Hi Neil,
I suspect that this is a common frustration for all Totara admins! but to answer your question, we set up a corporate (Outlook) email address and we now send all site traffic through this using SMTP. That gave us the ability to create an autoreply, advising the user that "this mailbox is not monitored, please forward your enquiry to..." or words to that effect. Like yourself, we've also added appropriate text into seminar confirmations.
Although I'm not convinced we'll ever reach zero replies, we have seen the volume drop over time, and as a side effect we now also have full visibility of all outgoing messages.
Hope this helps, and you're definitely not alone!
Thanks,
Ian