Now, I want to say this... A male character that gets turned into a female after having spent a significant amount of time as a male (with 10+ years definitely being significant) should not be having their views changed quickly at all; thus if a boy gets turned into a girl, he should not immediately start liking other boys right away, if ever. Further, my own view is that someone born male and later turning female would be highly more likely to continue pursuing other females. What I'm basically trying to say is that completely feminizing a male character is the basis of a femslash story, in my own personal opinion; this of course coincides with my own personal opinion that femslash is acceptable, but regular slash is not (maybe it's wrong of me, but I can't seem to get myself to care).
That being said, my idea right now is having Mewtwo actually concede to being able to fix Ash's "stoned" condition from the end of the first movie, but somehow screws it up and while Ash is released from his stone prison, he is permanently transformed into a girl in the process, and nothing Mewtwo tries to do, even with Mew's help, can reverse it. Ash is released, but has to come to terms with the fact that he's now female, all the while stressing over whether it's even right to pursue his crush on Misty or if he should give it up since they are both girls now.
The idea has yet to germinate, though, so I guess it'll have to be thought out a little more. Needless to say it'll be an Ash/Misty story, though how far I take it is still a mystery (actually writing it would require getting back to work on story writing, though...).