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Background: Small body size at birth has been reported to be associated with an atherogenic lipid profile in humans, and animal experiments have shown that undernutrition during pregnancy permanently alters cholesterol metabolism in the offspring. There is no direct evidence in humans that maternal malnutrition during pregnancy affects the lipid profiles of the offspring., Objectives: We assessed the effects of maternal malnutrition during specific periods of gestation on plasma lipid profiles in persons aged approximately 50 y., Design: This was a follow-up study of men and women born at term as singletons in a university hospital in Amsterdam between 1 November 1943 and 28 February 1947 around the time of a severe famine., Results: Persons exposed to famine in early gestation had a more atherogenic lipid profile than did those who were not exposed to famine in utero. Their LDL-HDL cholesterol ratios were significantly higher (by 13.9%; 95% CI: 2.6-26.4%). Additionally, their plasma HDL-cholesterol and apolipoprotein A concentrations tended to be lower, and their plasma total cholesterol, LDL-cholesterol, and apolipoprotein B concentrations tended to be higher, although these differences were not statistically significant. The effect of famine was independent of size at birth and adult obesity., Conclusions: An atherogenic lipid profile might be linked to a transition from poor maternal nutrition in early gestation to adequate nutrition later on. This suggests that maternal malnutrition during early gestation may program lipid metabolism without affecting size at birth.

To assess the effect of maternal malnutrition during different stages of gestation on plasma concentrations of fibrinogen and factor VII, we investigated 725 people, aged 50 years, born around the time of the Dutch famine 1944-5. After adjustment for sex, plasma fibrinogen concentrations differed by -0.01 g/l (95% confidence interval, -0.14-0.11) in those exposed in late gestation, by -0.03 g/l (-0.16-0.11) in those exposed in mid gestation, and by 0.13 g/l (-0.03-0.30) in those exposed in early gestation, compared with non-exposed people (those born before and those conceived after the famine pooled together). Plasma factor VII concentrations differed by 0.4% (-5.4% to 6.6%) in those exposed to famine in late gestation, by 1.5% (-4.6% to 8.1%) in those exposed in mid gestation. and by -11.8% (-18.4 to -4.8%) in those exposed in early gestation, compared with nonexposed people. Size at birth was not associated with plasma concentrations of fibrinogen or factor VII. Our finding that factor VII concentrations were significantly lower in people whose mothers had been exposed to famine in early pregnancy suggests that liver function may be affected by undernutrition in early gestation.

Background: Associations have been found between a large head size at birth and atopy, and between low birth weight and obstructive airways disease. A study was undertaken of people born around the time of the Dutch famine in 1944-5 to determine the effects of maternal malnutrition during specific periods of gestation on the prevalence of obstructive airways disease and atopy., Methods: Nine hundred and twelve people aged about 50, born at term between November 1943 and February 1947 in Amsterdam, were asked about their medical history. Lung function was measured in 733 and serum concentrations of total IgE and specific IgE against mite, pollen and cat were measured in 726. Those exposed in late, mid, and early gestation (exposed participants) were compared with those born before or conceived after the famine (non-exposed participants)., Results: Exposure to famine during gestation affected neither the concentrations of total or specific IgE nor lung function values. The prevalence of obstructive airways disease was increased in people exposed to famine in mid gestation (odds ratio adjusted for sex 1.7, 95% confidence interval (CI) 1.1 to 2.6) and tended to be higher in those exposed in early gestation (odds ratio 1.5, 95% CI 0. 9 to 2.6)., Conclusions: The observed increase in the prevalence of obstructive airways disease in people exposed to famine in mid and early gestation was not parallelled by effects on IgE concentrations or lung function. The link between exposure to famine in mid and early gestation and obstructive airways disease in adulthood suggests that fetal lungs can be permanently affected by nutritional challenges during periods of rapid growth.

In the spontaneous menstrual cycle, the mid-cycle gonadotrophin surge causes maturation of the cumulus-oocyte complex, mucification of cumulus cells and expansion of the cumulus oophorus, resumption of meiosis and maturation of the cytoplasm of the oocyte. Whether this is an effect purely of luteinizing hormone (LH) or whether follicle stimulating hormone (FSH) also plays a role is unknown. The effect of an artificially induced FSH surge at the time of human chorionic gonadotrophin (HCG) injection on maturation of the cumulus-oocyte complex was investigated in a prospective randomized double-blind trial. Twelve patients underwent controlled ovarian hyperstimulation [long gonadotrophin-releasing hormone agonist (GnRHa)/human menopausal gonadotrophin (HMG) protocol] for in-vitro fertilization (IVF) treatment. At the time of HCG administration, six patients received a bolus injection of FSH (450 IU i.m.); the other six patients received a placebo. The peak plasma concentrations of FSH of the experimental group were compared with the peak values of FSH obtained at the mid-cycle gonadotrophin surge of the natural cycle of a group of 12 volunteers to validate the bolus injection of FSH. Maturation of the cumulus-oocyte complex was quantified by measuring the expansion of the cumulus, by the fertilization rate and the implantation rate. The quality of the embryos was scored according the average morphology score. The bolus injection of FSH mimicked the mid-cycle gonadotrophin surge. The mean peak value of FSH (12.9 IU/l) in the experimental group was fully comparable with the mean peak value of FSH (10.0 IU/l) of the mid-cycle gonadotrophin surge in the natural cycle. No effect of a bolus injection of FSH on the maturation of the cumulus-oocyte complex or any other outcome variable was found. It is not advantageous to combine the final HCG injection with a bolus injection of FSH in GnRHa/HMG stimulated cycles.

Because the process of conception is affected by many variables, a multiple logistic regression analysis was performed to assess (i) the impact and relative weight of both patient and embryo variables and (ii) their possible effects on the probability of a vital pregnancy after embryo transfer. A statistical model was constructed predicting the probability of pregnancy after embryo transfer. The variables that contributed significantly to the predictive value of the model were the age of the patient, the cause of infertility, the number of embryos transferred and the average morphology score of the transferred embryos. Embryo variables appeared to have a significant but modest value in predicting the probability of pregnancy after embryo transfer. Other variables, such as the thickness of the endometrium, were found to have no prognostic value. Moreover, we found that their effect could be explained by the variables already included in the model.