Polycystic Ovary Syndrome Develops the Complications of Assisted Reproductive Technologies.

Ovarian hyperstimulation syndrome (OHSS) is a serious complication that remains a threat to every patient experiencing stimulation of ovulation. Polycystic ovary syndrome (PCOS) appears to be the most important predisposing factor for OHSS. The severity of OHSS is associated with the degree of the follicular response to the ovulation inducing agents. The objective of this study was to investigate the relationship between PCOS with the risk of moderate-to-severe OHSS in intracytoplasmic sperm injection treatment patients. Sixty patients in the reproductive ages (20-38), including OHSS patients and age-matched normoresponders were included in this study. Patients who had larger follicle counts on the day of hCG injection were considered at risk for developing moderate-to-severe OHSS. In addition, oocyte quality was assessed about 20-30 min after oocyte pickup. The incidence of OHSS in PCOS patients increased significantly up to 13.9 times higher than in patients without PCOS (OR=13.900; P=0.007). Moreover, moderate-to-severe OHSS increased significantly (OR=3.860; P=0.043) in patients with primary infertility than those with secondary infertility. In addition, oocyte quality was not affected with the severity of OHSS. In conclusion, the risk of moderate-to-severe OHSS is correlated with PCOS and primary infertility without affecting oocyte quality.

IL-1ß induces changes in expression of core circadian clock components PER2 and BMAL1 in primary human chondrocytes through the NMDA receptor/CREB and NF-κB signalling pathways.

The circadian clock is a specialised cell signalling circuit present in almost all cells. It controls the timing of key cell activities such as proliferation and differentiation. In osteoarthritis, expression of two components of the circadian clock, BMAL1 and PER2 is altered in chondrocytes and this change has been causally linked with the increase in proliferation and altered chondrocyte differentiation in disease. IL-1ß, an inflammatory cytokine abundant in OA joints, has previously been shown to induce changes in BMAL1 and PER2 expression in chondrocytes. The purpose of this study is to identify the mechanism involved. We found IL-1ß treatment of primary human chondrocytes led to activation of NMDA receptors as evidenced by an increase in phosphorylation of GluN1 and an increase in intracellular calcium which was blocked by the NMDAR antagonist MK801. Levels of phosphorylated CREB were also elevated in IL-1ß treated cells and this effect was blocked by co-treatment of cells with IL-1ß and the NMDAR antagonist MK-801. Knockdown of CREB or inhibition of CREB activity prevented the IL-1ß induced increase in PER2 expression in chondrocytes but had no effect on BMAL1. Phosphorylated p65 levels were elevated in IL-1ß treated chondrocytes indicating increased NF-κB activation. Inhibition of NF-κB activity prevented the IL-1ß induced reduction in BMAL1 expression and partially mitigated the IL-1ß induced increase in PER2 expression in chondrocytes. These data indicate that the NMDAR/CREB and NF-κB signalling pathways regulate the core circadian clock components PER2 and BMAL1 in chondrocytes. Given that changes in expression of these clock components have been observed in a wide range of diseases, these findings may be broadly relevant for understanding the mechanism leading to circadian clock changes in pathology.