Summary The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19–22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17–18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on >10 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile.

National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.

Background We aimed to examine the association of gestational weight gain (GWG) and pre-pregnancy weight with offspring adiposity and cardiovascular risk factors. Methods and results Data from 5,154 (for adiposity and blood pressure) and 3,457 (for blood assays) mother-offspring pairs from a UK prospective pregnancy cohort were used. Random effects multilevel models were used to assess incremental GWG (median and range of repeat weight measures per woman: 10 (1, 17)). Women who exceeded the 2009 Institute of Medicine recommended GWG were more likely to have offspring with greater body mass index, waist, fat mass, leptin, systolic blood pressure, CRP and IL-6 levels, and lower HDLc and Apolipoprotein A1 levels. Children of women who gained less than the recommended amounts had lower levels of adiposity, but other cardiovascular risk factor tended to be similar in this group to offspring of women gaining recommended amounts. When examined in more detail greater pre-pregnancy weight was associated with greater offspring adiposity and more adverse cardiovascular risk factors at age 9. GWG in early pregnancy (0 to 14 weeks) was positively associated with offspring adiposity across the entire distribution, but strengthened in women gaining more than 500g/week. By contrast, between 14 and 36 weeks GWG was only associated with offspring adiposity in women gaining at least 500g/week. GWG between 14-36 weeks was positively and linearly associated with adverse lipid and inflammatory profiles with these associations largely mediated by the associations with offspring adiposity. Conclusions Greater maternal pre-pregnancy weight and GWG up to 36 weeks gestation are associated with greater offspring adiposity and adverse cardiovascular risk factors. Before implementing any GWG recommendations, the balance of risks and benefits of attempts to control GWG for short- and long-term outcomes in mother and child should be ascertained.

BACKGROUND The measurement of circulating anti-Müllerian hormone (AMH) has been applied to a wide array of clinical applications, mainly based on its ability to reflect the number of antral and pre-antral follicles present in the ovaries. AMH has been suggested to predict the ovarian response to hyperstimulation of the ovaries for IVF and the timing of menopause, and to indicate iatrogenic damage to the ovarian follicle reserve. It has also been proposed as a surrogate for antral follicle count (AFC) in the diagnosis of polycystic ovary syndrome (PCOS). METHODS This paper is a summary of presentations at a European Society of Human Reproduction and Embryology campus workshop on AMH, with literature cited until September 2013. Published peer-reviewed medical literature about AMH was searched through MEDLINE and was subjected to systematic review and critical assessment by the panel of authors. RESULTS Physiologically, recent data confirm that AMH is a follicular gatekeeper limiting follicle growth initiation, and subsequently estradiol production from small antral follicles prior to selection. AMH assays continue to evolve and technical issues remain; the absence of an international standard is a key issue. The dynamics of circulating AMH levels throughout life can be split into several distinct phases, with a peak in the early 20s before a decline to the menopause, with a strong and positive correlation with non-growing follicle recruitment. There is a more complex rise during childhood and adolescence, which is likely to be more reflective of different stages of follicle development. AMH shows limited short-term variability, but the influence of states such as prolonged oral contraceptive use need to be considered in clinical assessment. There are only very limited data on relationships between AMH and natural fertility at different stages of reproductive life, and while it has a relationship to age at menopause the marked variability in this needs further exploration. AMH may be useful in assessing the need for fertility preservation strategies and detecting post-chemotherapy or surgical damage to the ovarian reserve. Long-term follow-up of patients to ascertain fully the value of post-cancer serum AMH in predicting long-term ovarian function is required. There is a linear relationship between AMH and oocyte yield after ovarian stimulation, which is of value in predicting ovarian hyperstimulation. AMH can also identify 'poor responders', but it seems inappropriate at present to withhold IVF purely on this basis. Women with PCOS show markedly raised AMH levels, due to both the increased number of small antral follicles and intrinsic characteristics of those granulosa cells, and this may contribute to anovulation. The value of AMH in the diagnosis of PCOS remains controversial, but it may replace AFC in the future. CONCLUSIONS For the first time in female reproductive biology, it is possible to measure the submerged part of the iceberg of follicle growth, i.e. the intrinsic, so-called 'acyclic' ovarian activity. ...

Background The nature and contribution of different pregnancy related complications to future cardiovascular disease (CVD) and its risk factors, as well as mechanisms underlying these associations remain unclear. Methods and Results We studied associations of pregnancy diabetes, hypertensive disorders of pregnancy (HDP), preterm delivery and size for gestational age with calculated 10 year CVD risk (based on the Framingham score) and a wide range of cardiovascular risk factors measured 18 years after pregnancy (mean age at outcome assessment: 48 years) in a prospective cohort of 3,416 women. Gestational diabetes (GDM) was positively associated with fasting glucose and insulin, even after adjusting for potential confounders whilst HDP were associated with BMI, waist circumference, blood pressure, lipids and insulin. Large for gestational age (LGA) was associated with greater waist circumference and glucose concentrations, whilst small for gestational age (SGA) and preterm delivery were associated with higher blood pressure. The association with the calculated 10 year CVD risk based on the Framingham prediction score was OR=1.31 (95%CI: 1.11, 1.53) for preeclampsia and 1.26 (0.95, 1.68) for GDM compared to women without preeclampsia and GDM respectively. Conclusions HDP and pregnancy diabetes are independently associated with an increased calculated 10 year CVD risk. Preeclampsia may be the better predictor of future CVD since it was associated with a wider range of cardiovascular risk factors. Our results suggest that pregnancy may be an important opportunity for early identification of women at increased risk of CVD later in life.

and Reggio Emilia, Italy. His clinical activity covers all fields of reproductive medicine and surgery. He has published extensively; his current h-index is 44, with more than 8000 citations.

Plasma AMH is a superior predictor of live birth and anticipated oocyte yield compared with FSH and age, facilitating individualization of therapy prior to first ART cycle.

BackgroundAnti-Müllerian hormone (AMH) is a product of growing ovarian follicles. The concentration of AMH in blood may also reflect the non-growing follicle (NGF) population, i.e. the ovarian reserve, and be of value in predicting reproductive lifespan. A full description of AMH production up to the menopause has not been previously reported.Methodology/Principal FindingsBy searching the published literature for AMH concentrations in healthy pre-menopausal females, and using our own data (combined ) we have generated and robustly validated the first model of AMH concentration from conception to menopause. This model shows that 34% of the variation in AMH is due to age alone. We have shown that AMH peaks at age 24.5 years, followed by a decline to the menopause. We have also shown that there is a neonatal peak and a potential pre-pubertal peak. Our model allows us to generate normative data at all ages.Conclusions/SignificanceThese data highlight key inflection points in ovarian follicle dynamics. This first validated model of circulating AMH in healthy females describes a transition period in early adulthood, after which AMH reflects the progressive loss of the NGF pool. The existence of a neonatal increase in gonadal activity is confirmed for females. An improved understanding of the relationship between circulating AMH and age will lead to more accurate assessment of ovarian reserve for the individual woman.