Be sure your Selle Italia saddle has a generous cutout for perineum relief. The earlier Selle Italias, like the Q-Bik, combined a small cutout with extra padding -- didn't really accomplish anything. The later Selle Italia SuperFlow models had a larger cutout. Ditto several other models with larger cutouts.

There are also noseless saddles from ISM and others, popular with time trialists and triathletes.

One of the more extreme saddles I've seen is the MoonSaddle. The cyclist said she really likes it, confirmed by the apparent wear on the saddle. I suspect it would require a little practice to adapt to that type of saddle, but it's worth considering.

Also, shorts padding that is too thick may defeat the purpose of the cutout saddle. I match my shorts to the saddle of the bike I plan to ride that day. One of my Selle Italia saddles has very little padding and no cutout or relief channel. It's most comfortable with the thickest, densest most resilient padded shorts and bibs I have. My Selle Italia Q-Bik is better with thinner padding -- excess padding fills the gap of the small cutout, while the saddle padding compresses -- the combination actually adds pressure rather than relieving pressure.

For my hybrid, I just got a Bontrager saddle with a generous cutout and a little more padding than I'd usually choose for a road bike. It's been comfortable on rides up to 20 miles wearing ordinary underwear and baggy shorts. Haven't tried it yet on a road bike with padded shorts.