Is it rude to ask the associate editor about manuscript status for second time? About six months ago I submitted a paper in one of the very reputed IEEE Transactions. I have observed from different papers published in that journal that the average time for receiving the first review is around 3 months. That is why I politely inquired about the status of the manuscript after around 4 months from the date of submission by sending a mail to the associate editor (AE). The AE promptly replied me about the status and said that two out of three reviews were still being awaited. However, it is now six months and I still do not see any change in the status of the manuscript in the online portal. 

So, my question is: is it too soon to send a second mail to the AE asking about the status of the manuscript and can such second mail irritate the AE to the point that it might negatively impact the review process of my manuscript?
I think it should be fine to inquire (politely, of course) at this point. While it may be a minor irritant, it should not affect the outcome of the acceptance decision provided the journal follows ethical practice. 

If you have a decision to make about the paper it is important to get the information. If it is just to ease your uncertainty then you could also let it go a bit longer. But there shouldn't really be a downside. Maybe a note would get the editor to prod the reviewers a bit.