It's an absolute pain for even single direction communication, as most NATs are going to be stateful — they have to retain, somewhere, the mapping between internal IP/port & external port. And that mapping is in finite memory, and old mappings are usually timed out of it, killing the connection, if there is one.

(You can hack around this with keepalives, but it's just another PITA because of the original sin of breaking the end to end principle.)