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In a recent population-based study, an elevated risk of the Metabolic syndrome (MetS) and type 2 diabetes was found in childless men compared to those who have fathered one or more children. Therefore, by using a larger cohort of more than 22 000 men from the Malmo Preventive Project (MPP) we aimed to expand our observations in order to evaluate the metabolic profile of childless men and to evaluate if childlessness is an additional and independent predictor of major adverse cardiovascular events (MACE), mortality and incident diabetes when accounting for well-known biochemical, anthropometric, socio-economic and lifestyle related known risk factors. Logistic regression was used to assess risk of MACE, diabetes and MetS at baseline. Multivariate Cox regression was used to evaluate the risks of MACE and mortality following the men from baseline screening until first episode of MACE, death from other causes, emigration, or end of follow-up (31(st)December 2016) adjusting for age, family history, marital status, smoking, alcohol consumption, educational status, body mass index, prevalent diabetes, high blood lipids, increased fasting glucose and hypertension. Childless men presented with a worse metabolic profile than fathers at the baseline examination, with elevated risk of high triglycerides, odds ratio (OR) 1.24 (95%CI: 1.10-1.42), high fasting glucose OR 1.23 (95%CI: 1.05-1.43) and high blood pressure, OR 1.28 (95%CI: 1.14-1.45), respectively. In the fully adjusted prospective analysis, childless men presented with elevated risk of cardiovascular mortality, HR: 1.33 (95% CI: 1.18-1.49) and all-cause mortality, HR 1.23 (95%CI: 1.14-1.33), respectively. In conclusion, these results add to previous studies showing associations between male reproductive health, morbidity and mortality. Male childlessness, independently of well-known socio-economic, behavioral and metabolic risk factors, predicts risk of cardiovascular disease and mortality. Consequently, this group

STUDY QUESTION: Is female infertility predictive of a woman's future risk of early cardiovascular disease (CVD)?SUMMARY ANSWER: Female infertility does not seem to be predictive of early CVD during a mean follow-up of 9 years.WHAT IS KNOWN ALREADY: Associations between infertility and comorbidity have been found in several studies, but data on the association between female infertility and risk of CVD are scarce and inconclusive.STUDY DESIGN, SIZE, DURATION: In this nationwide cohort study, we included 87 221 women registered in the Danish National IVF register, undergoing medically assisted reproduction (MAR) between 1st of January 1994 and 31st of December 2015. The cohort was followed for incident hospitalization due to CVD in the Danish National Patient Register from enrollment to 31 December 2015. Women with a history of CVD prior to enrollment were excluded. Cox proportional hazard models with age as the underlying time scale were used to estimate hazard ratios (HR) with 95% CI of CVD among women with an infertility diagnosis, compared to women without an infertility diagnosis. All analyses were adjusted for educational attainment.PARTICIPANTS/MATERIALS, SETTING, METHODS: Female infertility and the reason for infertility was diagnosed and registered in the IVF register by specialists in Danish public and private fertility clinics since 1st of January 1994. In our cohort, 53 806 women (61.7%) were diagnosed with female factor infertility, while 33 415 (38.3%) did not have a female factor infertility diagnosis and made up the reference group.MAIN RESULTS AND THE ROLE OF CHANCE: A total of 686 (1.3%) infertile women were hospitalized for CVD compared to 250 (0.7%) among women without an infertility diagnosis during a mean follow-up time of 9 years. We found no increased risk of early CVD in our analyses (adjusted HR 0.98, 95% CI: 0.85;1.14). Likewise, analyses stratified by specific infertility diagnosis, showed no risk diffe

Previous studies have reported reduced mortality among women undergoing assisted reproductive technology (ART) treatment, possibly related to selection of healthy women into ART treatment. The aim of this study was to explore the impact of relevant selection factors on the association between ART treatment and mortality and explore effect modification by parity. Women treated with ART in fertility clinics in Denmark during 1994-2009 (n = 42,897) were age-matched with untreated women from the background population (n = 204,514) and followed until ultimo 2010. With adjustment for relevant confounders, the risk of death was lower among ART-treated women immediately after ART treatment (HR = 0.68, 95% CI: 0.63, 0.74), but there was no apparent difference after 10 years (HR = 0.92, 95% CI: 0.79, 1.07). Having children prior to ART treatment was associated with a markedly reduced mortality (HR = 0.45, 95% CI: 0.38, 0.53), possibly due to better health among fertile women. While the frequency of previous medical and psychiatric diagnoses among ART-treated and untreated women was similar, differences in disease severity could explain the reduced mortality among ART-treated women, as poor prognosis would make ART treatment initiation unlikely. The survival advantage among ART-treated women is likely a selection rather than a biological phenomenon.

BACKGROUND: Gender, possibly due to the influence of gonadal hormones, is presumed to play a role in the pathogenesis of multiple sclerosis (MS), but no studies have evaluated whether male infertility is associated with MS.OBJECTIVE: To study the association between male factor infertility and prevalent as well as incident MS.METHOD: Our cohort was established by linkage of the Danish National in vitro fertilization (IVF) registry to The Danish Multiple Sclerosis Registry and consisted of 51,063 men whose partners had undergone fertility treatment in all public and private fertility clinics in Denmark between 1994 and 2015.RESULTS: With a median age of 34 years at baseline, 24,011 men were diagnosed with male factor infertility and 27,052 did not have male factor infertility and made up the reference group. Men diagnosed with male factor infertility had a higher risk of prevalent (odds ratio (OR) = 1.61, 95% confidence interval (95% CI) 1.04-2.51) and incident MS (hazard ratio (HR) = 1.28, 95% CI 0.76-2.17) when compared to the reference group.CONCLUSION: This nationwide cohort study has shown, for the first time, an association between male infertility and MS which may be due to underlying common etiologies such as hypogonadism, shared genetics, or a joint autoimmune component.

OBJECTIVE: To study whether male childlessness is associated with an increased risk of metabolic disorders such as metabolic syndrome (MetS) and diabetes.DESIGN: A population-based cohort study.SETTING: Not applicable.PARTICIPANTS: 2572 men from the population-based Malmö Diet and Cancer Cardiovascular Cohort.INTERVENTIONS: None.MAIN OUTCOME MEASURES: From cross-sectional analyses, main outcome measures were ORs and 95% CIs for MetS and diabetes among childless men. In prospective analyses, HRs and 95% CI for diabetes among childless men.RESULTS: At baseline, in men with a mean age of 57 years, the prevalence of MetS was 26% and 22% among childless men and fathers, respectively. Similarly, we observed a higher prevalence of diabetes of 11% among childless men compared with 5% among fathers. In the cross-sectional adjusted analyses, childless men had a higher risk of MetS and diabetes, with ORs of 1.22 (95% CI 0.87 to 1.72) and 2.12 (95% CI 1.34 to 3.36) compared with fathers. In the prospective analysis, during a mean follow-up of 18.3 years, we did not see any increase in diabetes risk among childless men (HR 1.02 (0.76 to 1.37)).CONCLUSION: This study provides evidence of an association between male childlessness and a higher risk of MetS and diabetes. However, as these associations were found in cross-sectional analyses, reverse causation cannot be excluded.

STUDY QUESTION: Is male factor infertility associated with an increased risk of developing diabetes?SUMMARY ANSWER: The study provides evidence that male factor infertility may predict later occurrence of diabetes mellitus with the risk being related to the severity of the underlying fertility problem.WHAT IS KNOWN ALREADY: Previous cross-sectional studies have shown an increased prevalence of comorbidities among infertile men when compared to controls.STUDY DESIGN, SIZE, DURATION: In this prospective cohort study, 39 516 men who had since 1994 undergone fertility treatment with their female partner were identified from the Danish national IVF register, which includes data on assumed cause of couple infertility (male/female factor, mixed and unexplained infertility) and type of fertility treatment. With a median follow-up time of 5.6 years, each man was followed for diabetes occurrence from enrollment until 31 December 2012 using the National Diabetes Register (NDR). Men with a history of diabetes prior to their fertility diagnosis were excluded. Hazard ratios (HR) were estimated by Cox proportional hazard models with age as the underlying time scale. In addition to analyzing the data for the entire IVF registration period (1994-2012), separate analyses were performed for men identified from the first (1994-2005) and second (2006-2012) IVF registration period owing to heterogeneity in the reporting of male factor infertility in these two time periods, because the reason for male factor infertility was not available from the first register.PARTICIPANTS/MATERIALS, SETTING, METHODS: Male factor infertility was identified from the variable 'yes' or 'no' from the first IVF register and through a diagnosis code (e.g. oligospermia, azoospermia) from the second IVF register. The reference group was men with male factor infertility (='no') and those with normal semen quality or sterilized men. Of the included men, 18 499 (46.8%) had male factor

The association between male infertility and increased risk of certain cancers is well studied. Less is known about the long-term risk of nonmalignant diseases in men with decreased fertility. A systemic literature review was performed on the epidemiologic evidence of male infertility as a precursor for increased risk of diabetes, cardiovascular diseases, and all-cause mortality. PubMed and Embase were searched from January 1, 1980, to September 1, 2016, to identify epidemiological studies reporting associations between male infertility and the outcomes of interest. Animal studies, case reports, reviews, studies not providing an accurate reference group, and studies including infertility due to vasectomy or malignancy were excluded. The literature search resulted in 2,485 references among which we identified seven articles fulfilling the eligibility criteria. Of these, four articles were prospective (three on risk of mortality, one on risk of chronic diseases) and three were cross-sectional relating male infertility to the Charlson Comorbidity Index. The current epidemiological evidence is compatible with an association between male infertility and risk of chronic disease and mortality, but the small number of prospective studies and insufficient adjustment of confounders preclude strong statements about male infertility as precursor of these outcomes.

BACKGROUND: More than 20 years ago, it was hypothesized that exposure to prenatal and early postnatal environmental xenobiotics with the potential to disrupt endogenous hormone signaling might be on the causal path to cryptorchidism, hypospadias, low sperm count and testicular cancer. Several consensus statements and narrative reviews in recent years have divided the scientific community and have elicited a call for systematic transparent reviews. We aimed to fill this gap in knowledge in the field of male reproductive disorders.OBJECTIVE AND RATIONALE: The aim of this study was to systematically synthesize published data on the risk of cryptorchidism, hypospadias, low sperm counts and testicular cancer following in utero or infant exposure to chemicals that have been included on the European Commission's list of Category 1 endocrine disrupting chemicals defined as having documented adverse effects due to endocrine disruption in at least one intact organism.SEARCH METHODS: A systematic literature search for original peer reviewed papers was performed in the databases PubMed and Embase to identify epidemiological studies reporting associations between the outcomes of interest and exposures documented by biochemical analyses of biospecimens including maternal blood or urine, placenta or fat tissue as well as amnion fluid, cord blood or breast milk; this was followed by meta-analysis of quantitative data.OUTCOMES: The literature search resulted in 1314 references among which we identified 33 papers(28 study populations) fulfilling the eligibility criteria. These provided 85 risk estimates of links between persistent organic pollutants and rapidly metabolized compounds (phthalates and Bisphenol A) and male reproductive disorders. The overall odds ratio (OR) across all exposures and outcomes was 1.11 (95% CI 0.91-1.35). When assessing four specific chemical subgroups with sufficient data for meta-analysis for all outcomes, we found that exposure t