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Study Question: Is there an evolution in the risk of operated cryptorchidism in France and does local geographical environment appear as an important trigger for this defect?Summary Answer: We observed an increase of the risk of operated cryptorchidism in boys under the age of 7 years during the period 2002-2014 and a strong spatial heterogeneity, with the detection of spatial clusters suggesting environmental factors.What Is Known Already: Epidemiologic data on cryptorchidism are scarce and its etiology is poorly understood. As part of the testicular dysgenesis syndrome, cryptorchidism is suspected to be a male genital developmental disorder caused by endocrine disruptor chemical (EDC) exposure during the prenatal period.Study Design, Size, Duration: This was a retrospective and descriptive study using data from the French national hospital discharge database, in the 2002-2014 study period. We built an indicator to reflect incident cases of operated cryptorchidism in boys under the age of 7 years in metropolitan France, with an algorithm using specific codes for diseases (ICD-10 codes) and surgical acts (CCAM codes).Participants/materials, Setting, Methods: The study population was composed of 89 382 new cases of operated cases of cryptorchidism in boys under the age of 7 years. We estimated the temporal evolution of the incidence rate. We fitted a spatial disease-mapping model to describe the risk of cryptorchidism at the postcode scale. We used Kulldorff's spatial scan statistic and Tango's flexibly shaped spatial scan statistic to identify spatial clusters.Main Results and the Role Of Chance: The estimated increase in the incidence of operated cryptorchidism from 2002 to 2014 was equal to 36.4% (30.8%; 42.1%). Cryptorchidism displayed spatial heterogeneity and 24 clusters (P < 0.0001) were detected. The main cluster was localized in a former coal mining and metallurgic area in northern France, currently an industrial area. The cluster analysis suggests the role of shared socio-economic and environmental factors that may be geographically determined and intertwined. The industrial activities identified in the clusters are potentially the source of persistent environmental pollution by metals, dioxins and polychlorinated biphenyls.Limitations, Reasons For Caution: The indicator we used reflects operated cases of cryptorchidism, with an under-evaluation of the health problem. We cannot exclude a possible role of the evolution and local differences in surgical practices in the observed trends. Our inclusion of boys under 7 years of age minimized the biases related to differences in practices according to age. Regarding the environmental hypothesis, this is an exploratory study and should be considered as a hypothesis-generating process for future research studies.Wider Implications Of the Findings: To our knowledge, this is the first descriptive study to address nationwide trends of operated cryptorchidism with detection of spatial clusters, with a very large sample allowing great statistical power. Our results generate plausible environmental hypotheses, which need to be further tested.Study Funding/competing Interest(s): This study was entirely funded by Santé publique France, the French National Public Health Agency. All authors declare they have no actual or potential competing financial interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Study Question: Are temporal trends and values of semen quality parameters in France identifiable in partners of totally infertile women?Summary Answer: Among a sample of 26 609 partners of totally infertile women undergoing an assisted reproductive technology (ART) procedures in the whole of France over a 17-year period, there was a continuous decrease in semen concentration of about 1.9% per year and a significant decrease in the percentage with morphologically normal forms but no global trend for motility.What Is Known Already: A global decrease in human sperm quality is still debated as geographical differences have been shown, and many criticisms have risen concerning studies with small and biased study populations or inappropriate statistical methodology. However, growing biological, toxicological, experimental and human exposure data support the endocrine disruptors' hypothesis assuming that fetal exposure to endocrine disruptors could impair reproductive outcomes.Study Design, Size, Duration: This was a retrospective and descriptive study using data registered by Fivnat, the professional association in charge of statistics for ART in France during the 1989-2005 study period. Data were provided by 126 main ART centres over the whole metropolitan territory. The source population included 154 712 men, aged 18-70, who were partners of couples undergoing their first ART cycle and for whom semen quality indicators (concentration, total motility and percentage of morphologically normal forms), measured on fresh ejaculated semen, were available.Participants/materials, Setting, Methods: The study population was 26 609 partners of women who had both tubes either absent or blocked. The temporal trends for each indicator of semen quality were modelled using a generalized additive model that allowed for nonlinear relationships between variables and were adjusted for season and age. In-depth sensitivity analyses included the reiteration of the analysis on data from a second spermiogram available for each man and on another subsample of men diagnosed as fertile. Variables such as centre, technique (standard in vitro fertilization or intra-cytoplasmic sperm injection) and an interaction factor between technique and time were also included in the model.Main Results and the Role Of Chance: There was a significant and continuous decrease in sperm concentration of 32.2% [26.3-36.3] during the study period. Projections indicate that concentration for a 35-year-old man went from an average of 73.6 million/ml [69.0-78.4] in 1989 to 49.9 million/ml [43.5-54.7] in 2005. A significant, but not quantifiable, decrease in the percentage of sperm with morphologically normal forms along the 17-year period was also observed. There was no global trend but a slight, significant increase in total motility between 1994 and 1998 was observed. The results were robust after sensitivity analysis.Limitations, Reasons For Caution: Socioeconomic status could not be controlled for. Despite universal access to medical services in France, couples undergoing ART are expected to have a higher educational level on average compared with those of the general population. Therefore, the real values in the general population could be slightly lower than those presented and the decrease possibly stronger, as the population study is less likely to smoke or be overweight, two factors known to impair semen quality.Wider Implications Of the Findings: As the men were selected without a priori knowledge regarding their semen quality characteristics, the results are expected to be close to the values in the general French population. The very large sample size and the robustness of the results confer great statistical power and credibility to the results. To our knowledge, it is the first study concluding a severe and general decrease in sperm concentration and morphology at the scale of a whole country over a substantial period. This constitutes a serious public health warning. The link with the environment particularly needs to be determined. [ABSTRACT FROM AUTHOR]