analyzed before treatment and after 3, 6, 12, and 24 months (T3-T24). PATIENT(S): Fifty-four TC patients and a control group of 10 fertile sperm donors. SETTING: University hospital laboratories. INTERVENTION(S): Routine semen analyses; sperm aneuploidy and diploidy. MAIN OUTCOME MEASURE(S): Comparison of sperm characteristics and sperm chromosome abnormalities during TC patient follow-up. RESULT(S): Semen characteristics recovered pretreatment values 12 months after radiotherapy and 24 months after more than two BEP cycles. A significant increase in sperm disomy YY and XX was observed in the TC group before treatment compared with the control group. After more than two BEP cycles, the mean sperm aneuploidy rate increased significantly at T12 and reached the pretreatment value at T24. After radiotherapy, the mean sperm aneuploidy returned to the pretreatment value at T12. At T24, nearly 40% of TC patients did not recover their pretreatment sperm aneuploidy rate. CONCLUSION(S): Genetic counseling of TC patients should include information on the potential elevated risk of aneuploid conceptus from sperm recovered after treatment and the necessity to postpone conception up to ≥12 months after radiotherapy and ≥24 months after more than two BEP chemotherapy cycles. However, few men receiving one or two BEP cycles and some dropouts are the main limitations of this study.

Impact of Hodgkin or non-Hodgkin lymphoma and their treatments on sperm aneuploidy: a prospective study by the French CECOS network.

OBJECTIVE: To assess sperm production and aneuploidy in Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) before and after treatments. DESIGN: Multicenter, prospective, longitudinal study of lymphoma patients analyzed before treatment and after 3, 6, 12, and 24 months. SETTING: University hospitals. PATIENT(S): Forty-five HL and 13 NHL patients were investigated before and after treatment. Treatment regimens were classified in two groups: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) with or without (±) radiotherapy, and CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)/MOPP-ABV (mechlorethamine, oncovin, procarbazine, prednisone-doxorubicin, bleomycin, vinblastine). A control group of 29 healthy men was also studied. INTERVENTION(S): Semen analyses and aneuploidy study by FISH were performed at each time point. MAIN OUTCOME MEASURE(S): Comparison of mean sperm characteristics and percentage of sperm aneuploidy rates before and after treatment. RESULT(S): Before treatment, HL and NHL men had altered semen characteristics and higher sperm aneuploidy rates (median 0.76 [interquartile range 0.56-0.64]) than the control group (0.54 [0.46-0.74]). After treatment, sperm production was significantly lowered 3 and 6 months after ABVD ± radiotherapy or CHOP/MOPP-ABV. After ABVD ± radiotherapy, the aneuploidy rate increased significantly only at 3 months, and values obtained 1 or 2 years later were lower than pretreatment values. In contrast, in the CHOP/MOPP-ABV treatment group, semen characteristics and aneuploidy rate did not return to normal levels until 2 years after treatment. CONCLUSION(S): Lymphoma itself has consequences on sperm aneuploidy frequency before treatment. Moreover, lymphoma treatments have deleterious effects on sperm chromosomes related to treatment type and time since treatment. Patient counseling is essential concerning the transient but significant sperm aneuploidy induced by lymphoma and its treatments.

Truncating Mutations in the Adhesion G Protein-Coupled Receptor G2 Gene ADGRG2 Cause an X-Linked Congenital Bilateral Absence of Vas Deferens.

In 80% of infertile men with obstructive azoospermia caused by a congenital bilateral absence of the vas deferens (CBAVD), mutations are identified in the cystic fibrosis transmembrane conductance regulator gene (CFTR). For the remaining 20%, the origin of the CBAVD is unknown. A large cohort of azoospermic men with CBAVD was retrospectively reassessed with more stringent selection criteria based on consistent clinical data, complete description of semen and reproductive excurrent ducts, extensive CFTR testing, and kidney ultrasound examination. To maximize the phenotypic prioritization, men with CBAVD and with unilateral renal agenesis were considered ineligible for the present study. We performed whole-exome sequencing on 12 CFTR-negative men with CBAVD and targeted sequencing on 14 additional individuals. We identified three protein-truncating hemizygous mutations, c.1545dupT (p.Glu516Ter), c.2845delT (p.Cys949AlafsTer81), and c.2002_2006delinsAGA (p.Leu668ArgfsTer21), in ADGRG2, encoding the epididymal- and efferent-ducts-specific adhesion G protein-coupled receptor G2, in four subjects, including two related individuals with X-linked transmission of their infertility. Previous studies have demonstrated that Adgrg2-knockout male mice develop obstructive infertility. Our study confirms the crucial role of ADGRG2 in human male fertility and brings new insight into congenital obstructive azoospermia pathogenesis. In men with CBAVD who are CFTR-negative, ADGRG2 testing could allow for appropriate genetic counseling with regard to the X-linked transmission of the molecular defect.

Sperm DNA fragmentation after radioiodine treatment for differentiated thyroid cancer.

BACKGROUND: Treatment of differentiated thyroid cancer usually consists of a total thyroidectomy followed by one or several courses of radioiodine ((131)I). (131)I is known to have deleterious effects on radiation sensitive tissues and irradiation to the testes has been shown after its administration. We investigated effects of such treatment on sperm DNA in a patient with differentiated thyroid carcinoma. METHODS: The patient, a 32-year-old male with differentiated thyroid carcinoma treated by total thyroidectomy and radioiodine therapy, performed 6 semen samples in total, 3 for sperm banking and 3 for semen exploration, that were analysed for classic semen parameters. DNA integrity was analysed by flow cytometry: sperm DNA fragmentation index (DFI) and high DNA stainability (HDS) were analyzed by sperm chromatin structure assay, DNA fragmentation was analyzed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. RESULTS: Moderate oligozoospermia was observed as early as 3 months after a first dose of (131)I and became severe at 5 months. Total sperm count was reduced up to 12 months after the second dose of (131)I. Sperm DFI was increased 3.25 months after the first dose of (131)I. All parameters returned to normal values 28 months after the second (131)I dose. CONCLUSIONS: Treatment with (131)I induces alterations in sperm chromatin as well as in sperm parameters a short time (3 months) after a first dose of (131)I with persistence of sperm alterations until 12 months after a second dose. Sperm banking should be recommended before treatment.

CONTEXTE: Le traitement du cancer différencié de la thyroïde consiste en général en une thyroïdectomie totale suivie d'un traitement par l'iode radioactif (131I). L'131I est connu pour ses effets délétères sur les tissus sensibles aux radiations et il a également été démontré une irradiation des testicules après administration d'iode radioactif. Nous avons donc cherché à savoir quels étaient les effets du traitement par l'iode radioactif sur l'ADN des spermatozoïdes. MÉTHODES: Le patient est un homme de 32 ans présentant un cancer différencié de la thyroïde traité par thyroïdectomie totale puis traitement par iodothérapie. Il a réalisé 6 prélèvements de sperme, 3 pour de l'autoconservation et 3 pour le suivi après traitement, dont les caractéristiques spermatiques ont été étudiées suivant les méthodes classiques. L'analyse de l'intégrité de la chromatine a été réalisée par cytométrie en flux : l'index de fragmentation de l'ADN (DFI) et la haute colorabilité de l'ADN (HDS) ont été analysés par le sperm chromatin structure assay (SCSA), la fragmentation de l'ADN a été évaluée par la technique de terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). RÉSULTATS: Une oligozoospermie modérée a été observée dès 3 mois après une première dose de 131I, et est devenue sévère à 5 mois. La numération des spermatozoïdes est restée réduite jusqu'à 12 mois après la seconde dose de 131I. Le DFI est élevé 3.25 mois après la première dose de 131I. Tous les paramètres ont retrouvé des valeurs normales 28 mois après la seconde dose d'131I. CONCLUSION: Le traitement par 131I induit des altérations de la chromatine du spermatozoïde en plus de celles des caractéristiques spermatiques une courte période (3mois) après une première dose de 131I, avec persistance de ces altérations spermatiques jusqu'à 12 mois après une seconde dose. L'autoconservation devrait être recommandée avant un tel traitement. MOTS CLÉ: Traitement par iode radioactif, SCSA, fragmentation de l'ADN du spermatozoïde, cancer différencié de la thyroïde, paramètres spermatiques.