Late 42 onwards with the Allies new ASW...prepare to enter the killing fields
Naval and airforces work together to cut short your patrol
The surface is not your friend always keep an eye in the sky, DD's will work together to hunt you down, they wont give up easy.
Not saying it is impossible..You just need to Think about your target, and a plan to escape after..It all comes down to tactics
One good thing is there is a scale of difficulty, so you arn't thrown into the deep end .