Completed a virgin run in warden difficulty using agility stat, man it's really hard without save scumming and I had to rely flaunting for the debuffs.
You can be defeated and not resort to save scumming. Just retreat. Besides, the "defeat fight" will not end with penetration, if you keep your desires low (which you should always do on a virgin run, during battle, which means forsaking using Ki or Focus just to keep a desire down; sucks but thats how it has to be). As a rule of thumb: dont get into fights when youre over 50% fatigued, as thats when you can no longer retreat from a fight (im not even mentioning the stat penalties). Fighting a orange/red/purple named Lizardman, if you cant one shot him at the start of the fight, will usually dictate a retreat; especially when youre heavily (up to 49%) fatigued.
Also, anyone knows how fatigue is calculated? does the number of enemies, number of turns and level of enemies have anything to do with it?
As for fatigue, im not sure on that, but it feels to me that the fatigue gain increases based on the level you are vs the level of enemies you fight. Dont think battle duration/turn count matters in this regard. There is, however, a direct correlation between fatigue and pleasure gain: the more fatigued you are, the quicker sadism will increase your pleasure. This can have a number of bad effects (low willpower regen + higher chance to fumble attacks when at high pleasure), bad passives included (orgasming mid-fight all the time does bad things to your stats, even if its unavoidable in some situations).