Inflammatory immune response plays a key role in reproductive failures such as multiple implantation failures (MIF), early pregnancy loss, and recurrent pregnancy losses (RPL). Cellular immune responses particularly mediated by natural killer (NK), and T cells are often dysregulated in these conditions. Excessive or inappropriate recruitment of peripheral blood NK cells to the uterus may lead to cytotoxic environment in utero, in which proliferation and differentiation of trophoblast is hampered. In addition, inadequate angiogenesis by uterine NK cells often leads to abnormal vascular development and blood flow patterns, which, in turn, leads to increased oxidative stress or ischemic changes in the invading trophoblast. T-cell abnormalities with increased Th1 and Th17 immunity, and decreased Th2 and T regulatory immune responses may play important roles in RPL and MIF. A possible role of stress in inflammatory immune response is also reviewed.
In pregnancy, trophoblast proliferation, migration and invasion are important for the establishment and maintenance of a successful pregnancy. Impaired trophoblast function has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy, but the underlying mechanisms remain unclear. Indoleamine 2,3-dioxygenase (IDO), an enzyme that catabolizes tryptophan along the kynurenine pathway, is highly expressed in the placenta and serum during pregnancy. Here, we identified a novel function of IDO in regulating trophoblast cell proliferation and migration. We showed that IDO expression and activity were decreased in unexplained recurrent spontaneous abortion (URSA) compared to normal pregnancy. Furthermore, blocking IDO in human trophoblast cells led to reduced proliferation and migration, along with decreased STAT3 phosphorylation and MMP9 expression. Increased STAT3 phosphorylation reversed the IDO knockdown-suppressed trophoblast cell proliferation and migration. In addition, the overexpression of IDO promoted cell proliferation and migration, which could be abolished by the STAT3 signaling inhibitor (AG490). Finally, we observed similar reductions of STAT3 phosphorylation and MMP9 expression in URSA patients. These results indicate that the level of IDO expression may be associated with pregnancy-related complications, such as URSA, by affecting trophoblast cell proliferation and migration via the STAT3 signaling pathway.
Aim: This study aimed to compare the efficacy of long-and short-acting gonadotropin-releasing hormone agonist on clinical outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) long protocol cycles. Methods: In this retrospective study, 478 patients were enrolled from October 2012 to November 2014. The pituitary downregulation result, serum hormone levels, gonadotropin (Gn) dose during controlled ovarian hyperstimulation, and outcome of IVF/ICSI-embryo transfer were compared between the two groups. Results: Compared with the long-acting group, in the short-acting group the duration of downregulation and stimulation was significantly shorter; the total Gn doses, cost of an IVF cycle, rate of ovarian hyperstimulation syndrome, superior-quality embryo rate, and implantation rate were significantly lower; and the serum luteinizing hormone concentrations on the day of Gn and human chorionic gonadotropin administration were significantly higher. The serum estradiol level on the day of human chorionic gonadotropin was higher in the long-acting group. However, no significant differences were noted in other parameters. Conclusion: The long-acting group was associated with greater amounts of Gn and a longer duration of use for ovarian stimulation. This increased the cost per IVF cycle and may have had a detrimental effect on the pregnancy outcome because of a subsequent increase in the rate of ovarian hyperstimulation syndrome and decrease in the superior-quality embryo rate and implantation rate.
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