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Assisted reproduction has a minor but increasing influence on childbearing trends in advanced societies. In Denmark, the use of assisted reproduction technology (ART) has become particularly widespread. At the same time, Danish women born in the late 1950s and the 1960s experienced stabilization or even a slight increase in their mean number of children. Broad availability and widespread use of assisted reproduction may become important factors contributing to maintaining relatively high completed fertility among the younger cohorts of Danish women. To explore this idea, we analyze and project cohort trends in fertility rates among native Danish women born in 1960‐78 and examine the likely contribution of assisted reproduction to these trends. The projected proportion of children born after ART treatment shows a substantial increase from 2.1 percent among women born in 1965 to 4‐5 percent among women born in 1978, with an estimated net impact of ART (as compared with the hypothetical situation where no ART treatment was available) on the order of 3‐4 percent. When intrauterine inseminations are included, this implies that up to 7 percent of children of those native Danish women born in 1975 and later will likely be conceived by infertility treatment.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access. ; Saturated fat intake has been associated with both cardiovascular disease and cancer risk, and a newly published study found an association between saturated fat intake and a lower sperm concentration in infertile men. ; The objective was to examine the association between dietary fat intake and semen quality among 701 young Danish men from the general population. ; In this cross-sectional study, men were recruited when they were examined to determine their fitness for military service from 2008 to 2010. They delivered a semen sample, underwent a physical examination, and answered a questionnaire comprising a quantitative food-frequency questionnaire to assess food and nutrient intakes. Multiple linear regression analyses were performed with semen variables as outcomes and dietary fat intakes as exposure variables, adjusted for confounders. ; A lower sperm concentration and total sperm count in men with a high intake of saturated fat was found. A significant dose-response association was found, and men in the highest quartile of saturated fat intake had a 38% (95% CI: 0.1%, 61%) lower sperm concentration and a 41% (95% CI: 4%, 64%) lower total sperm count than did men in the lowest quartile. No association between semen quality and intake of other types of fat was found. ; Our findings are of potentially great public interest, because changes in diet over the past decades may be part of the explanation for the recently reported high frequency of subnormal human sperm counts. A reduction in saturated fat intake may be beneficial for both general and reproductive health. ; Danish Council for Strategic Research, Program Commission on Health, Food and Welfare 2101-08-0058 Rigshospitalet 961506336 European Union DEER 212844 Danish Ministry of Health Danish Environmental Protection Agency Kirsten and Freddy ...

The EDEN project is an interdisciplinary effort conceived to address key issues that have hampered sound hazard and risk assessment for endocrine disrupting chemicals (EDCs) in the European Union. It has adopted an approach that fully integrates human, wildlife, exposures, mechanisms and low-dose/mixture evaluations. The project was structured into four interlocking themes focusing on EDC mixture exposures, mechanisms of action and novel endpoints, effects on male reproductive health and the evaluation of low-dose and mixture effects of EDCs. For the first time, the simultaneous occurrence of nearly 150 different EDCs in human and wildlife tissues was measured. These studies revealed that numerous EDCs occur together in humans, yet differences in the levels of individual EDCs in specimens from boys with cryptorchidism and from women suffering from breast cancer and their respective controls did not become apparent. It appears that the likelihood of developing any of the above conditions cannot be attributed to any individual chemical at relevant exposure levels. However, there are signs that simultaneous exposure to many different EDCs may play a cumulative role in these disease processes. This means that efforts to develop biomarkers of cumulative EDC exposure should be re-doubled. In contrast, symptoms of endocrine disruption in fish could be explained largely in terms of exposure to estrogenic chemicals, but the possible role of antiandrogenic chemicals in disrupting sexual development in fish requires urgent attention. Fish caught in certain Dutch rivers exceeded the EU permissible levels for polychlorinated dioxins and furans. Considerable progress has been made in establishing relevant modes of action of EDCs and in assessing new endpoints. The screening for EDCs, with its focus on steroid receptor interactions, has not kept up with the progress made in understanding rapid cellular signalling events that occur in the wake of receptor activation. In the interest of avoiding overlooking endocrine active agents it is necessary to expand screening tools to capture rapid signalling events. Substantial progress has been also achieved in characterising the role of the aromatase system in fish as a target of EDCs and the consequences of steroid synthesis disruption on sexual differentiation, reproduction as well as non-reproductive processes such as neurodifferentiation. Extensive investigations of the role of certain phthalates in disrupting male sexual development have revealed delays in germ cell differentiation and other molecular effects as key events underlying the induction of the testicular dysgenesis syndrome. The role of the InsL3 protein in promoting male sexual development proved to be more complex than thought previously. Although the development and validation of an assay for the measurement of InsL3 blood levels was successful, the differences in blood InsL3 levels in normal and cryptorchid boys were too small to exploit InsL3 as a biomarker indicative of disruption of testis descent. The hypothalamic pituitary unit proved to be exquisitely sensitive to the effects of several EDCs, and the effects may account for precocious sexual development observed after early EDC exposure. EDEN has advanced the study of endocrine disruption in fish with activities including the development of microarrays for assessing endocrine disruption in zebrafish and establishing sensitive screening tools for endocrine disruption in fish. The development of a transgenic fish model for the detection of EDC effects proved to be technically too demanding to be completed in time, but efforts continue to complete this project after conclusion of EDEN. An in vivo model in fish (the three-spined stickleback) for the detection of antiandrogenic EDC was developed as a complement to the Hershberger assay. Male reproductive health in Denmark and Finland showed a worrying declining trend. For the first time, it could be established that the same is true for young men in Germany. It is of concern that semen quality among young Germans is similar to the values found in young Danes, a group previously thought to show the lowest semen quality in Europe. Foetal exposure to smoking has been identified as one reason for these effects. Observations of a declining total natural conception rate among the young Danish cohorts imply that the current poor semen quality has an impact on the population fertility in the future – a situation which will be difficult to reverse in the short term. The current and projected widespread use of assisted reproductive technologies may be a sign of such an emerging public health problem which also adds to the load of medical costs in young population. It is of vital importance to continue surveillance of semen quality and all efforts should be made to identify the factors that may cause harm in order to prevent further deterioration. Extensive low-dose studies with EDCs have shown that the conventional estimation of no-observed-adverse-effect-levels (NOAEL), with their reliance on hypothesis testing methods is inadequate for capturing low-dose effects of EDCs. Whenever possible, regression-based approaches with benchmark dose limits should replace NOAEL as the basis for establishing acceptable human exposure levels. A framework was developed to combine the strengths of both methodologies by making considerations of statistical detection limits and statistical power the starting point of testing procedures. Implementation of this framework will require a significant change in toxicological testing practice. Determinants of additivity for EDC mixtures have been characterised and are now well understood for combinations of similarly acting EDCs. Experimental studies have produced evidence that EDCs of relatively low potency and at low exposure levels can still work together to produce significant combination effects when they are present in sufficient numbers. The perceived low potency of many EDCs alone is uninformative in anticipating possible risks stemming from these chemicals. Where EDCs act in concert with endogenous hormones, significant additional effects may result under certain circumstances. Uncertainty still exists in relation to the likelihood of synergistic mixture effects, and concerted efforts should be made to fill this gap. Another source of uncertainty that will hamper sound EDC mixture risk assessment is incomplete knowledge about the identity of EDCs, their exposure levels and number. This issue can only be resolved through the development of dedicated exposure assessment strategies that take account of cumulative exposures. Despite these uncertainties, knowledge about determinants and factors that govern the joint action of similarly acting EDCs is now sufficiently advanced to come to pragmatic risk assessment approaches that take mixture effects into consideration. A modus operandi for EDC mixtures was developed which includes the use of dose addition (including the toxic equivalency factor approach) to arrive at a "mixture no-observed-adverse-effect-level" (MNOAEL) for endpoints relevant to endocrine disruption. These are then combined with a safety factor to arrive at estimates of tolerable human exposure. "Data-poor" situations may require estimation of a crude MNOAEL by dividing individual NOAEL of certain prototype chemicals by the anticipated number of relevant similarly acting chemicals. ; European Commission, FP5 "Quality of Life and Management of Living Resources": Contract No. QLK4-CT2002-00603.

The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.