Critical and differential roles of NKp46- and NKp30-activating receptors expressed by uterine NK cells in early pregnancy.

In early human pregnancy, uterine decidual NK cells (dNK) are abundant and considered as cytokine producers but poorly cytotoxic despite their cytolytic granule content, suggesting a negative control of this latter effector function. To investigate the basis of this control, we examined the relative contribution to the cytotoxic function of different activating receptors expressed by dNK. Using a multicolor flow cytometry analysis, we found that freshly isolated dNK exhibit a unique repertoire of activating and inhibitory receptors, identical among all the donors tested. We then demonstrated that in fresh dNK, mAb-specific engagement of NKp46-, and to a lesser extent NKG2C-, but not NKp30-activating receptors induced intracellular calcium mobilization, perforin polarization, granule exocytosis and efficient target cell lysis. NKp46-mediated cytotoxicity is coactivated by CD2 but dramatically blocked by NKG2A coengagement, indicating that the dNK cytotoxic potential could be tightly controlled in vivo. We finally found that in dNK, mAb-specific engagement of NKp30, but not NKp46, triggered the production of IFN-gamma, TNF-alpha, MIP-1alpha, MIP-1beta, and GM-CSF proinflammatory molecules. These data demonstrate a differential, controlled role of NKp46- and NKp30-activating receptors expressed by dNK that could be critical for the outcome of pregnancy and the killing of uterine cells infected by pathogens.

Clinical and biological parameters influencing implantation: score to determine number of embryos to transfer.

Choosing the number of embryos to be transferred is a major problem in assisted reproductive technologies. This study aimed to establish and validate a score predicting implantation rates in order to help in the choice of the number of embryos to be transferred, allowing the best compromise between high pregnancy rate and low multiple pregnancy risk. Clinical and biological parameters influencing implantation rates were retrospectively analysed in 739 embryo transfers and an implantation score was established. This score was then prospectively validated in 521 embryo transfers. Three parameters (age, ovarian response to FSH stimulation and embryo morphology) appeared to be predictive of the implantation rates and were included in an implantation score (3-9). The prospective study confirmed the validity of the score since implantation rates were higher when the score increased (5.9% for score 3 versus 22.4% for score 9; P < 0.05). Therefore, success rates can be predicted by the implantation score, which is of clinical value in choosing the number of embryos to be transferred in order to decrease multiple pregnancies while keeping high pregnancy rates. However, choosing the right number of embryos to be transferred needs further studies, since the percentage of multiple pregnancies remained relatively high in this prospective study (27%).