Expression of natural antimicrobials by human placenta and fetal membranes.

Preterm birth associated with infection is a major clinical problem. We hypothesized that this condition is associated with altered expression of natural antimicrobial molecules (beta-defensins (HBD), elafin). Therefore, we examined expression of these molecules and their regulation by proinflammatory cytokines in placentae and fetal membranes from term pregnancy. HBD1-3 and elafin were localized by immunohistochemistry in fetal membranes and placenta. Real-time quantitative PCR was used to examine mRNA expression in primary trophoblast cells treated with inflammatory molecules. HBD1-3 and elafin were immunolocalized to placental and chorion trophoblast layers of fetal membranes and placenta. Immunoreactivity was also observed in amnion epithelium and decidua. No differences were noted between samples from women who were not in labour compared to those in active labour. In in vitro cultures of primary trophoblast cells, HBD2 and elafin mRNA expression was upregulated by the proinflammatory cytokine, IL-1beta. These results suggest that the chorion and placental trophoblast layers may be key barriers to the progression of infection in the pregnant uterus. Natural antimicrobial expression may be altered in response to inflammatory mediator expression associated with the onset of labour and/or uterine infection, providing increased protection when the uterus may be particularly susceptible to infection.

Falling estradiol levels as a result of intentional reduction in gonadotrophin dose are not associated with poor IVF outcomes, whereas spontaneously falling estradiol levels result in low clinical pregnancy rates.

BACKGROUND: Although estradiol levels remain an integral part of monitoring in most IVF programmes, the effect of falling estradiol on IVF outcome has not been adequately quantified. The objective of this study was to evaluate the effect of falling estradiol levels prior to hCG on IVF outcome. METHODS: This was a retrospective cohort study carried out in a university-based fertility clinic. A total of 112 IVF patients in whom estradiol levels fell prior to the administration of hCG were matched for age and year of treatment with 112 control IVF patients. IVF outcomes including oocytes retrieved, fertilization rate, embryos for transfer, and pregnancy rates were compared between the groups. RESULTS: Seventy per cent of women in the falling estradiol group experienced spontaneously falling estradiol levels. Spontaneously falling estradiol was associated with fewer oocytes retrieved (median 5 versus 8, P=0.001), increased rates of failed fertilization (18 versus 6%, P=0.018) and lower clinical pregnancy rates (12 versus 26%, P=0.012) compared to controls. Despite marked decreases in estradiol levels, IVF outcomes for patients whose estradiol levels fell as a result of deliberate protocol modification had similar fertilization and clinical pregnancy rates as controls. CONCLUSIONS: Subtle (<10%) spontaneous decreases in estradiol levels are associated with very poor IVF outcomes.